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Photochemical Reactions of Carbohydrates
.
ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY VOL . 38
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES BY ROGER W . BINKLEY Department of Chemistry. Cleueland State Uniuersity. Cleveland. Ohio 441 15
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I1. Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I11. Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Aldehydes and Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 . Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
................................................
Alditols. Aldohexoses. and Related Compounds . . . . . . . . . . . VI . Sulfur-Containing Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Dithioacetals and Sulfides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Sulfoxides. Sulfones. and Sulfonates . . . . . ...................... 3. Thiocarbamates and Xanthides ............................... VII . Nitrogen-Containing Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
......................................... ............................................ s ......................................... 4 . Oximes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. Azines ...................................... VIII . Iodo Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 . Deoxyiodo Sugars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 . o-Iodobiphenylyl Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IX . Organometallic Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . X . Phosphates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
105 106 122 122 129 142 147 150 151 153 157 160 160 176 178 179 186 186 186 187 190 192
I . INTRODUCTION Study of the photochemical reactions of carbohydrates is a topic of longstanding interest among chemists; in fact. publications on this subject first appeared shortly after the beginning of the present century . Much of the early work in this area was concerned with changes. in the physical properties of reaction mixtures. arising from irradiations conducted under various conditions . Relatively little identification of the photoproducts was undertaken prior to the introduction of modern instrumentation . In recent years. interest in the photochemistry of carbohydrates has 105 Copyright @ 1981 by Academic Press. Inc. All rights of reproduction in any form reserved .
lSBN 0-12-007238-6
106
ROGER W. BINKLEY
intensified, and the major orientation of research in this field has changed. Synthetic chemists have become increasingly aware of the advantages offered by photochemical reactions. The possibilities raised by these advantages (for example, conducting reactions under mild conditions, synthesizing molecules not obtainable by other routes, and selectively reacting particular functional groups in multifunctional molecules) have stimulated study of the photolysis of a wide variety of carbohydrates and their derivatives. Several photochemical processes already have emerged as important, synthetic reactions, and others are certain to follow. The purpose of the present article is to review comprehensively those photochemical reactions of carbohydrates for which product structures have been established, and to apply current mechanistic reasoning to the understanding of these reactions. Two reviews of carbohydrate photochemistry already exist. The first' was published in this Series in 1963, prior to the considerable recent growth in this field, and the second2 was a brief summary published in the Japanese literature in 1973. An organizational plan based upon the type of functional group has been adopted here in presenting and discussing the photochemical reactions of carbohydrates.
11. ALKENES The most important photochemical reaction of carbon to carbon unsaturated carbohydrates is addition to the unsaturated system. Two types of addition reaction are readily recognized. The first consists of those in which the molecule adding to the carbohydrate does so by involving a m-bond of its own. Processes of this type, listed in Table I, are those which lead to formation of a new ring-system (cycloaddition). The second class of addition reaction is one in which a u-bond is broken in the molecule adding to the unsaturated carbohydrate. The reactions that belong to the latter category (see Tables I1 and 111) follow two basic patterns, and comprise the majority of the addition processes reported. Cycloaddition reactions (see Table I) involving unsaturated carbohydrates are regio- and stereo-selective. These selectivities can be understood by assuming that the photochemical interaction between the two m-systems results in formation of the more stable 1,Pdiradical. The reaction between 3,4,6-tria-acetyl-D-glucal (1) and acetone pro(1)G. 0. Phillips, Ado. Carbohydr. Chem., 18 (1963)9-59. (2)K. Matsuura,Kagaku No Ryoiki, 27 (1973)35-42.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
107
TABLEI Photochemical Cycloaddition Reactions between Unsaturated Carbohydrate Derivatives and Carbonyl Compounds Reactants
0
Products
tJ
CH,OR
+
RO
MeiMe
RO
I 1
R
I
=
o-cue*
Ae
iG, +I$
a
3
99
4
99
5
33
6
33
7
14
8
CH,OR
R = Ae
G
CH,OR
OR
Ref.
27
2
RO
RO
Yields (%)
CH.OR
t Me;Me
OR
RO R = Ae
44
9
(combined yield)
.:Q
11=
10,11
mchb 0 Me,C-CMe,
A
32
n
(Continued)
108
ROGER W. BINKLEY
TABLEI (Continued) Photochemical Cycloaddition Reactions between Unsaturated Carbohydrate Derivatives and Carbonyl Compounds Reactants
Products
Yields (%)
Ref.
10. 11
d
Oxetane hydrolysis product formed. formed. Not determined.
* Non-oxetane
products formed.
c
Dimer
vides an illustration (see Scheme 1).Diradical stability is maximized by attack at C-2 (regiochemistry determined) and by allowing the larger group attached to C-2 to become the equatorial substituent (stereochemistry For addition reactions other than cycloaddition, unsaturated carbohydrates follow one of two fundamental pathways. The more common of the two begins with radical formation arising from bond homolysis in the noncarbohydrate reactant. Radicals are either produced directly, from absorption of light, or indirectly, from hydrogen abstrac(3) Y. Araki, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 60 (1978)389-395. (4) K. Matsuura, Y. Araki, and Y. Ishido, Carbohydr. Res., 29 (1973) 459-468. (5) K. Matsuura, Y. Araki, and Y. Ishido, Bull. Chem. Soc. Jpn., 45 (1972) 3496-3498. (6) K . 4 . Ong and R. L. Whistler,]. Org. Chem., 37 (1972) 572-574. (7) B. Helferich and E. von Cross, Chem. Ber., 85 (1952) 531-535. (8) Y. Araki, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 64 (1978) 109-117. (9) Y. Araki, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 65 (1978)159-165. (10) P. M. Collins and B. H. Whitton,]. Chem. Soc. Perkin Trans. 1 , (1973) 1470-1476. (11) P. M. Collins and B. Whitton, Carbohydr. Res., 21 (1972) 487-489.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
109
TABLEI1
Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
CH=CH,
Q+ RH
0-CMe,
Ref.
Q7
CH,CH,R
0-CMe,
3
R = --SCMe
54
II
12,13
0
R=
411
45
14
(4)
R = -PHPh
75
15
R = -PH,
24
15=
14
oAo
u 6
55
+ CH,O,CCH
0-CMe,
0 II
16
HCNH, CH,O,CCH 0-CMe, I o=cNH, 45
(Continued)
TABLEI1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
Ref.
11
xo
XO R = SEt
R' = Rz = SEt
R = OEt
R' = H, R2 = OEt
X = Ac
R' = OEt, R2 = H
O \
60
/O
C Me,
18
R = -SCMe
61
0 R = - SCH,Ph R = -P(OEt),
69
18
95
19
10
20b
II
II
S
H H,C-C 0 0 C '' Me*
0-CMe,
HCO,
I
H,CO R = -CNH, II
16
0 R = --Me, I OH R = -P(OEt),
,CM% 15
31 33
II
S
110
21 19
9
19
TABLEI1 (Continued)
Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Ref.
Products and Yields (%)
HCO, ,CM% H,CO
I
65
26
X = Ac
0 R=-
i
xo
" II
X = Ac, R = -CNH,
46
13
X=Ac, R =
38
21
X = Ac, R = -CMe, I
24
31
23
76
23
OH
111
(Continued)
TABLEI1
(Continued)
Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
CH,OX
CH,OX
+
xoQOMe
CH,OX
Ref. CH,OX
RH
R X = Ac, R = -SEt X = Ac, R = -SPr
-(I)
X=Ac,R= X=Ac, R =
81
25
94
25 39
FOHMe,
39
66
-
X=Ac, R =
26
32
OR(-J
xoQ + R H ox X = Ac, R = -SEt X = Ac, R = -SPr X = Ac, R = -CNH, I1 0
ox 25
77
25
79 55
42
X=Ac, R = X = Ac, R = -CMe, I OH
20
xo
ox
xo
15
CH,OX
CH,OX
CH,OX
20
16
51
7
16
17
20 8'
+
+RH
xo R X = H, R = -P(OEt), II
90
X = Ac, R = -SEt x = AC, R = a p r
44
44
25
47
47
25
19
S
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
113
TABLE I1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Products and Yields (%)
Reactants $!H,OX
FH,OX
X = H, R = -CH,OH
66 65-85
X = H, R = -CMe, I OH
Ref.
27,28 28 27,28,29
X = Ac, R = -CH,OH
75
OH I X = Ac, R = -CHCH,
65-85
28
42
29
75 65-85
27 28
75-79
30,31
X = Ac, R = -CH OH I
-(:I
X = Tr, R = -C&OH X = Tr, R = -CMe, I OH
X = Tr, R = -CHC&OH I OH
X = Tr, R = -CHCH,CH,OH I
49
30
32
30
67 62
30,32 32
42
32
58
30,32
OH
X = Tr, R = -CHC&C02Me I
OH X = Tr, R = Ac X = Tr, R = -CHC&CH,
A
0
P
X = Tr, R = -CHOH
I
O*O
U
X = Tr, R = Bz
(Continued)
ROGER W. BINKLEY
114
TABLEI1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
Ref.
CH,OX O
a
o
4
-
RH
CH3
<:I
30
29
X = Ac, Y = Et, R = -CH,OH
60
29
X = TT, Y = Et, R = -CH,OH OH
61
27
X = Tr, Y = Me, R = -CHCH,OH
71
30
X = T r , Y = M e , R = -CH
46
30
X = Ac, Y = Et, R = -CH OH I
I
I
OH
+
EtOH HOCHCH,
33
56
CKOX
CH,OX
HO
c%ox 28
Q
X=
O
Tr
M 0
e -!-
H O H , C Q 0M e
65
’ “ Q O M0 e
24
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
115
TABLEI1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants YH,OX
Products and Yields (%)
Ref.
qH,OX 34
X=
Tr
X=
Bz
" Minor product formed.
60
Five other products formed.
Acetone addition-product formed.
D. Horton and W. N. Turner, Carbohydr. Res., 1 (1966)444-454. D. Horton and W. N. Turner, Chem. Znd. (London),(1964) 76. J . S. Jewel1 and W. A. Szarek, Tetrahedron Lett., (1969) 43-46. R. L. Whistler, C.-C. Wang, and S. Inokawa,J. Org. Chem., 33 (1968)2495-2497. A. Rosenthal and M. Ratcliffe, Can. J . Chem., 54 (1976) 91-96. A. A. Othman, N. A. Al-Masudi, and U. S. Al-Timari, J. Antibiot., 31 (1978) 1007-1012. K. Matsuura, S. Maeda, Y. Araki, and Y. Ishido, Tetrahedron Lett., (1970) 2869-2872. K. Kumamoto, H. Yoshida, T. Ogata, and S. Inokawa, Bull. Chem. Sac. Jpn.. 42 (1969)3245-3248. K. Matsuura, K. Nishiyama, K. Yamada, Y. Araki, and Y. Ishido, Bull, Cham. Soc. J p n . , 46 (1973)2538-2542. A. Rosenthal and K. Shudo,J. Org. Chem., 37 (1972) 1608-1612. A. Rosenthal and M. Ratcliffe, Carbohydr. Res., 54 (1977) 61-73. Y. Araki, K. Nishiyama, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 64 (1978) 119-126. A. Rosenthal and M. Ratcliffe, Carbohydr. Res., 39 (1975) 79-86. Y. Araki, K. Matsuura, Y. Ishido, and K. Kushida, Chem. Lett., (1973) 383-386. K. Matsuura, Y. Araki, Y. Ishido, and S. Satoh, Chem. Lett., (1972) 849-852. B. Fraser-Reid, N. L. Holder, D. R. Hicks, and D. L. Walker, Can. J . Chem., 55 (1977) 3978-3985. B. Fraser-Reid, N. L. Holder, and M. B. Yunker,J. Chem. Soc. Chem. Commun., (1972) 1286-1287. B. Fraser-Reid, D. R. Hicks, D. L. Walker, D. E. Iley, M. B. Yunker, S. Y.-K. Tam, and R. C. Anderson, Tetrahedron Lett., (1975) 297-300. B. Fraser-Reid, R. C. Anderson, D. R. Hicks, and D. L. Walker, C a n ] . Chem., 55 (1977)3986-3995. D. L. Walker and B. Fraser-Reid,J. Am. Chem. Soc., 97 (1975) 6251-6253. D. R. Hicks, R. C. Anderson, and B. Fraser-Reid, Synth. Commun., 6 (1976) 417421. H. Paulsen and W. Koebernick, Carbohydr. Res., 56 (1977) 53-66. D. L. Walker, B. Fraser-Reid, and J. K. Saunders,J. Chem. Soc. Chem. Conamun., (1974)319-320.
ROGER W. BINKLEY
116
TABLEI11 Addition Reactions between Solvent Molecules and Electronically Excited, Unsaturated Carbohydrate Derivatives
&+Q+b
Reactants
0 +
CH,OX
RH
+
MeCMe II 0
xo
Ref.
Products and Yields (%)
xo
xo
xo R
4
74
X = Ac, R = -CMe, I
3
8 (9)
OH X = Ac, R = -CMe,
4
86
I
OH X = Ac, R = -CNH, II 0
22
X = Ac, R =
37
]I(-
0
iRH
xo
-(I]
X = Ac, R =
+
30
35
31
20
MeCMe I1
0 29
10
CHMe, I OH I
a
iCH,CHCH,
H2cQ
22
36
HOCMe,
+
MeCMe 0,
9
C Me,
6
19
5
9
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
117
TABLEI11 (Continued) Addition Reactions between Solvent Molecules and Electronically Excited, Unsaturated Carbohydrate Derivatives Products and Yields (%)
Reactants
Ref.
ROH
31
R = Me R =H
30 (unstable)
0 CH,OR
+
RO
Me;Me 0
hv
RO
-
CMe,
I
More stable
Less stable
(not formed)
J 2
More stable
0-CMe,
Less stable (not formed)
Scheme 1.-Proposed Mechanism for Cycloaddition between 3,4,6-Tri-O-acetyl-Dglucal (1) and Acetone. (35) A. Rosenthal and A. Zanlungo, C a n . ] . Chern., 50 (1972) 1192-1198. (36) Y. Araki, K. Nishiyama, K. Matsuura, and Y. Ishido, Carbohydr. Res., 63 (1978) 288-292. (37) B. A. Otter and E. A. Falco, Tetrahedron Lett., (1978) 4383-4386.
ROGER W. BINKLEY
118 MeCMe
hv
MeCMe
II 0
MeCMe II O*
+
0
(o)
It
O*
-
CH,;HCH, I
+
*(
OH
Initiation steps
1
0 0
n
LQll+.(l - b7by .Yo
CH=CH,
CH,-CH,.
0-CMe,
3
~' ( - H ,H cc
0-CMe,
L e s s stable (not formed)
0-CMe,
More stable
0-CMe, 4
Scheme 2.-Proposed Mechanism for Photochemically Initiated, Radical Addition of 1,3-Dioxolane t o 5,B-Dideoxy-1,2-0-isopropylidene-a-~-xyb-hex-5-enofuranose (3).
tion by excited acetone (see Scheme 2). Regioselectivity in these reactions (see Table 11) is determined by addition (anti-Markovnikov) to the double bond in order to maximize the stability of the new radical produced. An example of this selectivity is the photochemical addition of 1,3-dioxolane to 5,6-dideoxy-1,2-0-isopropylidene-a-~-xyZo-
119
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES less hindered MeC
,OCH,
I
Me,C:
52 +'
'OCH
0
n'
0-CMe,
H,C
/ II
5
"XO]
\.
H
O
Mk
more hindered
6
Scheme 3.-Proposed Mechanism for Photochemically Initiated, Radical Addition of 1,3-Dioxolane to 3-Deoxy-1,2:5,6-di-0-isopropylidene-3-C-methylene-~-~~~~~-hexofuranose ( 5 ) .
hex-5-enofuranose (3)to give exclusively14 2-(5,6-dideoxy- 1,2-0isopropylidene - a - D -xylo - hexofuranose - 6 - yl) - 1,3- dioxolane (4) (see Scheme 2). The stereochemistry in these reactions can usually be predicted by assuming that the radical resulting from initial reaction (for example, radical 7 in Scheme 3 ) will be approached from its less-hindered side. In contrast to the radical addition just described, the less-common of the two reaction pathways mentioned in the preceding paragraph requires that the unsaturated carbohydrate be electronically excited (see Scheme 4). A significant characteristic of alkenes experiencing this type of reaction (see Table 111) is that the double bond is conjugated with an oxygen atom. The triplet energy of such a molecule is sufficiently lowered b y conjugation to allow transfer of energy from acetone to the carbohydrate (see Scheme 4).Once transfer of energy has occurred, the excited carbohydrate can abstract a hydrogen atom from the solvent in the way shown in Scheme 4 for the reaction of 3,4,6tri-O-acetyl-D-glUca1 (1) with 2-propanol.
120
ROGER W. BINKLEY FH,OX n*
T
CH,CCH, (excited)
$"":
energy transfer
0 H
H I
(excited)
+
+
CH,CHCH, I OH
I
CH,CHCH, I OH
1
hydrogen abstraction
hydrogen abstraction
2 Me,eOH
Me,bOH
+
+
YH,OX
xoO
J
H H
radical addition ( s e e Scheme 2)
0 CH,OX
xo
H
HOCMe,
9
8
8%
74 46
X = Ac
Scheme 4.-Proposed Mechanism for Reaction between 2-Propanol and Excited 3,4,6-Tri~-acety~-D-g~ucal (1).
The relative proportions of unsaturated carbohydrate, sensitizer (usually acetone), and solvent may have a decided effect upon a photochemical addition reaction, as at least three competing processes (cycloaddition, radical addition, and energy transfer) are possible. The irradiation of 1in the presence of 2-propanol and acetone provides an illustration (see Scheme 4). When a small proportion of sensitizer
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
-O, I ,CMe,
R =
Me$,
HCO
1 I
HCO, ,C% Hzco
Scheme 5.-Photochemical, Bond.
and
121
/o-
I
OCH
l I H$O’
HCO,
CMez
E -Z Isomerization of Groups Attached to a Double
(acetone) is present, energy transfer and radical addition occur, although energy transfer dominates the reaction. (A detailed study of the competition between these two processes would be interesting.) If the concentration of acetone is raised sufficiently, the third process, cycloaddition (see Scheme l),becomes the major reaction-pathway? Several other types of photochemical reactions involving unsaturated carbohydrates have been reported. One of these is38photochemical, E -2 isomerization of the groups attached to a double bond (see Scheme 5). A second is the internal cycloaddition between two double bonds connected by a carbohydrate ~ h a i n H ~Although -~l the carbohydrate portion of the molecule is not directly involved in this cycloaddition, its presence induces optical activity in the cyclobutane derivatives produced photochemically. Finally, a group of acid-catalyzed addition-reactions has been observed for which the catalyst appears to arise from photochemical decomposition of a noncarbohydrate reactant?244 (38) A. Ducruix, C. Pascard-Billy, S. J. Eitelman, and D. Horton,]. Org. Chem., 41 (1976) 2652-2653. (39) B. S. Green, Y. Rabinsohn, and M. Rejto,J. Chem. Soc. Chem. Commun., (1975) 313-314. (40) B. S. Green, Y. Rabinsohn, and M. Rejto, Carbohydr. Res., 45 (1975) 115-126. (41) B. S. Green, A. T. Hagler, Y. Rabinsohn, and M. Rejto, Zsr. /. Chem., 15 (1976177) 124-130. (42) K. Matsuura, Y. Araki, Y. Ishido, and M. Kainosho, Chem. Lett., (1972) 853-856. (43) K. Matsuura, K. Senna, Y. Araki, and Y. Ishido, Bull. Chem. SOC. Jpn., 47 (1974) 1197-1200. (44) J. Csaszar and V. Bruckner, Ann. Univ. Sci. Budapest. Rolondo Eotvos Nominatae, Sect. Chim., (1973) 87.
122
ROGER W. BINKLEY a-cleavage
R
I
n
Rz
intermolecular
n*
t
R~R+-OH
R3H
% '\
+
..
W,,,
abstraction hydrogen Excited state
R', $-OH
intramolecular
R'
n = Electron in bonding n-orbital I*
= Electron in antibonding n-orbital
Scheme 6.-Potential
Reactions of a Carbonyl, n
-+
n*, Excited
State.
111. CARBONYL COMPOUNDS Carbonyl compounds have, thus far, more frequently been the subject of photochemical study than any other group of organic molecules. The reactions of these compounds may be understood by assuming that absorption of light leads to an n += T * excited state, that is, an excited state in which an electron has been promoted from the highest, nonbonding orbital (on oxygen) to the lowest, antibonding (T*)orbital (see Scheme 6). The reactions of such an excited system are similar to those of an alkoxyl radical and, thus, may include a-cleavage, hydrogen abstraction (intra- and inter-molecular), and addition to a .rr-system (see Scheme 6).
1. Aldehydes and Ketones A photochemical reaction initiated by a-cleavage in a carbonyl compound is called a Type I pr0cess.4~Photolysis of tert-butyl-3,4-O-iso(45) C. H. Bamford and R. G. W. Norrish,J. Chem. SOC., (1938) 1521-1525.
k3
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
123
\O 13.14 I
I
hydrogen transfer
-(OL0CMe3
Me+; Me 12
Scheme 7.-Proposed Mechanism for Type I Reaction of tert-Butyl3,4-O-Isopropylidene-cu-~-mythro-pentopyranosid-2-ulose(10).
propylidene-a-~-erythro-pentopyranosid-2-ulose (10) (see Scheme 7) produces three such reactions (decarbonylation, disproportionation, and ~tereoisomerization).46"~ Irradiation of 5-deoxy-1,2-O-isopropylidene-p-~-threo-pentofuranos-3-ulose (15) (see Scheme 8) provides an example of a fourth (carbene Type I reactions are more common for carbohydrate systems than for most other types of molecules, because the likelihood of occurrence of a Type I process is related to the stabilization, during formation, of the radicals produced (46) P. M . Collins, P. Gupta, and R. Iyer, Chem. Commun., (1970) 1261-1262. (47) P. M. Collins, R. Iyer, and A. S. Trdvis,J. Chem. Res. (S), (1978) 446-447 and J. Chem. Res. ( M ) , (1978) 5344-5360. (48) P. M. Collins, N. N. Oparaeche, and B. R. Whitton,J. Chem. SOC. Chem. Commun., (1974) 292-293.
124
ROGER W. BINKLEY
c 0
H,C
0-CMe, I5
0
rotation necessary for effective stabilization
Orbital picture for 3,4-c1eavage effective radical forms
L
J
Orbital picture for 2,3-cleavage
Hq!-!-
Me0
0-CMe,
0-CMe,
16, 17
Scheme 8.-Proposed Mechanism for Carbene Formation from Photolysis of 5Deoxy-1,2-O-isopropylidene-~-~~erythro-pentofuranos-3-ulose (15). Rationalization for the Direction of a-Cleavage.
by a-cleavage. In carbohydrate systems, where a radical center on carbon will usually have an adjacent, stabilizing, oxygen atom, a-cleavage is particularly f a ~ o r e d . 4The ~ . ~Type ~ I reactions of carbohydrates reported are listed in Table IV. Although an excited carbonyl can fragment at either of the two carbon to a-carbon bonds thereof, the favored direction of fragmentation (49) K.-G. Seifert, Tetrahedron Lett., (1974) 4513-4516. (50) S. Steenken, W. Jaenicke-Zauner,and D. Schulte-Frohlinde, Photochem. Photobiol., 21 (1975) 21-26.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
125
TABLEIV Type I Reactions of Excited Carbohydrate Derivatives Products and Yields (70)
Reactants
Me2
Me2
54
6
Ref.
51- 53
eOMe a
77
53
53
17
MezcLv '0
'02
OCMe,
0 10
I3
14
12
13
11
40
46,47
0 13
14
12
13
11
40
46,47
(Continued)
ROGER W. BINKLEY
126
TABLEIV (Continued) Type I Reactions of Excited Carbohydrate Derivatives Ref.
Products and Yields (%)
Reactants
P
Me
M e , C L d m M e 3
41
"+' 00CMe3 Me$ '
60
u-r+ CH,O
o\
9
o\
/o
0
Me&-0
0 0-CMe,
0-CMe,
55
10
Me&
'Q+
55
10
Me$-0 48
Me&-0
0
C
54
0
O?
0 I Me&-0
C
0-CMe,
EtoH
OEt
65
PHOTOCHEMICAL REACTIONS O F CARBOHYDRATES
127
TABLEIV (Continued) Type I Reactions of Excited Carbohydrate Derivatives ~~
Reactants
Products and Yields (%)
Ref.
48
MeoQY
0-CMe,
CHO ~ O A C
I
CH,OAc I
AcOCH
AcOCH
I
I
HCOAc
HCOAc
HCOAc
HCOAc
I
I I
CH,OAc
I
CH,OAc 16
may often be predicted by examining the structure of the reacting molecule. The critical factor in determining which a-cleavage will result is stabilization of the developing radicals (or diradicals, in cyclic ketones) during formation. This stabilization is not only dependent upon the presence of radical-stabilizing groups on the a-carbon atoms but also on the positioning of these groups. The photolysis of 15 (see Scheme 8) provides an informative illustration, because, as the C-2-C-3 bond in excited 15 begins to break, a nonbonding orbital on the oxygen atom on C-2 is properly aligned to stabilize the developing radical-center on C-2. In contrast, the radical center on C-4 that is being formed by fragmentation of the C-3-C-4 bond will not experience stabilization from a nonbonding orbital on the oxygen atom on C-4 until the C-3-C-4 bond is broken and rotation can occur. As a result, cleavage of the C-2-C-3 bond is favored.53 Intramolecular hydrogen-abstraction to produce a 1,4-diradical is the major, photochemical pathway for molecules in which the oxygen (51) P. (52) P. (53) P. (54) P. (55) K. (56) R.
M. Collins, Chem. Commun., (1968)403-405. M. Collins and P. Gupta,]. Chem. Soc., C, (1971) 1965-1968. M. Collins,J. Cheni. SOC., C, (1971) 1960-1965. M . Collins and P. Gupta, Chem. Commun., (1969) 1288-1289. Heyns, R. Neste, and M. Paal, Tetrahedron Lett., (1978) 4011-4014. L. Whistler and K . 3 . Ong,]. Org. Chem., 36 (1971) 2575-2576.
56
XO
XO 18
I
xo
X = Ac
19
Scheme 9.-Proposed Mechanism for Formation of Cyclobutanol from the Photolysis of 1,3,4,5,6-Penta-O-acetyl-keto-~-sorbose (18). Me
0
HO -5(
II
CH,OCCMe
*yH-O
,c=o
hv
0-CMe,
/
20
0-CMe,
Me&-0 0-CMe, 21
t H,C =C=O Scheme 10.-Proposed Mechanism for Type I1 Reaction of 1,2:3,4-DiO-isopropylidene-6-O-pyruvoyl-a-~-galactopyranose (20).
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
129
atom of an excited carbonyl can come within bonding distance of a hydrogen atom attached to a y-related carbon atom. (Such a process is possible for all of the compounds in Tables V and VI.) The reactions of the 1,Cdiradical produced by hydrogen abstraction are called Type I1 processes, and may include closure to form a cyclobutanol (see Scheme 9), fragmentation of the 2,3-bond to produce a new carbonyl compound (see Scheme lo), and reversal of the hydrogen-abstraction process to regenerate the starting material (or an epimer). Photolysis of a-ketoesters provides an example of the synthetic potential of the Type I1 reaction, as synthesis and irradiation of these compounds accomplish oxidation of alcohols to carbonyl compounds under quite mild conditions (see Table VI). For molecules in which intramolecular hydrogen-abstraction (Type I1 reaction) is structurally prevented, intermolecular abstraction from a hydrogen-donating solvent may take place (see Scheme 6). This type of reaction usually results in reduction of the carbonyl group (see Table VII). Cycloaddition reactions between alkenes and noncarbohydrate, carbonyl compounds have been described in discussing the reactions of alkenes (see Table I and Scheme 1). The depiction of the excited carbonyl given in Scheme 6 is useful in understanding the regiochemistry of the cycloaddition process, as it suggests that the electrondeficient oxygen atom in the excited carbonyl will react with the alkene to produce the (more-stable) 1,4-diradical. Table VIII lists cycloaddition reactions in which the excited carbonyl is part of a carbohydrate. 2. Esters When considered as a part of the photochemistry of carbonyl compounds, irradiations of esters constitute a minor component. The more frequent photolyses of other carbonyl compounds, in particular ketones, is not surprising, as, even though parallels exist between ester and ketone photochemistry (for example, both experience a-cleavage and hydrogen abstraction-reactions), esters require radiation of higher energy for reaction, and typically produce more-complex mixtures of products. In addition to their similarity to other carbonyl compounds in their reactivity, esters also experience reactions that are uniquely their own. When the esters listed in Table IX are irradiated, typical carbonyl reactions result; that is, each of these compounds (22-27) experiences both a-cleavage and hydrogen-abstraction reactions. For the esters of 1,2:3,4-di-O-isopropylidene-cr-~-galactopyranose (22-26), the hydrogen-abstraction reaction is internal, and leadsagto a Type I1 reaction
ROGER W. BINKLEY
130
TABLEV Type I1 Reactions of Excited Carbohydrate Derivatives" Reactants
OX
Ref.
Products and Yields (%) CH,OX
XOCH, x o V
C
H
,
O
X
xo
ox X = Ac
12
57
CH,OX
x o c ~ c . xo
xo
ox 18
Me,C-0 ' Q
O
57
26 (19)
M
5459
e 0
0
0 (No yield reported)
R=H R = Me
58
RCH
R C /OCH= f o o o M e
0 R = Ph R = Me
58,59
50
0
0 3
46
58
(No yields reported)
58
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
131
TABLEV (Continued)
Type I1 Reactions of Excited Carbohydrate Derivatives" Reactants
0
R R
=
Products and Yields (%)
HO
OMe
Ph
0
Ref.
0 4
65
58
(No yields reported)
= Me
58
" Additional examples of Type I1 reactions are probable, but product structures not established.60
TABLEVI. Type 11 Reactions of a-Ketoesters of Carbohydrates
Reactants
Products and Yields (%) RCH II 0
RCH,OCCMe I1 I1
00
R=
R=
References
0-J
xo
70
61,62
65
61,62
85
62
I
ox
X=
Ac
(Continued)
ROGER W. BINKLEY
132
TABLEVI
(Continued)
Type I1 Reactions of a-Ketoesters of Carbohydrates Products and Yields (%)
Reactants
62
References
61,62
Me&-0 \ ,c=o
-CH-OCCMe I IIII -7 00
R
R= I
74
61,62
57
61,62
100
62
70
62
1
(-J--r 0 0-CMe,
R=
0 I
Me$-0
I
XOCH,
R=
xo
I ox
X=
R=
AC
Qox
xo
X = AC
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
133
TABLEVI (Continued)
Type I1 Reactions of a-Ketoesters of Carbohydrates Reactants
Products and Yields (%)
R=
References
38
63
59
63
80
63
79
63
0-CMe, TrOCH,
0
R=
Q7
0-CMe,
X1= H, X = Me X1 = Me, X = H
X = Tr
X = Bz
61 68
63,64 63,64
(Continued)
ROGER W. BINKLEY
134
TABLEVI (Continued)
Type I1 Reactions of a-Ketoesters of Carbohydrates Products and Yields (%)
Reactants
References
0
X = Tr X = BZ
57
63,64
57
63,64
TABLEVII
Reactions of Excited Carbonyl Groups in Carbohydrate Derivatives with Solvent Molecules
Mecay mce? Products and Yields (70)
Reactants
0
0-CMe,
HOCH,
0-CMe,
0
0-CHEt
0-CMe,
HO
SO
Ref.
65
HOCH,
0-CHEt
HO
OH
HO
20
22
65
0-CHEt
66
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
135
TABLEVIII Cycloaddition Reactions between Excited Carbonyl Groups in Carbohydrate Derivatives and Unsaturated, Non-Carbohydrates Reactants
Products and Yields (%)
References
R b ° 0F o R = -CH,OAc
57
67
R = -COEt
23
67
19
68
II
0
RCH II
0 R=
+
0 I
OCH +CMe, HCO’ HC 0, ,CMe, H,CO
I
R = 0-CMe, X = CH,Ph
X = Me
10
14 19
68 68
68
ROGER W. BINKLEY
136
TABLEIX Photochemical Reactions of Esterified Carbohydrates" Products and Yields (%)
Reactants
0-CMe,
I
R = Ph (zd R = CH,Ph ( c d (24)
R = -CHPh, (25) R = -CPh, (no) I Me
I
0-CMe,
0-CMe, 28
R = CH,CH,Ph
References
29
3
12
69
26
50
69
3
8
69
10
29
69
5
27
69
0
EOMe
33
HOQOMe
HOO OH
27
O
M
+
e
70
OH R' = Rz = H
R'
=
(30)
H, R2 = -CH,OH
R' = -CH,OH,
RZ = H
(No yields reported)
(31)
(32)
&H
Ho
34
Additional examples of this type of reaction are probable, but product structures not e~tablished."-'~
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
137
TABLEX
Photochemical Reactions of Esterified Carbohydrates with Hexamethylphosphoric Triamide Reactants
Products and Yields (%) RH
ROAc
ROH
Ref.
85
74
65
75
0-bMe,
65
30
74
R= 65
75
81
74
70
75
78
74
60
14
R=
R=
I 1
Me$-0
(Continued)
ROGER W. BINKLEY
138
TABLEX
(Continued)
Photochemical Reactions of Esterified Carbohydrates with Hexamethylphosphoric Triamide Products and Yields (%)
Reactants ROAc
RH
Ref.
ROH
76
R=
’
Me,C-0 Q
R=
O
M
e
(No yields reported)
75
(No yields reported)
75
R= I
74
55
75
70
75
I
Me,C-0
R=
0c A C M CH,I e 2
I Me,C-0
’
Me$-0
G
H,C
O
ox M
e CH2
X = Ac
51
9
15
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
139
TABLEX (Continued) Photochemical Reactions of Esterified Carbohydrates with Hexamethylphosphoric Triamide Products and Yields (%)
Reactants ROAc
RH
Ref.
ROH
Me C / b o M e O\
ox 50
X = Ac XOCH,
HOQ
O
M
e
HOO
O
75
CH3
M
e
H O O O M e
OX X = Ac
10
20
75
X = -CCMe, 1 I 0
10
20
75
,OCH2 Me2C ‘OCH
I
G? 0
0-CMe,
X = -CCMe,
75
II
0
(57) R. L. Whistler and L. W. Doner,]. Org. Chem., 38 (1973) 2900-2904. (58) P. M. Collins, P. Gupta, and R. Iyer, J. Chem. SOC. Perkin Trans. 1 , (1972) 1670-1677. (59) P. M. Collins and P. Gupta, Chem. Commun., (1969) 90. (60) I. Kitagawa, K. S. Im, and Y. Fujimoto, Chem. Pharm. Bull., 25 (1977) 800-808. (61) R. W. Binkley, Carbohydr. Res., 48 (1976) cl-c4. (62) R. W. Binkley,]. Org. Chem., 42 (1977) 1216-1221. (63) R. W. Binkley, D. G. Hehemann, and W. W. Binkley, J . Org. Chem., 43 (1978) 2573-2576. (64) R. W. Binkley, D. G. Hehemann, and W. W. Binkley, Carbohydr. Res., 58 (1977) clO-cl2.
140
ROGER W. BINKLEY
J
I
22- 26
hydrogen abstraction
28
29
R' = alkyl or aromatic group,
".I;1.
R2 = Me,C-0
0-CMe,
Scheme 11.-Proposed
Mechanisms for Type I and Type I1 Reactions of Esters
22-26.
(Scheme 11).For methyl (methyl D-g1ucopyranosid)uronate (27a,b),acleavage is accompanied by a rearrangement'O initiated by hydrogen abstraction from the solvent (Scheme 12). A reaction unknown for other carbonyl compounds occurs when es~~~~
(65) P. M. Collins, V. R. N. Munasinghe, and N. N. Oparaeche,J. Chem. Soc. Perkin Trans. 1 , (1977) 2423-2428. (66) W. A. Szarek and A. Dmytraczenko, Synthesis, (1974) 579-580. (67) Y. Araki, J.-I. Nagasawa, and Y. Ishido, Carbohydr. Res., 58 (1977) C4-C6. (68) J. M. J. Tronchet and B. Baehler, J. Carbohydr. Nucleos. Nucleot., 1 (1974) 449-459. (69) R. W. Binkley and J . L. Meinzer, J. Carbohydr. Nucleos. Nucleot., 2 (1975) 465-469. (70) A. G. W. Bradbury and C. von Sonntag, Carbohydr. Res., 60 (1978) 183-186. (71) I. Kitagawa, M. Yoshikawa, and I. Yosioka, Tetrahedron Lett., (1973) 3997-3998. (72) I. Kitagawa, M. Yoshikawa, Y. Imakura, and I. Yosioka, Chem. Phann. Bull., 22 (1974) 1339-1347. (73) I. Kitagawa, M. Yoshikawa, Y. Imakura, and I. Yosioka, Chem. Znd. (London), (1973) 276-277. (74) J.-P. Pete and C. Portella, Synthesis, (1977) 774-775. (75) P. M. Collins and V. R. Z. Munasinghe,]. Chem. Soc. Chem. Commun., (1977) 927-928.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
141 OMe I 'COH
OMe
c=o
a-cleavage
H-abstraction
1 4COMe I
MeOH
p M e
+ no
CH,
OH
33
34
Scheme 12.-Proposed
Mechanism for Photochemical Reactions of Methyl (Methyl D-G1ucopyranosid)uronates(27a,b).
terified carbohydrates are photolyzed in hexamethylphosphoric triamide. Such irradiations result in replacement of the ester group by a hydrogen atom and, thus, are u s e f ~ l ' ~ for , ' ~ synthesizing deoxy sugars (see Table X). Although the yields of deoxy sugars are normally good, formation of an alcohol competes in some instances. Depicted in
ROGER W. BINKLEY
142
0 II
RTOCMe + (Me,N),PO
hv
transfer
:0: I
RSCOCMe H
.+
\CH,NPOX,
I
Me
R3CH R 3 = carbohydrate residue
X = -me,
O=C
f
,o‘Me
+
H,C=NPOX,
I
Me
Scheme 13.-Proposed Mechanism for Photochemical Reaction between Esters and Hexamethylphosphoric Triamide.
Scheme 13 is a mechanism for this reaction that is based upon an electron-transfer process. An electron-transfer mechanism has been proposed in order to explain similar reactions in noncarbohydrate system~.’~
IV. ACETALS Three types of photochemical reaction of carbohydrate acetals have been investigated. Early studies centered on the photochemical fragmentation of phenyl glycosides, and the photolysis of o-nitrobenzylidene acetals. (The latter reactions will be discussed with the photolysis of other nitro compounds; see Sect. VI1,l.) Later experiments were concerned with hydrogen-abstraction reactions from acetal carbon atoms by excited carbonyl compounds. The reactions that follow initial hydrogen-abstraction from an acetal carbon atom are those characteristic of radicals, and include coupling, ring opening, and reaction with molecular oxygen (see Table XI). The presence of molecular oxygen, even in low concentration, appears to exert a controlling influence on the course of acetal photochemistry by typically producing hydroxy esters as the major photoproducts. A mechanism proposeds1 for the formation of these hydroxy esters (and other acetal photoproducts), using methyl 3,4-0-ethylidene-P-~-arabinopyranoside (35) as an example, is given in Scheme 14. (Scheme 16 contains a mechanism proposed for a related reaction.) Study of model systems has revealed a tendency for photochemical abstraction of axial, rather than equatorial, acetal hydrogen atoms in (76) H. Deshayes, J. P. Pete, and C. Portella, Tetrahedron Lett., (1976) 2019-2022.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
Me,C=O
+
MeHC-0 ' 0 0 . . I
OH
1
35
hv
Me$-0 O /Q
30
+ 39
radical coupling
OMe
+
143
*'0 OMe + AcoQoMe
OH
1
Me,&OH
OH hydrogen abstraction
I
OH
3r
36
H0O>LQOMe Me
+
OH
Me,C =O
ring
opening-
Me
OH
*OQ
+
*O ' QOMe
OMe
J
40
OH
OH
hydrogen abstraction 41
Scheme 14.-Proposed Mechanism for Photochemical Reaction of Methyl 3,4-0Ethylidene-p-L-arabinopyranoside(35) with Excited Acetone.
ROGER W. BINKLEY
144
TABLEXI
Photochemical Reactions of Benzylidene and Ethylidene Acetals of Carbohydrates Products and Yields (70)
Reactants
1
I
OX
Ref.
OX
Ax
J
77,78
38 23 33
BzOYH,
9
77,78
7
77 ,I8
HOFH,
M e 2 C = 0 i O2
f
phc(@ 0
P
I
ox
OX 19 23 H f
O
C
U
+
O
77,78
77,78
C
U
79
Me,C=O BzO
0, / o HCPh
I
HO
OH
58
Q7
BzOCH, f
H
27
41
Me,C=O
HO
+
0
0-CMe,
,
OBz
Hoc;6 79
BzO
0-CMe,
TABLEXI (Continued)
Photochemical Reactions of Benzylidene and Ethylidene Acetals of Carbohydrates Reactants
Ref.
Products and Yields (%) BzFH,
+ BzOQ
O
ox
x = Bz
M
80
e
HOO
O
M
ox
ox
'OoMe
YH,OBz
,OCH, PhHC,
+
e
$H,OH
+
Me,C=O
80
BzoQoMe
/'FaoMe
OX
OX
X = Bz
+
MeC-0 H
+
Me,C=O
H ' Q O M e OH
OH 35
81
AcoQoMe
+
OH
H
37
36 7
Me,$!OH
Me
/
OH
C '/ I -CMe, 0
-0
U
O
i-
OMe
QO
38
39
17
7
+
HoQoMe
M OH
OH
AcoQoMe
I
OH
OH 41
40
59
e
'
146
ROGER W. BINKLEY
OMe
,
1
R. stabilization begins as radical forms
considerable bond breaking and rotation necessary before effective stabilization can begin
+ RH Scheme 15.-Rationalization for the Importance of Orbital Overlap to Radical Stabilization During Hydrogen Abstraction from an Acetal Carbon Atom.
pyranoid system^?^-^' This tendency has been r a t i ~ n a l i z e d ~as~ aris**~ ing from more-effective stabilization of the developing radical-center on the carbon atom by the adjacent oxygen atom during axial hydrogen-abstraction (see Scheme 15). Interestingly, there is a parallel between the importance of orbital overlap ( a )to radical stabilization dur(77) M. Suzuki, T. Inai, and R. Matsushima, Bull. Cheiii. SOC. J p n . , 49 (1976) 1585-1589. (78) S. Morio, R. Matsushima, T. Inai, and S. Tsujimoto, Asahi Garusu Kogyo Gijutsu Shoreikai Kenkyu Hokoku, (1977) 235-247; Chem. Abstr., 89 (1978) 180,240. (79) K. Matsuura, S. Maeda, Y. Araki, and Y. Ishido, Bull. Chem. SOC. J p n . , 44 (1971) 292. (80) W. Szeja and M. Lapokowski, Pol. J. Chem., 52 (1978) 673-675. (81) W. A. Szarek, R. J. Beveridge, and K. S. Kim,J. Carbohydr. Nucleos. Nucleot., 5 (1978) 273-284. (82) R. D. McKelvey, Carbohydr. Res., 42 (1975) 187-191. (83) K. Hayday and R. D. McKelvey,]. Org. Chem., 41 (1976) 2222-2223. (84) C. Bemasconi and G . Descotes, C. R. Acad. Sci. Ser. C , 280 (1975) 469-472. (85) C. Bernasconi, L. Cottier, and G. Descotes, Bull. S O C . Chim. Fr., (1977) 107-112. (86) C. Bemasconi, L. Cottier, and G. Descotes, Bull. SOC. Chim.Fr., (1977) 101-106. (87) C. Bemasconi, L. Cottier, G. Descotes, M. F. Grenier, and F. Metras, Nouu. J. Chim., 2 (1978) 79-84.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
147
ing hydrogen abstraction from an acetal carbon atom (see Scheme 15) and ( b )in a-cleavage of excited carbonyl compounds (see Scheme 8). Photolysis of aryl glycosides was not only one of the first photochemical reactions of carbohydrates to be but has continued to be an area of active investigation. Intriguing observations have been made concerning the effect of aromatic substituents upon glycosidic h y d r o l y s i ~ . ~ These , ~ ~ observations suggested that the photochemical, aromatic substitution observed in noncarbohydrate systems% may be responsible for the hydrolysis of aryl glycosides. Complete understanding of these effects must await further studies on product structures, chemical yields, and reaction mechanisms.
V. UNPROTECTED ALDITOLS,ALDOHEXOSES, AND RELATED COMPOUNDS Irradiation of unprotected carbohydrates was the subject of greatest photochemical interest to the early carbohydrate photochemists.l The investigations of these early workers were concerned primarily with the effect of reaction conditions upon the photochemical process, rather than with the identity of the reaction products. Between 1960 and 1969, a comprehensive series of papers was published on the photochemical reactions of D-glucose and D-glucit01?~-~~ These studies contributed greatly to understanding of the photochemistry of unprotected carbohydrates, as not only was the result of variation in the reaction conditions studied but also the structures of the products were determined. Extended irradiation of D-glucose and D-glucitol in the presence of oxygen result^^^-^^ in considerable degradation of the starting materials (see Table XII). Such degradation is consistent with the radical (88) (89) (90) (91) (92) (93) (94) (95) (96) (97) (98) (99)
L. J. Heidt,]. Am. Chem. Soc., 61 (1939) 2981-2982. L. J. Heidt,]. Franklin Znst., (1942) 473-486. G. Tanret, C. R . Acad. Sci., 202 (1936) 881-883. G. Tanret, Bull. Soc. Chim. B i d . , 18 (1936) 1344-1351; Chem. Abstr., 30 (1936) 7119. T. Yamada, M . Sawada, and M. Taki, Agric. Biol. Chem., 39 (1975) 909-910. W. G. Filby, G. 0. Phillips, and M. G. Webber, Carbohydr. Res., 51 (1976) 269-27 1. N. J. Turro, Modern Molecular Photochemistry, BenjaminEummings, Menlo Park, CA, 1978, pp. 404-408. G. 0. Phillips and G. J. Moody,]. Chem. Soc., (1960) 3398-3404. G. 0. Phillips and W. J . Criddle,]. Chem. Soc., (1963) 3984-3989. G. 0. Phillips and P. Barber,]. Chem. Soc., (1963) 3990-3997. G. 0. Phillips, P. Barber, and T. Rickards,]. Chem. Soc., (1964) 3443-3450. G. 0. Phillips and T. Rickards,]. Chem. Soc., B, (1969) 455-461.
ROGER W. BINKLEY
148
TABLEXI1 Photochemical Reactions of Unprotected Alditols and Aldohexoses Major Products and Percent Yields Reactants
D-Arabinose
D-Gluconic Acid
D-Glucuronic FormalAcid dehyde
References ~~
D-Glucose (low conversion) D-Glucose (high conversion) D-Ghcitol (high conversion)
13
4
6
0.5
0.6
4
5
&
HO OH
It'p" S
HO OH
0
+
*OOH
I
OH
ccH HOH
CH,OH
CH
95 96
OH
+
IoHu CH
22
I
OH
OH
99
0 OoH
HO@OH OH
Ho
47
23
o,
H2
It
0
+.OOH
OH
CH
\O
woH
HO
I
HO
I
OH
~-Arabinose ~-Gluconicacid aHydroxyl radicals derived from photolysis of waterlOo Scheme 16.-Proposed Mechanism for Photochemical Reaction between D-Glucose and the Oxygen in Water.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
149
reactions expected under these photolytic conditions. When reaction of D-glucose is conducted under conditions that maximize the percentage yield of primary products [that is, low (10%) conversion of Dglucose], D-arabinose and D-gluconic acid are the major products. These two products are those expected from a photochemically initiated, radical decomposition of an acetal (see Scheme 16). Several investigations have since been conducted on the photolysis of unprotected ~ u g a r s . ' ~ ~Spectroscopic -'~~ and chemical evidence has been offered for the formation of malonaldehyde from the photolysis of D-glucose in neutral or alkaline so1ution.lo0The formation of this compound has been suggested as the basis for the use of D-glucose as a chemical actinometer.lo1 Also, photolysis of D-glucose in the presence of L-lysine or glycine results in low yields of D-glucopyranosylamine; however, this photochemical reaction is probably not of D-ghcose, but rather, of the amino acids to form ammonia, which then reacts with the carbohydrate.lo2Finally, synthesis of a complex mixture of monosaccharides results when aqueous formaldehyde is irradiated in basic solutions.1o3 Two derivatives of unprotected carbohydrates, r i b o f l a ~ i n e ' ~ ~(42) J~' CH,OH HOkH
I
HOCH I
HOFH
0 42
and 2'-deo~yuridine'~* (43), experience intramolecular, photochemical reactions. The excited portion of each of these molecules (42 and 43) (100) K. Scherz, Carbohydr. Res., 14 (1970) 417-419. (101) R. K. Datta and K. N . Rao, IndianJ. Chem., Sect. A, 14 (1976) 122-123. (102) L. W. Doner, R. Balicki, and R. L. Whistler, Carbohydr. Res., 47 (1976) 342-344. (103) Y. Shigemasa, Y. Matsuda, C. Sakazawa, and T. Matsuura, Bull. Chem. Soc. Jpn., 50 (1977) 222-226. (104) W. J. Criddle, B. Jones, and E. Ward, Chem. Znd. (London), (1967) 1833-1834. (105) J.-Y. Peng, K. Minami, and T. Yoshimoto, Mokuzai Gakkaishi, 22 (1976) 511-517. (106) M. S. Joms and P. Hemmerich, 2. Naturforsch. Teil B , 27 (1972) 1040-1044. (107) M. S. Joms, G. Schollnhammer, and P. Hemmerich, Eur. J . Biochem., 57 (1975) 35-48. (108) J. Cadet, L . 3 . Kan, and S. Y. Wang,J. Am. Chem. Soc., 100 (1978) 6715-6720.
ROGER W. BINKLEY
150
hv
HO
HO 43
0
HO Scheme 17.-Proposed Mechanism for Photochemical Reaction of 2’-Deoxyuridine (43).
does not involve the carbohydrate part of the structure; consequently, the carbohydrate portion of each molecule is involved in reaction by adding to the excited system. This addition process, which is believed to involve zwitterionic intermediates, is illustrated for 2’-deoxyuridine (43) in Scheme 17.
VI. SULFUR-CONTAINING COMPOUNDS The types of sulfur compounds irradiated include dimethyl thiocarbamates, disulfides, dithioacetals, sulfides, sulfonates, sulfones, sulfoxides, and tetrasulfides. Also, such sulfur-containing compounds as simple alkanethiols have been added to unsaturated carbohydrates (see Table 11). Several of the photochemical reactions of sulfur-containing carbohydrates clearly have synthetic value (for example, photolytic removal of p-toluenesulfonate protecting groups), and study of such other reactions as sulfone transformations has contributed significantly to mechanistic understanding of the photochemistry of organic sulfur compounds.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
lhv 1
44
[RCH,. HOCH
+
151
*SEt]
MeOH
I
HOCH R = H~OH I
RCH,
I
48
HCOH CH,OH
+
*CH,OH
Scheme 18.-Proposed Mechanism for Photochemical Reaction of D-Galactose Diethyl Dithioacetal (44).
1. Dithioacetals and Sulfides Photolysis of D-galactose diethyl dithioacetal(44) results in carbonsulfur bond-fragmentation, leading to 1-S-ethyl-1-thio-D-galactitol (45) in 55-60% yield; in addition, minor proportion of L-fucitol (46) and 1-deoxy-1-ethylsulfinyl-D-galactitol(47) are formed.logSimilar irradiation of acetates (48-51) of the diethyl dithioacetals produces the corresponding 1-S-ethyl-1-thioalditol acetates in 79, 85, 87, and 84% yields, respectively.l1° The excellent yields from these reactions suggest that the photochemical transformation of dialkyl dithioacetals is an attractive means for accomplishing a net replacement of an S-alkyl group by hydrogen. A mechanism based upon homolytic carbon-sulfur bond-fragmentation well rationalizes product formation100(see Scheme 18). 0
H
EtSCSEt
I
I
HCOH I HOCH I HOCH I
HCOH I CH,OH 44
HCOH
hv MeOH ~
air
I
HOCH I
HOCH I HCOH I CH,OH 45
II
7% HCOH
H,CSEt
H,CSMe I HCOH I
I
+
HOCH I
HOCH I
HCOH I
+
HOCH I
HOCH I HCOH I
CH,OH
CH,OH
46
47
(109) D. Horton and J . S. Jewell,]. Org. Chem., 31 (1966) 509-513. (110) K. Matsuura, Y. Araki, and Y. Ishido, Bull. Chem. SOC.Jpn., 46 (1973) 2261-2262.
ROGER W. BINKLEY
152
H EtSCSEt
H EtSCSEt I
I
ROCH
HCOR
I
I
HCOR
HCOR
HCOR
HCOR
I
I I
I
CH,OR
C&OR 49
48
H EtSCSEt
H
EtSCSEt I HCOR I ROCH
I
HCOR I ROCH I
I
HCOR I CH,OR
HCOR I
HCOR I CH,OR 51
50
R = Ac CH,OH I HCOH I HOCH I
HOCH
HAOH I
CH,OH
52
Extended irradiation of the diethyl dithioacetal 44 increases the yield of L-fucitol (46) at the expense of l-S-ethyl-l-thio-D-galactitol (45); also galactitol (52) was isolated from the photolysis mixture.lo9 The intermediacy of 45 in the formation of 46, a possibility that was suggested by the extended photolysis of 44, is supported by the observation that irradiation of 45 in methanol produces L-fucitol(46) in 44% yield.log(Compounds 47 and 52 also are formed during irradiation of 45, but in low yield.) The mechanism for sulfide photoreaction parallels thatlogfor the alkyl dithioacetals (see Scheme 18). Other sulfide photoreactions result when appropriate nucleoside derivatives are photolyzed. Upon irradiation in acetonitrile, 9-[5-deoxy-2,3-0 -isopropylidene-5-(phenylthio)-~-~-ribofuranosyl]adenine (53) is converted into the anhydronucleoside 8,5'-anhydro(5'-deoxy-2',3'-0-isopropylidene-adenosine) (55) in 66% yield."' Similar reactions were observed when other sulfur-containing nucleosides were irradiated (see Table XIII). The reaction of the sulfide 53
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
0,
/o
CMe,
o\C&:2 54
53
0, / o CMe,
153
0,
/o
CMe,
55
Scheme 19.-Proposed Mechanism for Photochemical Reaction of 2’,3’-O-Isopropy~idene-5’-S-phenyl-5’-thioadenosine (53).
differs from the photoreaction of the sulfide 45, because a radical such as 54 (presumably an intermediate in the reaction of 53) can add internally to the nitrogenous-base moiety of the molecule. Such an intramolecular addition (see Scheme 19)should be favored over a bimolecular reaction (see Scheme 18). 2. Sulfoxides, Sulfones, and Sulfonates Photochemical, carbon-sulfur bond cleavage is also observed in compounds containing sulfur in oxidation states higher than that which exists in sulfides and in dialkyl dithioacetals. For example, the irradiation of the sulfoxide 47 in methanol produces10ga 58% yield of galactito1 (52). Even though homolysis of the carbon-sulfur bond does occur in 47, it is unlikely that 52 results from a simple, carbon-sulfur bondcleavage, as such a reaction predicts products that were not observed
ROGER W. BINKLEY
154
TABLEXI11 Photochemical Reactions of Sulfur-Containing, Nucleoside Derivatives Reactants
Products and Yields (%)
66
(Yield not reported)
(Yield not reported)
Ref,
111
111
111
112
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
155
TABLEXI11 (Continued) Photochemical Reactions of Sulfur-Containing, Nucleoside Derivatives Products and Yields (%)
Reactants
X O C Qs W
+
Ref.
XOCH,
+ xo
ox
xo ox
xo ox
5
9
X = Ac
113
XOCH, SH
xo ox 5
(see Scheme 20).A rationalization for formation of 52 on photolysis of 47 may be based on the suggestion that 47 experiences prior photochemical rearrangement to 56, a compound that, on photolysis, should be converted into 52 (see Scheme 21).This type of rearrangement (47 to 56) has been observed during photolysis of sulfoxides in noncarbohydrate system^."^*^^^ The photochemical reaction of 2,3,4,6-tetra-o-acetyl-P-D-glucopyranosyl sulfone (57) in benzene under nitrogen has been carefully studied, and a number of products identified116 (see Scheme 22). A mechanism that involves a photochemically initiated series of free-radical processes has been proposed that is consistent not only with product formation but also with the extent of incorporation of deuterium found in the various products following irradiation of 57 in benzene-&. The mechanism shown in Scheme 22 is compatible with proposals offered to explain sulfone photochemistry in noncarbohy(111) A. Matsuda, M. Tezuka, and T. Ueda, Nucleic Acids Res., (1976) s13-sl6. (112) A. Matsuda, M. Tezuka, and T. Ueda, Tetrahedron, 34 (1978) 2449-2452. (113) J.-L. Fourrey and P. Jouin,]. Org. Chem., 44 (1979) 1892-1894. (114) A. G . Schultz and R. H. Schlessinger, Chem. Commun., (1970) 1294-1295. (115) I. W. J. Still, M. S. Chauhau, and M . T. Thomas, Tetrahedron Lett., (1973) 1311-1315. (116) P. M. Collins and B. R. Whitton,]. Chem. Soc. Perkin Trans. I , (1974) 1069-1075.
ROGER W. BINKLEY
156
f[ [
RbH,
path A
RCH,
=
R&,
RCHsEt 47
path uath C
\
[
-
RCH,
,f:
SEt
]
MeOH
A
(not formed)
46
RCH,OMe
(notformed)
RCH,
(not formed)
46
I
HCOH
I
HOCH I
R = HOCH I
HCOH I CHPH
Scheme 20.-Potential, Photochemical-Reaction Pathways for Reaction of 1-Deoxyl-(ethysulfinyl)-D-galactitol(47).
drate and is also in accordance with the absence of methyl glycosides (the products expected from heterolytic, carbon-sulfur bond-cleavage) from irradiation of 57 in benzene -methanol. The carbohydrate sulfones that have been irradiated are listed in Table XIV. Quartz-filtered irradiation of carbohydrate p-toluenesulfonates in 0
II RCH,SEt 47
hu
RCH,OSEt 56
hv
[RCH,O* *SEt]
j
MeOH
RCH,OH 52
I HCOH I HOCH I R = HOCH I HCOH I CH,OH Scheme 21.-Proposed Mechanism for Photochemical Reaction of 1-Deoxy-1-(ethylsulfinyl)-D-galactitol(47).
(117) N. Kharasch and A. I. A. Khodair, Chem. Commun., (1967) 98-99.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
0
157
CHpAc
AcO
OAc
OAc
58
t
CHpAc
5Sa.b
t
(Jm CH OAc
L
o
AcO OAC
I
OAc
OAc
57
I
0 CHpAc
AcO
OAc
o+w v
YH,OAc
AcO
00
OAc
61
Scheme 22.-Proposed Mechanism for Photochemical Reaction of Phenyl 2,3,4,6Tetra-0-acetyl-P-D-glucopyranosyl Sulfone (57).
methanol in the presence of a base has been found to lead to desulfonylation. The results from various such photolyses are summarized in Table XV. The retention of configuration at C-3 during reaction of 62 and 63,for example, and the absence of deoxy compounds and methyl ethers, argue against any carbon-oxygen bond-cleavage and in favor of a sulfur-oxygen fission.
3. Thiocarbamates and Xanthides Studies have also been conducted on compounds containing a thiocarbonyl group. Photolysis of dimethylthiocarbamates mixtures of deoxy sugars and alcohols (see Table XVI). As the alcohols can be reconverted into dimethylthiocarbamates, and these re-irradiated, the synthesis and irradiation of these compounds offers a useful pathway to deoxy sugars. A simple mechanism for this reaction, based on the two possible a-cleavages resulting from thiocarbonyl excitation, is shown in Scheme 23. In addition, the possibility has been
ROGER W. BINKLEY
158
R = carbohydrate moiety
Scheme 23.-Proposed Mechanism for Photochemical Reaction of Dimethylthiocarbamates.
raised that a photochemical, “Freudenberg type” of rearrangement (see Scheme 24) prior to further photochemical reaction could explain the formation of the deoxy compounds from the photolysis of dimethylthiocarbamates,I2* Several, oxidatively coupled xanthates (64-66), compounds (also called xanthides) containing the photochemically reactive, sulfur-sulfur bond, have been studied.130 Homolytic cleavage of this reactive bond is the primary reaction for these compounds, although this process is normally masked by recombination of the radicals produced. This primary, light-initiated process becomes apparent when a mixture of the xanthide 64 and ethyl xanthide (67) is irradiated in cyclohexane, because an equilibrium between 64,67, and the mixed xanthide 68 is rapidly established. The photochemical reactions of xanthides are quite complex. They are solvent-, concentration-, temperature-, wavelength-, and time-dependent.130 The most thoroughly studied of these compounds is compound 64, whose irradiation (through a Corex filter) in cyclohexane under nitrogen produces tetrasulfide 69 (37% yield), xanthate 70 (35%), 1,2:3,4-di-O - isopropylidene -(Y-D-galactopyranose (71, 13%), sulfur, and carbonyl sulfide. Irradiation of a dilute solution of 64 produced only 70 (in 74% yield). The most intriguing finding from irradiation of the xanthides 64-66 is the fact that 66 produces a xanthate S II
ROCNMe,
Scheme 24.-Proposed, methylthiocarbamates.
hv
0 It
RSCNMe,
hv
RH
Photochemical, “Freudenberg” Rearrangement of Di-
S S II I1 CH,W-S-S-COEt
I
,
0-CMe, 64
67
68
S I1
$'H,W-S-S-
O-CMe, 64
69
70
i-
0-CMe, ?I
s
f
o=c=s
ROGER W. BINKLEY
160 r
-l
70 65 R '2==
OOMe
Me0
OMe
72
RZ= O-CMe,
(72) in which sulfur has replaced oxygen with at least 92%retention of configuration.
VII. NITROGEN-CONTAINING COMPOUNDS 1. Nitro Compounds A number of carbohydrates protected by groups containing o-nitrophenyl substituents has been studied photochemically. The primary reason for interest in these compounds is that they can be deprotected by irradiation. For example, o-nitrobenzyl glycosides of carbohyd r a t e ~ , ' ~ ' Jand ~ ~ ethers of n u c l e ~ s i d e s ' ~ ~ and J ~ ~oligoribonucleotide^,'^^-'^' experience loss of the o-nitrobenzyl group upon photolysis. The reported examples of this reaction are listed in Table XVII; in addition, there is preliminary evidence that glycosides formed from polymer-bound, o-nitrobenzyl-containing groups, and partially protected carbohydrates, release the carbohydrate upon p h o t o l y ~ i s .A ' ~detailed ~ explanation for the photochemical reactions of the o-nitrobenzyl
TABLEXIV Photochemical Reactions of Carbohydrate Sulfones Reactants
Products
0:Q
xya
+(-J+ xo
xo
xo
ox
Ref.
ox
5r
OX 88
61
R' = H, RZ = SOzPh X = AC XOFH,
J -(
xo
+
ox
OX
2
60
\R3=H
i
59a '
R 1 =@ - Ph
) R3 =*Ph
116
59b,
(R'=H R' = S02Ph, R2 = H, X = Ac
(Same products a s above)
116
1
XOYH,
ox R' = H, R2 = SOzPh
I
l
ox
ox R3 = H
X = Ac R4 = -@Ph
118
and
R3 = e
P
h
R4 = H R' =
S02Ph, R' = H, X = Ac
(Same products aa above)
118
ROGER W. BINKLEY
162
TABLEXV Photochemical Reactions of p-Toluenesulfonic Esters of Carbohydrates p-Toluenesulfonate
Product
~H,OTs
O
References
CH,OH
Q
HOQ
Yield (%)
M
e
o
M
e
90
119
100
119
80
119
HO OH
OH
/Qy
Me&-0 D /o
Me& -0
I 1 0-CMe,
0-CMe,
0 0 FH,OH
HO
HO
OH
I OH
119
0-CMe,
0-CMe, HZF -
Q 8
H,C 80
OTS
OH
YH,OH
I
v)1,
CH
0-CMe,
I
I
0-CMe,
120, 121. 1a2'
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
163
TABLEXV (Continued)
Photochemical Reactions of p-Toluenesulfonic Esters of Carbohydrates p-Toluenesulfonate
Product
Yield (%)
References
G fJ FH2
I
I
OTs
OH
hOR YH2
CH,OH
CH,OH
CH,OX
ROQOR
RO
R = Me, X = Me R=Me, X = H
0Q
O
OTs M
e
ooMe
0
81
124
62
124
60
125
OH
FH,OMe 1 26 M e 0O
O
X
=
M
e
TS
Hocv "OCd n
n
"Yo
O Y O
HO
OTs
HO
OH
127
TABLEXVI Photochemical Reactions of Carbohydrate-Containing Dimethylthiocarbamates" Products and Yields ( W )
Reactant
J-(/
FH"
Me2C-0
Me2drdy 0-CMe,
0-CMe,
0-CMe,
15
36
tl o/ '0,
S
19
17
Me$,
I
I
OCH
0
YQ
1
0-CMe, 17-23
0-CMe, 26-32
Me$-0 QOMe I
OCNMe,
OH
I1 S
11
36
S
/QT II
FH,OCNMe,
YH,OH
Me$-0
0-CMe,
0-CMe, 25
a
Refs. 128 and 129.
0-CMe, 35
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
165
group is proposed in Scheme 25. This mechanism is consistent with the suggestion that photolysis of o-nitrobenzyl compounds causes an intramolecular, oxidation-reduction r e a c t i ~ n , ' ~ 'and J ~ ~also with the finding140that excited nitro groups, such as those in nitrophenyl p-Dglycosides, are effective hydrogen-atom abstractors. A process similar to that proposed for o-nitrobenzyl ethers (see Scheme 25, path a), but including loss of carbon dioxide in a final step (see Scheme 25, path b), accounts for the photochemical regeneration of an amino function protected by an (o-nitrobenzy1)oxycarbonyl group.14' Table XVIII contains examples of this reaction involving carbohydrate systems. Cyclic acetals derived from diols and o-nitrobenzaldehyde produce hydroxynitrosobenzoates upon irradiation (see Scheme 26). Early studies of this reaction demonstrated that acetals involving carbohydrates and o-nitrobenzaldehyde experience facile, photochemical
(118) P. M. Collins and B. R. Whitton, Carbohydr. Res., 36 (1974) 293-301. (119) S. Zen, S. Tashima, and S. Kot6, Bull. Chem. Soc.Jpn., 41 (1968) 3025. (120) A. D. Barford, A. B. Foster, and J. H. Westwood, Carbohydr. Res., 13 (1970) 189-190. (121) A. D. Barford, A. B. Foster, J. H. Westwood, L. D. Hall, and R. N. Johnson, Carbohydr. Res., 19 (1971) 49-61. (122) L. Vegh and E. Hardegger, Nelu. Chim. Acta, 56 (1973) 2020-2025. (123) W. A. Szarek, R. G. S. Ritchie, and D. M. Vyas, Carbohydr. Res., 62 (1978) 89-103. (124) F. R. Seymour, Carbohydr. Res., 34 (1974) 65-70. (125) R. A. Borgegrain and B. Gross, Carbohydr. Res., 41 (1975) 135-140. (126) F. R. Seymour, M. E. Slodki, R. D. Plattner, and L. W. Tjarks, Carbohydr. Res., 46 (1976) 189-193. (127) C. D. Chang and T. L. Hullar, Carbohydr. Res., 54 (1977) 217-230. (128) R. H. Bell, D. Horton, D. M. Williams, and E. Winter-Mihaly, Carbohydr. Res., 58 (1977) 109-124. (129) R. H. Bell, D. Horton, and D. M. Williams, Chem. Commun., (1968) 323-324. (130) E. I. Stout, W. M. Doane, C. R. Russell, and L. B. Jones,J. Org. Chem., 40 (1975) 1331-1336. (131) U. Zehavi and A. Patchornik,j. Org. Chem., 37 (1972) 2285-2289. (132) U. Zehavi, B. Amit, and A. Patchomik, J . Org. Chem., 37 (1972) 2281-2285. (133) D. G. Bartholomew and A. D. Broom,J. Chem. Soc. Chem. Commun., (1975) 38. (134) E. Ohtsuka, S. Tanaka, and M. Ikehara, Nucleic Acid Chem., 1 (1978) 410-414. (135) E. Ohtsuka, S. Tanaka, and M. Ikehara, Synthesis, (1977) 453-454. (136) E. Ohtsuka, S. Tanaka, and M. Ikehara, Chem. Pharm. Bull., 25 (1977) 949-959. (137) E. Ohtsuka, S. Tanaka, and M. Ikehara, Nucleic Acids Res., 1 (1974) 1351-1357. (138) U. Zehavi and A. Patchornik,J. Am. Chem. Soc., 95 (1973) 5673-5677. (139) A. Patchomik, B. Amit, and R. B. Woodward, J . Am. Chem. SOC., 92 (1970) 6333-6334. (140) P. J. Baugh, K. Kershaw, and G. 0. Phillips, Carbohydr. Res., 22 (1972) 233-243. (141) B. Amit, U. Zehavi, and A. Patchomik,J. Org. Chem., 39 (1974) 192-196.
ROGER W. BINKLEY
166
R Ono- H Y g + "
L
J
b-
/
path A RNH,
+ co, +
OHC NO
onc NO
R = carbohydrate, nucleoside, or nucleotide residue
Scheme 25.-Proposed Compounds.
Mechanism for Photochemical Reaction of o-Nitrobenzyl
&!:
X
0
0
J Scheme 26.-Proposed dene Acetals.
Mechanism for Photochemical Reaction of o-Nitrobenzyli-
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
167
TABLEXVII Photochemical Reactions of o-Nitrophenyl Ethers of Carbohydrates and Nucleosides Reactants
HO
02N I
Products
HOO
O
,
R=H R = OMe
OCH,
Ref.
100
131
H
OH
OH
RZO
Yields (%)
RZO
ao
132
100
132
100
133, 134
OH
(Continued)
ROGER W. BINKLEY
168
TABLEXVII (Continued)
Photochemical Reactions of o-Nitrophenyl Ethers of Carbohydrates and Nucleosides Reactants
Products
Yields (%)
Ref.
(Not reported)
135
95
B=
.kN>
, R1 = Cytidylyl-(3'-5')
N
I
RZ=H
136
(Not reported)
136
(Not reported)
I37
0
II
r e a ~ t i o n ' ~ ~ however, -'~~; the products formed were complex and not fully characterized. Investigations of o-nitrobenzylidene derivatives of carbohydrates have since established the structure of the photoproducts by oxidation of these unstable (and often dimeric) nitroso compounds to their corresponding monomeric nitro derivatives, compounds that can readily be chara~terized.'~'-~*~ Because the 1,Sdioxo(142) I. Tanasescu and E. Craciunescu, Bull. SOC. Chim. F r . , 3 (1936) 581-598. (143) I. Tanasescu and E. Craciunescu, Bull. Soc. Chim.F r . , 5 (1936) 1517-1527. (144) I. Tanasescu and M. Ionescu, Bull. Soc. Chim.F r . , 7 (1940) 84-90. (145) I. Tanasescu and M. Ionescu, Bull. Soc. Chim. Fr., 7 (1940) 77-83. (146) I. Tanasescu and M. Ionescu, Bull Soc. Chim.Fr., 5 (1936) 1511-1517. (147) P. M. Collins and N. N. Oparaeche, J . Chem. Soc. Chem. Commun., (1972) 532-533. (148) P. M. Collins and N. N. Oparaeche, J . Chem. Soc. Perkin Trans. I , (1975) 1695- 1700. (149) P. M. Collins, N. N. Oparaeche, and V. R. N. Munasinghe,]. Chem. Soc. Perkin Trans. I, (1975) 1700-1706.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
169
TABLEXVIII Photochemical Reactions of o-Nitrobenzyloxycarbonyl Derivatives of Carbohydrates ~~~
Reactants
Products and Yields (%)
References
?&OH
R 82
R=H R = OMe
89
"0
CH,OH
OH
141
R
R=H R = OMe CH,OR
80 91
0 FH,OR
RO
141
R = Ac
lane and 1,Sdioxane rings of benzylidene acetals can open in two ways, photolysis of compounds containing o-nitrobenzylidene acetal groups invariably produces mixtures of products. Table XIX contains a tabulation of acetals irradiated, and the products
ROGER W. BINKLEY
170
TABLEXIX Photochemical Reactions of o-Nihvbenzylidene Acetals of Carbohydrates Reactants
Acov &
Products and Yields (%)
Ref.
141,148
AcoQ no me
0
hNO c=o
95
OH
0
5
p,OMe
(4
Me0
no
0 I
&NO
w
OH
0
bNO c=o
< 5
93
J (
I
147,148
?
0
HC-0
148
Me0
o=c I I OH
0
&No
&NO
< 5
I
OAc
5
95
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
171
TABLEXIX (Continued) Photochemical Reactions of o-Nitrobenzylidene Acetals of Carbohydrates Reactants
-.$’
Ho
Ref.
Products and Yields (%)
OMS
OMs
O N 5 ”
< 5
89
147,149
0Q I
OAc
O OAc M
e
HO
@r
OAc
I
30
59
147.149
OAc
OAc
50
23
HOCK2 149
o& I oMe
bNO
o=c OaN@
32
59
(Continued)
TABLEXIX (Continued) Photochemical Reactions of o-Nitrobenzylidene Acetals of Carbohydrates ~
Ref.
Products and Yields (%)
Reactants
NO
HOCH, HC/ O F . , I ' O W O M e Me0
&No 60
40
NO
4 N
OAC
OAc
OAc
20
50
It)
0
0
o=cI
149 I
OAC
OAc
40
17 NO
HciboMe 0O
O OTs M
I
O
Z
N
6
OTS
O
N
147,149
e
d 96 (total)
I
OTs
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
173
TABLEXIX (Continued)
Photochemical Reactions of o-Nitrobenzylidene Acetals of Carbohydrates Reactants
Products and Yields (%)
Ref.
HOCH,
149
; . $ i M e
o=c0Q
o
M
e
"'-0 I
(No yields reported)
NO
149
OZN@ ON@ 45
32
Photolysis of three 2,4-dinitroanilino-substitutedcarbohydrates, compounds that differ considerably from each other in photochemical reactivity, has been r e p ~ r t e d . ' ~ l-Deoxy-l-(2,4-dinitroanilino)-~~,'~~ glucitol (73) is photochemically unreactive ; in contrast, sodium 2deoxy-2-(2,4-dinitroanilino)-~-gluconate (74) produces D-arabinose in 52% yield upon irradiation.l5O The behavior of compounds 73 and 74 indicates that oxidative loss of the 2,4-dinitroanilino group during photolysis is only possible when it is accompanied by simultaneous decarboxylation. The evidence gathered from the considerable study of this reaction for noncarbohydrate systems suggested that this process is quite complex. Although useful, mechanistic proposals have (150) A. E. El Ashmawy, D. Horton, and K. D. Philips, Curbohydr. Res., 9 (1969) 350-355. (151) T. L. Nagabhushan, J. J . Wright, A. B. Cooper, W. N. Turner, and G. H. Miller, /. Antibiot., 31 (1978) 43-48.
ROGER W. BINKLEY
174
H , Ic m &Noz HCOH I HOCH
hv
I
HCOH I HCOH I CH,OH
HZO MeOH
no reaction
73
COO- Na' H Ib N ' W - P N O z
H°FH HCOH I
4N
HCOH I CqOH
hv
HZO
HOO I HO
O
H -I-
&=' NO2
74
been advanced,152a completely satisfactory pathway for this reaction has not yet been described. The nitroalkene (E)-6,7,8-trideoxy-1,2:3,4-di-O-isopropylidene-7~nitro-a-D-galacto-oct-6-enose (75) is the single nitro sugar thus far photochemically investigated in which the nitro group is not attached to an aromatic Irradiation of 75 results in isomerization of the double bond, producing the 2 isomer 76 (27%yield), and in a rearrangement-fragmentation process yielding @)-and (2)-6,8-dideoxy1,2:3,4-di~-isopropylidene-a-~-galacto-oct-5-enos-7-ulose (77 and 78) in 8 and 6%yields, respectively. A reasonable pathway for formation of compounds 77 and 78 begins with rearrangement of 75 to the intermediate nitrous ester 79, a process similar to that proposed for excited P-methyl-P-nitr~styrene.'~~ The reaction is complete when the nitrous ester experiences light-initiated, nitrogen-oxygen-bond homolysis and subsequent disproportionation (see Scheme 27). Photolysis of the nitric esters 80-82 causes nitrogen-oxygen bond0. Meth-Cohn, Tetrahedron Lett., (1970)1235-1236. G. B. Howarth, D. G. Lance, W. A. Szarek, and J. K. N. Jones, Chem. Commun., (1968)1349. G. B. Howarth, D. G. Lance, W. A. Szarek, and J. K. N. Jones, Can../.Chem., 47 (1969)81-87. 0. L. Chapman, P. G. Cleveland, and E. D. Hoganson, Chem. Commun., (1966) 101-102.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
175
__ hv
Me$-0 0-CMe, r5
76
ON0 I
Q H\C”C‘Me
hu
Me$-0
0-CMe,
0-CMe,
79
/ \ J
% / ”
1 0
%-Me /
0-CMe,
rr
0-CMe, 70
Scheme 27.-Proposed Mechanism for Photochemical Reaction of (E)-6,7,8-Trideoxy-1,2:3,4-di-O-isopropylidene-7C-nitro-a-~-galacto-oct-6-enose (75).
homolysis, to produce nitrogen dioxide and an alkoxyl radical.’= The alkoxyl radical abstracts a hydrogen atom from the solvent, to form an alcohol (see Scheme 28). This photochemical removal of a nitro group occurs in essentially quantitative yield (see Table XX). If an unstable (156) R. W. Binkley and D. J . Koholic,J. Org. Chem., 44 (1979) 2047-2048.
ROGER W. BINKLEY
176
lkv ,OCHZ
Me&,
I OCH
lhv
J \ Me&,
Q 0-CMe, ?
,OCH,
I
yo>
OCH
0
0-CMe,
Scheme 28.- Proposed Mechanism for Photochemical Reaction of 1,2:3,4-Di-O-isopropylidene-3-O-nitro-a-D-a~~ofuranose (81) and 1,2:3,4-Di-O-isopropylidene-3-Onitro-a-D-ghcofuranose (82).
alkoxyl radical is formed by photolysis, rearrangement occurs (see Scheme 28). 2. Azides Irradiation of a carbohydrate azide results in loss of nitrogen, and rearrangement (probably by way of a nitrene intermediate) to produce an imine (see Scheme 29). The imine, which, in many instances, exists
-..
RCH,-N-N=N:
Scheme 29.-Proposed Azides.
hv
RCH,N
+
N,
-
RCH=NH
Mechanism for Photochemical Reaction of Carbohydrate
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
177
TABLEXX Photochemical Reactions of Nitrous Esters of Carbohydrates Products and Y i e l d F (%)
Reactants
/Q7
Me& D / -0 o
Me$-0
I 1
0-CMe,
0-CMe, 100
80
R' = H, R2 = ONO, R' = ONO,, R2 = H
(81)
100
(82)
92
in a polymeric form,'@ is readily hydrolyzed to the corresponding carbony1 compound. This photolysis-hydrolysis sequence is effective in converting primary azides into aldehydes, but it produces low yields of ketones from secondary azides (see Table XXI). Photolysis of glycosyl azides affords products (see Table XXI) that differ significantly from those formed by photolysis of other a ~ i d e s . ' ~ ~ J ' ~ A probable explanation for this difference in reactivity is that, unlike other imines, the ring in iminolactones produced by irradiation of glycosyl azides can open spontaneously, to give unstable cyanohyd r i n ~ (see ' ~ ~ Scheme 30). The cyanohydrins can then lose hydrogen cyanide, to offord the next-lower aldoses. During photolysis of some glycosyl azides, an additional product is formed, one for which the general structure 83 has been proposed. This additional product, Carbohydratei+ portion of
TIN
molecule
0-N
H
83
ROGER W. BINKLEY
178
OH
OH
Jhv
lhV
-ha OH
QNH
OH
OH
1 OH Scheme 30.-Proposed Mechanism for Photochemical Reactions of Glycosyl Azides and of Sugar Oximes.
which may be photochemically rea~tive,”~ reverts to the starting material on standing.
3. Diazo Compounds Methyl 3,4,5,6-tetra-0-acetyl-2-deoxy-2-diazo-~-arabino-hexonate
(84) has been irradiated in methanol and in 2-propan01.’~~ In methanol, the only photoproduct is the enol acetate 85; however, irradiation in 2-propanol results in formation of minor proportions (6%) of 85 and
the alkene 86 (7%),but the major product is the deoxy sugar 87 (61%). The difference in reactivity of 84 in these two solvents is probably a reflection of the difference in the ability of methanol and 2-propanol to function as hydrogen donors when reacting with a carbene (see Scheme 31). In methanol, a 1,e-hydrogen atom shift to the divalent
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
179
C0,Me I
C=N=N I f XOCH I
R 84
C0,Me I CH I1
xoc I R
MeOH
C0,Me
I C:
X O h I
+
Nz
R
R =
I
C0,Me
I
CH II CH
HCOX I
CH,OX X =
AC
C0,Me I *CH I XOCH
+
Me,kOH
+
Me,kOH
I
R
85
HCOX
J iMezcHoH Me,CHOH
C0,Me I
I
+
I
R 86
85
YHa XO CH I
R major product 87
Scheme 31.-Proposed Mechanism for Photochemical Reaction of Methyl 3,4,5,6Tetra4)-acetyl-2-deoxy-2-diazo-~urabino-hexonate (84).
carbon atom occurs faster than reaction with the solvent. In 2-propanol, a more effective hydrogen-donor than methanol, hydrogen abstraction from the solvent competes effectively with internal rearrangement. 4. Oximes Photolysis of sugar oximes produces i m i n o l a ~ t o n e s . ' ~These * ~ ' ~ ~ are
the compounds proposed to arise from irradiation of glycosyl azides;
however, the mechanism leading to formation of iminolactones from these two starting-materials (azides and oximes) must be quite different (see Scheme 30). Photolysis of azides is considered to generate a nitrene, whereas photolysis of oximes produces an iminolactone that
ROGER W. BINKLEY
180
TABLEXXI Photochemical Reactions of Carbohydrate Azides Products and Yields" (%) RCH=NH
Reactants RCH2N3
R=
R=
xoO
O
M
Ref.
e
X = Bz
(Yield not reported)
157
X=H
38
157
X = Ac
62
157
62
158
50
159
43
160
(Yield not reported)
161
xoO
O
C
H
3
ox X = Ac
R= 0-CMe,
R=
Ic;J
F
4C /o
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
181
TABLEXXI (Continued)
Photochemical Reactions of Carbohydrate Azides Reactants RCH,N,
Products and Yields" (%) RCH=NH
Ref.
54
162
58
162
51
163
I
AcOCH
I 732
7%
R=
H,C-C-CH, I
OH
Me2C
,OCH2
I
'OCH
Q7
0
0-CMe,
18
164
34
165
(Continued)
ROGER W. BINKLEY
182
TABLEXXI (Continued) Photochemical Reactions of Carbohydrate Azides Reactants RCHPN3
Products and Yields" (%) RCH=NH
Ref.
I
HCOH I
HFOH 166
HQ
R=
O
M
e
OX X = C&Ph
R=
0-CMe,
HOYH
7% XCXZ I ==OH,
F = H X = H , ==OH
(-J
0
167
25
167
OH
HO
OH r
16
1
I j. J fo
169,170, 171
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
183
TABLEXXI (Continued)
I
Photochemical Reactions of Carbohydrate Azides Reactants RCHzNs
Products and Yields" (%) RCH=NH
Ref.
@ o
ox
172,173, 174
n
X=H X = Ac
(-J
HCN
RO
OH
+
Nz
+ HO
R = H
47
175,176
53
176
51
176
CH,OH
R = OH CH,OH
R = O "Q OH
175,176
R = OH
(Continued)
ROGER W. BINKLEY
184
TABLEXXI (Continued) Photochemical Reactions of Carbohydrate Azides Products and Yields" (%) RCH=NH
Reactants RCH2N,
ON3
HO
HCN
+
N,
Ref.
+
175,116
HO 60
Hot)
HCN
+
N,
+
D
O
H
HO
OH
HoQ
65
175,176
b
175,176
OH
b
"
175,176
O I C IU HO OH
0 CH,OX
xo
FH,OX
xoo
m
I
I
ox
X = Ac
ox 37
175,176 ~~
Product usually isolated as aldehyde or its derivative. that reverts to the starting azide. a
* Unstable product formed
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
185
TABLEXXII Photochemical Reactions of Carbohydrate Oximes Products and Percent Yields Reactant
Iminolactone
D-Galactose oxime DMannose oxime D-Ribose oxime D-Arabinose oxime DXylose oxime D-Lyxose oxime
81 33" 23 28 15
Aldose D-Lyxose (14)
D-Threose (3) D-Erythrose (18)
D-Arabinose is formed on standing.
may arise by way of nitrogen-oxygen-bond homolysis followed by hydrogen-atom transfer (see Scheme 30). The yield of the next-lower aldose from an oxime irradiation is quite dependent upon the particular oxime photolyzed (see Table XXII). D. Horton, W. Weckerle, and B. Winter, Carbolzydr. Res., 70 (1979) 59-73. R. L. Whistler and A. K. M. Anisuzzaman,J. Org. Chern., 34 (1969) 3823-3824. D. Horton, A. E. Luetzow, and J. C. Wease, Curbohydr. Res., 8 (1968)366-367. A. R. Gibson, L. D. Melton, and K. N. Slessor, Can. J . Chem., 52 (1974) 3905-3912. I. D. Jenkins, J. P. H. Verheyden, and J. G. Moffatt,J. Am. Chem. Soc., 93 (1971) 4323-4324. D. C. Baker and D. Horton, Carbohydr. Res., 21 (1972) 393-405. W. A. Szarek, D. M. Vyas, and L.-Y. Chen, Curbohydr. Res., 53 (1977) cl-c4. D. M. Clode and D. Horton, Carbohydr. Res., 14 (1970) 405-408. R. L. Whistler and L. W. Doner,J. Org. Chem., 35 (1970) 3562-3563. H. C. Jarrell and W. A. Szarek, Cat1.J. Chem., 56 (1978) 144-146. H. C. Jarrell and W. A. Szarek, Carbohydr. Res., 67 (1978) 43-54. H. F. C. Beving, A. E. Luetzow, and 0. Theander, Carbohydr. Res., 41 (1975) 105-115. D. M. Clode, D. Horton, M. H. Meshreki, and H. Shoji, Chem. Comrnun., (1969) 694-695. D. M. Clode and D. Horton, Curbohydr. Res., 17 (1971) 365-373. D. Horton, A. E. Luetzow, and 0. Theander, Carbohydr. Res., 27 (1973) 268-272. D. Horton, A. E. Luetzow, and 0. Theander, Carbohydr. Res., 26 (1973) 1-19. D. M. Clode and D. Horton, Carbohydr. Res., 19 (1971) 329-337. D. M. Clode and D. Horton, Curbohydr. Res., 12 (1970) 477-479. J. Plenkiewicz, G. W. Hay, and W. A. Szarek, Can. J. Chem., 52 (1974) 183-185. W. A. Szarek, 0.Achmatowicz, J. Plenkiewicz, and B. K. Radatus, Tetrahedron, 34 (1978) 1427- 1433. D. Horton and K. D. Philips, Carbohydr. Res., 22 (1972) 151-162. W. W. Binkley and R. W. Binkley, Tetruhedron Lett., (1970)3439-3442. R. W. Binkley and W. W. Binkley, Curbohydr. Res., 23 (1972) 283-288.
ROGER W. BINKLEY
186
RCH-CH=N-N=CH-CHR I I OH HO 88
RCH-CH=N I HO
*
ihv I
RCH-CH=NH I HO
*
N=CH-CHR I OH
N=CCR I
OH
1HP
NH,
+
I HOCH
RCH-CH=O I HO
O=CHR
+ HCN
I
R =
HOFH HTH CH,OH
Scheme 32.-Proposed (88).
Mechanism for Photochemical Reaction of D-Galactose Azine
5. Azines
An iminolactone also has been suggested as a key intermediate in the photolysis of D-galactose azine (88).Irradiation of 88 is thought to fragment the weak nitrogen-nitrogen bond. Subsequent disproportionation of the radical pair produceslS0a cyanohydrin and an iminolactone (see Scheme 32). The cyanohydrogen loses hydrogen cyanide to form D-lyxose (23% yield), and the acyclic iminolactone is hydrolyzed to D-galaCtOSe (37%yield). VIII. IODOCOMPOUNDS 1. Deoxyiodo Sugars
Photolysis of deoxyiodo sugars is an effective method for forming the corresponding deoxy compounds (see Scheme 33); however, both (180) R. W. Binkley and W. W. Binkley, Corbohydr. Res., 13 (1970) 163-166.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES H
I
I
1
I
I
-c-c-
-
H I I
-
hydrogen abstraction
I
from solvent
1.
-c-c-
-
H
I
H
-c-cI
187
I
I
disproportion (observed in absence of hydrogen donors)
Scheme 33.-Proposed Sugars.
\ I c=c / \
+ HI
Mechanism for Photochemical Reaction of Deoxyiodo
the type of solvent used, and the energy of the incident light, have a decided effect upon the yield of products and the complexity of the reaction mixture. For example, irradiation of 6-deoxy-6-iodo-1,2:3,4die-isopropylidene-a-D-galactopyranose(89) in methano1181.182or 2-propan01~~~ produces 6-deoxy-l,2:3,4-di-O-isopropylidene-a-~galactopyranose (90)in much higher yield than irradiation in 2-methyl2-propanol (see Table XXIII). Also, the yield of 90 obtained from photolysis of 89 with unfiltered light improves when the higher-energy light from the radiation source is removed by use of an appropriate filter (see Table XXIII). Irradiation of 3-deoxy-3-iodo-1,2:5,6-di-0-isopropylidene-a-D-glucofuranose(91) led to a similar observation concerning the dependence on w a ~ e l e n g t h . ' ~ ~ J ~ ~ The effect of the reaction solvent on iodide photolysis is similar to that observed in irradiation of the diazo compound 84. Among the various solvents used in iodide reactions, 2-propanol produces the highest yields of deoxy sugars (see Table XXIII). Irradiations in methanol, a good, but less effective, hydrogen donor than 2-propanol, afford deoxy sugars in fair to good yields (see Table XXIII). Hydrogen-atom transfer from 2-methyl-2-propanol is sufficiently difficult that other reactions, such as alkene formation (see Scheme 33), can become significant reaction-pathways in this solvent. 2. o-Iodobiphenylyl Ethers
The o-iodobiphenylyl ethers, 92 and 93, of 1,2:3,4-di-O-isopropylidene-a-D-galactopyranose and 1,2:5,6-di-O-isopropylidene-a-~-glucofuranose, respectively, have been irradiated in 2-propanol and in 2(181) W. W. Binkley and R. W. Binkley, Carbohydr. Res., 8 (1968) 370-371. (182) W. W. Binkley and R. W. Binkley, Carbohydr. Res., 11 (1969) 1-8. (183) R. W. Binkley and D. G . Hehemann, Carbohydr. Res., 74 (1979) 337-340.
ROGER W. BINKLEY
188
TABLEXXIII Photochemical Reactions of D e o x y i o d o Sugars
Filter
Sugar
Me,CHOH
Corexu
95
183
b
97
181,182
/Q7 I
Me$-0
0-CMe,
Ref.
Solvent
Reactants CHJ
Yield (%) of Deoxy
MeOH
Pyrex
MeOH
none
83
181,182
Me,COH
none'
36
181,182
Me,CHOH
Corex
99
183
MeOH
none
32
128
Me,CHOH
Corex
100
183
Me,CHOH
Corex
93
183
Me,CHOH
Corex
80
183
89
0-CMe, 91
Me,C /OTH2 'OCH
K4 0
I
0-CMe,
04Me,&O
OH
TABLEXXIII (Continued)
Photochemical Reactions of Deoxyiodo Sugars
Reactants
Solvent
Filter
Yield (%) of Deoxy Sugar
Ref.
Me,CHOH
Corex
72
183
Me,CHOH
Corex
90
183
MeOH
none
57
184
9
185
HCO, I ,CMe, H,CO
q
RO
RO
0
OR R = AC
H20, HCHO HOQ
O
M
none
e
HO ~~~~
" Transmittance at wavelengths <260 nm, 0%. Transmittance at wavelengths <280 nm, 0%. 6-Deoxy-l,2:3,4-di~-isopropylidene-~-~-u~u~ino-hex-5-enopyranose (96) formed in 32% yield.
ROGER W. BINKLEY
190
1
Me,COH
Ph
Ph
Scheme 34.-Proposed Ethers.
Mechanism for Photochemical Reaction of o-Iodobiphenylyl
methy1-2-propan01.'~~ Irradiation of these ethers (92 and 93) in 2-propanol resulted in essentially quantitative replacement of iodine by hydrogen (see Scheme 34) to give 94 and 95, respectively. In contrast, irradiation of 92 in 2-methyl-2-propanol produced the enol ether 96 as the major product. No alkene was formed from irradiation of 93 in 2methyl-2-propanol. Intramolecular hydrogen-abstraction, a process possible only when hydrogen-donating solvents are absent, has been proposed for explaining alkene formation during irradiation in 2methyl-2-propanol (see Scheme 34). The failure of 93 to form an enol ether upon photolysis demonstrated that other factors, such as ring strain arising from introduction of unsaturation, can determine the course of the reaction. IX. ORGANOMETALLIC COMPOUNDS The single, organometallic, carbohydrate derivative whose irradiation has thus far been reportedlS7is methyl 2-(acetoxymercuri)-3,4,6tri-O-acety~-2-deoxy-~-~-g~ucopyranoside (97). Irradiation of 97 in ~
~~
(184) E. R. Guilloux, J. Defaye, R. H. Bell, and D. Horton, Carbohydr. Res., 20 (1971) 421-426. (185) P. J. Garegg, J. Hoffman, B. Lindberg, and B. Samuelsson, Carbohydr. Res., 67 (1978) 263-269. (186) R. W. Binkley and D. J. Koholic,J. Org. Chem., 44 (1979) 3357-3360. (187) D. Horton, J . M. Tarelli, and J. D. Wander, Carbohydr. Res., 23 (1972) 440-446.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
hv
191
+
Pyrex
0-CMe,
0-CMe,
92
solvent Me,COH Me,CHOH
0-CMe,
94
96
14% 94%
80%
0%
hv Pyrex
(no alkene formed)
0-CMe, 93
95
solvent Me,COH Me,CHOH
51% 96%
methanol yields the corresponding deoxy compound, 3,4,6-tri-O-acetyl-2-deoxy-~-arabinohexopyranoside (99) and elemental mercury. The radical 98 is a probable intermediate in the photochemical process (see Scheme 35). YH,OX
YH,OX
CH,OX
-
+ CH,OH
99
X = Ac
Scheme 35.-Proposed Mechanism for Photochemical Reaction of Methyl 2-(Acetoxymercuri)-3,4,6-tri-0-acetyl-2-deoxy-~-~-glucopyranoside (97).
ROGER W. BINKLEY
192
TABLEXXIV Photochemical Reactions of Carbohydrate Phosphates Reactants
Products
CHO
C02H I HCOH I HOCH I HCOH I HCOH
I
HCOH I HOCH I HCOH
+ 0 2
I
HCOH I
CHO I
HOCH
188
I
HCOH
I
HCOH I CH20PO:-
I
CH20P032-
References
CH20P032-
100
0 CH,OH
HO
0po32-
CH20H
HO0
' 0 2
0
OH
f
"
OH V
OH
O
H
189
OH
101
CH20H I
c=o
I HOCH I HYOH HCOH
CHO
I
+ 0 2
HOCH I CH20P032-
I
CH20P032-
+
ol-pPoH HO""""' H
190
I02
+
OCHCH,OPO~~-
-I.
CHO HAOH I
CH20P032-
X. PHOSPHATES Compounds 100 and 101, unprotected carbohydrates containing a phosphate group, exhibit in photochemical reactivity a marked similarity to other unprotected, carbohydrate (see Scheme (188) C. Triantaphylides and M. Halmann,]. Chem. SOC. Perkin Trans. 1 , (1975)34-40. (189) M. Trachtman and M. Halmann,/. Chem. SOC.Perkin Trans. 2, (1977) 132-137. (190) C . Triantaphylides and R. Gerster, /. Chem. SOC. Perkin Trans. 2, (1977) 1719-1724. (191) J. Greenwald and M. Halmann,]. Chem. SOC.Perkin Trans. 2, (1972) 1095-1101.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
193
16). Irradiation of a-D-glucose 6-(disodium phosphate)lE8(100) yields products that retain the phosphate group (see Table XXIV) but are otherwise the same as those formed from irradiation of D-glucose itself (see Table XII). Photolysis of a-D-glucosyl (dipotassium phosphate) (101) causes rapid release of orthophosphate, followed by formation of the same carbohydrate p h o t o p r o d ~ c t sas '~~ are produced by irradiation of D-glucose (see Table XXIV). D-Fructose 6-(disodium phosphate)lS0 (102),a compound that exists to a significant extent in the keto form, experiences the a-cleavage reaction characteristic of carbonyl compounds (see Scheme 6 and Table XXIV).
ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY VOL . 38
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES BY ROGER W . BINKLEY Department of Chemistry. Cleueland State Uniuersity. Cleveland. Ohio 441 15
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I1. Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I11. Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Aldehydes and Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 . Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
................................................
Alditols. Aldohexoses. and Related Compounds . . . . . . . . . . . VI . Sulfur-Containing Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Dithioacetals and Sulfides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Sulfoxides. Sulfones. and Sulfonates . . . . . ...................... 3. Thiocarbamates and Xanthides ............................... VII . Nitrogen-Containing Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
......................................... ............................................ s ......................................... 4 . Oximes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. Azines ...................................... VIII . Iodo Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 . Deoxyiodo Sugars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 . o-Iodobiphenylyl Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IX . Organometallic Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . X . Phosphates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
105 106 122 122 129 142 147 150 151 153 157 160 160 176 178 179 186 186 186 187 190 192
I . INTRODUCTION Study of the photochemical reactions of carbohydrates is a topic of longstanding interest among chemists; in fact. publications on this subject first appeared shortly after the beginning of the present century . Much of the early work in this area was concerned with changes. in the physical properties of reaction mixtures. arising from irradiations conducted under various conditions . Relatively little identification of the photoproducts was undertaken prior to the introduction of modern instrumentation . In recent years. interest in the photochemistry of carbohydrates has 105 Copyright @ 1981 by Academic Press. Inc. All rights of reproduction in any form reserved .
lSBN 0-12-007238-6
106
ROGER W. BINKLEY
intensified, and the major orientation of research in this field has changed. Synthetic chemists have become increasingly aware of the advantages offered by photochemical reactions. The possibilities raised by these advantages (for example, conducting reactions under mild conditions, synthesizing molecules not obtainable by other routes, and selectively reacting particular functional groups in multifunctional molecules) have stimulated study of the photolysis of a wide variety of carbohydrates and their derivatives. Several photochemical processes already have emerged as important, synthetic reactions, and others are certain to follow. The purpose of the present article is to review comprehensively those photochemical reactions of carbohydrates for which product structures have been established, and to apply current mechanistic reasoning to the understanding of these reactions. Two reviews of carbohydrate photochemistry already exist. The first' was published in this Series in 1963, prior to the considerable recent growth in this field, and the second2 was a brief summary published in the Japanese literature in 1973. An organizational plan based upon the type of functional group has been adopted here in presenting and discussing the photochemical reactions of carbohydrates.
11. ALKENES The most important photochemical reaction of carbon to carbon unsaturated carbohydrates is addition to the unsaturated system. Two types of addition reaction are readily recognized. The first consists of those in which the molecule adding to the carbohydrate does so by involving a m-bond of its own. Processes of this type, listed in Table I, are those which lead to formation of a new ring-system (cycloaddition). The second class of addition reaction is one in which a u-bond is broken in the molecule adding to the unsaturated carbohydrate. The reactions that belong to the latter category (see Tables I1 and 111) follow two basic patterns, and comprise the majority of the addition processes reported. Cycloaddition reactions (see Table I) involving unsaturated carbohydrates are regio- and stereo-selective. These selectivities can be understood by assuming that the photochemical interaction between the two m-systems results in formation of the more stable 1,Pdiradical. The reaction between 3,4,6-tria-acetyl-D-glucal (1) and acetone pro(1)G. 0. Phillips, Ado. Carbohydr. Chem., 18 (1963)9-59. (2)K. Matsuura,Kagaku No Ryoiki, 27 (1973)35-42.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
107
TABLEI Photochemical Cycloaddition Reactions between Unsaturated Carbohydrate Derivatives and Carbonyl Compounds Reactants
0
Products
tJ
CH,OR
+
RO
MeiMe
RO
I 1
R
I
=
o-cue*
Ae
iG, +I$
a
3
99
4
99
5
33
6
33
7
14
8
CH,OR
R = Ae
G
CH,OR
OR
Ref.
27
2
RO
RO
Yields (%)
CH.OR
t Me;Me
OR
RO R = Ae
44
9
(combined yield)
.:Q
11=
10,11
mchb 0 Me,C-CMe,
A
32
n
(Continued)
108
ROGER W. BINKLEY
TABLEI (Continued) Photochemical Cycloaddition Reactions between Unsaturated Carbohydrate Derivatives and Carbonyl Compounds Reactants
Products
Yields (%)
Ref.
10. 11
d
Oxetane hydrolysis product formed. formed. Not determined.
* Non-oxetane
products formed.
c
Dimer
vides an illustration (see Scheme 1).Diradical stability is maximized by attack at C-2 (regiochemistry determined) and by allowing the larger group attached to C-2 to become the equatorial substituent (stereochemistry For addition reactions other than cycloaddition, unsaturated carbohydrates follow one of two fundamental pathways. The more common of the two begins with radical formation arising from bond homolysis in the noncarbohydrate reactant. Radicals are either produced directly, from absorption of light, or indirectly, from hydrogen abstrac(3) Y. Araki, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 60 (1978)389-395. (4) K. Matsuura, Y. Araki, and Y. Ishido, Carbohydr. Res., 29 (1973) 459-468. (5) K. Matsuura, Y. Araki, and Y. Ishido, Bull. Chem. Soc. Jpn., 45 (1972) 3496-3498. (6) K . 4 . Ong and R. L. Whistler,]. Org. Chem., 37 (1972) 572-574. (7) B. Helferich and E. von Cross, Chem. Ber., 85 (1952) 531-535. (8) Y. Araki, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 64 (1978) 109-117. (9) Y. Araki, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 65 (1978)159-165. (10) P. M. Collins and B. H. Whitton,]. Chem. Soc. Perkin Trans. 1 , (1973) 1470-1476. (11) P. M. Collins and B. Whitton, Carbohydr. Res., 21 (1972) 487-489.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
109
TABLEI1
Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
CH=CH,
Q+ RH
0-CMe,
Ref.
Q7
CH,CH,R
0-CMe,
3
R = --SCMe
54
II
12,13
0
R=
411
45
14
(4)
R = -PHPh
75
15
R = -PH,
24
15=
14
oAo
u 6
55
+ CH,O,CCH
0-CMe,
0 II
16
HCNH, CH,O,CCH 0-CMe, I o=cNH, 45
(Continued)
TABLEI1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
Ref.
11
xo
XO R = SEt
R' = Rz = SEt
R = OEt
R' = H, R2 = OEt
X = Ac
R' = OEt, R2 = H
O \
60
/O
C Me,
18
R = -SCMe
61
0 R = - SCH,Ph R = -P(OEt),
69
18
95
19
10
20b
II
II
S
H H,C-C 0 0 C '' Me*
0-CMe,
HCO,
I
H,CO R = -CNH, II
16
0 R = --Me, I OH R = -P(OEt),
,CM% 15
31 33
II
S
110
21 19
9
19
TABLEI1 (Continued)
Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Ref.
Products and Yields (%)
HCO, ,CM% H,CO
I
65
26
X = Ac
0 R=-
i
xo
" II
X = Ac, R = -CNH,
46
13
X=Ac, R =
38
21
X = Ac, R = -CMe, I
24
31
23
76
23
OH
111
(Continued)
TABLEI1
(Continued)
Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
CH,OX
CH,OX
+
xoQOMe
CH,OX
Ref. CH,OX
RH
R X = Ac, R = -SEt X = Ac, R = -SPr
-(I)
X=Ac,R= X=Ac, R =
81
25
94
25 39
FOHMe,
39
66
-
X=Ac, R =
26
32
OR(-J
xoQ + R H ox X = Ac, R = -SEt X = Ac, R = -SPr X = Ac, R = -CNH, I1 0
ox 25
77
25
79 55
42
X=Ac, R = X = Ac, R = -CMe, I OH
20
xo
ox
xo
15
CH,OX
CH,OX
CH,OX
20
16
51
7
16
17
20 8'
+
+RH
xo R X = H, R = -P(OEt), II
90
X = Ac, R = -SEt x = AC, R = a p r
44
44
25
47
47
25
19
S
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
113
TABLE I1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Products and Yields (%)
Reactants $!H,OX
FH,OX
X = H, R = -CH,OH
66 65-85
X = H, R = -CMe, I OH
Ref.
27,28 28 27,28,29
X = Ac, R = -CH,OH
75
OH I X = Ac, R = -CHCH,
65-85
28
42
29
75 65-85
27 28
75-79
30,31
X = Ac, R = -CH OH I
-(:I
X = Tr, R = -C&OH X = Tr, R = -CMe, I OH
X = Tr, R = -CHC&OH I OH
X = Tr, R = -CHCH,CH,OH I
49
30
32
30
67 62
30,32 32
42
32
58
30,32
OH
X = Tr, R = -CHC&C02Me I
OH X = Tr, R = Ac X = Tr, R = -CHC&CH,
A
0
P
X = Tr, R = -CHOH
I
O*O
U
X = Tr, R = Bz
(Continued)
ROGER W. BINKLEY
114
TABLEI1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants
Products and Yields (%)
Ref.
CH,OX O
a
o
4
-
RH
CH3
<:I
30
29
X = Ac, Y = Et, R = -CH,OH
60
29
X = TT, Y = Et, R = -CH,OH OH
61
27
X = Tr, Y = Me, R = -CHCH,OH
71
30
X = T r , Y = M e , R = -CH
46
30
X = Ac, Y = Et, R = -CH OH I
I
I
OH
+
EtOH HOCHCH,
33
56
CKOX
CH,OX
HO
c%ox 28
Q
X=
O
Tr
M 0
e -!-
H O H , C Q 0M e
65
’ “ Q O M0 e
24
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
115
TABLEI1 (Continued) Photochemically Initiated, Radical-Addition Reactions to Unsaturated Carbohydrate Derivatives Reactants YH,OX
Products and Yields (%)
Ref.
qH,OX 34
X=
Tr
X=
Bz
" Minor product formed.
60
Five other products formed.
Acetone addition-product formed.
D. Horton and W. N. Turner, Carbohydr. Res., 1 (1966)444-454. D. Horton and W. N. Turner, Chem. Znd. (London),(1964) 76. J . S. Jewel1 and W. A. Szarek, Tetrahedron Lett., (1969) 43-46. R. L. Whistler, C.-C. Wang, and S. Inokawa,J. Org. Chem., 33 (1968)2495-2497. A. Rosenthal and M. Ratcliffe, Can. J . Chem., 54 (1976) 91-96. A. A. Othman, N. A. Al-Masudi, and U. S. Al-Timari, J. Antibiot., 31 (1978) 1007-1012. K. Matsuura, S. Maeda, Y. Araki, and Y. Ishido, Tetrahedron Lett., (1970) 2869-2872. K. Kumamoto, H. Yoshida, T. Ogata, and S. Inokawa, Bull. Chem. Sac. Jpn.. 42 (1969)3245-3248. K. Matsuura, K. Nishiyama, K. Yamada, Y. Araki, and Y. Ishido, Bull, Cham. Soc. J p n . , 46 (1973)2538-2542. A. Rosenthal and K. Shudo,J. Org. Chem., 37 (1972) 1608-1612. A. Rosenthal and M. Ratcliffe, Carbohydr. Res., 54 (1977) 61-73. Y. Araki, K. Nishiyama, K. Senna, K. Matsuura, and Y. Ishido, Carbohydr. Res., 64 (1978) 119-126. A. Rosenthal and M. Ratcliffe, Carbohydr. Res., 39 (1975) 79-86. Y. Araki, K. Matsuura, Y. Ishido, and K. Kushida, Chem. Lett., (1973) 383-386. K. Matsuura, Y. Araki, Y. Ishido, and S. Satoh, Chem. Lett., (1972) 849-852. B. Fraser-Reid, N. L. Holder, D. R. Hicks, and D. L. Walker, Can. J . Chem., 55 (1977) 3978-3985. B. Fraser-Reid, N. L. Holder, and M. B. Yunker,J. Chem. Soc. Chem. Commun., (1972) 1286-1287. B. Fraser-Reid, D. R. Hicks, D. L. Walker, D. E. Iley, M. B. Yunker, S. Y.-K. Tam, and R. C. Anderson, Tetrahedron Lett., (1975) 297-300. B. Fraser-Reid, R. C. Anderson, D. R. Hicks, and D. L. Walker, C a n ] . Chem., 55 (1977)3986-3995. D. L. Walker and B. Fraser-Reid,J. Am. Chem. Soc., 97 (1975) 6251-6253. D. R. Hicks, R. C. Anderson, and B. Fraser-Reid, Synth. Commun., 6 (1976) 417421. H. Paulsen and W. Koebernick, Carbohydr. Res., 56 (1977) 53-66. D. L. Walker, B. Fraser-Reid, and J. K. Saunders,J. Chem. Soc. Chem. Conamun., (1974)319-320.
ROGER W. BINKLEY
116
TABLEI11 Addition Reactions between Solvent Molecules and Electronically Excited, Unsaturated Carbohydrate Derivatives
&+Q+b
Reactants
0 +
CH,OX
RH
+
MeCMe II 0
xo
Ref.
Products and Yields (%)
xo
xo
xo R
4
74
X = Ac, R = -CMe, I
3
8 (9)
OH X = Ac, R = -CMe,
4
86
I
OH X = Ac, R = -CNH, II 0
22
X = Ac, R =
37
]I(-
0
iRH
xo
-(I]
X = Ac, R =
+
30
35
31
20
MeCMe I1
0 29
10
CHMe, I OH I
a
iCH,CHCH,
H2cQ
22
36
HOCMe,
+
MeCMe 0,
9
C Me,
6
19
5
9
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
117
TABLEI11 (Continued) Addition Reactions between Solvent Molecules and Electronically Excited, Unsaturated Carbohydrate Derivatives Products and Yields (%)
Reactants
Ref.
ROH
31
R = Me R =H
30 (unstable)
0 CH,OR
+
RO
Me;Me 0
hv
RO
-
CMe,
I
More stable
Less stable
(not formed)
J 2
More stable
0-CMe,
Less stable (not formed)
Scheme 1.-Proposed Mechanism for Cycloaddition between 3,4,6-Tri-O-acetyl-Dglucal (1) and Acetone. (35) A. Rosenthal and A. Zanlungo, C a n . ] . Chern., 50 (1972) 1192-1198. (36) Y. Araki, K. Nishiyama, K. Matsuura, and Y. Ishido, Carbohydr. Res., 63 (1978) 288-292. (37) B. A. Otter and E. A. Falco, Tetrahedron Lett., (1978) 4383-4386.
ROGER W. BINKLEY
118 MeCMe
hv
MeCMe
II 0
MeCMe II O*
+
0
(o)
It
O*
-
CH,;HCH, I
+
*(
OH
Initiation steps
1
0 0
n
LQll+.(l - b7by .Yo
CH=CH,
CH,-CH,.
0-CMe,
3
~' ( - H ,H cc
0-CMe,
L e s s stable (not formed)
0-CMe,
More stable
0-CMe, 4
Scheme 2.-Proposed Mechanism for Photochemically Initiated, Radical Addition of 1,3-Dioxolane t o 5,B-Dideoxy-1,2-0-isopropylidene-a-~-xyb-hex-5-enofuranose (3).
tion by excited acetone (see Scheme 2). Regioselectivity in these reactions (see Table 11) is determined by addition (anti-Markovnikov) to the double bond in order to maximize the stability of the new radical produced. An example of this selectivity is the photochemical addition of 1,3-dioxolane to 5,6-dideoxy-1,2-0-isopropylidene-a-~-xyZo-
119
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES less hindered MeC
,OCH,
I
Me,C:
52 +'
'OCH
0
n'
0-CMe,
H,C
/ II
5
"XO]
\.
H
O
Mk
more hindered
6
Scheme 3.-Proposed Mechanism for Photochemically Initiated, Radical Addition of 1,3-Dioxolane to 3-Deoxy-1,2:5,6-di-0-isopropylidene-3-C-methylene-~-~~~~~-hexofuranose ( 5 ) .
hex-5-enofuranose (3)to give exclusively14 2-(5,6-dideoxy- 1,2-0isopropylidene - a - D -xylo - hexofuranose - 6 - yl) - 1,3- dioxolane (4) (see Scheme 2). The stereochemistry in these reactions can usually be predicted by assuming that the radical resulting from initial reaction (for example, radical 7 in Scheme 3 ) will be approached from its less-hindered side. In contrast to the radical addition just described, the less-common of the two reaction pathways mentioned in the preceding paragraph requires that the unsaturated carbohydrate be electronically excited (see Scheme 4). A significant characteristic of alkenes experiencing this type of reaction (see Table 111) is that the double bond is conjugated with an oxygen atom. The triplet energy of such a molecule is sufficiently lowered b y conjugation to allow transfer of energy from acetone to the carbohydrate (see Scheme 4).Once transfer of energy has occurred, the excited carbohydrate can abstract a hydrogen atom from the solvent in the way shown in Scheme 4 for the reaction of 3,4,6tri-O-acetyl-D-glUca1 (1) with 2-propanol.
120
ROGER W. BINKLEY FH,OX n*
T
CH,CCH, (excited)
$"":
energy transfer
0 H
H I
(excited)
+
+
CH,CHCH, I OH
I
CH,CHCH, I OH
1
hydrogen abstraction
hydrogen abstraction
2 Me,eOH
Me,bOH
+
+
YH,OX
xoO
J
H H
radical addition ( s e e Scheme 2)
0 CH,OX
xo
H
HOCMe,
9
8
8%
74 46
X = Ac
Scheme 4.-Proposed Mechanism for Reaction between 2-Propanol and Excited 3,4,6-Tri~-acety~-D-g~ucal (1).
The relative proportions of unsaturated carbohydrate, sensitizer (usually acetone), and solvent may have a decided effect upon a photochemical addition reaction, as at least three competing processes (cycloaddition, radical addition, and energy transfer) are possible. The irradiation of 1in the presence of 2-propanol and acetone provides an illustration (see Scheme 4). When a small proportion of sensitizer
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
-O, I ,CMe,
R =
Me$,
HCO
1 I
HCO, ,C% Hzco
Scheme 5.-Photochemical, Bond.
and
121
/o-
I
OCH
l I H$O’
HCO,
CMez
E -Z Isomerization of Groups Attached to a Double
(acetone) is present, energy transfer and radical addition occur, although energy transfer dominates the reaction. (A detailed study of the competition between these two processes would be interesting.) If the concentration of acetone is raised sufficiently, the third process, cycloaddition (see Scheme l),becomes the major reaction-pathway? Several other types of photochemical reactions involving unsaturated carbohydrates have been reported. One of these is38photochemical, E -2 isomerization of the groups attached to a double bond (see Scheme 5). A second is the internal cycloaddition between two double bonds connected by a carbohydrate ~ h a i n H ~Although -~l the carbohydrate portion of the molecule is not directly involved in this cycloaddition, its presence induces optical activity in the cyclobutane derivatives produced photochemically. Finally, a group of acid-catalyzed addition-reactions has been observed for which the catalyst appears to arise from photochemical decomposition of a noncarbohydrate reactant?244 (38) A. Ducruix, C. Pascard-Billy, S. J. Eitelman, and D. Horton,]. Org. Chem., 41 (1976) 2652-2653. (39) B. S. Green, Y. Rabinsohn, and M. Rejto,J. Chem. Soc. Chem. Commun., (1975) 313-314. (40) B. S. Green, Y. Rabinsohn, and M. Rejto, Carbohydr. Res., 45 (1975) 115-126. (41) B. S. Green, A. T. Hagler, Y. Rabinsohn, and M. Rejto, Zsr. /. Chem., 15 (1976177) 124-130. (42) K. Matsuura, Y. Araki, Y. Ishido, and M. Kainosho, Chem. Lett., (1972) 853-856. (43) K. Matsuura, K. Senna, Y. Araki, and Y. Ishido, Bull. Chem. SOC. Jpn., 47 (1974) 1197-1200. (44) J. Csaszar and V. Bruckner, Ann. Univ. Sci. Budapest. Rolondo Eotvos Nominatae, Sect. Chim., (1973) 87.
122
ROGER W. BINKLEY a-cleavage
R
I
n
Rz
intermolecular
n*
t
R~R+-OH
R3H
% '\
+
..
W,,,
abstraction hydrogen Excited state
R', $-OH
intramolecular
R'
n = Electron in bonding n-orbital I*
= Electron in antibonding n-orbital
Scheme 6.-Potential
Reactions of a Carbonyl, n
-+
n*, Excited
State.
111. CARBONYL COMPOUNDS Carbonyl compounds have, thus far, more frequently been the subject of photochemical study than any other group of organic molecules. The reactions of these compounds may be understood by assuming that absorption of light leads to an n += T * excited state, that is, an excited state in which an electron has been promoted from the highest, nonbonding orbital (on oxygen) to the lowest, antibonding (T*)orbital (see Scheme 6). The reactions of such an excited system are similar to those of an alkoxyl radical and, thus, may include a-cleavage, hydrogen abstraction (intra- and inter-molecular), and addition to a .rr-system (see Scheme 6).
1. Aldehydes and Ketones A photochemical reaction initiated by a-cleavage in a carbonyl compound is called a Type I pr0cess.4~Photolysis of tert-butyl-3,4-O-iso(45) C. H. Bamford and R. G. W. Norrish,J. Chem. SOC., (1938) 1521-1525.
k3
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
123
\O 13.14 I
I
hydrogen transfer
-(OL0CMe3
Me+; Me 12
Scheme 7.-Proposed Mechanism for Type I Reaction of tert-Butyl3,4-O-Isopropylidene-cu-~-mythro-pentopyranosid-2-ulose(10).
propylidene-a-~-erythro-pentopyranosid-2-ulose (10) (see Scheme 7) produces three such reactions (decarbonylation, disproportionation, and ~tereoisomerization).46"~ Irradiation of 5-deoxy-1,2-O-isopropylidene-p-~-threo-pentofuranos-3-ulose (15) (see Scheme 8) provides an example of a fourth (carbene Type I reactions are more common for carbohydrate systems than for most other types of molecules, because the likelihood of occurrence of a Type I process is related to the stabilization, during formation, of the radicals produced (46) P. M . Collins, P. Gupta, and R. Iyer, Chem. Commun., (1970) 1261-1262. (47) P. M. Collins, R. Iyer, and A. S. Trdvis,J. Chem. Res. (S), (1978) 446-447 and J. Chem. Res. ( M ) , (1978) 5344-5360. (48) P. M. Collins, N. N. Oparaeche, and B. R. Whitton,J. Chem. SOC. Chem. Commun., (1974) 292-293.
124
ROGER W. BINKLEY
c 0
H,C
0-CMe, I5
0
rotation necessary for effective stabilization
Orbital picture for 3,4-c1eavage effective radical forms
L
J
Orbital picture for 2,3-cleavage
Hq!-!-
Me0
0-CMe,
0-CMe,
16, 17
Scheme 8.-Proposed Mechanism for Carbene Formation from Photolysis of 5Deoxy-1,2-O-isopropylidene-~-~~erythro-pentofuranos-3-ulose (15). Rationalization for the Direction of a-Cleavage.
by a-cleavage. In carbohydrate systems, where a radical center on carbon will usually have an adjacent, stabilizing, oxygen atom, a-cleavage is particularly f a ~ o r e d . 4The ~ . ~Type ~ I reactions of carbohydrates reported are listed in Table IV. Although an excited carbonyl can fragment at either of the two carbon to a-carbon bonds thereof, the favored direction of fragmentation (49) K.-G. Seifert, Tetrahedron Lett., (1974) 4513-4516. (50) S. Steenken, W. Jaenicke-Zauner,and D. Schulte-Frohlinde, Photochem. Photobiol., 21 (1975) 21-26.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
125
TABLEIV Type I Reactions of Excited Carbohydrate Derivatives Products and Yields (70)
Reactants
Me2
Me2
54
6
Ref.
51- 53
eOMe a
77
53
53
17
MezcLv '0
'02
OCMe,
0 10
I3
14
12
13
11
40
46,47
0 13
14
12
13
11
40
46,47
(Continued)
ROGER W. BINKLEY
126
TABLEIV (Continued) Type I Reactions of Excited Carbohydrate Derivatives Ref.
Products and Yields (%)
Reactants
P
Me
M e , C L d m M e 3
41
"+' 00CMe3 Me$ '
60
u-r+ CH,O
o\
9
o\
/o
0
Me&-0
0 0-CMe,
0-CMe,
55
10
Me&
'Q+
55
10
Me$-0 48
Me&-0
0
C
54
0
O?
0 I Me&-0
C
0-CMe,
EtoH
OEt
65
PHOTOCHEMICAL REACTIONS O F CARBOHYDRATES
127
TABLEIV (Continued) Type I Reactions of Excited Carbohydrate Derivatives ~~
Reactants
Products and Yields (%)
Ref.
48
MeoQY
0-CMe,
CHO ~ O A C
I
CH,OAc I
AcOCH
AcOCH
I
I
HCOAc
HCOAc
HCOAc
HCOAc
I
I I
CH,OAc
I
CH,OAc 16
may often be predicted by examining the structure of the reacting molecule. The critical factor in determining which a-cleavage will result is stabilization of the developing radicals (or diradicals, in cyclic ketones) during formation. This stabilization is not only dependent upon the presence of radical-stabilizing groups on the a-carbon atoms but also on the positioning of these groups. The photolysis of 15 (see Scheme 8) provides an informative illustration, because, as the C-2-C-3 bond in excited 15 begins to break, a nonbonding orbital on the oxygen atom on C-2 is properly aligned to stabilize the developing radical-center on C-2. In contrast, the radical center on C-4 that is being formed by fragmentation of the C-3-C-4 bond will not experience stabilization from a nonbonding orbital on the oxygen atom on C-4 until the C-3-C-4 bond is broken and rotation can occur. As a result, cleavage of the C-2-C-3 bond is favored.53 Intramolecular hydrogen-abstraction to produce a 1,4-diradical is the major, photochemical pathway for molecules in which the oxygen (51) P. (52) P. (53) P. (54) P. (55) K. (56) R.
M. Collins, Chem. Commun., (1968)403-405. M. Collins and P. Gupta,]. Chem. Soc., C, (1971) 1965-1968. M. Collins,J. Cheni. SOC., C, (1971) 1960-1965. M . Collins and P. Gupta, Chem. Commun., (1969) 1288-1289. Heyns, R. Neste, and M. Paal, Tetrahedron Lett., (1978) 4011-4014. L. Whistler and K . 3 . Ong,]. Org. Chem., 36 (1971) 2575-2576.
56
XO
XO 18
I
xo
X = Ac
19
Scheme 9.-Proposed Mechanism for Formation of Cyclobutanol from the Photolysis of 1,3,4,5,6-Penta-O-acetyl-keto-~-sorbose (18). Me
0
HO -5(
II
CH,OCCMe
*yH-O
,c=o
hv
0-CMe,
/
20
0-CMe,
Me&-0 0-CMe, 21
t H,C =C=O Scheme 10.-Proposed Mechanism for Type I1 Reaction of 1,2:3,4-DiO-isopropylidene-6-O-pyruvoyl-a-~-galactopyranose (20).
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
129
atom of an excited carbonyl can come within bonding distance of a hydrogen atom attached to a y-related carbon atom. (Such a process is possible for all of the compounds in Tables V and VI.) The reactions of the 1,Cdiradical produced by hydrogen abstraction are called Type I1 processes, and may include closure to form a cyclobutanol (see Scheme 9), fragmentation of the 2,3-bond to produce a new carbonyl compound (see Scheme lo), and reversal of the hydrogen-abstraction process to regenerate the starting material (or an epimer). Photolysis of a-ketoesters provides an example of the synthetic potential of the Type I1 reaction, as synthesis and irradiation of these compounds accomplish oxidation of alcohols to carbonyl compounds under quite mild conditions (see Table VI). For molecules in which intramolecular hydrogen-abstraction (Type I1 reaction) is structurally prevented, intermolecular abstraction from a hydrogen-donating solvent may take place (see Scheme 6). This type of reaction usually results in reduction of the carbonyl group (see Table VII). Cycloaddition reactions between alkenes and noncarbohydrate, carbonyl compounds have been described in discussing the reactions of alkenes (see Table I and Scheme 1). The depiction of the excited carbonyl given in Scheme 6 is useful in understanding the regiochemistry of the cycloaddition process, as it suggests that the electrondeficient oxygen atom in the excited carbonyl will react with the alkene to produce the (more-stable) 1,4-diradical. Table VIII lists cycloaddition reactions in which the excited carbonyl is part of a carbohydrate. 2. Esters When considered as a part of the photochemistry of carbonyl compounds, irradiations of esters constitute a minor component. The more frequent photolyses of other carbonyl compounds, in particular ketones, is not surprising, as, even though parallels exist between ester and ketone photochemistry (for example, both experience a-cleavage and hydrogen abstraction-reactions), esters require radiation of higher energy for reaction, and typically produce more-complex mixtures of products. In addition to their similarity to other carbonyl compounds in their reactivity, esters also experience reactions that are uniquely their own. When the esters listed in Table IX are irradiated, typical carbonyl reactions result; that is, each of these compounds (22-27) experiences both a-cleavage and hydrogen-abstraction reactions. For the esters of 1,2:3,4-di-O-isopropylidene-cr-~-galactopyranose (22-26), the hydrogen-abstraction reaction is internal, and leadsagto a Type I1 reaction
ROGER W. BINKLEY
130
TABLEV Type I1 Reactions of Excited Carbohydrate Derivatives" Reactants
OX
Ref.
Products and Yields (%) CH,OX
XOCH, x o V
C
H
,
O
X
xo
ox X = Ac
12
57
CH,OX
x o c ~ c . xo
xo
ox 18
Me,C-0 ' Q
O
57
26 (19)
M
5459
e 0
0
0 (No yield reported)
R=H R = Me
58
RCH
R C /OCH= f o o o M e
0 R = Ph R = Me
58,59
50
0
0 3
46
58
(No yields reported)
58
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
131
TABLEV (Continued)
Type I1 Reactions of Excited Carbohydrate Derivatives" Reactants
0
R R
=
Products and Yields (%)
HO
OMe
Ph
0
Ref.
0 4
65
58
(No yields reported)
= Me
58
" Additional examples of Type I1 reactions are probable, but product structures not established.60
TABLEVI. Type 11 Reactions of a-Ketoesters of Carbohydrates
Reactants
Products and Yields (%) RCH II 0
RCH,OCCMe I1 I1
00
R=
R=
References
0-J
xo
70
61,62
65
61,62
85
62
I
ox
X=
Ac
(Continued)
ROGER W. BINKLEY
132
TABLEVI
(Continued)
Type I1 Reactions of a-Ketoesters of Carbohydrates Products and Yields (%)
Reactants
62
References
61,62
Me&-0 \ ,c=o
-CH-OCCMe I IIII -7 00
R
R= I
74
61,62
57
61,62
100
62
70
62
1
(-J--r 0 0-CMe,
R=
0 I
Me$-0
I
XOCH,
R=
xo
I ox
X=
R=
AC
Qox
xo
X = AC
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
133
TABLEVI (Continued)
Type I1 Reactions of a-Ketoesters of Carbohydrates Reactants
Products and Yields (%)
R=
References
38
63
59
63
80
63
79
63
0-CMe, TrOCH,
0
R=
Q7
0-CMe,
X1= H, X = Me X1 = Me, X = H
X = Tr
X = Bz
61 68
63,64 63,64
(Continued)
ROGER W. BINKLEY
134
TABLEVI (Continued)
Type I1 Reactions of a-Ketoesters of Carbohydrates Products and Yields (%)
Reactants
References
0
X = Tr X = BZ
57
63,64
57
63,64
TABLEVII
Reactions of Excited Carbonyl Groups in Carbohydrate Derivatives with Solvent Molecules
Mecay mce? Products and Yields (70)
Reactants
0
0-CMe,
HOCH,
0-CMe,
0
0-CHEt
0-CMe,
HO
SO
Ref.
65
HOCH,
0-CHEt
HO
OH
HO
20
22
65
0-CHEt
66
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
135
TABLEVIII Cycloaddition Reactions between Excited Carbonyl Groups in Carbohydrate Derivatives and Unsaturated, Non-Carbohydrates Reactants
Products and Yields (%)
References
R b ° 0F o R = -CH,OAc
57
67
R = -COEt
23
67
19
68
II
0
RCH II
0 R=
+
0 I
OCH +CMe, HCO’ HC 0, ,CMe, H,CO
I
R = 0-CMe, X = CH,Ph
X = Me
10
14 19
68 68
68
ROGER W. BINKLEY
136
TABLEIX Photochemical Reactions of Esterified Carbohydrates" Products and Yields (%)
Reactants
0-CMe,
I
R = Ph (zd R = CH,Ph ( c d (24)
R = -CHPh, (25) R = -CPh, (no) I Me
I
0-CMe,
0-CMe, 28
R = CH,CH,Ph
References
29
3
12
69
26
50
69
3
8
69
10
29
69
5
27
69
0
EOMe
33
HOQOMe
HOO OH
27
O
M
+
e
70
OH R' = Rz = H
R'
=
(30)
H, R2 = -CH,OH
R' = -CH,OH,
RZ = H
(No yields reported)
(31)
(32)
&H
Ho
34
Additional examples of this type of reaction are probable, but product structures not e~tablished."-'~
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
137
TABLEX
Photochemical Reactions of Esterified Carbohydrates with Hexamethylphosphoric Triamide Reactants
Products and Yields (%) RH
ROAc
ROH
Ref.
85
74
65
75
0-bMe,
65
30
74
R= 65
75
81
74
70
75
78
74
60
14
R=
R=
I 1
Me$-0
(Continued)
ROGER W. BINKLEY
138
TABLEX
(Continued)
Photochemical Reactions of Esterified Carbohydrates with Hexamethylphosphoric Triamide Products and Yields (%)
Reactants ROAc
RH
Ref.
ROH
76
R=
’
Me,C-0 Q
R=
O
M
e
(No yields reported)
75
(No yields reported)
75
R= I
74
55
75
70
75
I
Me,C-0
R=
0c A C M CH,I e 2
I Me,C-0
’
Me$-0
G
H,C
O
ox M
e CH2
X = Ac
51
9
15
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
139
TABLEX (Continued) Photochemical Reactions of Esterified Carbohydrates with Hexamethylphosphoric Triamide Products and Yields (%)
Reactants ROAc
RH
Ref.
ROH
Me C / b o M e O\
ox 50
X = Ac XOCH,
HOQ
O
M
e
HOO
O
75
CH3
M
e
H O O O M e
OX X = Ac
10
20
75
X = -CCMe, 1 I 0
10
20
75
,OCH2 Me2C ‘OCH
I
G? 0
0-CMe,
X = -CCMe,
75
II
0
(57) R. L. Whistler and L. W. Doner,]. Org. Chem., 38 (1973) 2900-2904. (58) P. M. Collins, P. Gupta, and R. Iyer, J. Chem. SOC. Perkin Trans. 1 , (1972) 1670-1677. (59) P. M. Collins and P. Gupta, Chem. Commun., (1969) 90. (60) I. Kitagawa, K. S. Im, and Y. Fujimoto, Chem. Pharm. Bull., 25 (1977) 800-808. (61) R. W. Binkley, Carbohydr. Res., 48 (1976) cl-c4. (62) R. W. Binkley,]. Org. Chem., 42 (1977) 1216-1221. (63) R. W. Binkley, D. G. Hehemann, and W. W. Binkley, J . Org. Chem., 43 (1978) 2573-2576. (64) R. W. Binkley, D. G. Hehemann, and W. W. Binkley, Carbohydr. Res., 58 (1977) clO-cl2.
140
ROGER W. BINKLEY
J
I
22- 26
hydrogen abstraction
28
29
R' = alkyl or aromatic group,
".I;1.
R2 = Me,C-0
0-CMe,
Scheme 11.-Proposed
Mechanisms for Type I and Type I1 Reactions of Esters
22-26.
(Scheme 11).For methyl (methyl D-g1ucopyranosid)uronate (27a,b),acleavage is accompanied by a rearrangement'O initiated by hydrogen abstraction from the solvent (Scheme 12). A reaction unknown for other carbonyl compounds occurs when es~~~~
(65) P. M. Collins, V. R. N. Munasinghe, and N. N. Oparaeche,J. Chem. Soc. Perkin Trans. 1 , (1977) 2423-2428. (66) W. A. Szarek and A. Dmytraczenko, Synthesis, (1974) 579-580. (67) Y. Araki, J.-I. Nagasawa, and Y. Ishido, Carbohydr. Res., 58 (1977) C4-C6. (68) J. M. J. Tronchet and B. Baehler, J. Carbohydr. Nucleos. Nucleot., 1 (1974) 449-459. (69) R. W. Binkley and J . L. Meinzer, J. Carbohydr. Nucleos. Nucleot., 2 (1975) 465-469. (70) A. G. W. Bradbury and C. von Sonntag, Carbohydr. Res., 60 (1978) 183-186. (71) I. Kitagawa, M. Yoshikawa, and I. Yosioka, Tetrahedron Lett., (1973) 3997-3998. (72) I. Kitagawa, M. Yoshikawa, Y. Imakura, and I. Yosioka, Chem. Phann. Bull., 22 (1974) 1339-1347. (73) I. Kitagawa, M. Yoshikawa, Y. Imakura, and I. Yosioka, Chem. Znd. (London), (1973) 276-277. (74) J.-P. Pete and C. Portella, Synthesis, (1977) 774-775. (75) P. M. Collins and V. R. Z. Munasinghe,]. Chem. Soc. Chem. Commun., (1977) 927-928.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
141 OMe I 'COH
OMe
c=o
a-cleavage
H-abstraction
1 4COMe I
MeOH
p M e
+ no
CH,
OH
33
34
Scheme 12.-Proposed
Mechanism for Photochemical Reactions of Methyl (Methyl D-G1ucopyranosid)uronates(27a,b).
terified carbohydrates are photolyzed in hexamethylphosphoric triamide. Such irradiations result in replacement of the ester group by a hydrogen atom and, thus, are u s e f ~ l ' ~ for , ' ~ synthesizing deoxy sugars (see Table X). Although the yields of deoxy sugars are normally good, formation of an alcohol competes in some instances. Depicted in
ROGER W. BINKLEY
142
0 II
RTOCMe + (Me,N),PO
hv
transfer
:0: I
RSCOCMe H
.+
\CH,NPOX,
I
Me
R3CH R 3 = carbohydrate residue
X = -me,
O=C
f
,o‘Me
+
H,C=NPOX,
I
Me
Scheme 13.-Proposed Mechanism for Photochemical Reaction between Esters and Hexamethylphosphoric Triamide.
Scheme 13 is a mechanism for this reaction that is based upon an electron-transfer process. An electron-transfer mechanism has been proposed in order to explain similar reactions in noncarbohydrate system~.’~
IV. ACETALS Three types of photochemical reaction of carbohydrate acetals have been investigated. Early studies centered on the photochemical fragmentation of phenyl glycosides, and the photolysis of o-nitrobenzylidene acetals. (The latter reactions will be discussed with the photolysis of other nitro compounds; see Sect. VI1,l.) Later experiments were concerned with hydrogen-abstraction reactions from acetal carbon atoms by excited carbonyl compounds. The reactions that follow initial hydrogen-abstraction from an acetal carbon atom are those characteristic of radicals, and include coupling, ring opening, and reaction with molecular oxygen (see Table XI). The presence of molecular oxygen, even in low concentration, appears to exert a controlling influence on the course of acetal photochemistry by typically producing hydroxy esters as the major photoproducts. A mechanism proposeds1 for the formation of these hydroxy esters (and other acetal photoproducts), using methyl 3,4-0-ethylidene-P-~-arabinopyranoside (35) as an example, is given in Scheme 14. (Scheme 16 contains a mechanism proposed for a related reaction.) Study of model systems has revealed a tendency for photochemical abstraction of axial, rather than equatorial, acetal hydrogen atoms in (76) H. Deshayes, J. P. Pete, and C. Portella, Tetrahedron Lett., (1976) 2019-2022.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
Me,C=O
+
MeHC-0 ' 0 0 . . I
OH
1
35
hv
Me$-0 O /Q
30
+ 39
radical coupling
OMe
+
143
*'0 OMe + AcoQoMe
OH
1
Me,&OH
OH hydrogen abstraction
I
OH
3r
36
H0O>LQOMe Me
+
OH
Me,C =O
ring
opening-
Me
OH
*OQ
+
*O ' QOMe
OMe
J
40
OH
OH
hydrogen abstraction 41
Scheme 14.-Proposed Mechanism for Photochemical Reaction of Methyl 3,4-0Ethylidene-p-L-arabinopyranoside(35) with Excited Acetone.
ROGER W. BINKLEY
144
TABLEXI
Photochemical Reactions of Benzylidene and Ethylidene Acetals of Carbohydrates Products and Yields (70)
Reactants
1
I
OX
Ref.
OX
Ax
J
77,78
38 23 33
BzOYH,
9
77,78
7
77 ,I8
HOFH,
M e 2 C = 0 i O2
f
phc(@ 0
P
I
ox
OX 19 23 H f
O
C
U
+
O
77,78
77,78
C
U
79
Me,C=O BzO
0, / o HCPh
I
HO
OH
58
Q7
BzOCH, f
H
27
41
Me,C=O
HO
+
0
0-CMe,
,
OBz
Hoc;6 79
BzO
0-CMe,
TABLEXI (Continued)
Photochemical Reactions of Benzylidene and Ethylidene Acetals of Carbohydrates Reactants
Ref.
Products and Yields (%) BzFH,
+ BzOQ
O
ox
x = Bz
M
80
e
HOO
O
M
ox
ox
'OoMe
YH,OBz
,OCH, PhHC,
+
e
$H,OH
+
Me,C=O
80
BzoQoMe
/'FaoMe
OX
OX
X = Bz
+
MeC-0 H
+
Me,C=O
H ' Q O M e OH
OH 35
81
AcoQoMe
+
OH
H
37
36 7
Me,$!OH
Me
/
OH
C '/ I -CMe, 0
-0
U
O
i-
OMe
QO
38
39
17
7
+
HoQoMe
M OH
OH
AcoQoMe
I
OH
OH 41
40
59
e
'
146
ROGER W. BINKLEY
OMe
,
1
R. stabilization begins as radical forms
considerable bond breaking and rotation necessary before effective stabilization can begin
+ RH Scheme 15.-Rationalization for the Importance of Orbital Overlap to Radical Stabilization During Hydrogen Abstraction from an Acetal Carbon Atom.
pyranoid system^?^-^' This tendency has been r a t i ~ n a l i z e d ~as~ aris**~ ing from more-effective stabilization of the developing radical-center on the carbon atom by the adjacent oxygen atom during axial hydrogen-abstraction (see Scheme 15). Interestingly, there is a parallel between the importance of orbital overlap ( a )to radical stabilization dur(77) M. Suzuki, T. Inai, and R. Matsushima, Bull. Cheiii. SOC. J p n . , 49 (1976) 1585-1589. (78) S. Morio, R. Matsushima, T. Inai, and S. Tsujimoto, Asahi Garusu Kogyo Gijutsu Shoreikai Kenkyu Hokoku, (1977) 235-247; Chem. Abstr., 89 (1978) 180,240. (79) K. Matsuura, S. Maeda, Y. Araki, and Y. Ishido, Bull. Chem. SOC. J p n . , 44 (1971) 292. (80) W. Szeja and M. Lapokowski, Pol. J. Chem., 52 (1978) 673-675. (81) W. A. Szarek, R. J. Beveridge, and K. S. Kim,J. Carbohydr. Nucleos. Nucleot., 5 (1978) 273-284. (82) R. D. McKelvey, Carbohydr. Res., 42 (1975) 187-191. (83) K. Hayday and R. D. McKelvey,]. Org. Chem., 41 (1976) 2222-2223. (84) C. Bemasconi and G . Descotes, C. R. Acad. Sci. Ser. C , 280 (1975) 469-472. (85) C. Bernasconi, L. Cottier, and G. Descotes, Bull. S O C . Chim. Fr., (1977) 107-112. (86) C. Bemasconi, L. Cottier, and G. Descotes, Bull. SOC. Chim.Fr., (1977) 101-106. (87) C. Bemasconi, L. Cottier, G. Descotes, M. F. Grenier, and F. Metras, Nouu. J. Chim., 2 (1978) 79-84.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
147
ing hydrogen abstraction from an acetal carbon atom (see Scheme 15) and ( b )in a-cleavage of excited carbonyl compounds (see Scheme 8). Photolysis of aryl glycosides was not only one of the first photochemical reactions of carbohydrates to be but has continued to be an area of active investigation. Intriguing observations have been made concerning the effect of aromatic substituents upon glycosidic h y d r o l y s i ~ . ~ These , ~ ~ observations suggested that the photochemical, aromatic substitution observed in noncarbohydrate systems% may be responsible for the hydrolysis of aryl glycosides. Complete understanding of these effects must await further studies on product structures, chemical yields, and reaction mechanisms.
V. UNPROTECTED ALDITOLS,ALDOHEXOSES, AND RELATED COMPOUNDS Irradiation of unprotected carbohydrates was the subject of greatest photochemical interest to the early carbohydrate photochemists.l The investigations of these early workers were concerned primarily with the effect of reaction conditions upon the photochemical process, rather than with the identity of the reaction products. Between 1960 and 1969, a comprehensive series of papers was published on the photochemical reactions of D-glucose and D-glucit01?~-~~ These studies contributed greatly to understanding of the photochemistry of unprotected carbohydrates, as not only was the result of variation in the reaction conditions studied but also the structures of the products were determined. Extended irradiation of D-glucose and D-glucitol in the presence of oxygen result^^^-^^ in considerable degradation of the starting materials (see Table XII). Such degradation is consistent with the radical (88) (89) (90) (91) (92) (93) (94) (95) (96) (97) (98) (99)
L. J. Heidt,]. Am. Chem. Soc., 61 (1939) 2981-2982. L. J. Heidt,]. Franklin Znst., (1942) 473-486. G. Tanret, C. R . Acad. Sci., 202 (1936) 881-883. G. Tanret, Bull. Soc. Chim. B i d . , 18 (1936) 1344-1351; Chem. Abstr., 30 (1936) 7119. T. Yamada, M . Sawada, and M. Taki, Agric. Biol. Chem., 39 (1975) 909-910. W. G. Filby, G. 0. Phillips, and M. G. Webber, Carbohydr. Res., 51 (1976) 269-27 1. N. J. Turro, Modern Molecular Photochemistry, BenjaminEummings, Menlo Park, CA, 1978, pp. 404-408. G. 0. Phillips and G. J. Moody,]. Chem. Soc., (1960) 3398-3404. G. 0. Phillips and W. J . Criddle,]. Chem. Soc., (1963) 3984-3989. G. 0. Phillips and P. Barber,]. Chem. Soc., (1963) 3990-3997. G. 0. Phillips, P. Barber, and T. Rickards,]. Chem. Soc., (1964) 3443-3450. G. 0. Phillips and T. Rickards,]. Chem. Soc., B, (1969) 455-461.
ROGER W. BINKLEY
148
TABLEXI1 Photochemical Reactions of Unprotected Alditols and Aldohexoses Major Products and Percent Yields Reactants
D-Arabinose
D-Gluconic Acid
D-Glucuronic FormalAcid dehyde
References ~~
D-Glucose (low conversion) D-Glucose (high conversion) D-Ghcitol (high conversion)
13
4
6
0.5
0.6
4
5
&
HO OH
It'p" S
HO OH
0
+
*OOH
I
OH
ccH HOH
CH,OH
CH
95 96
OH
+
IoHu CH
22
I
OH
OH
99
0 OoH
HO@OH OH
Ho
47
23
o,
H2
It
0
+.OOH
OH
CH
\O
woH
HO
I
HO
I
OH
~-Arabinose ~-Gluconicacid aHydroxyl radicals derived from photolysis of waterlOo Scheme 16.-Proposed Mechanism for Photochemical Reaction between D-Glucose and the Oxygen in Water.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
149
reactions expected under these photolytic conditions. When reaction of D-glucose is conducted under conditions that maximize the percentage yield of primary products [that is, low (10%) conversion of Dglucose], D-arabinose and D-gluconic acid are the major products. These two products are those expected from a photochemically initiated, radical decomposition of an acetal (see Scheme 16). Several investigations have since been conducted on the photolysis of unprotected ~ u g a r s . ' ~ ~Spectroscopic -'~~ and chemical evidence has been offered for the formation of malonaldehyde from the photolysis of D-glucose in neutral or alkaline so1ution.lo0The formation of this compound has been suggested as the basis for the use of D-glucose as a chemical actinometer.lo1 Also, photolysis of D-glucose in the presence of L-lysine or glycine results in low yields of D-glucopyranosylamine; however, this photochemical reaction is probably not of D-ghcose, but rather, of the amino acids to form ammonia, which then reacts with the carbohydrate.lo2Finally, synthesis of a complex mixture of monosaccharides results when aqueous formaldehyde is irradiated in basic solutions.1o3 Two derivatives of unprotected carbohydrates, r i b o f l a ~ i n e ' ~ ~(42) J~' CH,OH HOkH
I
HOCH I
HOFH
0 42
and 2'-deo~yuridine'~* (43), experience intramolecular, photochemical reactions. The excited portion of each of these molecules (42 and 43) (100) K. Scherz, Carbohydr. Res., 14 (1970) 417-419. (101) R. K. Datta and K. N . Rao, IndianJ. Chem., Sect. A, 14 (1976) 122-123. (102) L. W. Doner, R. Balicki, and R. L. Whistler, Carbohydr. Res., 47 (1976) 342-344. (103) Y. Shigemasa, Y. Matsuda, C. Sakazawa, and T. Matsuura, Bull. Chem. Soc. Jpn., 50 (1977) 222-226. (104) W. J. Criddle, B. Jones, and E. Ward, Chem. Znd. (London), (1967) 1833-1834. (105) J.-Y. Peng, K. Minami, and T. Yoshimoto, Mokuzai Gakkaishi, 22 (1976) 511-517. (106) M. S. Joms and P. Hemmerich, 2. Naturforsch. Teil B , 27 (1972) 1040-1044. (107) M. S. Joms, G. Schollnhammer, and P. Hemmerich, Eur. J . Biochem., 57 (1975) 35-48. (108) J. Cadet, L . 3 . Kan, and S. Y. Wang,J. Am. Chem. Soc., 100 (1978) 6715-6720.
ROGER W. BINKLEY
150
hv
HO
HO 43
0
HO Scheme 17.-Proposed Mechanism for Photochemical Reaction of 2’-Deoxyuridine (43).
does not involve the carbohydrate part of the structure; consequently, the carbohydrate portion of each molecule is involved in reaction by adding to the excited system. This addition process, which is believed to involve zwitterionic intermediates, is illustrated for 2’-deoxyuridine (43) in Scheme 17.
VI. SULFUR-CONTAINING COMPOUNDS The types of sulfur compounds irradiated include dimethyl thiocarbamates, disulfides, dithioacetals, sulfides, sulfonates, sulfones, sulfoxides, and tetrasulfides. Also, such sulfur-containing compounds as simple alkanethiols have been added to unsaturated carbohydrates (see Table 11). Several of the photochemical reactions of sulfur-containing carbohydrates clearly have synthetic value (for example, photolytic removal of p-toluenesulfonate protecting groups), and study of such other reactions as sulfone transformations has contributed significantly to mechanistic understanding of the photochemistry of organic sulfur compounds.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
lhv 1
44
[RCH,. HOCH
+
151
*SEt]
MeOH
I
HOCH R = H~OH I
RCH,
I
48
HCOH CH,OH
+
*CH,OH
Scheme 18.-Proposed Mechanism for Photochemical Reaction of D-Galactose Diethyl Dithioacetal (44).
1. Dithioacetals and Sulfides Photolysis of D-galactose diethyl dithioacetal(44) results in carbonsulfur bond-fragmentation, leading to 1-S-ethyl-1-thio-D-galactitol (45) in 55-60% yield; in addition, minor proportion of L-fucitol (46) and 1-deoxy-1-ethylsulfinyl-D-galactitol(47) are formed.logSimilar irradiation of acetates (48-51) of the diethyl dithioacetals produces the corresponding 1-S-ethyl-1-thioalditol acetates in 79, 85, 87, and 84% yields, respectively.l1° The excellent yields from these reactions suggest that the photochemical transformation of dialkyl dithioacetals is an attractive means for accomplishing a net replacement of an S-alkyl group by hydrogen. A mechanism based upon homolytic carbon-sulfur bond-fragmentation well rationalizes product formation100(see Scheme 18). 0
H
EtSCSEt
I
I
HCOH I HOCH I HOCH I
HCOH I CH,OH 44
HCOH
hv MeOH ~
air
I
HOCH I
HOCH I HCOH I CH,OH 45
II
7% HCOH
H,CSEt
H,CSMe I HCOH I
I
+
HOCH I
HOCH I
HCOH I
+
HOCH I
HOCH I HCOH I
CH,OH
CH,OH
46
47
(109) D. Horton and J . S. Jewell,]. Org. Chem., 31 (1966) 509-513. (110) K. Matsuura, Y. Araki, and Y. Ishido, Bull. Chem. SOC.Jpn., 46 (1973) 2261-2262.
ROGER W. BINKLEY
152
H EtSCSEt
H EtSCSEt I
I
ROCH
HCOR
I
I
HCOR
HCOR
HCOR
HCOR
I
I I
I
CH,OR
C&OR 49
48
H EtSCSEt
H
EtSCSEt I HCOR I ROCH
I
HCOR I ROCH I
I
HCOR I CH,OR
HCOR I
HCOR I CH,OR 51
50
R = Ac CH,OH I HCOH I HOCH I
HOCH
HAOH I
CH,OH
52
Extended irradiation of the diethyl dithioacetal 44 increases the yield of L-fucitol (46) at the expense of l-S-ethyl-l-thio-D-galactitol (45); also galactitol (52) was isolated from the photolysis mixture.lo9 The intermediacy of 45 in the formation of 46, a possibility that was suggested by the extended photolysis of 44, is supported by the observation that irradiation of 45 in methanol produces L-fucitol(46) in 44% yield.log(Compounds 47 and 52 also are formed during irradiation of 45, but in low yield.) The mechanism for sulfide photoreaction parallels thatlogfor the alkyl dithioacetals (see Scheme 18). Other sulfide photoreactions result when appropriate nucleoside derivatives are photolyzed. Upon irradiation in acetonitrile, 9-[5-deoxy-2,3-0 -isopropylidene-5-(phenylthio)-~-~-ribofuranosyl]adenine (53) is converted into the anhydronucleoside 8,5'-anhydro(5'-deoxy-2',3'-0-isopropylidene-adenosine) (55) in 66% yield."' Similar reactions were observed when other sulfur-containing nucleosides were irradiated (see Table XIII). The reaction of the sulfide 53
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
0,
/o
CMe,
o\C&:2 54
53
0, / o CMe,
153
0,
/o
CMe,
55
Scheme 19.-Proposed Mechanism for Photochemical Reaction of 2’,3’-O-Isopropy~idene-5’-S-phenyl-5’-thioadenosine (53).
differs from the photoreaction of the sulfide 45, because a radical such as 54 (presumably an intermediate in the reaction of 53) can add internally to the nitrogenous-base moiety of the molecule. Such an intramolecular addition (see Scheme 19)should be favored over a bimolecular reaction (see Scheme 18). 2. Sulfoxides, Sulfones, and Sulfonates Photochemical, carbon-sulfur bond cleavage is also observed in compounds containing sulfur in oxidation states higher than that which exists in sulfides and in dialkyl dithioacetals. For example, the irradiation of the sulfoxide 47 in methanol produces10ga 58% yield of galactito1 (52). Even though homolysis of the carbon-sulfur bond does occur in 47, it is unlikely that 52 results from a simple, carbon-sulfur bondcleavage, as such a reaction predicts products that were not observed
ROGER W. BINKLEY
154
TABLEXI11 Photochemical Reactions of Sulfur-Containing, Nucleoside Derivatives Reactants
Products and Yields (%)
66
(Yield not reported)
(Yield not reported)
Ref,
111
111
111
112
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
155
TABLEXI11 (Continued) Photochemical Reactions of Sulfur-Containing, Nucleoside Derivatives Products and Yields (%)
Reactants
X O C Qs W
+
Ref.
XOCH,
+ xo
ox
xo ox
xo ox
5
9
X = Ac
113
XOCH, SH
xo ox 5
(see Scheme 20).A rationalization for formation of 52 on photolysis of 47 may be based on the suggestion that 47 experiences prior photochemical rearrangement to 56, a compound that, on photolysis, should be converted into 52 (see Scheme 21).This type of rearrangement (47 to 56) has been observed during photolysis of sulfoxides in noncarbohydrate system^."^*^^^ The photochemical reaction of 2,3,4,6-tetra-o-acetyl-P-D-glucopyranosyl sulfone (57) in benzene under nitrogen has been carefully studied, and a number of products identified116 (see Scheme 22). A mechanism that involves a photochemically initiated series of free-radical processes has been proposed that is consistent not only with product formation but also with the extent of incorporation of deuterium found in the various products following irradiation of 57 in benzene-&. The mechanism shown in Scheme 22 is compatible with proposals offered to explain sulfone photochemistry in noncarbohy(111) A. Matsuda, M. Tezuka, and T. Ueda, Nucleic Acids Res., (1976) s13-sl6. (112) A. Matsuda, M. Tezuka, and T. Ueda, Tetrahedron, 34 (1978) 2449-2452. (113) J.-L. Fourrey and P. Jouin,]. Org. Chem., 44 (1979) 1892-1894. (114) A. G . Schultz and R. H. Schlessinger, Chem. Commun., (1970) 1294-1295. (115) I. W. J. Still, M. S. Chauhau, and M . T. Thomas, Tetrahedron Lett., (1973) 1311-1315. (116) P. M. Collins and B. R. Whitton,]. Chem. Soc. Perkin Trans. I , (1974) 1069-1075.
ROGER W. BINKLEY
156
f[ [
RbH,
path A
RCH,
=
R&,
RCHsEt 47
path uath C
\
[
-
RCH,
,f:
SEt
]
MeOH
A
(not formed)
46
RCH,OMe
(notformed)
RCH,
(not formed)
46
I
HCOH
I
HOCH I
R = HOCH I
HCOH I CHPH
Scheme 20.-Potential, Photochemical-Reaction Pathways for Reaction of 1-Deoxyl-(ethysulfinyl)-D-galactitol(47).
drate and is also in accordance with the absence of methyl glycosides (the products expected from heterolytic, carbon-sulfur bond-cleavage) from irradiation of 57 in benzene -methanol. The carbohydrate sulfones that have been irradiated are listed in Table XIV. Quartz-filtered irradiation of carbohydrate p-toluenesulfonates in 0
II RCH,SEt 47
hu
RCH,OSEt 56
hv
[RCH,O* *SEt]
j
MeOH
RCH,OH 52
I HCOH I HOCH I R = HOCH I HCOH I CH,OH Scheme 21.-Proposed Mechanism for Photochemical Reaction of 1-Deoxy-1-(ethylsulfinyl)-D-galactitol(47).
(117) N. Kharasch and A. I. A. Khodair, Chem. Commun., (1967) 98-99.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
0
157
CHpAc
AcO
OAc
OAc
58
t
CHpAc
5Sa.b
t
(Jm CH OAc
L
o
AcO OAC
I
OAc
OAc
57
I
0 CHpAc
AcO
OAc
o+w v
YH,OAc
AcO
00
OAc
61
Scheme 22.-Proposed Mechanism for Photochemical Reaction of Phenyl 2,3,4,6Tetra-0-acetyl-P-D-glucopyranosyl Sulfone (57).
methanol in the presence of a base has been found to lead to desulfonylation. The results from various such photolyses are summarized in Table XV. The retention of configuration at C-3 during reaction of 62 and 63,for example, and the absence of deoxy compounds and methyl ethers, argue against any carbon-oxygen bond-cleavage and in favor of a sulfur-oxygen fission.
3. Thiocarbamates and Xanthides Studies have also been conducted on compounds containing a thiocarbonyl group. Photolysis of dimethylthiocarbamates mixtures of deoxy sugars and alcohols (see Table XVI). As the alcohols can be reconverted into dimethylthiocarbamates, and these re-irradiated, the synthesis and irradiation of these compounds offers a useful pathway to deoxy sugars. A simple mechanism for this reaction, based on the two possible a-cleavages resulting from thiocarbonyl excitation, is shown in Scheme 23. In addition, the possibility has been
ROGER W. BINKLEY
158
R = carbohydrate moiety
Scheme 23.-Proposed Mechanism for Photochemical Reaction of Dimethylthiocarbamates.
raised that a photochemical, “Freudenberg type” of rearrangement (see Scheme 24) prior to further photochemical reaction could explain the formation of the deoxy compounds from the photolysis of dimethylthiocarbamates,I2* Several, oxidatively coupled xanthates (64-66), compounds (also called xanthides) containing the photochemically reactive, sulfur-sulfur bond, have been studied.130 Homolytic cleavage of this reactive bond is the primary reaction for these compounds, although this process is normally masked by recombination of the radicals produced. This primary, light-initiated process becomes apparent when a mixture of the xanthide 64 and ethyl xanthide (67) is irradiated in cyclohexane, because an equilibrium between 64,67, and the mixed xanthide 68 is rapidly established. The photochemical reactions of xanthides are quite complex. They are solvent-, concentration-, temperature-, wavelength-, and time-dependent.130 The most thoroughly studied of these compounds is compound 64, whose irradiation (through a Corex filter) in cyclohexane under nitrogen produces tetrasulfide 69 (37% yield), xanthate 70 (35%), 1,2:3,4-di-O - isopropylidene -(Y-D-galactopyranose (71, 13%), sulfur, and carbonyl sulfide. Irradiation of a dilute solution of 64 produced only 70 (in 74% yield). The most intriguing finding from irradiation of the xanthides 64-66 is the fact that 66 produces a xanthate S II
ROCNMe,
Scheme 24.-Proposed, methylthiocarbamates.
hv
0 It
RSCNMe,
hv
RH
Photochemical, “Freudenberg” Rearrangement of Di-
S S II I1 CH,W-S-S-COEt
I
,
0-CMe, 64
67
68
S I1
$'H,W-S-S-
O-CMe, 64
69
70
i-
0-CMe, ?I
s
f
o=c=s
ROGER W. BINKLEY
160 r
-l
70 65 R '2==
OOMe
Me0
OMe
72
RZ= O-CMe,
(72) in which sulfur has replaced oxygen with at least 92%retention of configuration.
VII. NITROGEN-CONTAINING COMPOUNDS 1. Nitro Compounds A number of carbohydrates protected by groups containing o-nitrophenyl substituents has been studied photochemically. The primary reason for interest in these compounds is that they can be deprotected by irradiation. For example, o-nitrobenzyl glycosides of carbohyd r a t e ~ , ' ~ ' Jand ~ ~ ethers of n u c l e ~ s i d e s ' ~ ~ and J ~ ~oligoribonucleotide^,'^^-'^' experience loss of the o-nitrobenzyl group upon photolysis. The reported examples of this reaction are listed in Table XVII; in addition, there is preliminary evidence that glycosides formed from polymer-bound, o-nitrobenzyl-containing groups, and partially protected carbohydrates, release the carbohydrate upon p h o t o l y ~ i s .A ' ~detailed ~ explanation for the photochemical reactions of the o-nitrobenzyl
TABLEXIV Photochemical Reactions of Carbohydrate Sulfones Reactants
Products
0:Q
xya
+(-J+ xo
xo
xo
ox
Ref.
ox
5r
OX 88
61
R' = H, RZ = SOzPh X = AC XOFH,
J -(
xo
+
ox
OX
2
60
\R3=H
i
59a '
R 1 =@ - Ph
) R3 =*Ph
116
59b,
(R'=H R' = S02Ph, R2 = H, X = Ac
(Same products a s above)
116
1
XOYH,
ox R' = H, R2 = SOzPh
I
l
ox
ox R3 = H
X = Ac R4 = -@Ph
118
and
R3 = e
P
h
R4 = H R' =
S02Ph, R' = H, X = Ac
(Same products aa above)
118
ROGER W. BINKLEY
162
TABLEXV Photochemical Reactions of p-Toluenesulfonic Esters of Carbohydrates p-Toluenesulfonate
Product
~H,OTs
O
References
CH,OH
Q
HOQ
Yield (%)
M
e
o
M
e
90
119
100
119
80
119
HO OH
OH
/Qy
Me&-0 D /o
Me& -0
I 1 0-CMe,
0-CMe,
0 0 FH,OH
HO
HO
OH
I OH
119
0-CMe,
0-CMe, HZF -
Q 8
H,C 80
OTS
OH
YH,OH
I
v)1,
CH
0-CMe,
I
I
0-CMe,
120, 121. 1a2'
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
163
TABLEXV (Continued)
Photochemical Reactions of p-Toluenesulfonic Esters of Carbohydrates p-Toluenesulfonate
Product
Yield (%)
References
G fJ FH2
I
I
OTs
OH
hOR YH2
CH,OH
CH,OH
CH,OX
ROQOR
RO
R = Me, X = Me R=Me, X = H
0Q
O
OTs M
e
ooMe
0
81
124
62
124
60
125
OH
FH,OMe 1 26 M e 0O
O
X
=
M
e
TS
Hocv "OCd n
n
"Yo
O Y O
HO
OTs
HO
OH
127
TABLEXVI Photochemical Reactions of Carbohydrate-Containing Dimethylthiocarbamates" Products and Yields ( W )
Reactant
J-(/
FH"
Me2C-0
Me2drdy 0-CMe,
0-CMe,
0-CMe,
15
36
tl o/ '0,
S
19
17
Me$,
I
I
OCH
0
YQ
1
0-CMe, 17-23
0-CMe, 26-32
Me$-0 QOMe I
OCNMe,
OH
I1 S
11
36
S
/QT II
FH,OCNMe,
YH,OH
Me$-0
0-CMe,
0-CMe, 25
a
Refs. 128 and 129.
0-CMe, 35
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
165
group is proposed in Scheme 25. This mechanism is consistent with the suggestion that photolysis of o-nitrobenzyl compounds causes an intramolecular, oxidation-reduction r e a c t i ~ n , ' ~ 'and J ~ ~also with the finding140that excited nitro groups, such as those in nitrophenyl p-Dglycosides, are effective hydrogen-atom abstractors. A process similar to that proposed for o-nitrobenzyl ethers (see Scheme 25, path a), but including loss of carbon dioxide in a final step (see Scheme 25, path b), accounts for the photochemical regeneration of an amino function protected by an (o-nitrobenzy1)oxycarbonyl group.14' Table XVIII contains examples of this reaction involving carbohydrate systems. Cyclic acetals derived from diols and o-nitrobenzaldehyde produce hydroxynitrosobenzoates upon irradiation (see Scheme 26). Early studies of this reaction demonstrated that acetals involving carbohydrates and o-nitrobenzaldehyde experience facile, photochemical
(118) P. M. Collins and B. R. Whitton, Carbohydr. Res., 36 (1974) 293-301. (119) S. Zen, S. Tashima, and S. Kot6, Bull. Chem. Soc.Jpn., 41 (1968) 3025. (120) A. D. Barford, A. B. Foster, and J. H. Westwood, Carbohydr. Res., 13 (1970) 189-190. (121) A. D. Barford, A. B. Foster, J. H. Westwood, L. D. Hall, and R. N. Johnson, Carbohydr. Res., 19 (1971) 49-61. (122) L. Vegh and E. Hardegger, Nelu. Chim. Acta, 56 (1973) 2020-2025. (123) W. A. Szarek, R. G. S. Ritchie, and D. M. Vyas, Carbohydr. Res., 62 (1978) 89-103. (124) F. R. Seymour, Carbohydr. Res., 34 (1974) 65-70. (125) R. A. Borgegrain and B. Gross, Carbohydr. Res., 41 (1975) 135-140. (126) F. R. Seymour, M. E. Slodki, R. D. Plattner, and L. W. Tjarks, Carbohydr. Res., 46 (1976) 189-193. (127) C. D. Chang and T. L. Hullar, Carbohydr. Res., 54 (1977) 217-230. (128) R. H. Bell, D. Horton, D. M. Williams, and E. Winter-Mihaly, Carbohydr. Res., 58 (1977) 109-124. (129) R. H. Bell, D. Horton, and D. M. Williams, Chem. Commun., (1968) 323-324. (130) E. I. Stout, W. M. Doane, C. R. Russell, and L. B. Jones,J. Org. Chem., 40 (1975) 1331-1336. (131) U. Zehavi and A. Patchornik,j. Org. Chem., 37 (1972) 2285-2289. (132) U. Zehavi, B. Amit, and A. Patchomik, J . Org. Chem., 37 (1972) 2281-2285. (133) D. G. Bartholomew and A. D. Broom,J. Chem. Soc. Chem. Commun., (1975) 38. (134) E. Ohtsuka, S. Tanaka, and M. Ikehara, Nucleic Acid Chem., 1 (1978) 410-414. (135) E. Ohtsuka, S. Tanaka, and M. Ikehara, Synthesis, (1977) 453-454. (136) E. Ohtsuka, S. Tanaka, and M. Ikehara, Chem. Pharm. Bull., 25 (1977) 949-959. (137) E. Ohtsuka, S. Tanaka, and M. Ikehara, Nucleic Acids Res., 1 (1974) 1351-1357. (138) U. Zehavi and A. Patchornik,J. Am. Chem. Soc., 95 (1973) 5673-5677. (139) A. Patchomik, B. Amit, and R. B. Woodward, J . Am. Chem. SOC., 92 (1970) 6333-6334. (140) P. J. Baugh, K. Kershaw, and G. 0. Phillips, Carbohydr. Res., 22 (1972) 233-243. (141) B. Amit, U. Zehavi, and A. Patchomik,J. Org. Chem., 39 (1974) 192-196.
ROGER W. BINKLEY
166
R Ono- H Y g + "
L
J
b-
/
path A RNH,
+ co, +
OHC NO
onc NO
R = carbohydrate, nucleoside, or nucleotide residue
Scheme 25.-Proposed Compounds.
Mechanism for Photochemical Reaction of o-Nitrobenzyl
&!:
X
0
0
J Scheme 26.-Proposed dene Acetals.
Mechanism for Photochemical Reaction of o-Nitrobenzyli-
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
167
TABLEXVII Photochemical Reactions of o-Nitrophenyl Ethers of Carbohydrates and Nucleosides Reactants
HO
02N I
Products
HOO
O
,
R=H R = OMe
OCH,
Ref.
100
131
H
OH
OH
RZO
Yields (%)
RZO
ao
132
100
132
100
133, 134
OH
(Continued)
ROGER W. BINKLEY
168
TABLEXVII (Continued)
Photochemical Reactions of o-Nitrophenyl Ethers of Carbohydrates and Nucleosides Reactants
Products
Yields (%)
Ref.
(Not reported)
135
95
B=
.kN>
, R1 = Cytidylyl-(3'-5')
N
I
RZ=H
136
(Not reported)
136
(Not reported)
I37
0
II
r e a ~ t i o n ' ~ ~ however, -'~~; the products formed were complex and not fully characterized. Investigations of o-nitrobenzylidene derivatives of carbohydrates have since established the structure of the photoproducts by oxidation of these unstable (and often dimeric) nitroso compounds to their corresponding monomeric nitro derivatives, compounds that can readily be chara~terized.'~'-~*~ Because the 1,Sdioxo(142) I. Tanasescu and E. Craciunescu, Bull. SOC. Chim. F r . , 3 (1936) 581-598. (143) I. Tanasescu and E. Craciunescu, Bull. Soc. Chim.F r . , 5 (1936) 1517-1527. (144) I. Tanasescu and M. Ionescu, Bull. Soc. Chim.F r . , 7 (1940) 84-90. (145) I. Tanasescu and M. Ionescu, Bull. Soc. Chim. Fr., 7 (1940) 77-83. (146) I. Tanasescu and M. Ionescu, Bull Soc. Chim.Fr., 5 (1936) 1511-1517. (147) P. M. Collins and N. N. Oparaeche, J . Chem. Soc. Chem. Commun., (1972) 532-533. (148) P. M. Collins and N. N. Oparaeche, J . Chem. Soc. Perkin Trans. I , (1975) 1695- 1700. (149) P. M. Collins, N. N. Oparaeche, and V. R. N. Munasinghe,]. Chem. Soc. Perkin Trans. I, (1975) 1700-1706.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
169
TABLEXVIII Photochemical Reactions of o-Nitrobenzyloxycarbonyl Derivatives of Carbohydrates ~~~
Reactants
Products and Yields (%)
References
?&OH
R 82
R=H R = OMe
89
"0
CH,OH
OH
141
R
R=H R = OMe CH,OR
80 91
0 FH,OR
RO
141
R = Ac
lane and 1,Sdioxane rings of benzylidene acetals can open in two ways, photolysis of compounds containing o-nitrobenzylidene acetal groups invariably produces mixtures of products. Table XIX contains a tabulation of acetals irradiated, and the products
ROGER W. BINKLEY
170
TABLEXIX Photochemical Reactions of o-Nihvbenzylidene Acetals of Carbohydrates Reactants
Acov &
Products and Yields (%)
Ref.
141,148
AcoQ no me
0
hNO c=o
95
OH
0
5
p,OMe
(4
Me0
no
0 I
&NO
w
OH
0
bNO c=o
< 5
93
J (
I
147,148
?
0
HC-0
148
Me0
o=c I I OH
0
&No
&NO
< 5
I
OAc
5
95
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
171
TABLEXIX (Continued) Photochemical Reactions of o-Nitrobenzylidene Acetals of Carbohydrates Reactants
-.$’
Ho
Ref.
Products and Yields (%)
OMS
OMs
O N 5 ”
< 5
89
147,149
0Q I
OAc
O OAc M
e
HO
@r
OAc
I
30
59
147.149
OAc
OAc
50
23
HOCK2 149
o& I oMe
bNO
o=c OaN@
32
59
(Continued)
TABLEXIX (Continued) Photochemical Reactions of o-Nitrobenzylidene Acetals of Carbohydrates ~
Ref.
Products and Yields (%)
Reactants
NO
HOCH, HC/ O F . , I ' O W O M e Me0
&No 60
40
NO
4 N
OAC
OAc
OAc
20
50
It)
0
0
o=cI
149 I
OAC
OAc
40
17 NO
HciboMe 0O
O OTs M
I
O
Z
N
6
OTS
O
N
147,149
e
d 96 (total)
I
OTs
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
173
TABLEXIX (Continued)
Photochemical Reactions of o-Nitrobenzylidene Acetals of Carbohydrates Reactants
Products and Yields (%)
Ref.
HOCH,
149
; . $ i M e
o=c0Q
o
M
e
"'-0 I
(No yields reported)
NO
149
OZN@ ON@ 45
32
Photolysis of three 2,4-dinitroanilino-substitutedcarbohydrates, compounds that differ considerably from each other in photochemical reactivity, has been r e p ~ r t e d . ' ~ l-Deoxy-l-(2,4-dinitroanilino)-~~,'~~ glucitol (73) is photochemically unreactive ; in contrast, sodium 2deoxy-2-(2,4-dinitroanilino)-~-gluconate (74) produces D-arabinose in 52% yield upon irradiation.l5O The behavior of compounds 73 and 74 indicates that oxidative loss of the 2,4-dinitroanilino group during photolysis is only possible when it is accompanied by simultaneous decarboxylation. The evidence gathered from the considerable study of this reaction for noncarbohydrate systems suggested that this process is quite complex. Although useful, mechanistic proposals have (150) A. E. El Ashmawy, D. Horton, and K. D. Philips, Curbohydr. Res., 9 (1969) 350-355. (151) T. L. Nagabhushan, J. J . Wright, A. B. Cooper, W. N. Turner, and G. H. Miller, /. Antibiot., 31 (1978) 43-48.
ROGER W. BINKLEY
174
H , Ic m &Noz HCOH I HOCH
hv
I
HCOH I HCOH I CH,OH
HZO MeOH
no reaction
73
COO- Na' H Ib N ' W - P N O z
H°FH HCOH I
4N
HCOH I CqOH
hv
HZO
HOO I HO
O
H -I-
&=' NO2
74
been advanced,152a completely satisfactory pathway for this reaction has not yet been described. The nitroalkene (E)-6,7,8-trideoxy-1,2:3,4-di-O-isopropylidene-7~nitro-a-D-galacto-oct-6-enose (75) is the single nitro sugar thus far photochemically investigated in which the nitro group is not attached to an aromatic Irradiation of 75 results in isomerization of the double bond, producing the 2 isomer 76 (27%yield), and in a rearrangement-fragmentation process yielding @)-and (2)-6,8-dideoxy1,2:3,4-di~-isopropylidene-a-~-galacto-oct-5-enos-7-ulose (77 and 78) in 8 and 6%yields, respectively. A reasonable pathway for formation of compounds 77 and 78 begins with rearrangement of 75 to the intermediate nitrous ester 79, a process similar to that proposed for excited P-methyl-P-nitr~styrene.'~~ The reaction is complete when the nitrous ester experiences light-initiated, nitrogen-oxygen-bond homolysis and subsequent disproportionation (see Scheme 27). Photolysis of the nitric esters 80-82 causes nitrogen-oxygen bond0. Meth-Cohn, Tetrahedron Lett., (1970)1235-1236. G. B. Howarth, D. G. Lance, W. A. Szarek, and J. K. N. Jones, Chem. Commun., (1968)1349. G. B. Howarth, D. G. Lance, W. A. Szarek, and J. K. N. Jones, Can../.Chem., 47 (1969)81-87. 0. L. Chapman, P. G. Cleveland, and E. D. Hoganson, Chem. Commun., (1966) 101-102.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
175
__ hv
Me$-0 0-CMe, r5
76
ON0 I
Q H\C”C‘Me
hu
Me$-0
0-CMe,
0-CMe,
79
/ \ J
% / ”
1 0
%-Me /
0-CMe,
rr
0-CMe, 70
Scheme 27.-Proposed Mechanism for Photochemical Reaction of (E)-6,7,8-Trideoxy-1,2:3,4-di-O-isopropylidene-7C-nitro-a-~-galacto-oct-6-enose (75).
homolysis, to produce nitrogen dioxide and an alkoxyl radical.’= The alkoxyl radical abstracts a hydrogen atom from the solvent, to form an alcohol (see Scheme 28). This photochemical removal of a nitro group occurs in essentially quantitative yield (see Table XX). If an unstable (156) R. W. Binkley and D. J . Koholic,J. Org. Chem., 44 (1979) 2047-2048.
ROGER W. BINKLEY
176
lkv ,OCHZ
Me&,
I OCH
lhv
J \ Me&,
Q 0-CMe, ?
,OCH,
I
yo>
OCH
0
0-CMe,
Scheme 28.- Proposed Mechanism for Photochemical Reaction of 1,2:3,4-Di-O-isopropylidene-3-O-nitro-a-D-a~~ofuranose (81) and 1,2:3,4-Di-O-isopropylidene-3-Onitro-a-D-ghcofuranose (82).
alkoxyl radical is formed by photolysis, rearrangement occurs (see Scheme 28). 2. Azides Irradiation of a carbohydrate azide results in loss of nitrogen, and rearrangement (probably by way of a nitrene intermediate) to produce an imine (see Scheme 29). The imine, which, in many instances, exists
-..
RCH,-N-N=N:
Scheme 29.-Proposed Azides.
hv
RCH,N
+
N,
-
RCH=NH
Mechanism for Photochemical Reaction of Carbohydrate
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
177
TABLEXX Photochemical Reactions of Nitrous Esters of Carbohydrates Products and Y i e l d F (%)
Reactants
/Q7
Me& D / -0 o
Me$-0
I 1
0-CMe,
0-CMe, 100
80
R' = H, R2 = ONO, R' = ONO,, R2 = H
(81)
100
(82)
92
in a polymeric form,'@ is readily hydrolyzed to the corresponding carbony1 compound. This photolysis-hydrolysis sequence is effective in converting primary azides into aldehydes, but it produces low yields of ketones from secondary azides (see Table XXI). Photolysis of glycosyl azides affords products (see Table XXI) that differ significantly from those formed by photolysis of other a ~ i d e s . ' ~ ~ J ' ~ A probable explanation for this difference in reactivity is that, unlike other imines, the ring in iminolactones produced by irradiation of glycosyl azides can open spontaneously, to give unstable cyanohyd r i n ~ (see ' ~ ~ Scheme 30). The cyanohydrins can then lose hydrogen cyanide, to offord the next-lower aldoses. During photolysis of some glycosyl azides, an additional product is formed, one for which the general structure 83 has been proposed. This additional product, Carbohydratei+ portion of
TIN
molecule
0-N
H
83
ROGER W. BINKLEY
178
OH
OH
Jhv
lhV
-ha OH
QNH
OH
OH
1 OH Scheme 30.-Proposed Mechanism for Photochemical Reactions of Glycosyl Azides and of Sugar Oximes.
which may be photochemically rea~tive,”~ reverts to the starting material on standing.
3. Diazo Compounds Methyl 3,4,5,6-tetra-0-acetyl-2-deoxy-2-diazo-~-arabino-hexonate
(84) has been irradiated in methanol and in 2-propan01.’~~ In methanol, the only photoproduct is the enol acetate 85; however, irradiation in 2-propanol results in formation of minor proportions (6%) of 85 and
the alkene 86 (7%),but the major product is the deoxy sugar 87 (61%). The difference in reactivity of 84 in these two solvents is probably a reflection of the difference in the ability of methanol and 2-propanol to function as hydrogen donors when reacting with a carbene (see Scheme 31). In methanol, a 1,e-hydrogen atom shift to the divalent
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
179
C0,Me I
C=N=N I f XOCH I
R 84
C0,Me I CH I1
xoc I R
MeOH
C0,Me
I C:
X O h I
+
Nz
R
R =
I
C0,Me
I
CH II CH
HCOX I
CH,OX X =
AC
C0,Me I *CH I XOCH
+
Me,kOH
+
Me,kOH
I
R
85
HCOX
J iMezcHoH Me,CHOH
C0,Me I
I
+
I
R 86
85
YHa XO CH I
R major product 87
Scheme 31.-Proposed Mechanism for Photochemical Reaction of Methyl 3,4,5,6Tetra4)-acetyl-2-deoxy-2-diazo-~urabino-hexonate (84).
carbon atom occurs faster than reaction with the solvent. In 2-propanol, a more effective hydrogen-donor than methanol, hydrogen abstraction from the solvent competes effectively with internal rearrangement. 4. Oximes Photolysis of sugar oximes produces i m i n o l a ~ t o n e s . ' ~These * ~ ' ~ ~ are
the compounds proposed to arise from irradiation of glycosyl azides;
however, the mechanism leading to formation of iminolactones from these two starting-materials (azides and oximes) must be quite different (see Scheme 30). Photolysis of azides is considered to generate a nitrene, whereas photolysis of oximes produces an iminolactone that
ROGER W. BINKLEY
180
TABLEXXI Photochemical Reactions of Carbohydrate Azides Products and Yields" (%) RCH=NH
Reactants RCH2N3
R=
R=
xoO
O
M
Ref.
e
X = Bz
(Yield not reported)
157
X=H
38
157
X = Ac
62
157
62
158
50
159
43
160
(Yield not reported)
161
xoO
O
C
H
3
ox X = Ac
R= 0-CMe,
R=
Ic;J
F
4C /o
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
181
TABLEXXI (Continued)
Photochemical Reactions of Carbohydrate Azides Reactants RCH,N,
Products and Yields" (%) RCH=NH
Ref.
54
162
58
162
51
163
I
AcOCH
I 732
7%
R=
H,C-C-CH, I
OH
Me2C
,OCH2
I
'OCH
Q7
0
0-CMe,
18
164
34
165
(Continued)
ROGER W. BINKLEY
182
TABLEXXI (Continued) Photochemical Reactions of Carbohydrate Azides Reactants RCHPN3
Products and Yields" (%) RCH=NH
Ref.
I
HCOH I
HFOH 166
HQ
R=
O
M
e
OX X = C&Ph
R=
0-CMe,
HOYH
7% XCXZ I ==OH,
F = H X = H , ==OH
(-J
0
167
25
167
OH
HO
OH r
16
1
I j. J fo
169,170, 171
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
183
TABLEXXI (Continued)
I
Photochemical Reactions of Carbohydrate Azides Reactants RCHzNs
Products and Yields" (%) RCH=NH
Ref.
@ o
ox
172,173, 174
n
X=H X = Ac
(-J
HCN
RO
OH
+
Nz
+ HO
R = H
47
175,176
53
176
51
176
CH,OH
R = OH CH,OH
R = O "Q OH
175,176
R = OH
(Continued)
ROGER W. BINKLEY
184
TABLEXXI (Continued) Photochemical Reactions of Carbohydrate Azides Products and Yields" (%) RCH=NH
Reactants RCH2N,
ON3
HO
HCN
+
N,
Ref.
+
175,116
HO 60
Hot)
HCN
+
N,
+
D
O
H
HO
OH
HoQ
65
175,176
b
175,176
OH
b
"
175,176
O I C IU HO OH
0 CH,OX
xo
FH,OX
xoo
m
I
I
ox
X = Ac
ox 37
175,176 ~~
Product usually isolated as aldehyde or its derivative. that reverts to the starting azide. a
* Unstable product formed
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
185
TABLEXXII Photochemical Reactions of Carbohydrate Oximes Products and Percent Yields Reactant
Iminolactone
D-Galactose oxime DMannose oxime D-Ribose oxime D-Arabinose oxime DXylose oxime D-Lyxose oxime
81 33" 23 28 15
Aldose D-Lyxose (14)
D-Threose (3) D-Erythrose (18)
D-Arabinose is formed on standing.
may arise by way of nitrogen-oxygen-bond homolysis followed by hydrogen-atom transfer (see Scheme 30). The yield of the next-lower aldose from an oxime irradiation is quite dependent upon the particular oxime photolyzed (see Table XXII). D. Horton, W. Weckerle, and B. Winter, Carbolzydr. Res., 70 (1979) 59-73. R. L. Whistler and A. K. M. Anisuzzaman,J. Org. Chern., 34 (1969) 3823-3824. D. Horton, A. E. Luetzow, and J. C. Wease, Curbohydr. Res., 8 (1968)366-367. A. R. Gibson, L. D. Melton, and K. N. Slessor, Can. J . Chem., 52 (1974) 3905-3912. I. D. Jenkins, J. P. H. Verheyden, and J. G. Moffatt,J. Am. Chem. Soc., 93 (1971) 4323-4324. D. C. Baker and D. Horton, Carbohydr. Res., 21 (1972) 393-405. W. A. Szarek, D. M. Vyas, and L.-Y. Chen, Curbohydr. Res., 53 (1977) cl-c4. D. M. Clode and D. Horton, Carbohydr. Res., 14 (1970) 405-408. R. L. Whistler and L. W. Doner,J. Org. Chem., 35 (1970) 3562-3563. H. C. Jarrell and W. A. Szarek, Cat1.J. Chem., 56 (1978) 144-146. H. C. Jarrell and W. A. Szarek, Carbohydr. Res., 67 (1978) 43-54. H. F. C. Beving, A. E. Luetzow, and 0. Theander, Carbohydr. Res., 41 (1975) 105-115. D. M. Clode, D. Horton, M. H. Meshreki, and H. Shoji, Chem. Comrnun., (1969) 694-695. D. M. Clode and D. Horton, Curbohydr. Res., 17 (1971) 365-373. D. Horton, A. E. Luetzow, and 0. Theander, Carbohydr. Res., 27 (1973) 268-272. D. Horton, A. E. Luetzow, and 0. Theander, Carbohydr. Res., 26 (1973) 1-19. D. M. Clode and D. Horton, Carbohydr. Res., 19 (1971) 329-337. D. M. Clode and D. Horton, Curbohydr. Res., 12 (1970) 477-479. J. Plenkiewicz, G. W. Hay, and W. A. Szarek, Can. J. Chem., 52 (1974) 183-185. W. A. Szarek, 0.Achmatowicz, J. Plenkiewicz, and B. K. Radatus, Tetrahedron, 34 (1978) 1427- 1433. D. Horton and K. D. Philips, Carbohydr. Res., 22 (1972) 151-162. W. W. Binkley and R. W. Binkley, Tetruhedron Lett., (1970)3439-3442. R. W. Binkley and W. W. Binkley, Curbohydr. Res., 23 (1972) 283-288.
ROGER W. BINKLEY
186
RCH-CH=N-N=CH-CHR I I OH HO 88
RCH-CH=N I HO
*
ihv I
RCH-CH=NH I HO
*
N=CH-CHR I OH
N=CCR I
OH
1HP
NH,
+
I HOCH
RCH-CH=O I HO
O=CHR
+ HCN
I
R =
HOFH HTH CH,OH
Scheme 32.-Proposed (88).
Mechanism for Photochemical Reaction of D-Galactose Azine
5. Azines
An iminolactone also has been suggested as a key intermediate in the photolysis of D-galactose azine (88).Irradiation of 88 is thought to fragment the weak nitrogen-nitrogen bond. Subsequent disproportionation of the radical pair produceslS0a cyanohydrin and an iminolactone (see Scheme 32). The cyanohydrogen loses hydrogen cyanide to form D-lyxose (23% yield), and the acyclic iminolactone is hydrolyzed to D-galaCtOSe (37%yield). VIII. IODOCOMPOUNDS 1. Deoxyiodo Sugars
Photolysis of deoxyiodo sugars is an effective method for forming the corresponding deoxy compounds (see Scheme 33); however, both (180) R. W. Binkley and W. W. Binkley, Corbohydr. Res., 13 (1970) 163-166.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES H
I
I
1
I
I
-c-c-
-
H I I
-
hydrogen abstraction
I
from solvent
1.
-c-c-
-
H
I
H
-c-cI
187
I
I
disproportion (observed in absence of hydrogen donors)
Scheme 33.-Proposed Sugars.
\ I c=c / \
+ HI
Mechanism for Photochemical Reaction of Deoxyiodo
the type of solvent used, and the energy of the incident light, have a decided effect upon the yield of products and the complexity of the reaction mixture. For example, irradiation of 6-deoxy-6-iodo-1,2:3,4die-isopropylidene-a-D-galactopyranose(89) in methano1181.182or 2-propan01~~~ produces 6-deoxy-l,2:3,4-di-O-isopropylidene-a-~galactopyranose (90)in much higher yield than irradiation in 2-methyl2-propanol (see Table XXIII). Also, the yield of 90 obtained from photolysis of 89 with unfiltered light improves when the higher-energy light from the radiation source is removed by use of an appropriate filter (see Table XXIII). Irradiation of 3-deoxy-3-iodo-1,2:5,6-di-0-isopropylidene-a-D-glucofuranose(91) led to a similar observation concerning the dependence on w a ~ e l e n g t h . ' ~ ~ J ~ ~ The effect of the reaction solvent on iodide photolysis is similar to that observed in irradiation of the diazo compound 84. Among the various solvents used in iodide reactions, 2-propanol produces the highest yields of deoxy sugars (see Table XXIII). Irradiations in methanol, a good, but less effective, hydrogen donor than 2-propanol, afford deoxy sugars in fair to good yields (see Table XXIII). Hydrogen-atom transfer from 2-methyl-2-propanol is sufficiently difficult that other reactions, such as alkene formation (see Scheme 33), can become significant reaction-pathways in this solvent. 2. o-Iodobiphenylyl Ethers
The o-iodobiphenylyl ethers, 92 and 93, of 1,2:3,4-di-O-isopropylidene-a-D-galactopyranose and 1,2:5,6-di-O-isopropylidene-a-~-glucofuranose, respectively, have been irradiated in 2-propanol and in 2(181) W. W. Binkley and R. W. Binkley, Carbohydr. Res., 8 (1968) 370-371. (182) W. W. Binkley and R. W. Binkley, Carbohydr. Res., 11 (1969) 1-8. (183) R. W. Binkley and D. G . Hehemann, Carbohydr. Res., 74 (1979) 337-340.
ROGER W. BINKLEY
188
TABLEXXIII Photochemical Reactions of D e o x y i o d o Sugars
Filter
Sugar
Me,CHOH
Corexu
95
183
b
97
181,182
/Q7 I
Me$-0
0-CMe,
Ref.
Solvent
Reactants CHJ
Yield (%) of Deoxy
MeOH
Pyrex
MeOH
none
83
181,182
Me,COH
none'
36
181,182
Me,CHOH
Corex
99
183
MeOH
none
32
128
Me,CHOH
Corex
100
183
Me,CHOH
Corex
93
183
Me,CHOH
Corex
80
183
89
0-CMe, 91
Me,C /OTH2 'OCH
K4 0
I
0-CMe,
04Me,&O
OH
TABLEXXIII (Continued)
Photochemical Reactions of Deoxyiodo Sugars
Reactants
Solvent
Filter
Yield (%) of Deoxy Sugar
Ref.
Me,CHOH
Corex
72
183
Me,CHOH
Corex
90
183
MeOH
none
57
184
9
185
HCO, I ,CMe, H,CO
q
RO
RO
0
OR R = AC
H20, HCHO HOQ
O
M
none
e
HO ~~~~
" Transmittance at wavelengths <260 nm, 0%. Transmittance at wavelengths <280 nm, 0%. 6-Deoxy-l,2:3,4-di~-isopropylidene-~-~-u~u~ino-hex-5-enopyranose (96) formed in 32% yield.
ROGER W. BINKLEY
190
1
Me,COH
Ph
Ph
Scheme 34.-Proposed Ethers.
Mechanism for Photochemical Reaction of o-Iodobiphenylyl
methy1-2-propan01.'~~ Irradiation of these ethers (92 and 93) in 2-propanol resulted in essentially quantitative replacement of iodine by hydrogen (see Scheme 34) to give 94 and 95, respectively. In contrast, irradiation of 92 in 2-methyl-2-propanol produced the enol ether 96 as the major product. No alkene was formed from irradiation of 93 in 2methyl-2-propanol. Intramolecular hydrogen-abstraction, a process possible only when hydrogen-donating solvents are absent, has been proposed for explaining alkene formation during irradiation in 2methyl-2-propanol (see Scheme 34). The failure of 93 to form an enol ether upon photolysis demonstrated that other factors, such as ring strain arising from introduction of unsaturation, can determine the course of the reaction. IX. ORGANOMETALLIC COMPOUNDS The single, organometallic, carbohydrate derivative whose irradiation has thus far been reportedlS7is methyl 2-(acetoxymercuri)-3,4,6tri-O-acety~-2-deoxy-~-~-g~ucopyranoside (97). Irradiation of 97 in ~
~~
(184) E. R. Guilloux, J. Defaye, R. H. Bell, and D. Horton, Carbohydr. Res., 20 (1971) 421-426. (185) P. J. Garegg, J. Hoffman, B. Lindberg, and B. Samuelsson, Carbohydr. Res., 67 (1978) 263-269. (186) R. W. Binkley and D. J. Koholic,J. Org. Chem., 44 (1979) 3357-3360. (187) D. Horton, J . M. Tarelli, and J. D. Wander, Carbohydr. Res., 23 (1972) 440-446.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
hv
191
+
Pyrex
0-CMe,
0-CMe,
92
solvent Me,COH Me,CHOH
0-CMe,
94
96
14% 94%
80%
0%
hv Pyrex
(no alkene formed)
0-CMe, 93
95
solvent Me,COH Me,CHOH
51% 96%
methanol yields the corresponding deoxy compound, 3,4,6-tri-O-acetyl-2-deoxy-~-arabinohexopyranoside (99) and elemental mercury. The radical 98 is a probable intermediate in the photochemical process (see Scheme 35). YH,OX
YH,OX
CH,OX
-
+ CH,OH
99
X = Ac
Scheme 35.-Proposed Mechanism for Photochemical Reaction of Methyl 2-(Acetoxymercuri)-3,4,6-tri-0-acetyl-2-deoxy-~-~-glucopyranoside (97).
ROGER W. BINKLEY
192
TABLEXXIV Photochemical Reactions of Carbohydrate Phosphates Reactants
Products
CHO
C02H I HCOH I HOCH I HCOH I HCOH
I
HCOH I HOCH I HCOH
+ 0 2
I
HCOH I
CHO I
HOCH
188
I
HCOH
I
HCOH I CH20PO:-
I
CH20P032-
References
CH20P032-
100
0 CH,OH
HO
0po32-
CH20H
HO0
' 0 2
0
OH
f
"
OH V
OH
O
H
189
OH
101
CH20H I
c=o
I HOCH I HYOH HCOH
CHO
I
+ 0 2
HOCH I CH20P032-
I
CH20P032-
+
ol-pPoH HO""""' H
190
I02
+
OCHCH,OPO~~-
-I.
CHO HAOH I
CH20P032-
X. PHOSPHATES Compounds 100 and 101, unprotected carbohydrates containing a phosphate group, exhibit in photochemical reactivity a marked similarity to other unprotected, carbohydrate (see Scheme (188) C. Triantaphylides and M. Halmann,]. Chem. SOC. Perkin Trans. 1 , (1975)34-40. (189) M. Trachtman and M. Halmann,/. Chem. SOC.Perkin Trans. 2, (1977) 132-137. (190) C . Triantaphylides and R. Gerster, /. Chem. SOC. Perkin Trans. 2, (1977) 1719-1724. (191) J. Greenwald and M. Halmann,]. Chem. SOC.Perkin Trans. 2, (1972) 1095-1101.
PHOTOCHEMICAL REACTIONS OF CARBOHYDRATES
193
16). Irradiation of a-D-glucose 6-(disodium phosphate)lE8(100) yields products that retain the phosphate group (see Table XXIV) but are otherwise the same as those formed from irradiation of D-glucose itself (see Table XII). Photolysis of a-D-glucosyl (dipotassium phosphate) (101) causes rapid release of orthophosphate, followed by formation of the same carbohydrate p h o t o p r o d ~ c t sas '~~ are produced by irradiation of D-glucose (see Table XXIV). D-Fructose 6-(disodium phosphate)lS0 (102),a compound that exists to a significant extent in the keto form, experiences the a-cleavage reaction characteristic of carbonyl compounds (see Scheme 6 and Table XXIV).