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Chiral cyclic imides with c2-symmetry. Novel reagents for the synthesis of optically pure lactones containing three contiguous tertiary centers
Tetrahedron Letters. Vo1.32.N0.28.p~3401-3404, 1991
oo40-4039/91 $3.00+.00 Pergamml Ressplc
Printed in Great Britain
CHIRAL CYCLIC IMIDES WITH C2-SYMMETRY. NOVEL REAGENTS FOR THE SYNTHESIS OF OPTICALLY PURE LACTONES CONTAINING THREE CONTIGUOUS TERTIARY CENTERS *
Koji Shirakawa, and Kunihiko Takabe * Department of Applied Chemistry, Faculty of Engineering, Hidemi Yoda,
Shizuoka University, Hamamatsu 432, Japan
Summary: Asymmetric reactions employing C2-symmetrical imides readily prepared from L-tartaric acid with Griqnard reagents and sodium borohydride afforded a separable mixture of two hydroxyamides with high diastereoselectivity. Products were lactonized respectively to provide optically pure Yalkylated lactones with contiguous tertiary carbon centers. The reaction mechanisms in asymmetric induction were also discussed.
In recent years
the chemistry of asymmetric reactions using compounds
with C2-axis of symmetry as a chiral source
has attracted increased atten-
tion since these species can serve as novel intermediates for the synthesis chiral substances possessing a wide range of biological activity. 1)
of
Therefore, a great deal of effort for the construction of the reagents with C2-symmetrical carbon skeletons from readily available precursors has been devoted until now 2) and further exploitation of much more convenient methods is strongly desired. Recently nucleophilic addition to N-acyliminium ions obtained from the partial reduction of chiral cyclic imides was demonstrated
and utilized as an efficient method for the synthesis of several alkaloids. 3) Nevertheless, there has been little general approach toward the new employment of carbi4) In the nolamides prepared from the direct alkylations of cyclic imides. preceding paper, we reported the asymmetric synthesis of optically active 5) butenolides using C2-symmetrical imides in 89-92% enantiomeric excess. Here
we wish to describe the details of the reaction of chiral imides with
nucleophiles followed by cyclization and the mechanistic aspects in asymmetric induction. Consecutive treatment of L-tartaric acid (1) with acetyl chloride, primary amine, acetyl chloride aqain,3b' and hydrolysis6' followed by silylprotection provided chiral starting imides (1) in 43-67% yields (Scheme 1). Reactions of 2
thus obtained
with Griqnard reagents in THF at -78 to 0 OC bearing a trans-relation-
would occur from either of two symmetrical sides 3401
3402
1)CH3COCl OH
HO,, % HO 0J-f
Ace,,
2I RlNH2
0
0’ d N
3CH3COCI
COOH
OAC *.
Scheme
respect
which
@j7'
were
to the silyloxy successively
of two hydroxyamides
Specific
rotations
to r.t.
with
after
that
and gave unstable
under
mild
highly
a
conditions
isolation
on silica-gel
increasing
a steric submitted
bulkiness
reaction
column
in these
respectively
NaBHa
1.
chro-
reactions
of the silyl-protecting
to cyclization
in
in Table
are summerized
the stereoselectivity
Then 5 were
carbinolamides with NaBH4
diastereoselective
The results
(5).
were measured
It is apparent
I-3).
functions
reduced
to produce
at 0 OC
(entry
‘0
A1
1.
products
increases
2 Z: RgSi X : Cl I OSO2CF3
ethanol
matography.
OG d N
2) zx
A1
1
ship with
‘0
oz
ZO,, 5.
CH3COCI ‘EtOH *
groups
with
3M HCl
*
EtOH 4
Scheme 2.
9
Table 1. Asymmetric Reactions Using Chiral Imides (2) a) Entry
R'
R:
1
Me
i-PrMe2
2
Me
t-BuMe2
3 Me i-Pr 3 4 C6H5CH2 t-BuMe2
Diastereomer
c) [alD,deg (Temp/'C,c) Diastereomer I, Diastereomer II d)
R3 23(a)
921 8
+27.0(21,2.55)
+7.36(20,0.10)
n-C13H27 n-C13H27
64(z) 74(5c)
931 7
+44.8(24,1.72)
+10.5(24,2.25)
n-C13H27
54(5d)
8211 ad)
n-C1
3H27
5
Me
t-BuMe2
6
Me
t-BuMe2
n-C8H17 n-C11H23
52(5e) 6O(lf)
7
Me
t-BuMe2
C6H5CH2
82(a)
8
Me
t-BuMe2 p-MeOC6H4CH2
+38.0
22,1.28)
+37.8
26,1.82)
c16.8
941 sd' +52.6
21,2.03)
+7.04
19,0.98)
95/ 5
23,1.79)
+10.5
23,1.88)
>99/ 1
96.5/3.5
87(z)
96/ 4
+46.9
27,0.58)
+68.4
23,1.39)
+37.5
22,0.68)
+62.0
23,1.68)
+11.5
23,0.55)
a)
Isolated yield. b) Determined by HPLC (Cosmosi. SPYE and 5Cl8 columns were used). c) Measured in CHC13. d) Isolated by silica-gel column chromatograpy; Numerals I and II indicate the elution order of the diastereomers.
in refluxing groups genie
dioxane
to furnish centers
in good yields
tations.
The results
of newly
created
optically
for 2 h followed
optically
active
which
are listed
chiral
by concomitant
active y-lactones exhibited
in Table
2.
of silyl
deprotection
(g)8) containing
three
stereo-
the same sigh of specific The stereochemical
ro-
assignments
centers in 6 were determined by converting butenolides 9) according to reported methods. 5,lO)
them to
3403
8M
HCI *
Dioxane B
Scheme 3.
Table 2. Synthesis of Optically Pure Y-Alkylated La&ones
5b -
I II
-5e
I II
5f Is -5h
70
+52.9(23,1.25)
73
+62.3(23,1.07)
S
66
+71.9(19,0.78)
R
81
+50.9(22,0.61
75
*57.9(23,1.21)
88
+61.3(18,1
61
+122.8(20,2.1
68
+109.3(23,1
I II
c) configuration
b)
a) Yield of 6 I%
Diastereomer of 5
Entry
(6)
I I
R
S
1
(R) .30)
(S)
31d)
(R)
.28jd)
(R)
Isolated yield. b) Measured in CHC13. c) Those in parentheses are predicted absolute configuration on the bases of reaction mechanisms. d) Measured in MeOH. a)
The observed tionalized models
would
the amide both
on the basis
A, B, and C
amides12' A
stereochemical
under
be prefered group
and the alkyl
repulsion.
CONHI+
F&i,
indicate
0
using
reactions
As shown
in which
moiety
the remotest
tautomeric
in Fig.
the steric
on the ketone positions
11) would
keto-
open
1, the conformation between interaction
is minimized
each
be ra-
structure
the transition
the corresponding
control.
over B and C
occupy
of these
of consideration
non chelation
silyl groups
steric
which
outcome
other
owing
and
the
to
the
3404
In summary, optically been
pure
developed.
an efficient y-alkylated
method
lactones
We anticipated
in the synthesis
of polyhydroxylated We thank
natural
synthesis
tertiary will
centers
of has
find application
products.
and Dr. K. Hosoya,
Mr. K. Kimata
for measurements
contiguous
this procedure
that
Acknowledgment: of Technology,
for the stereoselective with
of diastereomeric
ratios
Kyoto
Institute
of the products
by
HPLC. References and notes 1) See. for examole: T. Katsuki and K. B. Sharpless, J. Am. Chem. Sot., 102, 5974(198;); R. Noyori, Pure Appl. Chem:, 53; 2315(1981); R. Noyori, "Advances in Asymmetric Synthesis and Optical Resolution" ed by S. Otsuka and T. Mukaivama. Kaqaku-dozin, 1982, Chapter 5; T. Katsuki and Yuki Gosei Kagaku Kyokaishi, 44, 532(1986); A. Sakamoto, M. Yamaguchi, Y. Yamamoto, and J. Oda, J. Am. Chem. Sot., 109, 7188(1987); K. Maruoka, T. Itoh, T. Shirasaka, and H. Yamamoto, J. Am. Chem. Sot., 110, 310(1988); Y. Yamamoto, A. Sakamoto, T. Nishioka, and J. Oda, J. Org. Chem., 56_, 1112(1991). and M. Hasegawa, Bull. Chem. Sot. 2) K. Saiqo, N. Kubota, S. Takebayashi, R. H. Schlessinger and E. J. Iwanowicz, TetraJpn., 351, 931(1986); hedron Lett.. 28, 2083(1987): S. Takano, M. Moriva. Y. Iwabuchi, and K. Ogasawara; zid., 0, 3805(1989); R..P. Short; R. M. Kennedy; and 1755(1989); H. A. Watson, Jr. and B. T. S. Masamune, J. Org. Chem, 2, O'Neill, ibid., 55, 2950(1990). 3) a) S. Bienz, C. Busacca, and A. I. Meyers, J. Am. Chem. SoC., x, 1905(1989); b) W. J. Klaver, H. Hiemstra, and W. N. Speckamp, ibid., 111, 2588(1989) and references cited therein; c) S. A. Miller and A. R. Chamberlin, J. Org. Chem., 54, 2502(1989); d) S. A. Miller and A. R. Chamberlin, J. Am. Chem. Sot ., 112, 8100(1990). 4) H. Yoda, H. Morishita, M. Kudo, T. Katagiri, and K. Takabe, Chem. Express, 4, 515(1989); T. Ohta, S. Shiokawa, R. Sakamoto, and S. Nozoe, Tetrahedron Lett., 31, 7329(1990). 489. 5) H. Yoda, K. Shirakawa, and K. Takabe, Chem. Lett., 1991, 6) H. Niwa, 0. Okamoto, Y. Miyachi, Y. Uosaki, and K. Yamada, J. Org. Chem., 52, 2941(1987). ketoamide of 4 was not detected..in the reaction products. 7) Tautomexc (2) before cyclization 8) It is essential to isolate the two hydroxyamides because the mixture of two diastereomeric hydroxylactones (5) was not separated on silica gel. 9) See, for example: T. Mukaiyama and K. Suzuki, Chem. Lett., 1980, 255; J. P. Vigneron and J. M. Blanchard, Tetrahedron Lett., 21, 1739(1980); R. Bloch and L. Gilbert, J. Org. Chem., 12, 4603(1987); H. Kosugi, Y. Watanabe, and H. Uda, Chem Lett., 1989, 1865. 10) N. Yamazaki and C. Kibayashi, J. Am. Chem. Sot., 111, 1396(1989). ketone (7) which isot equilibrated 11) Reduction of the corresponding with its hydroxylactam form after oxidation of 5b afforded almost the same diastereomeric ratio (95:5) of two hydroxyzides (z).
$
’
n-Cl3%74 5_b (93: 12)
n-%$+27 -& ‘7)
Z=
t-BUM&i
I:
0
‘CONHCH9
75%
- EtOH
YFOH 5_b: 85% (9s: 5)
R. Chiron and Y. Graff, Bull Sot. Chim. Fr., 1970, Fayat, and A. Foucaud, ibid., 1970, 2293.
(ReceivedinJapan 13 March 1991)
‘CONHCH9 i ) X= n-f&H=, Y=H ii) x=H, Y=n-CsHm
575; Y. Gouriou,
C.
oo40-4039/91 $3.00+.00 Pergamml Ressplc
Printed in Great Britain
CHIRAL CYCLIC IMIDES WITH C2-SYMMETRY. NOVEL REAGENTS FOR THE SYNTHESIS OF OPTICALLY PURE LACTONES CONTAINING THREE CONTIGUOUS TERTIARY CENTERS *
Koji Shirakawa, and Kunihiko Takabe * Department of Applied Chemistry, Faculty of Engineering, Hidemi Yoda,
Shizuoka University, Hamamatsu 432, Japan
Summary: Asymmetric reactions employing C2-symmetrical imides readily prepared from L-tartaric acid with Griqnard reagents and sodium borohydride afforded a separable mixture of two hydroxyamides with high diastereoselectivity. Products were lactonized respectively to provide optically pure Yalkylated lactones with contiguous tertiary carbon centers. The reaction mechanisms in asymmetric induction were also discussed.
In recent years
the chemistry of asymmetric reactions using compounds
with C2-axis of symmetry as a chiral source
has attracted increased atten-
tion since these species can serve as novel intermediates for the synthesis chiral substances possessing a wide range of biological activity. 1)
of
Therefore, a great deal of effort for the construction of the reagents with C2-symmetrical carbon skeletons from readily available precursors has been devoted until now 2) and further exploitation of much more convenient methods is strongly desired. Recently nucleophilic addition to N-acyliminium ions obtained from the partial reduction of chiral cyclic imides was demonstrated
and utilized as an efficient method for the synthesis of several alkaloids. 3) Nevertheless, there has been little general approach toward the new employment of carbi4) In the nolamides prepared from the direct alkylations of cyclic imides. preceding paper, we reported the asymmetric synthesis of optically active 5) butenolides using C2-symmetrical imides in 89-92% enantiomeric excess. Here
we wish to describe the details of the reaction of chiral imides with
nucleophiles followed by cyclization and the mechanistic aspects in asymmetric induction. Consecutive treatment of L-tartaric acid (1) with acetyl chloride, primary amine, acetyl chloride aqain,3b' and hydrolysis6' followed by silylprotection provided chiral starting imides (1) in 43-67% yields (Scheme 1). Reactions of 2
thus obtained
with Griqnard reagents in THF at -78 to 0 OC bearing a trans-relation-
would occur from either of two symmetrical sides 3401
3402
1)CH3COCl OH
HO,, % HO 0J-f
Ace,,
2I RlNH2
0
0’ d N
3CH3COCI
COOH
OAC *.
Scheme
respect
which
@j7'
were
to the silyloxy successively
of two hydroxyamides
Specific
rotations
to r.t.
with
after
that
and gave unstable
under
mild
highly
a
conditions
isolation
on silica-gel
increasing
a steric submitted
bulkiness
reaction
column
in these
respectively
NaBHa
1.
chro-
reactions
of the silyl-protecting
to cyclization
in
in Table
are summerized
the stereoselectivity
Then 5 were
carbinolamides with NaBH4
diastereoselective
The results
(5).
were measured
It is apparent
I-3).
functions
reduced
to produce
at 0 OC
(entry
‘0
A1
1.
products
increases
2 Z: RgSi X : Cl I OSO2CF3
ethanol
matography.
OG d N
2) zx
A1
1
ship with
‘0
oz
ZO,, 5.
CH3COCI ‘EtOH *
groups
with
3M HCl
*
EtOH 4
Scheme 2.
9
Table 1. Asymmetric Reactions Using Chiral Imides (2) a) Entry
R'
R:
1
Me
i-PrMe2
2
Me
t-BuMe2
3 Me i-Pr 3 4 C6H5CH2 t-BuMe2
Diastereomer
c) [alD,deg (Temp/'C,c) Diastereomer I, Diastereomer II d)
R3 23(a)
921 8
+27.0(21,2.55)
+7.36(20,0.10)
n-C13H27 n-C13H27
64(z) 74(5c)
931 7
+44.8(24,1.72)
+10.5(24,2.25)
n-C13H27
54(5d)
8211 ad)
n-C1
3H27
5
Me
t-BuMe2
6
Me
t-BuMe2
n-C8H17 n-C11H23
52(5e) 6O(lf)
7
Me
t-BuMe2
C6H5CH2
82(a)
8
Me
t-BuMe2 p-MeOC6H4CH2
+38.0
22,1.28)
+37.8
26,1.82)
c16.8
941 sd' +52.6
21,2.03)
+7.04
19,0.98)
95/ 5
23,1.79)
+10.5
23,1.88)
>99/ 1
96.5/3.5
87(z)
96/ 4
+46.9
27,0.58)
+68.4
23,1.39)
+37.5
22,0.68)
+62.0
23,1.68)
+11.5
23,0.55)
a)
Isolated yield. b) Determined by HPLC (Cosmosi. SPYE and 5Cl8 columns were used). c) Measured in CHC13. d) Isolated by silica-gel column chromatograpy; Numerals I and II indicate the elution order of the diastereomers.
in refluxing groups genie
dioxane
to furnish centers
in good yields
tations.
The results
of newly
created
optically
for 2 h followed
optically
active
which
are listed
chiral
by concomitant
active y-lactones exhibited
in Table
2.
of silyl
deprotection
(g)8) containing
three
stereo-
the same sigh of specific The stereochemical
ro-
assignments
centers in 6 were determined by converting butenolides 9) according to reported methods. 5,lO)
them to
3403
8M
HCI *
Dioxane B
Scheme 3.
Table 2. Synthesis of Optically Pure Y-Alkylated La&ones
5b -
I II
-5e
I II
5f Is -5h
70
+52.9(23,1.25)
73
+62.3(23,1.07)
S
66
+71.9(19,0.78)
R
81
+50.9(22,0.61
75
*57.9(23,1.21)
88
+61.3(18,1
61
+122.8(20,2.1
68
+109.3(23,1
I II
c) configuration
b)
a) Yield of 6 I%
Diastereomer of 5
Entry
(6)
I I
R
S
1
(R) .30)
(S)
31d)
(R)
.28jd)
(R)
Isolated yield. b) Measured in CHC13. c) Those in parentheses are predicted absolute configuration on the bases of reaction mechanisms. d) Measured in MeOH. a)
The observed tionalized models
would
the amide both
on the basis
A, B, and C
amides12' A
stereochemical
under
be prefered group
and the alkyl
repulsion.
CONHI+
F&i,
indicate
0
using
reactions
As shown
in which
moiety
the remotest
tautomeric
in Fig.
the steric
on the ketone positions
11) would
keto-
open
1, the conformation between interaction
is minimized
each
be ra-
structure
the transition
the corresponding
control.
over B and C
occupy
of these
of consideration
non chelation
silyl groups
steric
which
outcome
other
owing
and
the
to
the
3404
In summary, optically been
pure
developed.
an efficient y-alkylated
method
lactones
We anticipated
in the synthesis
of polyhydroxylated We thank
natural
synthesis
tertiary will
centers
of has
find application
products.
and Dr. K. Hosoya,
Mr. K. Kimata
for measurements
contiguous
this procedure
that
Acknowledgment: of Technology,
for the stereoselective with
of diastereomeric
ratios
Kyoto
Institute
of the products
by
HPLC. References and notes 1) See. for examole: T. Katsuki and K. B. Sharpless, J. Am. Chem. Sot., 102, 5974(198;); R. Noyori, Pure Appl. Chem:, 53; 2315(1981); R. Noyori, "Advances in Asymmetric Synthesis and Optical Resolution" ed by S. Otsuka and T. Mukaivama. Kaqaku-dozin, 1982, Chapter 5; T. Katsuki and Yuki Gosei Kagaku Kyokaishi, 44, 532(1986); A. Sakamoto, M. Yamaguchi, Y. Yamamoto, and J. Oda, J. Am. Chem. Sot., 109, 7188(1987); K. Maruoka, T. Itoh, T. Shirasaka, and H. Yamamoto, J. Am. Chem. Sot., 110, 310(1988); Y. Yamamoto, A. Sakamoto, T. Nishioka, and J. Oda, J. Org. Chem., 56_, 1112(1991). and M. Hasegawa, Bull. Chem. Sot. 2) K. Saiqo, N. Kubota, S. Takebayashi, R. H. Schlessinger and E. J. Iwanowicz, TetraJpn., 351, 931(1986); hedron Lett.. 28, 2083(1987): S. Takano, M. Moriva. Y. Iwabuchi, and K. Ogasawara; zid., 0, 3805(1989); R..P. Short; R. M. Kennedy; and 1755(1989); H. A. Watson, Jr. and B. T. S. Masamune, J. Org. Chem, 2, O'Neill, ibid., 55, 2950(1990). 3) a) S. Bienz, C. Busacca, and A. I. Meyers, J. Am. Chem. SoC., x, 1905(1989); b) W. J. Klaver, H. Hiemstra, and W. N. Speckamp, ibid., 111, 2588(1989) and references cited therein; c) S. A. Miller and A. R. Chamberlin, J. Org. Chem., 54, 2502(1989); d) S. A. Miller and A. R. Chamberlin, J. Am. Chem. Sot ., 112, 8100(1990). 4) H. Yoda, H. Morishita, M. Kudo, T. Katagiri, and K. Takabe, Chem. Express, 4, 515(1989); T. Ohta, S. Shiokawa, R. Sakamoto, and S. Nozoe, Tetrahedron Lett., 31, 7329(1990). 489. 5) H. Yoda, K. Shirakawa, and K. Takabe, Chem. Lett., 1991, 6) H. Niwa, 0. Okamoto, Y. Miyachi, Y. Uosaki, and K. Yamada, J. Org. Chem., 52, 2941(1987). ketoamide of 4 was not detected..in the reaction products. 7) Tautomexc (2) before cyclization 8) It is essential to isolate the two hydroxyamides because the mixture of two diastereomeric hydroxylactones (5) was not separated on silica gel. 9) See, for example: T. Mukaiyama and K. Suzuki, Chem. Lett., 1980, 255; J. P. Vigneron and J. M. Blanchard, Tetrahedron Lett., 21, 1739(1980); R. Bloch and L. Gilbert, J. Org. Chem., 12, 4603(1987); H. Kosugi, Y. Watanabe, and H. Uda, Chem Lett., 1989, 1865. 10) N. Yamazaki and C. Kibayashi, J. Am. Chem. Sot., 111, 1396(1989). ketone (7) which isot equilibrated 11) Reduction of the corresponding with its hydroxylactam form after oxidation of 5b afforded almost the same diastereomeric ratio (95:5) of two hydroxyzides (z).
$
’
n-Cl3%74 5_b (93: 12)
n-%$+27 -& ‘7)
Z=
t-BUM&i
I:
0
‘CONHCH9
75%
- EtOH
YFOH 5_b: 85% (9s: 5)
R. Chiron and Y. Graff, Bull Sot. Chim. Fr., 1970, Fayat, and A. Foucaud, ibid., 1970, 2293.
(ReceivedinJapan 13 March 1991)
‘CONHCH9 i ) X= n-f&H=, Y=H ii) x=H, Y=n-CsHm
575; Y. Gouriou,
C.