Oxidations with Lead Tetraacetate

C H A P T E R

I

Oxidations with Lead Tetraacetate GEORGE

M.

RUBOTTOM

I. Introduction II. LTA Reactions with Hydroxyl Groups A. Alcohols B. 1,2-Diols and Related Systems C. Enols and Related Systems D. Phenols E. Monocarboxylic Acids F. Dicarboxylic Acids III. LTA Reactions with Nitrogen-Containing Compounds A. Amines and Related Compounds B. Amides C. Hydrazines and Related Compounds D. Azomethines IV. LTA Reactions with Hydrocarbons A. Alkanes B. Aromatic Hydrocarbons C. Alkenes V. LTA Reactions with Organometallics

1 2 2 27 37 5 5

61 81 89 89 98 101 118 122 122 127 131 140

I. Introduction Lead tetraacetate [(LTA), m p 175°C] was first isolated in 1851 and has been used extensively as an oxidant by organic chemists since 1920. Although L T A can be produced in the laboratory by the reaction of red lead oxide ( P b 0 ) with acetic acid in the presence of acetic a n h y d r i d e , the reagent is commercially available at moderate cost. The commercial L T A contains 10% acetic acid to retard decomposition due to reaction with water. This acetic acid is readily removed either by washing the L T A with anhydrous 1

2

3

1

2

4

A. Jacquelain, J. Praku Chem. 53, 151 (1851). J. C. Bailar, Inorg. Synth. 1, 47 (1939). 1 Oxidation in Organic Chemistry, Part D Copyright © 1982 by A c a d e m i c Press, Inc. All rights of reproduction in any form reserved I S B N 0-12-697253-2

2

GEORGE Μ. RUBOTTOM

ether or by azeotropic distillation with benzene just prior to use. L T A is compatible with a number of c o m m o n solvents including acetic acid, ben­ zene, methylene chloride, chloroform, nitrobenzene, pyridine, D M F , and DMSO. L T A exists as a m o n o m e r in the solid state and in both benzene and acetic acid solution. A distorted cubic geometry has been proposed with both oxygen atoms of each acyloxy group coordinated with l e a d . Infrared mea­ surements support this a r r a n g e m e n t . The solubility and conductance properties of L T A suggest that the c o m p o u n d is covalent, but in acetic acid or carboxylic acid solvents, in general, rapid ligand exchange occurs between L T A and the solvent. Oxidation of inorganic compounds by L T A is facilitated by the high redox potential, 1.6 V in perchloric acid, of the reagent. With organic c o m p o u n d s L T A is normally reduced to lead(II) acetate in reactions involving both homolytic and heterolytic mechanisms. Photolysis of L T A affords lead(II) acetate and acetoxy radicals as primary p r o d u c t s . The basic properties of L T A as an oxidizing agent have been reviewed and several excellent general reviews on the reactions of L T A with organic substrates are e x t a n t . Reviews concerning the behavior of L T A toward specific functional groups are cited where appropriate in the text. The primary literature included in this chapter covers mainly the period of 1970 through January, 1980. 3

4

5

4

6

7

8

7

9-

1

2

II. LTA Reactions with Hydroxyl Groups A. ALCOHOLS

The treatment of alcohols with L T A leads to the formation of acetates, oxidation to the corresponding aldehyde or ketone, fragmentation, and 3 4 5 6 7

9

1 0

G. Rudakoff, Z. Naturforsch. B. Anorg. Chem., Org. Chem. 17, 623 (1962). R. Partch and J. Monthony, Tetrahedron Lett., 4427 (1967). K. Huesler and H. Loeliger, Helv. Chim. Acta 52, 1495 (1969). E. A. Evans, J. L. Huston, and Τ. H. Norris, J. Am. Chem. Soc. 74, 4985 (1952). J. Zyka, Pure Appl. Chem. 13, 569 (1966). V. Franzen and R. Edems, Angew. Chem. 73, 579 (1961). R. N. Butler, in "Synthetic Reagents" (J. S. Pizey, ed.), p. 277, Ellis Horwood, Chichester, England, 1977. L. F. Fieser and M. Fieser, "Reagents for Organic Synthesis," p. 537; Vol. 2, p. 234; Vol. 3, p. 168; Vol. 4, p. 278; Vol. 5, p. 365; Vol. 6, p. 313; Vol. 7, p. 185. Wiley, New York, 1967. G. W. Rotermund, in "Houben-Weyl, Methoden der Organischen Chemie" (E. Muller, ed.), 4th ed., Vol. IV/lb, p. 167. Thieme, Stuttgart, 1975. H. O. House, "Modern Synthetic Reactions," 2nd ed., p. 359. Benjamin, California, 1972. R. Criegee, in "Oxidation in Organic Chemistry" (Κ. B. Wiberg, ed.), Part A, p. 277. Academic Press, New York, 1965.

1 0 a

1 1 1 2

/. Oxidations

with Lead

Tetraacetate

3

cyclization. The parameters leading to each mode of behavior have been thoroughly discussed with respect to substrate structure and solvent effects. Comprehensive lists of examples have also been t a b u l a t e d . The formation of acetates is a process that accompanies most L T A oxidations. The retention of configuration encountered in the acetate has led to postulation of the generalized attack of the alcohol on the acetate carbonyl of a lead(IV) species and/or acetic acid (or anhydride) attack on an alkoxy lead(IV) i n t e r m e d i a t e . Although the use of benzene seems to maximize acetate production (when cyclization is not possible) whereas 1 3 , 1 4

13

ο

X Χ = Η, Pb(OAc) , or COCH3 3

pyridine minimizes it, generalizations are dangerous as shown by the p r o ­ duction of l . 1 5

(ref. 15) 1 (62%)

The L T A oxidation of primary and secondary alcohols to the correspond­ ing aldehyde or ketone can be a moderately high yield p r o c e s s . With the 1 6 - 1 8

(ref. 16)

(74%) 1 3

1 4 1 5

1 6

M. Lj. Mihailovic and R. E. Partch, in "Selective Organic Transformations" (B. S. Thyagarajan, ed.), Vol. II, p. 97. Wiley (Interscience), New York, 1972. M. Lj. Mihailovic and 1. Cekovic, Synthesis, 209 (1970). Β. M. Trost, R. M. Cory, P. H. Scudder, and Η. B. Neubold, J. Am. Chem. Soc. 95, 7813 (1973). D. J. Ward, W. A. Szarek, and J. Κ. N. Jones, Carbohydr. Res. 21, 305 (1972).

4

GEORGE Μ. RUBOTTOM

3 4

33 55

co-(2-adamantyl)alkan-l-ols, the production of aldehyde was accompanied by acetate formation as w e l l . As noted by the examples, the use of pyridine gives maximum yields of carbonyl derivatives. This is in sharp contrast to the role of acidic or apolar solvents such as acetic acid or benzene wherein products of substitution, fragmentation, and cyclization become para­ m o u n t . This dramatic shift in reaction pathway can be attributed to the occurrence of a heterolytic mechanism in pyridine while homolytic routes prevail in both acetic acid and b e n z e n e . It has been suggested that the carbonyl formation that does occur in the absence of pyridine arises from heterolytic disproportionation of the dialkoxylead(IV) derivative 2 ' " 18

1 7

1 3 , 1 4

1 4

Η

1 9

2 1

V OCHRR'

RR'Cv> £Pb(OAc)

2

2

in line, for instance, with studies on the oxidation of benzyl alcohol and 1-phenylethanol in which the reaction is first order with respect to L T A and second order with respect to a l c o h o l . The role of pyridine is generally believed to involve [ R O P b ( O A c ) · py] f o r m a t i o n , and the suggestion has been made that P b — Ν bond formation increases the electrophilicity of 20

1 4 , 2 0

3

1 7

1 8 1 9 2 0 2 1

J. Burkhard, J. Janku, V. Kubelka, J. Mitera, and S. Landa, Collect. Czech. Chem. Commun. 39, 1083 (1974). J. Burkhard, J. Janku, and S. Landa, Collect. Czech. Chem. Commun. 39, 1072 (1974). Y. Pocker and B. C. Davis, J. Chem. Soc. Chem. Commun., 803 (1974). Κ. K. Banerji, S. K. Banerjee, and R. Shanker, Indian J. Chem. Sect. A 15, 702 (1977). Κ. K. Banerji, S. K. Banerjee, and R. Shanker, Bull. Chem. Soc. Jpn. 51, 2153 (1978).

/. Oxidations

with Lead

Tetraacetate

5

the complex and thus favors α-hydrogen removal over the homolysis which occurs when neutral or acidic conditions p e r t a i n . The rate-determining nature of the p r o t o n removal step has been shown by isotope s t u d i e s , ' and transition state 3 has been proposed for the carbonyl forming oxidation of both benzyl alcohol and 1-phenylethanol. 20

1 4

2 0 , 2 1

20

3

In cases where either 1,4- or 1,5-hydrogen transfer is possible, another m o d e of carbonyl formation becomes important when benzene (homolytic conditions) is used as s o l v e n t . 2 2 , 2 3

OPb(OAc),

«.

D l o s s

NCHJ<°

" γ ( C H ^ R

homolysis

1. -e; Ό' or "(CHJP^

2.-H

+

Ο (CH )^ ^ S

2

R

As noted above, although the reactions of alcohols with L T A to form esters and to undergo heterolysis in pyridine have received attention, a great deal more work has been devoted to the study of homolytic fragmentation and cyclization of alcohols by L T A in neutral a n d / o r acidic m e d i a . Scheme 1 indicates the generally accepted pathway leading to b o t h cycliza­ tion and f r a g m e n t a t i o n . Fragmentation occurs best when substituents favor the stabilization of 4 and when ring strain can be released. Radical 4 then is oxidized to the corresponding carbocation 5 that undergoes typical 1 3 , 1 4

14,233

2 2

2 3 2 3 a

D. Jeremic, S. Milosavljevic, V. Andrejevic, M. Jakovljevic-Marinkovic, 2. Cekovic, and M. Lj. Mihailovic, J. Chem. Soc. Chem. Commun., 1612 (1971). S. Milosavljevic, D. Jeremic, and M. Lj. Mihailovic, Tetrahedron 29, 3547 (1973). W. S. Trahanovsky, in "Methods in Free-Radical Chemistry" (E. S. Huyser, ed.), Vol. 4, p. 133. M. Dekker, New York, 1973.

6

GEORGE Μ. RUBOTTOM

+ Pb(OAc)

2

SCHEME 1

carbonium ion r e a c t i o n s . ' Production of 6 , 7 , and 8 reflects the importance of radical stabilization as does the increased a m o u n t of frag­ mentation noted from irafls-2-methylcyclohexanol as opposed to cycloh e x a n o l . The preparative cleavage of both a- and jS-amyrin to give the corresponding seco aldehyde is another case in p o i n t . 1 4

2 3 3

2 4

2 5

2 5 a

26

2 6 3

(ref. 24)

6 (99%) 2 4 2 5 2 5 a 2 6 2 6 a

H. Kakisawa, T. Horie, and T. Kusumi, Bull. Chem. Soc. Jpn. 48, 727 (1975). W. P. Schneider and R. A. Morge, Tetrahedron Lett., 3283 (1976). K. Shankaran and A. S. Rao, Indian J. Chem. Sect. Β 18, 507 (1979). J. Bosnjak, V. Andrejevic, £. Cekovic, and M. Lj. Mahailovic, Tetrahedron 28, 6031 (1972). A. K. Devi, G. K. Trivedi, and S. C. Bhattacharyya, Indian J. Chem. Sect. Β 16, 8 (1978).

/. Oxidations with Lead

α-amyrin β-amyrin

Η Me

1

Tetraacetate

Me Η

The effect of relieving ring strain can be seen in the oxidation of a series of steroidal and triterpenoidal cyclobutanols to give either the corresponding hydroxyketones or h e m i a c e t a l s . " Arguments involving substituent steric interactions have been advanced to explain the predominance of both types of p r o d u c t . Patchouli alcohol fragments when treated with L T A in 2 7

2 9

29

(ref. 27)

2 7 2 8 2 9

H. Wehrli, M. S. Heller, K. Schaffner, and O. Jeger, Helv. Chim. Acta 44, 2162 (1961). R. Imhof, W. Graf, H. Wehrli, and K. Schaffner, J. Chem. Soc. Chem. Commun., 852 (1969). W. Herz and D. H. White J. Org. Chem. 39, 1 (1974).

8

GEORGE Μ. RUBOTTOM

Λ

OH

AcO LTA (ref. 29)

benzene **C0 Me 2

benzene/calcium carbonate, give a 40% yield of 9 in a reaction that may well be c o n c e r t e d . ' Fragmentation of bridged steroidal alcohols has been 3 0

3 0 3

r-.B (refs. 30, 30a)

9(40%)

used as part of a scheme directed toward the study of photolytically mediated remote o x i d a t i o n . 31

K>

Although treatment of 10 with L T A led to no useful cleavage p r o d u c t s , recent studies have shown that, in general, cyclopropanols fragment readily when treated with L T A . ' Cleavages of both 11 and 12 are stereospecific. Comparisons of the products obtained from L T A ^-fragmentation of alcohols with those obtained from L T A decarboxylation of analogous carboxylic acids (Section ΙΙ,Ε) point to the intervention of similar, if not 32

3 3

3 0 3 0 a 3 1

3 2 3 3

3 4 3 5

3 4

35

A. F. Thomas and M. Ozainne, J. Chem. Soc. Chem. Commun., 120 (1977). A. F. Thomas and M. Ozainne, Helv. Chim. Acta 62, 361 (1979). R. Breslow, S. Baldwin, T. Flechtner, P. Kalicky, S. Liu, and W. Washburn, J. Am. Chem. Soc. 95, 3251 (1973). E. J. Corey, Z. Arnold, and J. Hutton, Tetrahedron Lett., 307 (1970). G. M. Rubottom, R. Marrero, D. S. Krueger, and J. L. Schreiner, Tetrahedron Lett., 4013 (1977). T. L. Macdonald, Tetrahedron Lett., 4201 (1978). G. M. Rubottom, unpublished results.

/. Oxidations with Lead

Tetraacetate

1. LTA HOAc 2.H 0

9

(ref. 33)

2

(62-92%)

(ref. 35)

identical, reaction intermediates, presumably the alkyl r a d i c a l s . ' ' The case p r e s e n t e d is illustrative and similar findings have been noted for systems leading to the cyclopropylcarbinyl/cyclobutyl interface. Another interesting aspect of the fragmentation reaction involves the reversibility of the cleavage process that can lead to stereochemical changes 2 3 3

36

37

3 6

3 7

10

GEORGE Μ. RUBOTTOM I^N/^OH

OH

t-Bu

(ref. 36)

,CO H

COJJH

A

Products t-Bu

t-Bu

in 13. T h e examples given indicate that the p h e n o m e n o n is quite gen­ eral,

2 6

'

2 9

'

3 8

•o

Products

R

1

R

2

^R

4

R

R

3

4

R

13

R ^ R 1

S v

2

s

a n d the reader is directed to references 29 a n d 38 for m o r e examples. LTA

ΓΥ \ Μ

Other oxidation products

OR R

% yield

Η Ac

5.7 2.3

(ref. 26)

OMe

(ref. 38) CO M(: A

3 6

3 7

3 8

M. Lj. Mihailovic, J. Bosnjak, and 1. Cekovic, Helv. Chim. Acta 57, 1015 (1974). M. Lj. Mihailovic, J. Bosnjak, and 1. Cekovic, Helv. Chim. Acta 59, 475 (1976). J. J. Partridge, Ν. K. Chada, S. Faber, and M. R. Ushokovic, Synth. Commun. 1, 233 (1971).

/. Oxidations with Lead

Tetraacetate

11

(ref. 29)

(40%)

The products shown above reflect the other major pathway noted in alcohol oxidation with LTA, c y c l i z a t i o n . Table I contains the results of other recent studies involving cyclic a l c o h o l s . " The mechanism of cyclization has been extensively studied and these findings r e v i e w e d . The generally accepted pathway is shown below. 13,14

1 8 , 2 6 , 3 9

4 2

1 3 , 1 4

R

16 3 9

3 9 a 4 0

4 1 4 2

W. T. Borden, V. Varma, M. Cabell, and T. Ravindranathan, J. Am. Chem. Soc. 93, 3800 (1971). A. B. Crow and W. T. Borden, J. Am. Chem. Soc. 101, 6666 (1979). T. Kato, S. Kumazawa, C. Kabuto, T. Honda, and Y. Kitahara, Tetrahedron Lett., 2319 (1975). P. Brun and B. Waegell, Bull. Soc. Chim. Fr., 1825 (1972). P. Brun and B. Waegell, Tetrahedron 32, 1137 (1976).

12

/%

OH

/Of

OH

Τ

y

—

u

—OR

^OH

%V

Γ

R

OH

R

2

Γ Γ

.OH

Substrate

Benzene/CaC0

Benzene/CaC0

—

3

3

3

3

3

Benzene/CaC0

Benzene/CaC0

Benzene/CaC0

Conditions

> Η

^i\^"""Cl

o""

|o

V>·

o—*

o ^ /

1

*S

R

R2

)

Product

LTA-PROMOTED CYCLIZATION OF ALCOHOLS

TABLE I

Rf

Rf

0.8 1.5 Η

77

Η 25-28 Me 51

JR

44

60

Η

3 Η Η Me 9.5 Η Me Me 55 Η

t-Bu

Η

% Yield

42

41

40

39, 39a

26

26

Reference

13

υ

Benzene/CaC0 3

3

3

Benzene/CaC0

—

Benzene/CaC0

f n

0·*

c Ρ

0 gQ

Jg g 0

-(CH,)

rL

^ 1

2

57

1

29

1 67 2 1

2?. 1 — 2 21

18

18

18

14

GEORGE Μ. RUBOTTOM

As noted in Table I and the generalized mechanism, the product most commonly formed is a tetrahydrofuran derivative rather than a tetrahydropyran, a fact accounted for by the favorable transition state 14 for 1,5-hydrogen m i g r a t i o n . ' The optimal nonbonded distance between the 1 3

1 4

14

(5-carbon and oxygen has been determined to be 2.5-2.7 A 1 3 , 1 4 In general, alkyl substitution at the <5-center aids abstraction due to stabilization of 14, whereas substitution at the α-center slows the process. Since the radical 15 and/or carbonium ion 16 are intermediates, stereospecificity is not observed in the final cyclization s t e p . ' ' When rigid geometry offers close prox­ imity to a remote hydrogen, formation of rings other than those containing five members can o c c u r . On the other hand, geometry that can remove 1 3

1 4

4 3

4 4 - 4 6

(49%)

(19%)

M. Lj. Mihailovic, S. Gojkovic, and S. Konstantinovic, Tetrahedron 29, 3675 (1973). V. Pouzar and A. Vystr£il, Collect. Czech. Chem. Commun. 43, 2190 (1978).

/. Oxidations with Lead

No _LTA/CaCQ reaction benzene R=OH;R'=H

Tetraacetate

15

LTA/CaC0 benzene R= H; R' = OH 3

3

R

(ref. 46) (77%)

LTA/CaCQ benzene

3

No reaction

(ref. 42)

the oxygen from a remote hydrogen retards the r e a c t i o n . ' ' In one instance, rearrangement occurs prior to ether formation resulting, once again, in the production of a five-membered r i n g . 4 2

4 5

4 6

47

LTA cyclohexane

(ref. 47) AcO

AcO

Oxidation of 17 with L T A to give 18 as the major product has been interpreted to involve carbonium ion 19 since oxidation with both H g O / B r or A g C 0 / B r should not involve ionic i n t e r m e d i a t e s . 2

48

2

3

2

PhsC

[Ox]

OH

Ph

PhsC

Ph OH

18

17

LTA HgO/Br Ag C0 /Br 2

2

3

2

5.5 6 4

59 33 19

19

(ref. 48)

V. Pouzar, J. Protiva, E. Lisa, E. Klinotova, and A. Vystroil, Collect. Czech. Chem. Commun. 40, 3046 (1975). M. Fisch, S. Smallcombe, J. C. Gramain, M. A. McKervey, and J. E. Anderson, J. Org. Chem. 35, 1886(1970). P. Morand and A. Palakova-Paquet, Can. J. Chem. 51, 4098 (1973). M. Lj. Mihailovic, G. Misosevic, and A. Milovanovic, Tetrahedron 34, 2587 (1978).

16

GEORGE Μ. RUBOTTOM

The cis/trans ratios obtained from the oxidation of 2 0 with L T A relative to those encountered with added F e ( C 1 0 ) or C u ( B F ) indicate that cationic cyclization predominates with LTA, whereas cyclization in the presence of Cu(II) or Fe(III) proceeds via intermediates such as 2 1 . 4

3

4

2

4 9

[OK]

OH 20

cis/trans LTA LTA/Fe(III) LTA/Cu(II)

3.9 2.0 0.2

(ref. 49)

Cu-

21

Isotope studies utilizing 2 2 and 2 3 have shown a 20-fold preference for trans-hydrogen abstraction via a chair (or "half-chair-like") transition

t-Bu

i-Bu

OH 22

OH 23

s t a t e . The process has also been found to parallel closely abstraction reactions induced by electron i m p a c t . ' Introduction of remote double bonds into alcohols oxidized with L T A gives the opportunity for neighboring group p a r t i c i p a t i o n . ~ In these 50

5 0

5 1

1 3 , 5 2

4 9 5 0 5 1 5 2

5 3 5 4 5 4 a 5 5 5 5 a 5 5 b

5 5 b

J. T. Groves, Tetrahedron Lett., 3113 (1975). G. Eadon, J. Am. Chem. Soc. 98, 7313 (1976). Μ. M. Green, J. G. McGrew, II, and J. M. Moldowan, J. Am. Chem. Soc. 93, 6700 (1971). R. M. Moriarty in "Selective Organic Transformations" (B. S. Thyagarajan, ed.), Vol. II, p. 183. Wiley (Interscience), New York, 1972. T. Sasaki, S. Eguchi, and T. Kiriyama, J. Org. Chem. 38, 2230 (1973). M. P. Zink, J. Ehrenfreund, and H. R. Wolf, Helv. Chim. Acta 57, 1116 (1974). N. Langlois and R. Z. Andriamialisoa, J. Org. Chem. 44, 2468 (1979). P. K. Grant, R. T. Weavers, and C. Huntrakul, Tetrahedron 29, 245 (1973). M. P. Bertrand, J. M. Surzur, M. Boyer, and M. Lj. Mihailovic, Tetrahedron 35, 1365 (1979). R. B. Gupta and R. N. Khanna, Indian J. Chem. Sect. Β 16, 35 (1978).

/. Oxidations

with Lead

Tetraacetate

17

(ref. 53)

(ref. 54) (61%)

(ref. 54a)

(ref. 55)

cases π-interaction with L T A can mediate p r o d u c t s ; however, " n o r m a l " alcohol fragmentation and cyclization can compete as w e l l . ' " An interesting example of epoxide formation occurs when the appropriate allylic alcohol is treated with either L T A or P b ( O C O C F ) . 5 4

5 8

5 7

5 8 5 9

5 8

5 9

3

5 6

5 6

4

Μ. Lj. Mahailovic, 2. Cekovic, J. Stankovic, S. Djokic-Mazinjanin, D. Marinkovic, and S. Konstantinovic, Glas. Hem. Drus., Beograd 43, 69 (1978). M. Lj. Mahailovic, 2. Cekovic, J. Stankovic, N. Pavlovic, S. Konstantinovic, and S. DjokicMazinjanin, Helv. Chim. Acta 56, 3056 (1973). J. Ehrenfreund, M. P. Zink, and H. R. Wolf, Helv. Chim. Acta 57, 1098 (1974). D. Westphal and E. Zbiral, Liebigs Ann. Chem., 2038 (1975).

GEORGE Μ. RUBOTTOM

18

(ref. 59) CH N0 3

*s<-^2

2

(12%) A c o m b i n a t i o n of L T A a n d iodine (the hypoiodite reaction) has also been used with varying degrees of success for the formation of cyclic ethers, especially in polycyclic s y s t e m s . A representative n u m b e r of examples are given in Table I I " a n d others can be found in reference 60. 60

6 1

6 7 c

?

6 0 6 1 6 2 6 3 6 3 a

6 3 b

6 4 6 5 6 6 6 7 6 7 a 6 7 b 6 7 c

J. Kaluoda and K. Heusler, Synthesis, 501 (1971). T. Nakano and A. K. Banerjee, Tetrahedron 28, 471 (1972). T. Nakano and A. K. Banerjee, Tetrahedron Lett., 165 (1971). H. Khan, A. Zaman, G. L. Chetty, A. S. Gupta, and S. Dev, Tetrahedron Lett., 4443 (1971). A. K. Banerjee, C. D. Ceballo, Μ. N. Vallejo, and Ε. H. Bolivar, Bull. Chem. Soc. Jpn. 52, 608 (1979). A. L. Campbell, Η. N. Leader, C. L. Spencer, and J. D. McChesney, J. Org. Chem. 44, 2746 (1979). J. Bull and C. Van Zyl, Tetrahedron 28, 3957 (1972). J. Wicha, Tetrahedron Lett., 2877 (1972). P. Roller, B. Tursch, and C. Djerassi, J. Org. Chem. 35, 2585 (1970). M. Kaufman, P. Morand, and S. A. Samad, J. Org. Chem. 37, 1067 (1972). P. Kooovsky and V. Cerny, Coll. Czech. Chem. Commun. 44, 2275 (1979). H. Suginome, N. Sato, and T. Masamune, Bull. Chem. Soc. Jpn. 52, 3043 (1979). P. K. Jadhav and U. R. Nayak, Indian J. Chem. Sect. Β 16, 952 (1978).

/\ Η

χ

c

i

]1

OH

i

OH

I

OH

1?I τ

Substrate

3

LTA/CaC0 /I cyclohexane

2

LTA/I /Av

2

2

1. L T A / C a C 0 cyclohexane 2. I /Av

Conditions

3

2

00%)

ΓΗΤ

6 3

^ \ ^ O R

^y^o (%) X w JJ

^-Ο

Η

Product

LTA/1 -PROMOTED CYCLIZATION OF ALCOHOLS

T A B L E II

(43%)

100

30

% Yield

(cont.)

63a

63

61,62

Reference

20

ρ

Τ

HOy Η

Substrate

=5

R

CH

17

2

LTA/I benzene

2

LTA/I benzene

2

LTA/I /Av benzene

Conditions

/ \

C

Ο

C)

\ ^

S

1

(

Product

CIV

9

TABLE II (cont.)

>

£ β

Η

1 7

'

10

68, mixture

% Yield

65

64

63b

Reference

21

RCT

AcO^

AcO^

^ \

Br 1 OH

c

R'O. /

1 Η J ΒJ

C

H

. 8 17

3

LTA/CaC0 /I benzene

2

3

2

1. LTA/CaC0 cyclohexane 2. l /hv

2

LTA/I /Av/HOAc cyclohexane

c ο

1

J κ1

RO^^^ Br

A c O ^ ^

C

1

°Y

<

D

Β J

1

ΤΗ jC '

/

17

Η

. 8 17

C«H

R R' (%) Ac Bz 43 Bz Bz 80 Bz Ac 25

43

—

67a

67

66

(cont.)

2

|^ Η

\/

OH

**CH OH

Oc

0

c

AcO

Substrate

\

Η

LTA/Ι,/Λν cyclohexane

2

LTA/I //zv cyclohexane

3

2

LTA/CaC0 /I Av/cyclohexane

Conditions

ΤΗ

/

c

^ £ ^

V Η

Η /

Product

^· ι—^

TABLE II (cont.)

J""H

\

73

~ 8 0 as 1/1 mixture

27

% Yield

67c

67c

67b

Reference

/. Oxidations

with Lead

Tetraacetate

23

The generally accepted mechanism of the r e a c t i o n involves initial trans­ formation of the alcohol to a hypoiodite 2 4 which then undergoes homolysis to afford 2 5 . Hydrogen abstraction followed by iodohydrin formation 2 6 and ring closure via an S 2 process produces 2 7 . In the presence of a second 60

N

OH

LTA

+

-I

25

24

R^ . / H

OH

Q/H

26

27

equivalent of L T A , the iodohydrin 2 6 can be diverted to 2 8 and thus to 2 9 . This reaction has been put to practical use as a lactone s y n t h e s i s . W h e n 29

Λ

OH

LTA

R

OPb(OAc)

"

26

3

28

29

access of iodine radical (or iodine) to the radical 3 0 is sterically blocked, HO,

^ \

1. LTA/I /CaCO h v/cyclohexane 2

s

Q-

Ο^^Ν***^

2. Jones Ox.

(ref. 29) HO

1. LTA/VCaC0 h ν /cyclohexane 3

°

:

2. Jones Ox. Me0 C 2

Me0 C 2

(40%)

24

GEORGE Μ. RUBOTTOM

or S 2 displacement from 31 is sterically or geometrically unfavored, the formation of 3 2 can p r e d o m i n a t e . ' Subsequent transformations of the N

2 9

6 8

u

31

alkene 3 2 with the LTA/iodine reagent led to the products isolated from the reaction. The product spectrum obtained from the LTA/iodine treatment of 16-e«M7-kauranol is illustrative. 68

LTA/Ia/CaCOjA^ cyclohexane

(ref. 68)

A. J. McAlees and R. McCrindle, Can. J. Chem. 51, 4103 (1973). C. Singh, J. Singh, and S. Dev, Tetrahedron 33, 1759 (1977). W. H. W. Lunn, J. Chem. Soc. C, 2124 (1970).

/. Oxidations

with Lead

Tetraacetate

25

Cyclic ether formation from straight-chain aliphatic alcohols has also been observed with the LTA/iodine r e a g e n t . ' With 3 3 cyclization is 4 3

6 9

(ref. 69)

(40%)

accompanied by f r a g m e n t a t i o n . This latter process becomes the major pathway when cyclization is impossible. This reaction has been put to excellent synthetic use in the fragmentation of a n u m b e r of a d a m a n t a n o i d systems. Fragmentation was also noted with both the enmein-type 69

7 0 - 7 2

(ref. 70, 70a)

(ref. 71)

(refs. 71a, 71b)

7 0 8 7 1 7 1 a 7 1 b 7 1 c 7 2

Z. Majerski and Z. Hamersak, Org. Synth. 59, 147 (1979). Z. Hamersak, D. Skare, and Z. Majerski, J. Chem. Soc. Chem. Commun., 478 (1977). Z. Majerski, Z. Hamersak, and D. Skare, Tetrahedron Lett., 3943 (1977). Z. Majerski, S. Djiga§, and V. Vinkovic, J. Org. Chem. 44, 4064 (1979). Z. Majerski and J. Janjatovic, Tetrahedron Lett., 3977 (1979). R. M. Black and G. B. Gill, J. Chem. Soc. Chem. Commun., 172 (1971).

26

GEORGE Μ. RUBOTTOM

compounds 3 4 and the cage molecule 3 5 . In each instance, the respec­ tive iodo formates 36 and 37 were obtained. Finally, a combination of 7 3

7 3 a

Η OMe Η

Η OAc OAc

37 (81%) 7 3 7 3 a

Ε. Fujita, I. Uchida, and T. Fujita, Chem. Pharm. Bull. 22, 1656 (1974). L. A. Paquette, W. J. Begley, D. Balogh, M. J. Wyvratt, and D. Bremner, J. Org. Chem. 44, 3630 (1979).

/. Oxidations with Lead

Tetraacetate

27

fragmentation, oxidation, and cyclization was observed with 3 8 .

2 9

B. 1,2-DIOLS A N D R E L A T E D S Y S T E M S

The cleavage of 1,2-diols to afford carbonyl c o m p o u n d s is one of the most commonly used L T A reactions. The ability of L T A to cleave trans-aioh and the compatibility of the reagent with aprotic as well as protic solvents recommend L T A when comparison is m a d e with other standard 1,2-diol cleaving agents such as periodate. The mechanistic aspects of the reaction have been well studied and the results r e v i e w e d , ' ' ' and the picture shown in Scheme 2 emerges. In cases where geometry is favorable, oxidation 9

+ LTA

1 0 a

7 4

7 4 a

vLoPbiOAcJs

-HOAc

+ HOAc

OH

^OH base acid O—Pb(OAc) ^ (OAc

2

-^Pb(OAc)

2

+

HOAc

Baset^H-^O^T^ O^JOAc),

40

\

Η—Ο

39

^C—Me H

+

41

Base Η + 2

AII

+ Pb(OAc), + AcO"

H

+

+

2 ^Jj^

A +

SCHEME 2

HOAc +

Pb(OAc)

+

2

Pb(OAc)

2

28

GEORGE Μ. RUBOTTOM

via 3 9 occurs in a two-electron process. With trans-diols this pathway is n o t feasible and trans-periplanar fragmentation becomes important. The role of both base and acid in enhancing the cleavage of trans-diols has been ration­ alized by involving transition states such as 4 0 and 4 1 . A large body of work, beyond the scope of this chapter, exists concerning the use of glycol cleavage in structural determination and in the degradation of sugars. A n u m b e r of reviews on the latter have a p p e a r e d . The following summary will outline some of the specific synthetic uses of L T A diol cleavage. F o r instance, the sequential oxidation of 1,2-diols followed by treatment of the ensuing dicarbonyl c o m p o u n d with base offers a general high yield method for the preparation of cyclic s y s t e m s , " whereas the 1 0 a

7 5 - 7 7

7 8

8 0

COMe

(ref. 78)

(29%)

(64%)

/. Oxidations with Lead

Tetraacetate

29

cleavage of bridged diols allows entry into medium or large rings as indicated by the following e x a m p l e s . " 8 1

OH

Rr r

OH

8 5

LTA/MeOH

ΟΥ · 1

Ο

Br

(55%)

7 4

7 4 a 7 5

7 6 7 7 7 8

7 9

8 0

8 1 8 2 8 3 8 4 8 5

C. A. Bunton, in "Oxidation in Organic Chemistry" (Κ. B. Wiberg, ed.), Part A, p. 367. Academic Press, New York, 1965. W. S. Trahanovsky, J. R. Gilmore, and P. C. Heaton, J. Org. Chem. 38, 760 (1973). A. S. Perlin, Adv. Carbohydr. Chem. 14, 9 (1959). C. T. Bishop, Methods Carbohydr. Chem. 6, 350 (1972). P. S. O'Colla, Methods Carbohydr. Chem. 5, 382 (1965). W. S. Johnson, M. F. Semmelhack, M. U. S. Sultanbawa, and L. A. Dolak, J. Am. Chem. Soc. 90, 2994 (1968). R. E. Ireland, P. Bey, K. F. Cheng, R. J. Czarny, J. F. Moser, and R. I. Trust, J. Org. Chem. 40, 1000 (1975). E. J. Corey, R. L. Danheiser, S. Chandrasekaran, P. Siret, G. E. Keck, and J.-L. Gras, J. Am. Chem. Soc. 100, 8031 (1978). P. J. Mulligan and F. Sondheimer, J. Am. Chem. Soc. 89, 7118 (1967). B. W. Roberts, J. J. Vollmer, and K. L. Servis, J. Am. Chem. Soc. 90, 5264 (1968). I. J. Borowitz, A. Liberies, K. Megerle, and R. D. Rapp., Tetrahedron 30, 4209 (1974). A. Tahara and T. Ohsawa, Tetrahedron Lett., 2469 (1969). D. Termont, P. De Clereq, D. De Keukeleire, and M. Vandewalle, Synthesis, 46 (1977).

30

GEORGE Μ. RUBOTTOM

OH

LTA (ref. 84)

CO-Me

OH LTA HOAc

(ref. 85)

OH OH cis-syn-cis and cis-anti-cis mixture

OH LTA HOAc HO

OH cis-syn-cis and cis-anti-cis mixture

(ref. 85) HO

Ο (83%)

The strategic placement of the 1,2-diol system in cyclic precursors also allows controlled placement of remote functional groups in the resulting cleavage p r o d u c t s . The examples presented show not only the feasi­ bility of this approach but also indicate the wide range of substitution that 8 6 - 8 9

Η

OH

V O H

1

H O ' ^ ^ ^ H

LTA HOAc

(ref. 86)

H O - ^ ^ S ^

C0 Me

CO Me

2

a

(45%, 3 isomers) NC(CH ) 2

6

OHCNH^^H

LTA acetone

NC(CH )

2 e

OHCNH (?)

8 6

8 7

(ref. 87)

G. Biichi, B. Gubler, R. S. Schneider, and J. Wild, J. Am. Chem. Soc. 89, 2776 (1967). E. J. Corey, Ν. H. Andersen, R. M. Carlson, J. Paust, E. Vedejs, I. Vlattas, and R. Ε. K. Winter, J. Am. Chem. Soc. 90, 3245 (1968).

/. Oxidations with Lead

Tetraacetate

31

88)

is compatible with the cleavage reaction. This is especially noteworthy in cases where the molecule contains either a c y c l o p r o p y l or cyclobutyl ring. Oxidation of α-hydroxy carbonyl c o m p o u n d s is also an efficient process, and although reports exist wherein cleavage is affected in aprotic solvent or the solvent is not n o t e d , the general conditions for the transforma8 9 - 9 2

9 2 a

9 3 - 9 5

8 8 8 9 9 0 9 1

9 2 9 2 a 9 3

9 4 9 5

Y. Fukuyama, C. L. Kirkemo, and J. D. White, J. Am. Chem. Soc. 99, 646 (1977). N. Andersen, Y. Ohta, A. Moore, and C. W. Tseng, Tetrahedron 34, 41 (1978). Η. E. Zimmerman and P. S. Mariano, / . Am. Chem. Soc. 91, 1718 (1969). Η. E. Zimmerman, P. Hackett, D. F. Juers, J. M. McCall, and B. Schroder, J. Am. Chem. Soc. 93, 3653 (1971). A. S. Narula and S. Dev, Tetrahedron 29, 569 (1973). S. Ohuchida, N. Hamanaka, and M. Hayashi, Tetrahedron Lett., 3661 (1979). D. Helmlinger, P. de Mayo, Μ Nye, L. Westfelt and R. B. Yeats, Tetrahedron Lett., 349 (1970). J. Cadet and R. Teoule, Tetrahedron Lett., 3229 (1972). F. M. Beringer, P. Ganis, G. Avitabile, and H. Jaffe, J. Org. Chem. 37, 879 (1972).

GEORGE Μ. RUBOTTOM

32

tion include the use of protic media such as water or alcohol. These solvents apparently encourage hydrate or hemiketal formation and thus increase

OH

the rate of o x i d a t i o n .

74

ROH

OH

LTA

Oxidation

Table III gives some typical e x a m p l e s .

96

1 0 0

When

TABLE III LTA CLEAVAGE OF OC-HYDROXY KETONES

Substrate

OH

% Yield

Product

Solvent

90% HOAc

Reference

96

COMe ^y^co H 2

(CH^n Γ ^ ^ O H

, /^7^C0 Me
1. MeOH/LTA 2. MeOH/H

+

2 n

V^

CH(OMe)

AcQ

*

2 42 3 58

97

49

98

91

99

86

100

OH CHO CO Me

AcO.

a

MeOH/HOAc

EtOH/benzene CO.Et

1. MeOH/LTA 2. MeOH/H

CHO CH(OMe).

+

CO Me a

9 6 9 7 9 8 9 9 1 0 0

R. L. Cargill, D. M. Pond, and S. O. LeGrand, J. Org. Chem. 35, 359 (1970). J. R. Hazen, J. Org. Chem. 35, 973 (1970). Y. Shizuri, H. Wada, K. Sugiura, K. Yamada, and Y. Hirata, Tetrahedron 29, 1773 (1973). R. J. Anderson and C. A. Henrick, / . Am. Chem. Soc. 97, 4327 (1975). A. Barco, S. Benetti, G. P. Pollini, P. G. Baraldi, M. Guarneri, and C. B. Vincentini, Synth. Commun. 7, 13 (1977).

/. Oxidations

with Lead

Tetraacetate

33

pyridine, benzene, or acetic acid is used as solvent, α-oxygenated carbonyl c o m p o u n d s can sometimes be i s o l a t e d . " It is also possible to prepare 1 0 1

OH

1 0 3

COMe Κ OH

LTA HOAc

(ref. 101)

1. LTA/HOAc/H 0 2. Jones Ox. 2

(ref. 102)

1,2-diones 4 2 by this m o d i f i c a t i o n . The use of pyridine is crucial to the success of this particular reaction. F o r instance, when Ζ = S, oxidation 104

ο

OH LTA py

1 0 6

ο

^Z"^

i-BuN

42

at sulfur occurs with benzene as s o l v e n t . as a synthetic p r o c e d u r e .

106

% yield 42

Reference

65 68 80

104 105 106

This reaction also has been used

107

LTA

OAc

py

(ref. 107)

(30%) 1 0 1 1 0 2 1 0 3 1 0 4 1 0 5

R. C. Nickolson and M. Gut, J. Org. Chem. 37, 2119 (1972). W. Herz and R. C. Ligon, J. Org. Chem. 37, 1400 (1972). S. W. Pelletier, Κ. N. Iyer, and C. W. J. Chang, J. Org. Chem. 35, 3535 (1970). P. Y. Johnson, J. Zitsman, and C. E. Hatch, J. Org. Chem. 38, 4087 (1973). P. Y. Johnson, I. Jacobs, and D. J. Kerkman, / . Org. Chem. 40, 2710 (1975).

34

GEORGE Μ. RUBOTTOM

Extension of the oxidation process t o a,/?-dihydroxy ketones excellent yields of the corresponding bis-cleavage p r o d u c t s . " 1 0 8

OAc

affords

1 1 1

OAc 1. Os0

4

(ref. 108)

2. LTA/MeOH

(100%)

1 0 6 1 0 7 1 0 8 1 0 9 1 1 0

1 1 1

A. Krebs and H. Kimling, Liebigs Ann. Chem. 740, 126 (1970). P. Y. Johnson and M. Berman, 7. Org. Chem. 40, 3046 (1975). N. S. Crossley, Tetrahedron Lett., 3327 (1971). S. Danishefsky, P. Schuda, and K. Kato, J. Org. Chem. 41, 1081 (1976). S. Danishefsky, P. F. Schuda, T. Kitahara, and S. J. Etheredge, J. Am. Chem. Soc. 99, 6066 (1977). S. Danishefsky, M. Hirama, K. Gombatz, T. Harayama, E. Berman, and P. Schuda, J. Am. Chem. Soc. 100, 6536 (1978).

/. Oxidations

with Lead

Tetraacetate

35

The cleavage of 1,2-amino alcohols with L T A proceeds in a m a n n e r analogous to the 1,2-diol cleavage. T h u s , b o t h 4 3 and 4 4 afford moderate yields of the corresponding cleavage p r o d u c t s . The reaction of 4 5 1 1 2 , 1 1 3

COMe

Η-4γ -| _ LTA R 4 ^ ά

N

JL

IKT

benzene

Η rmr^

U

n

C

V /

_ >^K R C _H O_ + OHC Η OHC

\

v

(ref. 112)

43

(ref. 113)

44

with L T A results in a 6 8 % yield of 4 6 . In this case, it is postulated that the initially formed i m m o n i u m salt 4 7 undergoes further oxidation and re1 1 4

(ref. 114)

47

arrangement leading to 4 6 . A similar pathway could account for the a p ­ pearance of 4 8 . 1 1 5

1 1 2 1 1 3 1 1 4

1 1 5

H. Suginome, H. Umeda, and T. Masamune, Tetrahedron Lett., 4571 (1970). H. J. Roth, T. Schrauth, and Μ. H. El Raie, Arch. Pharm. (Weinheim) 307, 482 (1974). H. De Koning, A. Springer-Fidder, M. J. Moolenaar, and H. O. Huisman, Reel. Trav. Chim. Pays-Bas 92, 237 (1973). M. Narisada, F. Watanabe, and W. Nagata, Tetrahedron Lett., 3681 (1971).

36

GEORGE Μ. RUBOTTOM

(ref. 115)

The oxidation of α-substituted α-amino ketones results in cleavage between the carbonyl a n d carbinamine functions. In the presence of an alcohol, an ester is formed from the acyl group and a nitrile from the carbinamine portion of the original s u b s t r a t e . 116

LTA/R Ό Η

ArCOCH(NH )R

—

2

ArCO R' + RCN a

c

LTA/EtOH

S

CH C1

L

2

NHg CI

2

2

2

(ref. 116)

^C0 Et 2

CN

(25%)

A series of recent investigations indicates that the cleavage of jS-hydroxy sulfides ' ' and ) 5 - h y d r o x y d i t h i a n e s ' ' has great synthetic 1 1 7

1 1 8

1 1 8 3

(ά)7Γ

UxSPh

'"SPh

1 1 9

LTA benzene/py

^

1 1 9 a

1 2 0

OAc PhS

(

A^(CH ) 2

n

r

e

f

n

8

)

^CHO

(ref. 119a)

potential. The mechanistic aspects of the former reaction have yet to be clearly defined, but it has been noted that a trans diaxial disposition of the hydroxy and thiophenoxy groupings is r e q u i r e d . The mechanism of the 118

1 1 6

1 1 7

1 1 8

1 1 8 a

Η. E. Baumgarten, D. F. McLaen, and H. W. Taylor, Jr., / . Org. Chem. 36, 3668 (1971). Β. M. Trost and K. Hiroi, J. Am. Chem. Soc. 97, 6911 (1975). Β. M. Trost, M. Ochiai, and P. G. McDougal, J. Am. Chem. Soc. 100, 7103 (1978). D. Caine and A. S. Frobese, Tetrahedron Lett., 3107 (1977).

/. Oxidations

with Lead

Tetraacetate

37

latter reaction is also c o m p l e x . Evidence has been obtained implicating 4 9 as a key intermediate in the ring expansion p r o c e s s . 1 1 9

1 1 9

R

OH

p s

(CH ) 2

X W

Pb(OAc)

49

3

Treatment of the /J-amidosulfide 5 0 with L T A yields a mixture containing two products resulting from the oxidation of sulfur and 51 a unique product in which migration of the thiomethyl group o c c u r r e d . 121

H H H RCON>J pSMe

O ^ K J ^

SMe Ι Η OAc R C O N J U

H H H RCON J p z

^ h e n z e n e

*

ο ^ -

Ν

CO R'

+

Γ ^

ο < ^

CO R'

A

Γ ^ C0 R'

A

2

50

51 (40%)

Ζ

% yield

SOMe SCH OAc

15 35

2

C. ENOLS AND RELATED

Ν

(ref. 121)

SYSTEMS

The reaction of enolizable carbonyl c o m p o u n d s with L T A has emerged as a standard method for α-acyloxylation. A n extensive review of synthetic applications through 1971 e x i s t s and discussions concerning the mecha­ nisms of the transformation are also a v a i l a b l e . ' ' Evidence points to rate-determining e n o l i z a t i o n , ' with a fast second step involving either radical or ionic p a t h w a y s , ' ' most workers favoring the latter 1 2 2

1 0 3

1 2

1 0 3

1 1 9

1 1 9 8

1 2 0

1 2 1

1 2 2

1 2 3

1 2 4

1 2 , 5 2

1 2 2

1 2 3

1 2

1 2 4

Β. M. Trost, K. Hiroi, and L. N. Jungheim, / . Org. Chem. 45, 1839 (1980). Β. M. Trost and K. Hiroi, / . Am. Chem. Soc. 98, 4313 (1976). W. Lottenbach and W. Graf, Helv. Chim. Acta 61, 3087 (1978). E. G. Brain, A. J. Eglington, J. H. C. Nayler, M. J. Pearson, and R. Southgate, J. Chem. Soc. Chem. Commun., 229 (1972). D. J. Rawlinson and G. Sosnovsky, Synthesis, 567 (1973). P. S. Radhakrishnamurti and S. H. Pati, Indian J. Chem. Sect. A 16, 319 (1978). R. O. C. Norman and D. R. Harvey, J. Chem. Soc, 4860 (1964).

GEORGE Μ. RUBOTTOM

38

Pb(OAc)

3

slow

RCOCH R' 2

Pb(OAc) Q

s

homolysis

R

Ό ^=cf RI

heterolysis RCOCHROAc

+ · OAc + Pb(OAc)

2

R'

/

route. Intramolecular acetoxy transfer has also been suggested as a syn­ chronous m e c h a n i s m . Boron trifluoride has been used successfully to 1 0 3

Ο

facilitate the reaction, causing m o r e rapid enol f o r m a t i o n . Enolates have also been found to undergo acetoxylation with L T A b u t this process may not be g e n e r a l . A n indication of the synthetic use of α-acetoxylation with L T A is provided in Table I V . " Reference 122 m a y also be consulted for a c o m p r e h e n ­ sive listing. T h e sequential ring B, a n d ring A a r o m a t i z a t i o n of 5 2 represents 1 2 , 1 2 2

1 2 5

1 2 6

1 2 7

1 2 5 1 2 6 1 2 7 1 2 8 1 2 9 1 3 0 1 3 0 a 1 3 1 1 3 2

1 3 3

1 3 3 8 1 3 4 1 3 5 1 3 6

1 3 9 3

J. W. Ellis, J. Chem. Soc. Chem. Commun., 406 (1970). R. K. Boeckman, Jr. and M. Ramaiah, / . Org. Chem. 42, 1581 (1977). D. Gorenstein and F. H. Westheimer, J. Am. Chem. Soc. 92, 634 (1970). T. A. Spencer, R. A. Ariel, D. S. Rouse, and W. P. Dunlap, Jr., J. Org. Chem. 37,2349 (1972). J. B. Press and H. Shechter, J. Org. Chem. 40, 2446 (1975). M. Lj. Mahailovic, J. Forsek, and Lj. Lorenc, Tetrahedron 33, 235 (1977). V. S. Kamat, G. K. Trivedi, and S. C. Bhattacharyya, Indian J. Chem. Sect. Β16,184 (1978). Y. Fukuyama, T. Tokoroyama, and T. Kubota, Tetrahedron Lett., 4869 (1973). G. A. Russell, R. L. Blankespoor, K. D. Trahanovsky, C. S. C. Chung, P. R. Wittle, J. Mattox, C. L. Myers, R. Penny, T. Ku, Y. Kosugi, and R. S. Givens, J. Am. Chem. Soc. 97, 1906 (1975). D. Caine, A. A. Boucugnani, S. T. Chao, J. B. Dawson, and P. F. Ingwalson, J. Org. Chem. 41,1539(1976). K. Shimada, T. Nambara, I. Uchida, and S. M. Kupchan, Heterocycles 12, 1445 (1979). G. R. Pettit, C. L. Herald, and J. P. Yardley, J. Org. Chem. 35, 1389 (1970). T. Ibuka, K. Tanaka, and Y. Inubushi, Tetrahedron Lett., 4811 (1970). D. N. Kirk and M. S. Rajagopalan, J. Chem. Soc. Perkin Trans. 1, 1860 (1975).

*

κ

Ο

0

I

6ζ

Ο

0

oAt

jX>

Substrate

2

HOAc

HOAc/Ac 0

HOAc

2

Benzene/HOAc Ac 0

Benzene

Solvent

OAc

Ο

Ο

^\<^OAc

"Xfc!

& Η

ο

Ο

Product

LTA ACETOXYLATION OF ENOLIZABLE CARBONYL COQPOUNDS

TABLE IV

65

100

100

3

60 30

% Yield

130a

130

129

128

127 128

(cont.)

Reference

40

)

\

3

3

*R

R

R

2

1

'R

JF X

| I

0

II

V k)

4

R'

R°jf

/ R*

0

κ

=0

(

\=J

Substrate

2

—

HOAc/Ac 0

Benzene

Benzene

Benzene

Solvent

TABLE IV

4

°

^R> R»

R»

>

R

^OAc

[JΛ

OAc

0 0 CO

R5

i

x

/

Ο

>=O

OAc

Product

r"' Cx

AcO

(cont.)

—

44

—

—

% Yield

133a

133

132

132

131

Reference

41

y

I

COCH.

AcO^

OMe

3

OAc ^ /COCH

Κ rσQ

Accr^

COCHg

2

3

2

a

2

1. Benzene/MeOH BF E t 0 2. NaHCO H 0/EtOH

3

2

Benzene BF E t 0

3

2

Benzene/MeOH BF E t 0

3

Benzene/MeOH BF E t 0

J5 y

OMe

2

OAc COCH OAc

AcOv^^i^

>

2

COCH OAc

AcO /

r

2

COCH OAc

i:b r Λ

—

65

71

69

136

135

134

134

(cow/.)

cr

3

3

nr2rs

1

2

\

2

υ

. — N.

II

R

/ Ν

X

< HOAc (I also present) 2

—

—

Solvent

Benzene

R = Me, Ph R = R == Et or N R = R = 7V-piperidinyl, iV-morpholino

A^

Qy ο

r1

0

ό

Substrate

Product

XT

_ .

V—OAc

\

J

&

ll

Ν

R

AcO* \

A

ο

V

\ ^ O A c

ΰ

TABLE IV (cont.)

X R Η Η Η Me CI Η

32

(%) >85 >78 >85

139a

139

138

137

a-45-50 ^-10-15

—

Reference

% Yield

/. Oxidations with Lead Tetraacetate

43

a new approach to this type of transformation and a novel use for L T A acetoxylation. 140

(50%)

Several drawbacks to the acetoxylation procedure have been reported. F o r instance, in isolated cases, rearrangement occurs during the re­ action. ' ' A more c o m m o n problem involves the fact that enolization under the reaction conditions employed is not regiospecific a n d hence, 1 4 1

1 4 1 3

1 4 2

(ref. 141) (?) 1 3 7 1 3 8 1 3 9 1 3 9 a 1 4 0 1 4 1 1 4 1 8 1 4 2

(30%)

M. Stefonic, Z. Djarmati, and M. Gasic, Glas. Hem. Drus., Beograd. 37, 373 (1972). H. Moehrle, W. Haug, and E. Federolf, Arch. Pharm. (Weinheim) 306, 44 (1973). E. Ohler, F. Tataruch, and U. Schmidt, Chem. Ber. 106, 396 (1973). T. Kovao, M. Oklobdzija, V. Sunjic, and F. Kajfez, J. Heterocycl. Chem. 16, 1449 (1979). M. Lj. Mihailovic, J. Forsek, and Lj. Lorenc, J. Chem. Soc. Chem. Commun., 916 (1978). J. A. Marshall and G. L. Bundy, J. Chem. Soc. Chem. Commun., 500 (1966). H. Miura, Y. Fujimoto, and T. Tatsuno, Synthesis, 898 (1979). Μ. H. A. Elgamal, Β. A. H. El-Tawil, and Μ. Β. E. Fayez, Tetrahedron 30, 4083 (1974).

44

GEORGE Μ. RUBOTTOM

(ref. 142) (20%) regioisomers r e s u l t as well as the p r o d u c t i o n of d i a c e t a t e s . It was also discovered that rates of enolization d o not correspond to p r o d u c t ratios in acyclic c a s e s . Several efforts have been m a d e t o w a r d solving 1 4 3 , 1 4 4

1 4 4

1 4 4

1 Ο

Ο

:

1

(ref. 143)

Ο

Ο

(ref. 144) this problem. T h e use of e n a m i n e s , enol a c e t a t e s , silyl e t h e r s a p p e a r to offer the best alternatives. 1 4 5 - 1 5 2

1 4 4 , 1 5 3

a n d enol

1 5 4 - 1 5 6

1 4 3 1 4 4 1 4 5 1 4 6 1 4 7 1 4 8 1 4 9 1 5 0 1 5 0 a

G. A. Ellestad, R. H. Evans, Jr., and M. P. Kunstmann, Tetrahedron Lett., 497 (1971). S. Moon and H. Bohm, J. Org. Chem. 37, 4338 (1972). F. Corbani, B. Rindone, and C. Scolastico, Tetrahedron 31, 455 (1975). F. Corbani, B. Rindone, and C. Scolastico, Tetrahedron 29, 3253 (1973). F. Corbain, B. Rindone, and C. Scolastico, Tetrahedron Lett., 2597 (1972). S. K. Khetan, J. Chem. Soc. Chem. Commun., 917 (1972). P. L. Majumder, S. Joardar, and Τ. K. Chanda, Tetrahedron 34, 3341 (1978). M. Ohno, T. F. Spande, and B. Witkop, / . Am. Chem. Soc. 92, 343 (1970). Η. H. Eckhardt and H. Perst, Tetrahedron Lett., 2125 (1979).

/. Oxidations with Lead

Tetraacetate

45

The oxidation of enamines with L T A results in products consistent with diacetate intermediates and, in systems capable of i m i n e - e n a m i n e tautomerization, oxidation of the latter form p r e d o m i n a t e s . Although the wide 145 - 1 4 7

R \

1

/

R

2

LTA

RN

AcO OAc R—^C—C—R R N , Η 1

OAc R^O—
+

2

2

AcNRj

3

3

3

2

w

R

1

RN 3

OAc R

R^H—COR

2

NR|

2

range of products obtained generally precludes the use of the L T A oxidation of enamines for synthetic purposes, useful applications have been reported for 5 3 , 54, and for a series of e n a m i d e s . 1 4 8

1 4 9

1 5 0 - 1 5 2

Me0 C

MeO-C Η \ / C=C / \ PhHN C0 Me

2

2

LTA CH C1 2

C0 Me

W

MeO C

2

2

a

2

(ref. 148)

I

53

Ph MeO AcO

OMe LTA CH C1 2

2

(ref. 149) OH

OH C-3H/3 C-3H<* ,C0 Et 2

C-3H0, C-7 0Ac/3 (24%) C-3Ha, C—7 OAc a (22%) AcO

#

CO Et a

(ref. 150)

(ref. 150a)

46

GEORGE Μ. RUBOTTOM

(ref. 151)

(ref. 152)

Η

Η

(84%)

(100%)

Oxidation of enol a c e t a t e s ' and enol silyl e t h e r s gives high yields of the corresponding α-acetoxy derivatives. The several examples presented 1 4 4

1 5 3

1 5 4

(ref. 144)

(ref. 153)

1 5 1

1 5 2

1 5 3

R. B. Boar, J. F. McGhie, M. Robinson, D. H. R. Barton, D. C. Horwell, and R. V. Stick, J. Chem. Soc. Perkin Trans. 1, 1237 (1975). R. B. Boar, J. F. McGhie, M. Robinson, and D. H. R. Barton, /. Chem. Soc. Perkin Trans. 7, 1242 (1975). K. Oka and S. Hara, J. Am. Chem. Soc. 99, 3859 (1977).

/. Oxidations with Lead OSi(Me) A

Tetraacetate

47

LTA

3

. / ^ As

—

A r ^ ^°

b G n Z e n e

lr

CA

C

(ref. 154)

(91-95%)

are illustrative. With enol silyl ethers the use of lead(IV) benzoate (LTB) is to be r e c o m m e n d e d . In general, the reaction of both enol acetates and enol silyl ethers can be carried out at ambient temperatures, another 1 5 5 , 1 5 6

9Si(Me)

Ο

8

1. LTB/CH C1 2

J-L^OBz 2

2. EtgNHF

^ s / ^ (80%)

OSi(Me)

1. LTB/CH C1 2. EtgNHF 2

c!!x.

O B Z

s

2

(92%)

advantage of the method. Isolation of intermediates such as 5 5

1 5 4

and 5 6

3 5

point to a normal alkene addition process in the L T A reaction with enol (Me)gSiO^ ^OAc

I CI 55

1 5 4 1 5 5 1 5 6

(Me) SiO^ 3

OAc

Ac 56

G. M. Rubottom, J. M. Gruber, and K. Kincaid, Synth. Commun. 6, 59 (1976). G. M. Rubottom, J. M. Gruber, and G. M. Mong, J. Org. Chem. 41, 1673 (1976). G. M. Rubottom and J. M. Gruber, J. Org. Chem. 42, 1051 (1977).

48

GEORGE Μ. RUBOTTOM

silyl ethers. The treatment of trimethylsiloxy-l,3-dienes with LTB is also a OSi(Me)

3

OBz

1. LTB/CH. 2. EtsNHF (91%)

(ref. 156) OSi(Me)

3

1. LTB/CH C1 2

2

2. EtsNHF

OBz (54%)

high yield process; however, certain cyclic cases afford products rationalized by 1 , 4 - a d d i t i o n . 156

OSi(Me)

2

f^jl

OBz

1. L I B / C H ^ l , 2. EtjNHF

OBz (55%) 1. BzO" 2. EtjNHF

OSi(Me)

s

(ref. 156)

OSi(Me)

(OBz), OCOPh

Vinyl ethers undergo L T A oxidation in a manner similar to that of enol silyl ethers. Such a system has been i m p l i c a t e d in the conversion of 5 7 to 5 8 . ' ' The analogous systems 5 9 and 6 0 also afford high yields of oxidation p r o d u c t . 136

1 3 6

1 5 7

1 5 7 a

1 5 8

1 5 7 1 5 7 a 1 5 8

W. Slaunwhite and A. Solo, / . Pharm. Sci. 64, 168 (1975). M. Hossain and D. N. Kirk, Steroids 34, 677 (1979). G. R. Lenz, J. Chem. Soc. Chem. Commun., 241 (1978).

/. Oxidations

with Lead

Tetraacetate

49 OR

(refs. 136, 157, 157a) R= Ac or Η OH

(ref. 158)

60

Systems in which enol formation is directed are also useful in solving the problem of regioselectivity. The treatment of jS-keto sulfides with L T A in hot benzene produces α-acetoxy-a-phenylthioketones in excellent yield. ' ' The latter represent a versatile class of synthetic intermediates. 1 5 9

1

1 6 0

1 6 0 3

Β. M. Trost and A. J. Bridges, J. Am. Chem. Soc. 98, 5017 (1976). Β. M. Trost and G. S. Massiot, J. Am. Chem. Soc. 99, 4405 (1977). Β. M. Trost, W. C. Vladuchick, and A. J. Bridges, J. Am. Chem. Soc. 102, 3554 (1980).

50

GEORGE Μ. RUBOTTOM

(ref. 160)

(90%)

Enol thioethers react with L T A to give thionium ions which then partition to produce allylic acetates and/or bis-acetoxylation p r o d u c t s . The for­ mation of the allylic acetates is favored in T H F whereas methylene chloride 1 6 1

favors diacetate formation. Also, treatment of the latter with boron trifluoride etherate or 5 Ν K O H leads to excellent yields of the corresponding allylic acetates. The reaction of 61 to 6 2 indicates that isomerization of the

1 6 1

Β. M. Trost and Y. Tanigawa, / . Am. Chem. Soc. 101, 4413 (1979).

/. Oxidations with Lead

Tetraacetate

51

kinetically formed 6 3 to the thermodynamieally more stable 6 2 is occur­ ring. Alkyl-substituted ketene thioacetals also react with L T A . 1 6 1

1 6 1 a > 1 6 1 b

SPh

SPh

\ J\ η

SPh . OAc

AcO^

(\J

=1,2

1 (V_y

62

63

In this case oxidation affords the corresponding 3-alkyl-l,4-dithiepan-2-ones in moderate yield.

c S

R

/ S

LTA ^ benzene

Γ r~K^P \

1 ^ S ^ R

(ref. 161a)

(34-74%)

The oxidation of 1,3-diones leads not only to the production of a-acetoxy derivatives, but to 1,2-diones as w e l l . ' Use of C - l a b e l i n g studies shows that to a large extent the carbon flanked by the two carbonyls is the one expelled and intermediates such as 6 4 have been i m p l i c a t e d . The 1 6 2

1 6 3

14

162

O

OPb(OAc)

3

Ar^^j^^Ar R 64

R = H,OAc

picture is not complete since 6 5 and 6 6 do not give similar results and loss ?

H

αΛΛατ 65

/

Ο

Ο

LTA H0Ac

Jy*

+

°

\

(JUL) DAc 66 1 6 1 8 1 6 1 b 1 6 2 1 6 3

K. Hiroi and S. Sato, Chem. Lett., 923 (1979). K. Hiroi, S. Sato, and K. Matsuo, Heterocycles 12, 213 (1979). K. Kurosawa and A. Moriyama, Bull. Chem. Soc. Jpn. 47, 2717 (1974). K. Ezoe and K. Kurosawa, Bull. Chem. Soc. Jpn. 50, 443 (1977).

ArC0 H 2

(ref. 162)

52

GEORGE Μ. RUBOTTOM

(ref. 163)

of C is not total. A n intermediate analogous to 6 4 may also be involved in the oxidation of l-phenylheptane-l,3,4,6-tetrone to give 6 7 and 6 8 . 1 4

1 6 4

(ref. 164)

67 68

R = Ph, R' = Me (43%) R = Me, R' = Ph (14%)

Another example of an interesting L T A reaction with a 1,3-dione involves the oxidation of h u m u l o n e to give T C D . Although the T C D structure shown is favored, 6 9 is also possible, whereas 7 0 , a previously postulated structure, is ruled out by spectral data. The mechanism of the transformation is not clear at present. 1 6 5

(ref. 165)

TCD (Tricyclodehydroisohumulone)

M. Poje, B. Gaspert, and K. Balenovic, Reel. Trav. Chim. Pays-Bos 97, 242 (1978). L. De Taeye, D. De Keukeleire, A. De Bruyn, and M. Verzele, Bull. Soc. Chim. Belg. 87, 471 (1978).

/. Oxidations with Lead

53

Tetraacetate

Both acyclic and cyclic 1,3-diones react with aryllead(IV) tricarboxylates to produce the corresponding arylated d e r i v a t i v e s . The examples cited are representative of the method. 165a

Me ArPb(OAc) CHCVpy (CH ) 2

3

(ref. 165a)

rt

MeCOCHXOMe

ArPb(OAc) CHCL/py

3

-MeCOCHCOMe

L

Nonenolizable 1,2-diones are cleaved by L T A in benzene. In rigid systems, anhydrides are obtained in high yield, and when a solvent mixture of 1:1 benzene: methanol is employed, diesters are formed. The latter oxidation is postulated to occur from the corresponding h e m i k e t a l . The oxidation of 166

MeO-C LTA benzene

(91%)

CO,Me

LTA benzene MeOH

(ref. 166) (85%)

the nonenolizable ketone 7 1 gives a 55% yield of 7 2 and the reaction is rationalized by involving carbonium ion i n t e r m e d i a t e s . 167

1 6 5 a 1 6 6 1 6 7

J. T. Pinhey and B. A. Rowe, Aust. J. Chem. 32, 1561 (1979). L. Canonica, B. Danieli, P. Manitto, and G. Russo, Gazz. Chim. Ital. 100, 1026 (1970). H. Miura, K. Hirao, and O. Yonemitsu, Tetrahedron 34, 1805 (1978).

54

GEORGE Μ. RUBOTTOM

LTA HOAc N^-O^Pb(OAc) OAc

71

C0 Ac

s

2

(ref. 167)

Ο 72

(55%)

Nonenolizable thioearbonyl derivatives also react with L T A and generally yield the corresponding carbonyl c o m p o u n d . With sugar derivatives, 1 6 8 - 1 7 0

PIT

^Ph

(ref. 168)

1. LTA/HOAc 2. H 0 2

Ph*

σ TO .o^

α°τ Ό

.ο

Ο

(ref. 169)

(62%)

S

Ο

A

λ 0 \

Ph

(T^o (ref. 170) \ / R production of disulfides can subvert the reaction and trithiocarbonates lead to 7 3 . Finally, the selenocarbonyl c o m p o u n d 7 4 is reported to give a high /

X

0 ^

LTA HOAc

1 7 0

ΜR 73

/. Oxidations with Lead Tetraacetate yield of 7 5 with 7 6 postulated as an i n t e r m e d i a t e .

55

171

LTA HOAc

s

74

Se /

75 (87%)

76

+

I

S

W>V (4%)

(ref. 171) D. PHENOLS

Phenols react readily with L T A , usually in acetic acid, to give excellent yields of the corresponding acetoxy cyclohexadienones. Although h o m o 12

LTA

lytic pathways were originally postulated for the r e a c t i o n , more recent work favors either heterolysis of 7 7 or electrophilic attack by the phenol 12

1 7 2

Pb(OAc) OAc

77

2

78

on L T A . Concerted transfer of acetate from lead to carbon (78) can account for the generally encountered predominance of α-acetoxylation and is analogous to the mechanism proposed for enol o x i d a t i o n . The systems 7 9 - 8 1 are some typical e x a m p l e s . 1 7 3

174

1 7 5 - 1 7 7

1 6 8 1 6 9 1 7 0 1 7 1 1 7 2 1 7 3 1 7 4

1 7 5 1 7 6 1 7 7

J. W. Lown and T. W. Maloney, J. Org. Chem. 35, 1716 (1970). M. Mori and T. Taguchi, Synthesis, 469 (1975). W. M. Doane, B. S. Shasha, C. R. Russell, and C. E. Rist, J. Org. Chem. 30, 3071 (1965). S. Tamagaki, S. Sakaki, and S. Oae, Heterocycles 2, 45 (1974). M. J. Harrison and R. O. C. Norman, / . Chem. Soc. C, 728 (1970). W. A. Bubb and S. Sternhell, Tetrahedron Lett., 4499 (1970). A. Lethbridge, R. O. C. Norman, and C. B. Thomas, J. Chem. Soc. Perkin Trans. 1, 2465 (1975). J. R. van der Veck, H. Steinberg, and Th. J. de Boer, Tetrahedron Lett., 2157 (1970). R. J. Andersen and D. J. Faulkner, J. Am. Chem. Soc. 97, 936 (1975). J. B. Henderson, R. W. Alder, D. R. Dalton, and D. G. Hey, J. Org. Chem. 34, 2667 (1969).

56

GEORGE Μ. RUBOTTOM

79 (50%)

80 (75%)

81 (62%)

(ref. 175)

(ref. 176)

(ref. 177)

The application of the reaction to the synthesis of a wide range of isoquinoline alkaloids has been r e v i e w e d . In general, tetrahydroisoquinolinols of type 8 2 give /j-quinol acetates, while type 8 3 gave 4-aeetoxytetra178

OAc

R

R

82

(-20%) (ref. 178) OAc LTA

ΜβΟ-^^γ^^Μβ

C H a C l 2

MeO

R 83

hydroisoquinolinols. Intermediate 8 4 has been implicated in the latter HO ^Me OAc

MeO 84

case. A third m o d e of behavior has recently been discovered, demon­ strated by the 8 5 to 8 6 t r a n s f o r m a t i o n . A mechanism has been proposed 1 7 8

179

1 7 8

1 7 9

B. Umezawa and O. Hoshino, Heterocycles 3, 1005 (1975). H. Hara, M. Hosaka, O. Hoshino, and B. Umezawa, Tetrahedron Lett., 3809 (1978).

/. Oxidations

with Lead

Tetraacetate

57

involving cleavage of a /7-quinol acetate to produce 8 7 which then recyclizes to give 8 6 . OAc HO

X J Q C ~*

MeO

85

(ref. 179)

L T A oxidation of phenols carried out in the presence of alcohols gives rise to the production of a l k o x y d i e n o n e s . Whereas this reaction has been used as evidence against a homolytic mechanism for the oxidation, it is n o t clear whether the actual oxidizing agent is L T A or a mixed Pb(IV) species resulting from a l c o h o l - L T A ligand e x c h a n g e . T h e oxidation of pentafluorophenol with L T A gives a 75% yield of 8 8 and 8 9 in a reaction where n o acetoxy products are r e p o r t e d . W h e n a phenol is treated with L T A using 1 7 2 , 1 7 4

175

1 8 0

(ref. 180)

a carboxylic acid can be effectively examples involve conjunction with

0

1

other than acetic acid as solvent, the external nucleophile incorporated into the oxidation product. T w o interesting the reactions of mesitol and 9 0 , respectively, with L T A in acrylic acid as s o l v e n t . 181

L. S. Kobrina, V. N. Kovtonyuk, and G. G. Yakobson, Zh. Org. Khim. 13, 1447 (1977). D. J. Bichan and P. Yates, Can. J. Chem. 53, 2054 (1975).

58

GEORGE Μ. RUBOTTOM

f

CCLH

Ρ

•JL

Δ

Ό (41%)

+ />-isomer

(ref. 181)

X0 H

ί

2

+ p- isomer + o, o-disubstituted product

nI—ο

(23%)

The oxidation of 9 1 with L T A in acetic acid gives 9 2 as the major p r o ­ duct with no apparent interaction with the remote double bond. 1 7 4 , 1 8 2

OG

LTA HOAc

Ρ OAc

(refs. 174, 182)

92

91

However, with c h a l c o n e s , 2-hydroxybenzophenones, 2-hydroxystilbenes, and 3-(2-hydroxphenyl)coumarins treatment with L T A leads 183

1 8 5

1 8 2

1 8 3

1 8 4

184

186

E. Zibral, W. Wessely, and J. Jorg, Monatsh. Chem. 92, 654 (1961). K. Kurosawa and J. Higuchi, Bull. Chem. Soc. Jpn. 45, 1132 (1972). K. Kurosawa, Y. Sasaki, and M. Ikeda, Bull. Chem. Soc. Jpn. 46, 1498 (1973).

/. Oxidations

with Lead Tetraacetate

LTA HOAc

LTA HOAc

1 8 5

1 8 6

59

(ref. 183)

(ref.f. 184) 184)

LTA benzene or HOAc

(ref. 185)

LTA benzene

(ref. 186)

Κ. Nogami and Κ. Kurosawa, Bull. Chem. Soc. Jpn. 47, 505 (1974). K. Kurosawa and K. Nogami, Bull. Chem. Soc. Jpn. 49, 1955 (1976).

60

GEORGE Μ. RUBOTTOM

to oxidative cyclization. The presence of methoxy groups on the phenolic substrate can lead to predominant formation of q u i n o n e s . T h e use of 1 8 7

(ref. 187)

(31%)

acetic acid enhances the process whereas benzene can lead to other reaction pathways. ' Treatment of 9 3 with 2 equivalents of L T A in benzene 1 8 8

1 8 9

ο

OMe

(refs. 188, 189)

t-Bu 94

gives further oxidation (via 94) to afford 9 5 , 9 6 , and 9 7 . The presence of water in the benzene accounts for the production of 9 6 and 9 7 , and thus, a coherent mechanism is p r e s e n t e d . Finally, the reaction of phenols with aryl lead(IV) triacetates in chloroform/pyridine produces moderate yields of o- or /?-dienones with n o acetoxylation o c c u r r i n g . With 1 8 8 - 1 9 0

1 8 8 , 1 9 0

1 9 1 , 1 9 1 3

1 8 7 1 8 8

1 8 9 1 9 0

1 9 1 1 9 1 8

F. R. Hewgill and S. L. Lee, J. Chem. Soc. C, 1556 (1968). F. R. Hewgill, D. G. Hewitt, G. B. Howie, C. L. Raston, R. J. Webb, and A. H. White, J. Chem. Soc. Perkin Trans. 1, 290 (1979). F. R. Hewgill and D. G. Hewitt, J. Chem. Soc. C, 726 (1967). F. R. Hewgill and D. G. Hewitt, G. B. Howie, and W. L. Spencer, Aust. J. Chem. 30, 1971 (1977). H. C. Bell, G. L. May, J. T. Pinhey, and S. Sternhell, Tetrahedron Lett., 4303 (1976). H. C. Bell, J. T. Pinhey, and S. Sternhell, Aust. J. Chem. 32, 1551 (1979).

/. Oxidations

93

LTA benzene

94

with Lead

MeO

LTA benzene

61

Tetraacetate

f-Bu

(refs. 188, 189)

i-Bu 95

t-Bu

(refs. 188, 190)

MeO + (Z, Z)-isomer 97

f-Bu 96

methylated phenols, the yields are highest when both ortho positions are substituted and the reaction fails when the phenol in question bears only electron-withdrawing g r o u p s . 1 9 1 3

ArPb(OAc)

s

CHCVPY

(refs. 191, 191a) E. MONOCARBOXYLIC ACIDS

T h e reaction of monocarboxylic acids with L T A has been studied ex­ tensively and an excellent review of the topic is a v a i l a b l e . A general consensus as to mechanism exists as outlined below in Scheme 3 . 192

1 9 2

Pb(IV)(OAc) . (OCOR)

Metathesis:

RC0 H + LTA

Initiation:

Pb(IV)OCOR

Propagation:

R. + Pb(lV)(OCOR)

4 n

2

Δ or hv

Pb(m)(OCOR) Termination:

•

*-R

+

+ Pb(m)(OCOR)

Pb(H) + R- + C 0 •

R

+

2

+ Pb(n)(OCOR)

hydrogen abstraction; dimerization; etc. SCHEME 3

1 9 2

+ HOAc

Pb(m) + R · + COa

R* + Pb(m)(OCOR) R*

n

R. A. Sheldon and J. K. Kochi, Org. React. 19, 279 (1972).

62

GEORGE Μ. RUBOTTOM

Product formation can thus occur from either R- or R leading to the formation of alkanes, alkenes, and acetates. The structure of the carboxylic acid is crucial to the outcome of the reaction since oxidation rates of primary, secondary, and tertiary R · vary considerably with tertiary R · being oxidized most rapidly to R . Addition of C u ( X ) (X is normally OAc) with both primary and secondary carboxylic acids, gives enhanced rates of R · oxida­ tion with concomitant proton loss and thus, high yields of alkenes. Actual rates of oxidation of primary radicals with Cu(II) approach diffusion +

+

2

R- (1° or 2°) + Cu(II) -> R ( - H ) + H + Cu(I) Cu(I) + Pb(IV) -> Cu(II) + Pb(III) +

control whereas secondary radicals are oxidized at least 100 times faster by Cu(II) than by P b ( I V ) . As noted, the Cu(II) can be used in catalytic amounts since efficient Cu(I) to Cu(II) oxidation is accomplished by Pb(IV). Because tertiary R · is oxidized by Pb(IV), addition of C u ( O A c ) to reactions involving tertiary acids generally has little effect. Solvents such as H M P A , T H F , and D M F in conjunction with pyridine are employed most commonly and are, in general, to be preferred over benzene, acetonitrile, or ethyl a c e t a t e . 1 9 2

2

1 9 2

1. PRIMARY A C I D S

In the presence of pyridine the Pb(IV)/Cu(II) reagent has been used to degrade steroidal acids to give excellent yields of the corresponding al­ kenes, ' and a similar procedure gave 9 8 , an intermediate in the 1 9 3

1 9 4

LTA/Δ ^

C u ( O A c ) z

py

synthesis of prostaglandin E , t

1 9 5

X)

2

e

VV\A/°^

(refs. 193, 194)

Extending the L T A / C u ( O A c ) method to 2

(CH ) CO Me H (

^

J

(CH ) CO Me

a

2

e

a

^"νΛ/V \-/ l 0

LTA/Cu(OAc) /^ LTA/Cu(OAc) /ftj> 2

2


98 (37%) 1 9 3

1 9 4

1 9 5

J. Meney, Y.-H. Kim, R. Stevenson, and Τ. N. Margulis, Tetrahedron 29, 21 (1973). J. F. W. Keana and R. R. Schumaker, J. Org. Chem. 41, 3840 (1976). D . Taub, R. D. Hoffsommer, C. H. Kuo, H. L. Slates, Z. S. Zelawski, and N. L. Wendler, Tetrahedron 29, 1447 (1973).

/. Oxidations with Lead

63

Tetraacetate

include jS-carboxy ketones gives a useful synthesis of a,/?-unsaturated ketones. ' Model studies indicate that the procedure has general syn1 9 6

1 9 7

(ref. 196)

CO.H LTA/Cu(OAc) benzene/py

2

(ref. 197)

(92%)

thetic potential. The variety of c o m p o u n d s available from 9 9 is i l l u s t r a t i v e . CO-H

1. Li/NH3(97%) 2. LTA/Οu(OAc),

197

Γ^Ψ^Ν

benzene/py Η LTA/Cu(OAc) benzene/py

(89%)

2

1. H /Pd-C (97%) 2. LTA/Cu(OAc) benzene/py 2

2

(ref. 197)

Η (88%)

(92%)

The oxidation of β-carboxy lactones with L T A / C u ( O A c ) gives rise to the corresponding α-methylene l a c t o n e s . 2

198

1 9 6 1 9 7 1 9 8

P. P. Sane, K. J. Divakar, and A. S. Rao, Synthesis, 541 (1973). J. E. Mc Murry and L. C. Blaszczak, J. Org. Chem. 39, 2217 (1974). K. J. Divakar, P. P. Sane, and A. S. Rao, Tetrahedron Lett., 399 (1974).

GEORGE Μ. RUBOTTOM

64

LTA Cu(OAc) py

CO H a

ocx

2

(30%)

(ref. 198) C0 H 2

LTA Cu(OAc) py

2

Decarboxylation of 5-(r-naphthyl)-pentanoic acid with L T A in benzene gives a mixture of tetrahydrophenanthrene and 1 0 0 in overall yields of 58%. Deuteration studies indicate that the primary radical formed in 1 9 9 , 2 0 0

CO,H 2

LTA benzene 100 (4.5%)

(53.5%)

(refs. 199, 200) the reaction gives tetrahydrophenanthrene via competitive formation of both 101 and 1 0 2 .

102

In a related case, 1 0 3 affords 20% of the cyclic product 1 0 4 , and 4-pentonic acid has been found to yield substituted γ-lactones when treated with either L T A or LTA/LiCl m i x t u r e s . 2 0 1

37

LTA/Cu(OAc) benzene/py

2

(ref. 201)

CO,H 103

104

(20%)

/. Oxidations

with Lead

Tetraacetate

65

2. SECONDARY ACIDS

The L T A / C u ( O A c ) decarboxylation of 105 in benzene/pyridine is opti­ mized by removal of acetic acid from the L T A prior to the reaction. In this manner, a 35% yield of 1 0 6 was r e a l i z e d . Decarboxylation of 107 is 2

202

(ref. 202)

(minor product isolated as phenol)

accomplished in high yield in the presence of H O A c / K O A c .

(ref. 202a)

(65%)

L T A oxidation of 108 in benzene/pyridine produces a n u m b e r of products including alkenoic acids, acetates, a n d lactones from selective loss of the secondary carboxy group over the p r i m a r y . Addition of C u ( O A c ) 2 0 3 , 2 0 4

2

COH 2

R—CH —CH(CH ) C0 H 2

2 N

2

108

1 9 9 2 0 0 2 0 1 2 0 2

2 0 2 8 2 0 3

2 0 4

J. C. Chottard and M. Julia, Tetrahedron Lett., 2561 (1971). J. C. Chottard and M. Julia, Tetrahedron 28, 5615 (1972). C. Descoins, M. Julia, and Η. V. Sang, Bull. Soc. Chim. Fr., 2037 (1972). R. L. Petty, M. Ikeda, G. E. Samuelson, C. J. Boriack, K. D. Onan, A. T. McPhail, and J. Meinwald, J. Am. Chem. Soc. 100, 2464 (1978). M. Cushman and F. W. Dekow, J. Org. Chem. 44, 407 (1979). Yu. N. Ogibin, Μ. I. Katsin, and G. I. Nikishin, Izv. Akad. Nauk SSSR, Ser. Khim., 1345 (1975). Yu. N. Ogibin, Μ. I. Katsin, and G. I. Nikishin, Izv. Akad. Nauk SSSR, Ser. Khim., 1225 (1972).

66

GEORGE Μ. RUBOTTOM

subverts acetate and lactone formation thereby giving alkenoic acids as the major products. There is a preference for alkene formation occurring away from the primary carboxy group a n d varying the nature of X in C u X has little effect u p o n product r a t i o s . Decarboxylation of 1 0 9 , regardless of the C u X used, gave mixtures of alkenes, again favoring the structure with the double bond placement farthest from the O A c g r o u p . 2

2 0 4

2

2 0 5

COH I 2

AcO(CH ) CHCH CH3 2 N

2

109

Selectivity between carboxy groups was also noted in the oxidation of 110. The stereochemical relationship of the carboxy groups is crucial 2 0 6

HOC S

Η

,

Η LTA/Cu(OAc), benzene/py

iv-A.

/

(ref. 206)

C0 H 2

110

since 111 gives 1 1 2 in 30% yield along with several other products. The latter COH 2

T

LTA/Cu(OAc)

a

benzene/py

(ref. 206)

CO H z

111

112 (30%)

case is a unique example of a secondary carboxyl decarboxylation in pre­ ference to a tertiary. It is not clear what role steric crowding might play in the ability of the two diacids to undergo a ligand exchange reaction with L T A , and thus affect decarboxylation rates. L T A decarboxylation of secondary acids in the absence of C u ( O A c ) can lead to the production of moderate to good yields of the corresponding acetates. Table V summarizes some typical e x a m p l e s . " 2

2 0 7

5

6

17 8

2 1 2

Μ. I. Katsin, Yu. N. Ogibin, and G. I. Nikishin, Izv. Akad. Νauk SSSR, Ser. Khim, 139 (1974). P. K. Jadhav, V. S. Dalavoy, A. S. C. Prakasa Rao, and U. R. Nayak, Indian J. Chem. Sect. Β 15, 589 (1977). Μ. Fetizon, F. J. Kakis, and V. Ignatiadou-Ragoussis, Tetrahedron 30, 3981 (1974). J. B. Lambert, F. R. Koeng, and J. W. Hamersma, J. Org. Chem. 36, 2941 (1971).

2

2

\θ Η

0s

<>

2

C0 H

<>

C0 H

AcO"

AcO'

2

>

Λ 2

\^ C 0 H

>

>_-C0 H

Substrate

Solvent

Benzene/py

Benzene/py

Benzene/py

Benzene/py

^L-OAc

κ

<

(sole product)

yr

-

1

OAc

^—

I

OAc

\^OAc

5 t5

0

I ^

\ ^

\^OAc

Product

DECARBOXYLATION OF SECONDARY CARBOXYLIC ACIDS

Benzene/py

LTA

TABLE V

—

73

66

45

% Yield

(cont.)

209

208

208

207

207

Reference

2

TsN^*

AcO'

h

2

a

J

ή

^\L*CO Me

C0 H

Η

3 1

\

/

NTS

—^^co k 1 :

xNTs /

Substrate

Benzene/py

Benzene/py

Py

Py

Solvent

I

TsN OAc

(-)

+ (-)

a

^CO Me

c)Ac

.I^COaMe

^OAc

^OAc

(isolated as 3/?-alcohol

+

ΛϊΤβ

:

.NTs

(60%)

} :

c

Product

TABLE V {com.)

35 90:10, exorendo

( + 16% alkene)

>47

18 (+14% alkene)

% Yield

212

211

210

210

Reference

/. Oxidations

with Lead

69

Tetraacetate

Perusal of Table V indicates that the decarboxylation of secondary acids is not a stereospecific process. A n u m b e r of examples are accommodated by the intervention of c a r b o n i u m ion intermediates, i.e., the conversions of 113 and 1 1 4 . The reaction of system 1 1 5 is not so clear-cut since, in 2 1 3

2 1 3 a

LTA benzene/py

OAc

(ref. 213)

(CH )

2 ;

η = 4,5,6

113

AcO

(ref. 213a) Sole product

the absence of a carbonyl group, mixtures of both rearranged and unrearranged products result with the latter p r e d o m i n a t i n g . T h e fact that 214

(81%)

(4.9%)

(4.9%) (ref. 214)

b o t h epimers 1 1 6 and 117 give identical mixtures of axial a n d equatorial acetates and that erythro- and threo-HS give equivalent a m o u n t s of erythroand threo-119 has been cited as evidence for cationic intermediates as

2 0 9 2 1 0 2 1 1 2 1 2 2 1 3 2 1 3 a 2 1 4

P. K. Freeman, D. M. Balls, and J. N. Blazevich, J. Am. Chem. Soc. 92, 2051 (1970). Th. Reints Bok and W. N. Speckamp, Tetrahedron 35, 267 (1979). P. Rosen and G. Oliva, /. Org. Chem. 38, 3040 (1973). R. D. Gleim and L. A. Spurlock, J. Org. Chem. 41, 1313 (1976). Y. Sakai, S. Toyotani, Y. Tobe, and Y. Odaira, Tetrahedron Lett., 3855 (1979). R. L. Cargill and A. M. Foster, J. Org. Chem. 35, 1971 (1970). A. L. J. Beckwith, G. E. Gream, and D. L. Struble, Aust. J. Chem. 25, 1081 (1972)

70

GEORGE Μ. RUBOTTOM OAc LTA benzene/py

< L

CO,H

> J

LTA benzene/py

(refs. 36,215)

ι f~Bu (53%) cis -Acetate (47%) trans -Acetate

' W"""' " ' OAc <«r. 2, /P

(erythro- or threo -118)

63 :37, erythro-: tareo -119

6)

3 6 , 2 1 5 , 2 1 6 Decarboxylation of both 120 and 121 in the presence of C u ( O A c ) in pyridine also yields similar a m o u n t s of cis- and /ra«s-alkenes, among other products. Therefore, a c o m m o n , nonstereospecifically gener­ ated carbonium ion intermediate is i m p l i c a t e d . The foregoing conclusions

W

E

L

L

2

217

Ph 120

LTA benzene/py

A

\

™ \ (29.9%)

Ph

Q

A

t

—OAc

c

(3.5%)

C0 H 2

121

cannot be extrapolated to a number of examples of L T A decarboxylation involving bicyclic systems. Extensive studies of the L T A reactions of a series of bicyclic acids lead to a more complex view of the oxidation p r o c e s s . Initial decarboxylation of Pb(IV) carboxylates generates secondary radicals that can participate in typical radical reactions. Secondary radicals can also couple with Pb(III) or Pb(IV) carboxylates to give Pb(IV) alkyls. Heterolysis leads to carbonium ions, products of cis elimination, or the S i production 2 1 8 _ 2 2 0 a

N

2 1 5

2 1 6 2 1 7 2 1 8 2 1 9 2 2 0 2 2 0 a

S. D. Elakovich and J. G. Traynham, J. Org. Chem. 38, 873 (1973). A. Theine and J. G. Traynham, J. Org. Chem. 39, 153 (1974). T. Shono, I. Nishiguchi, and R. Oda, Tetrahedron Lett., 373 (1970). G. E. Gream, C. F. Pincombe, and D. Wege, Aust. J. Chem. 27, 603 (1974). J. B. Stothers and K. C. Teo, Can. J. Chem. 54, 1222 (1976). B. C. C. Cantello, J. M. Mellor, and G. Scholes, J. Chem. Soc. Perkin Trans. 2, 348 (1974). P. K. Jadhav and U. R. Nayak, Indian J. Chem. Sect, Β 16, 947 (1978).

/. Oxidations

R

R

1

C0 H Η C0 H Me Η Η Me Me Η Η Me Me

R

2

Η C0 H Me C0 H Η Η Η Η Me Me Me Me

2

Η Η Me Me Η C0 Η C0 Η C0 C0 Η

2

2

2

3

2

H

2

H

2 2

H H

with Lead

R Η Η Me Me C0 Η C0 Η C0 Η Η C0

4

2

H

2

H

2

H

2

H

R

Tetraacetate

5

Η Η Η Η Me Me Η Η Η Η Η Η

R

R

6

Η Η Η Η Me Me Η Η Η Η Η Η

71

Reference

7

Η Η Η Η Me Me Η Η Η Η Η Η

218 218 218 218 218 218 219 219 219, 220 219, 220 220a 220a

of esters. Initially formed radicals, in the presence of Cu(II), give Cu(II) derivatives that, in turn, lead to Cu(II) alkyls. T h e Cu(II) alkyls then give products by heterolysis, elimination, and substitution via S i or ligand exchange p a t h w a y s . T h e high yield production of 122 from either longifolic acid, 1 2 3 , or its epimer, indicates that ring formation can be a consequence of L T A - p r o m o t e d decarboxylation as w e l l . Even in acyclic cases the nature of the reaction can be complex. F o r instance, the L T A N

2 1 8

2 2 0 a

^CO H 2

LTA/ Cu(OAc)

LTA Cu(OAc)

2

123

2

UCQ H 2

benzene/py (69%)

benzene/py (74%) 122

(ref. 220a)

72

GEORGE Μ. RUBOTTOM

oxidation of 2,3,3-trimethylbutanoic acid, in the presence or absence of C u X , gives inordinate a m o u n t s of b o t h substitution and elimination p r o ­ ducts in which the carbon skeleton has not rearranged, thus militating against free cationic i n t e r m e d i a t e s . It should be noted that treatment of (£)-( +)-2-methylbutanoic acid with L T A in the presence of cinnamic acid gives (JF)-3-methyl-l -phenyl-1 -pentene via free radical i n t e r m e d i a t e s . The product is racemic and substitution of 2

221

222

COH 2

Μ Me

I

T

«

H

χ

+

^^/C0 H

^ benzene/py" L

2

Et

T

A

^x^CHMeEt

(ref. 222)

(34%)

cinnamic by /?-methoxycinnamic acid diverts the reaction and jS-acetoxy-/?methoxy styrene is formed as an i s / Z - m i x t u r e . 223

3. TERTIARY ACIDS The mechanistic parameters discussed above are also applicable to the reaction of L T A with tertiary carboxylic acids. As an example, the de­ carboxylations of both cis- and /ra«,y-decalin-9-earboxylic acids afford similar a m o u n t s of A ' - and A - o c t a l i n . Differences in product ratios engendered by C u X addition are lessened with tertiary acids due to the comparable oxidation rates of R · by Cu(II) and P b ( I V ) . 1

9

9,10

2

2 2 4

CO,H

CO

LTA/benzene

2.3

LTA/Cu(OAc) benzene

COH 2

CD

LTA/benzene LTA/Cu(OAc) benzene

CO 1.0

2

3.0

1.0

2

2.0 3.0

1.0 1.0

(ref. 224)

Η

The oxidation reaction generally leads to good yields of alkenes, but regioselectivity is not particularly high. Three examples of olefin formation 2 2 1 2 2 2 2 2 3 2 2 4

A. L. J, Beckwith, R. T. Cross, and G. Ε. Gream, Aust. J. Chem. 27, 1693 (1974). B. Danieli, P. Manitto, F. Ronchetti, and G. Russo, Chem. Ind. (London), 430 (1973). B. Danieli, F. Ronchetti, and G. Russo, Chem. Ind. (London), 1067 (1973). A. L. J. Beckwith, R. T. Cross, and G. Ε. Gream, Aust. J. Chem. 27, 1673 (1974).

/. Oxidations

with Lead Tetraacetate

with terpenoid acid derivatives are given b e l o w .

2 2 5

'

73

2 2 6

'

2 2 6

* Tertiary acids

LTA (68%) CH 2

3

CH3

1 (ref. 225)

OAc

OAc LTA benzene/py

(ref. 226)

H0 C 2

(61%)

(ref. 226a) Ζ= Ο .OH Ζ =

Ζ=Ο (67%) .OH (90%) Ζ=C

such as 1 2 4 that are structurally not able to give alkenes can give substitution products in excellent y i e l d . T h e acid 1 2 5 underwent decarboxylation 2 2 4

OAc

COH 2

124

2 2 5 2 2 6 2 2 6 8

LTA/benzene LTA/Cu(OAc) benzene

2

J. W. Huffman, / . Org. Chem. 35, 478 (1970). R. Caputo, L. Mangoni, L. Previtera, and R. Iaccarino, Tetrahedron 29, 2047 (1973). S. Amagaya, T. Takeda, Y. Ogihara, and K. Yamasaki, J. Chem. Soc. Perkin Trans. 1, 2044 (1979).

74

GEORGE Μ. RUBOTTOM

followed by cyclization during experiments conducted to obtain structural proof for 1 2 6 . Cyclization prior to decarboxylation was noted for L T A 1 8 1

(ref. 181)

126

treatment of acid 1 2 7 .

2 2 7

(ref. 227)

(50%)

An interesting decarboxylation involving 128 gave a mixture containing 1 2 9 , 1 3 0 , and 1 3 1 . These results are best rationalized by cyclization of an intermediate radical followed by oxidation leading to the products observed. 2 2 7 a

co Et 2

V 128

LTA Cu(OAc)

U 2

°

/\/C0 Et 2

129(22%)

130(11%)

131 (4%) (ref. 227a)

2 2 7

2 2 7 a

Y. Hayashi, T. Matsumoto, T. Hyono, N. Nishikawa, M. Uemura, M. Nishizawa, M. Togami, and T. Sakan, Tetrahedron Lett., 3311 (1979). M. Julia, J. M. Salard, and J. C. Chottard, Bull. Soc. Chim. Fr., 2478 (1973).

/. Oxidations

with Lead

Tetraacetate

75

4. α-SuBSTiTUTED ACIDS

Oxidation of α-hydroxy carboxylic acids is a high yield method for the production of ketones. One example of the usefulness of the reaction in the presence of multiple oxidizable functionality involves 1 3 2 . The mech2 2 8

COH 2

H NCONHCH CHOHCH < 2

132

2

2

Η

LTA HOAc/H O z

HoN

HN 2

(ref. 228)

anism of the decarboxylation has been i n v e s t i g a t e d and intermediates such as 1 3 3 p o s t u l a t e d . ' The catalysis of the reaction by bases, such as amines, water, and acetate ion, has been rationalized in terms of oxidant modification rather than by p r o t o n r e m o v a l . 2 2 9 - 2 3 2

2 3 0

2 3 1

2 3 2

R

> ^

yb(OAc)

2

133

α-Alkoxy acids also decarboxylate readily and the degradation of oligoglycosides represents a synthetically useful c a s e . Treatment of sodium 2 3 3

CO,H

AcO OR

OR

LTA benzene

MeO

(ref. 233)

OMe 45% a-OAc 42% /3-OAc 2 2 8 2 2 9

2 3 0 2 3 1

2 3 2 2 3 3

S. Harada, E. Mizuta, and T. Kishi, J. Am. Chem. Soc. 100, 4895 (1978). R. Shanker, S. K. Banerjee, and O. P. Sachdeo, Z. Naturforsch. B. Anorg. Chem., Org. Chem. 28, 375 (1973). Y. Pocker and B. C. Davis, /. Am. Chem. Soc. 95, 6216 (1973). K. Swaminathan, S. Sundaram, and N. Venkatasubramanian, Indian J. Chem. 13, 1163 (1975). Y. Pocker and B. C. Davis, J. Org. Chem. 40, 1625 (1975). I. Kitagawa, M. Yoshikawa, Y. Ikenishi, K. S. Im, and I. Yosioka, Tetrahedron Lett., 549 (1976).

76

GEORGE Μ. RUBOTTOM

glycidates with L T A gives moderate to high yields of the corresponding α-acetoxy a l d e h y d e s or k e t o n e s . Thermolysis of the latter leads to the 234

2 3 4 3

ο

,

OAc I — RWCCOR*

/ \ LTA/py R \ V \ .CO Na — γ γ benzene ^ z

(refs. 234, 234a)

(35-94%)

3

production of α,/J-unsaturated ketones, again in high y i e l d . Decar­ boxylation of 2-methyl-2-terf-butylperoxypropanoic acid has also been i n v e s t i g a t e d . The decomposition of 134 by L T A / C u ( O A c ) is a convenient method for alcohol regeneration in a sequence designed to obtain optically pure a l c o h o l . 2 3 4 3

235

2

2 3 6

OCOCOH 2

LTA Cu(OAc)

2

dioxane/py

\

A

cO/|

(ref. 236)

Oxidation of α-amino acids such as 7V,7V-dimethylglycine has been used as a degradative procedure for documenting biosynthetic p a t h w a y s . Some question as to the reliability of the method was r a i s e d , but control experiments seem to justify the a p p r o a c h . The method is also successful 2 3 7 , 2 3 8

238

2 3 7

HCl •

(ΘΗΛΝΘΗ,ΘΟ,Η

Τ ΦΑ

benzene

- H,CO + (CH,) NH + CO, 2

z

(refs. 237,238)

for the degradation of hippuric a c i d . Sequential treatment of oxazolin-5ones with hydroxide or acid and then L T A provides a general synthesis for both aldehydes and k e t o n e s . The preparation of 135 and 136 is illustrative. 2 3 9

2 4 0

2 3 4

234a

2 3 5 2 3 6 2 3 7

2 3 8 2 3 9 2 4 0

B. D. Kulkarni and A. S. Rao., Synthesis, 454 (1975). γ Reutrakul, S. Nimgirawath, S. Panichanun, and Y. Srikirin, Tetrahedron Lett., 1321 (1979). W. H. Richardson and W. C. Koskinen, J. Org. Chem. 41, 3188 (1976). J. G. Molotkovsky and L. D. Bergelson, Tetrahedron Lett., 4791 (1971). A. A. Liebman, B. P. Mundy, M. L. Rueppel, and H. Rapoport, J. Chem. Soc. Chem. Commun., 1022 (1972). E. Leete, J. Chem. Soc. Chem. Commun., 1524 (1971). E. Leete and S. A. Slattery, J. Am. Chem. Soc. 98, 6326 (1976). R. Lohmar and W. Steglich, Angew. Chem. Int. Ed. Engl. 17, 450 (1978).

/. Oxidations with Lead

11

Tetraacetate

1. *-BuOK/H 0 2. LTA/THF * HMPA (70%) 2

135

P-C H CI 6

4

(ref. 240)

1. 2N HC1 2. LTA/THF HMPA (61%)

"CHO

Ph 136

Two additional examples of α-amino acid oxidation involve the /Mactam 137 and the preparation of both cyclic and acyclic α-acetoxy nitrosamines from the corresponding nitrosoamino a c i d s . TV-Nitrosopipecolic acid 2 4 1

2 4 2 , 2 4 3

C0 H Ph

OAc -Ph

2

PhO-

LTA Cu(OAc)

PhO 2

(ref. 241)

benzene OMe

OMe (68%)

137

MjK X 0 H

LTA CH Cl /py 2

2

2

NO

cx S

N ' ^OAc NO

(35-44%) (refs. 242, 243) CHgNCH C0 H 2

NO

2

LTA CH Cl /py 2

2

CHsNCH OAc a

NO (37%)

1 2 3

A. K. Bose, M. Tsai, J. C. Kapur, and M. S. Manhas, Tetrahedron 29, 2355 (1973). J. E. Saavedra, J. Org. Chem. 44, 4511 (1979). J. Ε. Saavedra, Tetrahedron Lett., 1923 (1978).

78

GEORGE Μ. RUBOTTOM

affords a complex mixture of products in which the α-acetoxynitrosamine is accompanied by c o m p o u n d s derived from alkene formation. With the nitrosamine derivatives, the oxidation is materially enhanced by pyridine and inhibited by o x y g e n . 242

5. HALODECARBOXYLATION Perhaps the most useful modification of the L T A reaction with carboxylic acids involves carrying out the normal procedure in the presence of halide ion. In this m a n n e r excellent yields of the corresponding alkyl halide are produced. Table VI gives some representative e x a m p l e s ' " 2 0 9

2 1 0 , 2 1 2 , 2 4 4

2 5 0

TABLE VI LTA-HALIDE HALODECARBOXYLATION OF CARBOXYLIC ACIDS

Substrate

Conditions

; Yield

Product

244

LTA/LiCl CO,H

Reference

C

C1 CI

CO H a

43

LTA/LiCl/benzene

245

CI

CI

CI

CI

246

LTA/LiCl CI

C0 H 2

α

£1

C0 H 2

LTA/LiCl benzene/ether

65

247

46

248

Cl

H0 C 2

LTA/LiCl benzene

{cont.) 2 4 4

2 4 5

A. F. Thomas and M. Ozainne, J. Chem. Soc. Chem. Commun., 746 (1973). Η. K. Hall, Jr., C. D. Smith, E. P. Blanchard, Jr., S. C. Cherkofsky, and J. B. Sieja, J. Am. Chem. Soc. 93, 121 (1970).

/. Oxidations with Lead

Tetraacetate

79

TABLE VI (cont.) Substrate

Conditions

Product

% Yield

Reference

249

6 7 8 9 0

LTA/LiCl/benzene

210

1. LTA/benzene/py 2. 40% HC1

212

LT A/LiX/benzene

250

LTA/LiCl/benzene

209

Ε. N. Cain, Tetrahedron Lett., 1865 (1971). R. D. Miller and M. Schneider, Tetrahedron Lett., 1557 (1975). G. E. Gream, Aust. J. Chem. 25, 1051 (1972). Κ. B. Wiberg, G. A. Epling, and M. Jason, J. Am. Chem. Soc. 96, 912 (1974). R. R. Sauers, K. W. Kelly, and B. R. Sickles, J. Org. Chem. 37, 537 (1972).

80

GEORGE Μ. RUBOTTOM

and reference 192 includes many more. Another modification uses treatment of the acid with L T A followed by iodine a n d l i g h t . ' The mechanism 3 5 , 2 5 1

Μ

benzene

2 5 2

i / \ L

(

r e f

-

)

2 5 1

C0 H 9

(ref. 252) (56%)

LTA/I /fty ^ CCl^ 2

H0 C^\^\^^OAc 2

I^^^^^^^OAc

(ref. 35)

(82%)

of the halodecarboxylation process is rationalized in terms of rapid ligandtransfer oxidation of alkyl radicals by h a l o l e a d ( I V ) . Studies o n the 192

R- + Pb(IV)X

• RX + Pb(III)

stereochemistry of the reaction reveal that the reaction is nonstereospecific. ' ' ' Remote functionality can alter epimer ratios by polar 3 6

2 1 5

2 1 6

2 5 3 , 2 5 4

COH

ci

2

LTA/LiCl benzene HOAc

L

t-Bu

COH 2

LTA/LiCl benzene HOAc

J

t-Bu

t-Bu

x ν cis- chloride (33%) irims.chloride

P

{ /

/\θ Η 2

erythro threo

LTA/LiCl ^ benZGne

Ρ

> ζ /

/Λΐ

0 ( r e f s

' f

(ref 216)

1.43:1.00 threo: erythro 1.37:1.00 threo \ erythro

'

3 6

'

2 1 5

'

__

2 5 3 )

λ

/. Oxidations

with Lead Tetraacetate

81

effects as noted by comparing the products formed from 138 versus 1 3 9 .

A

CO H

CI

z

2 5 5

CI

Λ

LTA/LiCl benzene (60%)

138

64:35 (ref. 255)

C0 H

CI

2

CI

LTA/LiCl benzene (60%) 139

79:21

F. DICARBOXYLIC ACIDS

The bis-decarboxylation of 1,2-dicarboxylic acids by L T A , generally carried out in pyridine solvent, has proven to be an extremely useful method for the introduction of an alkene linkage, especially in cyclic systems. One example involves the preparation of 1,4-cyclohexadienes, c o m p o u n d s which are inaccessible by other standard methodology such as the Birch reduction of a r o m a t i c s . Yields are generally low, but the certainty of placement of 256

(ref. 256)

(35%)

the double bond makes the reaction attractive. Some additional cases, including examples of the synthesis of bridged polycyclic alkenes, are noted in Table V I I . References 12 and 192 contain many further examples. 2 5 6 - 2 6 4

2 5 1 2 5 2 2 5 3 2 5 4 2 5 5 2 5 6

J. J. Gajewski and L. T. Burka, J. Am. Chem. Soc. 94, 8860 (1972). L. A. Paquette, W. B. Farnham, and S. V. Ley., J. Am. Chem. Soc. 97, 7273 (1975). R. D. Stolow and T. W. Giants, Tetrahedron Lett., 695 (1971). See also reference 37. R. D. Stolow and T. W. Giants, J. Am. Chem. Soc. 93, 3536 (1971). F. Stoos and J. Rooek, / . Am. Chem. Soc. 94, 2719 (1972).

82

GEORGE Μ. RUBOTTOM TABLE VII LTA

B l S - D E C A R B O X Y L A T I O N OF 1 , 2 - D l C A R B O X Y L I C

Substrate

Solvent

Product

ACIDS

% Yield

DMSO/py

11

256

DMSO/py

30

256

Py

257

Benzene/py

32 12% Η at C-3 and C-6

1

Η Η Η D

R

2

Η Η Η Η

R

R

3

Η D Na Η

257a

257a

Benzene/py

R

Reference

1

Η Η Η D

R

2

Η Η Η Η

% yield

% Η at C-3 and C-6

35-42 41 14 38

10 8 9 9

DMSO/py

—

258

Dioxane/py

10

259

/. Oxidations

with Lead

Tetraacetate

83

TABLE VII (cont.) Substrate

Solvent

Product

45

260

Py

—

261

Benzene/py

36

262

30-40

263

Benzene/py/N

Z

Reference

DMSO/py or dioxane

Benzene/py

MeO C

% Yield

2

21

263a

25

263b

Py/0

2

31

Py/0

2

27 MeO C Z

264

84

GEORGE Μ. RUBOTTOM

The last entry in Table VII is illustrative of the fact that the presence of molecular oxygen often enhances the yields from the reaction. This same oxygen effect was also noted in the preparation of 140 from the corresponding dicarboxylic a c i d s . 2 6 5

140

R

R'

Η Η CH,

Η CH

(ref. 265) 3

Use of excess LTA, or the sequential treatment of the appropriate di­ carboxylic acid with L T A and a dehydrogenation agent, affords a method for the preparation of substituted aromatic systems I 4 i - i 4 4 . ~ Several reports have appeared concerning the preparation of acenaphthylene 2 6 6

C0 H 2

^CO H

X

2

1. LTA 2. Pd/C

(ref. 266) 141

CO,H LTA (ref. 267)

CO,H 142 (-5%)

HO-C

HO-C

C0 H 2

1. LTA 2. DDQ

C0 H 2

(ref. 268) 143 (12%)

CO,H 1. LTA 2. DDQ

(ref. 268a)

COH Z

144 (10%)

2 6 8 a

/. Oxidations derivatives 1 4 5 .

2 0 2

>

2 6 9

2

7

1

with Lead Tetraacetate

85

R e p o r t e d yields are variable a n d reproducibility

of experimental conditions has been q u e s t i o n e d .

2 0 2

T h e use of anhydrides

such as 146 for producing a l k e n e s has a special advantage in that m a n y anhydrides are available via [2 + 2]- or [4 + 2]cycloadditions of alkenes or dienes, respectively, with maleic anydride. T h e synthesis of D e w a r benzene ( 1 4 7 ) represents a n o t h e r pertinent e x a m p l e . In certain cases anhydrides 2 6 9

2 7 2

py Ο

2 5 7 2 5 7 a

2 5 8

2 5 9 2 6 0 2 6 1

2 6 2 2 6 3 2 6 3 8 2 6 3 b 2 6 4

2 6 5 2 6 6 2 6 7 2 6 8 2 6 8 a

2 6 9

2 7 0 2 7 1 2 7 2

IL-LJ 147 (5-20%)

I. Fleming and E. Wildsmith, J. Chem. Soc. Chem. Commun., 223 (1970). S. Wolfe and J. R. Campbell, Synthesis, 117 (1979). H. G. Selander, D. M. Jerina, D. E. Piccolo, and G. A. Berchtold, J. Am. Chem. Soc. 97, 4428 (1975). Η. E. Zimmerman and L. M. Tolbert, J. Am. Chem. Soc. 97, 5497 (1975). Ν. B. Chapman, S. Sotheeswaran, and K. J. Toyne, J. Org. Chem. 35, 917 (1970). G. A. Russell, R. G. Keske, G. Holland, J. Mattox, R. S. Givens, and K. Stanley, J. Am. Chem. Soc. 97, 1892(1975). P. E. Schueler and Υ. E. Rhodes, J. Org. Chem. 39, 2063 (1974). Υ. E. Rhodes, P. E. Schueler, and V. G. DiFate, Tetrahedron Lett., 2073 (1970). 1. Willner and M. Rabinovitz, J. Org. Chem. 45, 1628 (1980). I. Willner and M. Rabinovitz, Tetrahedron 35, 2359 (1979). J. Wolinsky and R. B. Login, J. Org. Chem. 37, 121 (1972). L. A. Paquette, R. S. Beckley, and W. B. Farnham, J. Am. Chem. Soc. 97, 1089 (1975). T. Tokoroyama, K. Matsuo, and T. Kubota, Tetrahedron 34, 1907 (1978). R. P. Thummel, J. Am. Chem. Soc. 98, 628 (1976). R. P. Thummel and W. Nutakul, J. Am. Chem. Soc. 100, 6171 (1978). K. G. Bilyard, P. J. Garratt, A. J. Underwood, and R. Zahler, Tetrahedron Lett., 1815 (1979). J. E. Shields, D. Gavrilovic, J. Kopecky, W. Hartmann, and H.-G. Heine, J. Org. Chem. 39, 515 (1974). S. F. Nelsen and J. P. Gillespie, J. Am. Chem. Soc. 95, 1874 (1973). J. Meinwald, G. E. Samuelson, and M. Ikeda, J. Am. Chem. Soc, 92, 7604 (1970). Ε. E. van Tamelen, S. P. Pappas, and K. L. Kirk, J. Am. Chem. Soc. 93, 6092 (1971).

86

GEORGE Μ. RUBOTTOM

are formed as reaction side products which, in turn, do not afford alkenes under the conditions e m p l o y e d . ' In the latter example, a 1 5 - 2 0 % yield of diarylallenes could be realized without concomitant anhydride formation. 2 6 4

2 7 3

1. LTA/O. benzene ΗΟ 0^Χ^\^0Ο Η 2

2

(ref. 264)

RR C=C: ,

v

CH C0 H 2

2

LTA benzene/py

RR'C=C=CH + RR'C=<

|^

2

A^O

(ref. 273)

The possibility of concerted bis-decarboxylation seems to be ruled out by orbital symmetry a r g u m e n t s . A transition state such as 148 requires a 2 7 4

Pb(OAc)

2

148

Huckel array of eight electrons and is therefore forbidden. The probable mechanism is stepwise and involves carbonium ion i n t e r m e d i a t e s . Sup192

.COPb(OAc)

COH 2

3

^TCO-H

port for this picture arises from a n u m b e r of observations. First, transdicarboxylic acids can be successfully b i s - d e c a r b o x y l a t e d . ' ' The results noted in reference 257a are especially interesting in that bis-decar­ boxylation of the corresponding cw-l,2-dicarboxylic acids leads to significant 2 5 7 a

2 7 3 2 7 4 2 7 5 2 7 6

2 7 5

2 7 6

J. K. Crandall, R. A. Colyer, and D. C. Hampton, Synth. Commun. 3, 13 (1973). J. S. Littler, Tetrahedron 27, 81 (1971). J. D. Slee and E. LeGoff, J. Org. Chem. 35, 3897 (1970). W. B. Dauben, C. H. Schallhorn, and D. L. Whalen, /. Am. Chem. Soc. 93, 1446 (1971).

/. Oxidations

HO C

with Lead

LTA/0

2

Tetraacetate

2

Ο

py HCLC

(ref. 275)

(5.2%)

(ref. 276) C (

^

(25%)

H

C0 H 2

LTA CHgCN/py

(ref. 276) (40%)

C0 H 2

D

D

>Oco*H

LTA/py benzene

- £

(ref. 257a)

D ^ D (40%) (no scrambling)

D.

D

R ««γ R

2

1

R

2>

. >C

RR' " R R 1

2

C0 H 2

LTA/py benzene

2

R D Η C H 6

5

Η Η Η

(ref. 257a)

1

2

R

1

2

% yield

D Η 43 Η Η 46 - H Η 69 (no scrambling noted) 6

5

88

GEORGE Μ. RUBOTTOM

deuterium scrambling (see Table VII). Second, products arising from carbonium ion (or radical) intermediates have been i s o l a t e d . ' 2 0 2

HOC 2

2 7 7 , 2 7 7 3

1. LTA 2. Cu(OAc)

CO,H

2

#

1. LTA/py benzene 2. Cu(OAc) DMSO

2

(7.2%)

LTA Cu(OAc)

2

C

°2

H

benzene/py

^

CO H A

(ref. 277) ?0 H 2

HO C A

V

LTA/py/0

+ (40-50%)

(10-15%)

(ref. 277a)

2

anhydride + (20-25%)

On the other h a n d , the reactions of 1 4 9 and 1 5 0 with L T A might be concerted since a Huckel array involving six electrons may be i n v o l v e d . 2 6 4

2 7 7 b

274

2 7 7 2 7 7 3

2 7 7 b

R. S. Givens and W. F. Oettle, J. Am. Chem. Soc. 93, 3963 (1971). Κ. T. Mak, K. Srinivasachar, and N.-C. C. Yang, J. Chem. Soc. Chem. Commun., 1038 (1979). E. J. Corey and H. L. Pearce, J. Am. Chem. Soc. 101, 5841 (1979).

/. Oxidations with Lead

Tetraacetate

89

It is also of interest to note that 151 is reported to give a high yield of the iraws-alkene 1 5 2 . 2 7 8

III. LTA Reactions with Nitrogen-Containing Compounds A. AMINES AND RELATED COMPOUNDS 1. ALKYLAMINES

The reaction of primary alkylamines with L T A to produce nitriles a n d / o r aldimines as well as the reaction of primary aryl amines to form azo com­ pounds has been r e v i e w e d . ' Recent studies have been mainly concerned with the effects of neighboring groups during amine oxidation. One ex­ tremely useful example involves the L T A treatment of primary amines 1 2

2 7 9

D. J. Cram, R. B. Hornsby, E. A. Truesdale, H. J. Reich, Μ. H. Delton, and J. M. Cram, Tetrahedron 30, 1757 (1974). J. B. Aylward, Quart. Rev. (London) 25, 407 (1971).

90

GEORGE Μ. RUBOTTOM

containing a δ-ε double bond. With these systems, aziridines are formed in high yield; representative examples are g i v e n . Oxidation of 1 5 3 re2 8 0 - 2 8 3

fj^m,

..ΤΛ/Κ,ΟΟ,,

*s^>

benzene

<^ J (ref. 280) (55-60%) R = H, Me

LTA/I^CO,

-NH,

2

3

benzene

(ref. 282) (90%)

iLy

7

1. LTA benzene

NH

2

2.MeI/Et 0 2

+ M e - N ^ ^

(ref. 283)

(52%)

suits in a complex mixture with the nitrile 1 5 4 the only identifiable product, thus indicating that δ-ε double bond placement in the amine is c r u c i a l . 282

Ο

-

/

™

2

» °»,

/k lta

c

(py

benzene

CN

(ref. 282)

153

154

With 155, the aziridine 156 was obtained in 78% yield and no trace of the 1,4-addition product 157 was d e t e c t e d . Aziridenes constructed by the L T A method have been used as synthetic intermediates for the preparation 284

0 1 2 13 4

W. Nagata, S. Hirai, K. Kawata, and T. Aoki, J. Am. Chem. Soc. 89, 5045 (1967). W. Nagata, S. Hirai, T. Okumura, and K. Kawata, /. Am. Chem. Soc. 90, 1650 (1968). W. Nagata, T. Wakabayashi, and N. Haga, Synth. Commun. 2, 11 (1972). P. S. Portoghese and D. T. Sepp, Tetrahedron 29, 2253 (1973). M. Narisada, F. Watanabe, and W. Nagata, Synth. Commun. 2, 21 (1972).

/. Oxidations

with Lead

Tetraacetate

91

(ref. 284)

157

156 (78%)

155

of diverse structural t y p e s . " The mechanistic aspects of the aziridineforming reactions are not clear. However, several instances where the behavior of primary amines with L T A has been directly compared to the behavior of nitrenes generated from azides of analogous structure indicate that nitrenes are not involved in the former c a s e s . F o r instance, whereas pyrolysis of 158 affords 159, the treatment of 160 with L T A gives an 8 5 % yield of 1 6 1 , probably via a concerted r e a r r a n g e m e n t . Either concerted fragmentations or reactions involving nitrenium ions have been 2 8 1

2 8 3

2 8 5 - 2 8 7

285

(ref. 285)

160 161 (85%)

postulated to explain the formation of iraws-cinnamaldehyde from a 2-phenycyclopropylamine and the production of benzonitrile from L T A treatment of 1 - p h e n y l c y c l o p r o p y l a m i n e . ' Alkoxyamines react with L T A in the presence of alkenes to yield TV-alkoxyaziridines. " Initially, a stepwise addition of nitrenium ion to alkene 286

2 8 8

2 8 5 2 8 6 2 8 7 2 8 8 2 8 9 2 9 0 2 9 1 2 9 2

287

2 9 2

A. J. Sisti and S. R. Milstein, J. Org. Chem. 39, 3932 (1974). T. Hiyama, H. Koide, and H. Nozaki, Tetrahedron Lett., 2143 (1973). T. Hiyama, H. Koide, and H. Nozaki, Bull. Chem. Soc. Jpn. 48, 2918 (1975). S. J. Brois, J. Am. Chem. Soc. 92, 1079 (1970). Β. V. Ioffe and Ε. V. Koroleva, Khim. Geterotsikl. Soedin, 1514 (1972). Β. V. Ioffe and Ε. V. Koroleva, Tetrahedron Lett., 619 (1973). F. A. Carey and L. J. Hayes, J. Org. Chem. 38, 3107 (1973). Β. V. Ioffe, Yu. P. Artsybasheva, and I. G. Zenkovich, Dokl. Akad. Nauk SSSR 231, 1130 (1976).

92

GEORGE Μ. RUBOTTOM

X

LTA

•

RO-N

was postulated since it was believed that the reaction of w-butoxyamine with cis- and trans-2-butenQ was n o n s t e r e o s p e c i f i c . Recent work, however, has shown that this reaction is in fact stereospecific so that a singlet nitrene may well be i n v o l v e d . At least a two-step addition process involving a 291,293

292

Η Me

Me

N c = (

—/l

C

, * M

Me Me C=C

/

X

„.BuO-NH

k

2

LTA

+

"

^

M

»

e

M

W

e

(ref. 292)

Ν

ISJ

w-BuO

n-BuO

nitrenium ion can be excluded. When alkene is omitted, a major pathway for alkoxyamine oxidation is hyponitrite ester 162 formation with subsequent de­ composition to alkoxy radicals and finally, production of a l c o h o l s . ' 2 9 1

-N

2 9 4 - 2 9 6

2

R-0-N=N-0-R

[RO-]

»-ROH

162

The cyclic system 163 is oxidized to the corresponding oxazine by L T A .

O IN

-

^ CH C1 2

— Γ 2

I ^

2 9 6 a

(ref. 296a)

I

(50%)

H

163

Oxidation of 164 in the presence of electron-rich alkenes leads to the formation of a z i r i d i n e s . The reaction has been shown to be nonstereo­ specific with (Z)-l-phenylpropene and an equilibrating singlet and triplet nitrene has been implicated to explain the stereochemical r e s u l t s . When treatment of 164 with L T A is carried out in the presence of allyl aryl sufides, 296b

2960

2 9 3 2 9 4

2 9 5 2 9 6

2 9 6 3

2 9 6 b 2 9 6 c

L. J. Hayes, F. P. Billingsley II, and Carl Trindle, J. Org. Chem. 37, 3924 (1972). R. Partch, B. Stokes, D. Bergman, and M. Budnik, J. Chem. Soc. Chem. Commun., 1504 (1971). A. J. Sisti and S. Milstein, / . Org. Chem. 38, 2408 (1973). R. O. C. Norman, R. Purchase, and C. B. Thomas, J. Chem. Soc. Perkin Trans. 7, 1701 (1972). V. J. Lee and R. B. Woodward, J. Org. Chem. 44, 2487 (1979). R. S. Atkinson and B. D. Judkins, J. Chem. Soc. Chem. Commun., 832 (1979). R. S. Atkinson and B. D. Judkins, J. Chem. Soc. Chem. Commun., 833 (1979).

/. Oxidations

with Lead

Tetraacetate

93

iV-arylthiosulfenamides are produced. This reaction may be specific for the singlet n i t r e n e , and the mechanism of product formation is discussed in more detail in Section III, C with regard to diazene trapping. 2 9 6 c

R

SNHo

R I ArSNCHCH=CH

2

SAr I

/ s

2

SAr' (ref. 296c)

1

/

C=C

Ar'SCH CH=CHR LTA

R

4

\

NO,

Ο,Ν'

R

s

R

Ν

R1

Rz

164

R

3

(refs. 296b, 296c)

Secondary and tertiary alkylamines react with L T A to form imine deriva­ tives when α-hydrogen is available; thus 165 is oxidized to a mixture of

165

Δ - and A - a z o m e t h i n e isomers 1 6 6 . The oxidation of alkaloid 167 is accompanied by fragmentation to yield 1 6 8 , whereas a series of bicyclic 1 5 ( Ν )

16(N)

2 9 7

2 9 8

(ref. 298)

168

94

GEORGE Μ. RUBOTTOM

aziridines 1 6 9 fragment to produce the useful ω-cyanocarbonyl derivatives R

(ref. 287)

170 (29-85%)

170. Treatment of either 171 or 1 7 2 with L T A affords the immonium salt 173, and subsequent N a B H reduction of 173 generates 1 7 2 . ' Further, it has been shown that with base 173 can be transformed into the correspond­ ing enamine 1 7 4 enabling R-group epimerization to o c c u r . Enamine 2 8 7

2 9 9

3 0 0

4

3 0 0

Η R 173

Η R 174

(ref. 300)

7

8 9

10

W. Nagata, T. Wakabayashi, Y. Hayase, M. Narisada, and S. Kamata, J. Am. Chem. Soc. 92, 3202 (1970). R. E. Moore and H. Rapoport, J. Org. Chem. 38, 215 (1973). R. T. Brown, C. L. Chappie, and A. A. Charalambides, J. Chem. Soc. Chem. Commun., 756 (1974). M. Barczai-Beke, G. Dornyei, M. Kajtar, and Cs. Szantay, Tetrahedron 32, 1019 (1976).

/. Oxidations

with Lead Tetraacetate

formation is also noted in the oxidation of 1 7 5 ,

LTA benzene

3 0 1

95 176,

3 0 2

177,

and

3 0 3

(ref. 301)

175 Me

Me

LTA benzene

(ref. 302)

I Η 176

(28%)

Me \ Ν—Ν H(OEt)

Me \ Ν—Ν

1. LTA 2. hydrolysis

MeMgBr

Me \ Ν—Ν CHOHCftj

CHO

2

177

(ref. 303)

several alkaloid s y s t e m s , and demethylation has been noted as well. ' In one case, the use of pyridine enhanced the demethylation 304

3 0 5

3 0 6

3 0 6

MeO

COJVIe

I Me solvent benzene pyridine

C0 Me 2

(ref. 305) 17%

20% 10%

MeO 'Me

Me

LTA

LTA

MeO

MeO OMe

OMe

OMe

(7-10%) (ref. 306)

96

GEORGE Μ. RUBOTTOM

process, and when substituted Af-alkyl-N-methylanilines are treated with L T A / A c 0 / C H C 1 , high yields of the corresponding acetamides result, presumably via 1 7 8 . " 305

2

3

3 0 7

3 0 9

R

R

Ar—NMe — A r — Ν

Ac + CH 0 2

R I (Ar—N=CH ) + (178)

(ref. 307-309)

2

2. AROMATIC AMINES Neighboring groups also effect the course of the L T A oxidation of a r o ­ matic a m i n e s . F o r example, 1 7 9 180 and 1 8 1 give cyclic de­ rivatives, often in high yield. The reaction has been rationalized in terms of both cation and radical i n t e r m e d i a t e s . Oxidative cyclization can also be 2 7 9

3 1 0

3 1 1

3 1 2

3123

I

ο

Ν

2

LTA

2

Ν ^ Λ NH

(ref. 310)

(28%)

179

γ γ Ν Η

V^W~

benzene

H O A c Η

γΥν.

Κ

Ν

γ ^ /

NH

Ph

(ref. 311) R

% yield

2

Ph NH Η

WO

90 75 86

2

(ref. 312)

181

R

% yield

R

Η Me NH

82 86 87

NMe SMe Ph

2

% yield 2

75 72 82

used with quinoidal systems, again with excellent r e s u l t s . However, in one instance, the TV-oxide 182 was obtained as major p r o d u c t . As yet the mechanism for the formation of 1 8 2 is unclear. 3 1 1 > 3 1 3

3 1 4

/. Oxidations

with Lead

Tetraacetate

97

Me LTA

° γ

Ν ^

Ν

ΜΛΑΝ

H O A C

/ Ν

_ ^

( R E F 3 , , )

ο (25%)

(19%)

182 (67%)

(ref. 314) Pyrrolopyrimidines when treated with L T A u n d e r g o ring expansion to the pyrimido-pyrimidine s y s t e m . ' This high-yield transformation has 3 1 5

3 0 1 3 0 2 3 0 3 3 0 4

3 0 5

3 0 6 3 0 7 3 0 8 3 0 9 3 1 0 3 1 1 3 1 2 3 1 2 a 3 1 3 3 1 4 3 1 5 3 1 6

3 1 6

M. Watanabe, S. Kajigaeshi, and S. Kanemasa, Synthesis, 761 (1977). J. Daunis, H. Lopez, and G. Maury, J. Org. Chem. 42, 1018 (1977). D. S. Noyce and Β. B. Sandel, J. Org. Chem. 41, 3640 (1976). G. Stork and A. G. Schultz, / . Am. Chem. Soc. 93, 4074 (1971). J. P. Kutney, U. Bunzli-Trepp, Κ. K. Chan, J. P. de Souza, Y. Fujise, T. Honda, J . Katsube, F. K. Klein, A. Leutwiler, S. Morehead, M. Rohr, and B. R. Worth, J. Am. Chem. Soc. 100, 4220(1978). L. Castedo, R. Suau, and A. Mourino, Heterocycles 3, 449 (1975). G. Galliani, B. Rindone, and P. L. Beltrame, J. Chem. Soc. Perkin Trans. 2, 1803 (1976). G. Galliani, B. Rindone, and C. Scolastico, Tetrahedron Lett., 1285 (1975). B. Rindone and C. Scolastico, Tetrahedron Lett., 3379 (1974). A. Matsumoto, M. Yoshida, and O. Simamura, Bull. Chem. Soc. Jpn. 47, 1493 (1974). Y. Maki and E. C. Taylor, Chem. Pharm. Bull. 20, 605 (1972). E. C. Taylor, G. P. Beardsley, and Y. Maki, J. Org. Chem. 36, 3211 (1971). L. K. Dyall, Aust. J. Chem. 32, 643 (1979). W. Schafer, H. W. Moore, and A. Aquado, Synthesis, 30 (1974). E. C. Taylor, Y. Maki, and A. McKillop, J. Org. Chem. 37, 1601 (1972). F. Yoneda and M. Higuchi, J. Chem. Soc. Chem. Commun., 402 (1972). F. Yoneda and M. Higuchi, Bull. Chem. Soc. Jpn. 46, 3849 (1973).

98

GEORGE Μ. RUBOTTOM

been shown to involve 1 8 3 as an intermediate, and an attempted trapping experiment with cyclohexene failed to provide evidence for a free nitrene.

Ph CI Br

90 86 72

B. AMIDES

The reaction of primary amides with L T A in the presence of an alcohol is a very useful alternative to classical methods for the oxidative rearrange­ ment of amides into isocyanates and, hence, c a r b a m a t e s . " The latter step is catalyzed by addition of t r i e t h y l a m i n e . W h e n the oxidation is performed in D M F , and the resulting isocyanate treated with tert-butylamine, excellent yields of wHsyra-ureas r e s u l t . The ter t-butyl carbamates 3 1 7

3 1 9

317

317

RNHCONH—t-Bu {

RCONH

[

2

RNHC0 i-Bu 2

(ref. 317)

formed by the procedure also have the advantage of being rapidly cleaved to the corresponding amine hydrochlorides by treatment with a n h y d r o u s H C l in dry ethanol. Discrete nitrene intermediates could not be trapped from the oxidation and rearrangement from an intermediate 1 8 4 has R—C ί

^Pb(OAc)

2

Η 184

been p r o p o s e d . Rearrangement of 1 8 5 into 186 indicates that the reaction occurs with retention of c o n f i g u r a t i o n . This point has also been proven with the LTA/pyridine rearrangement of β-hydroxy primary 3 1 7

317

3 1 7 3 1 8 3 1 9

Η. E. Baumgarten, H. L. Smith, and A. Staklis, J. Org. Chem. 40, 3554 (1975). B. Acott, A. L. J. Beckwith, and A. Hassanali, Aust. J. Chem. 21, 185 (1968). B. Acott, A. L. J. Beckwith, and A. Hassanali, Aust. J. Chem. 21, 197 (1968).

/. Oxidations

with Lead

99

Tetraacetate

amides which afford extremely high yields (73-100%) of the corresponding 2-oxazolidinones. ' 32 0

3

2 1

Ph

Ph

'\/C0 NH 2

LTA f-BuOH

2

(ref. 317) 186 (13%)

185

LTA py

(refs. 320, 321)

(95%)

W h e n the above reaction is carried out in the presence of iodine and light, AModoamides are formed which subsequently homolyze and cyclize. After treatment with dilute alkali γ- and ^-lactones are p r o d u c e d . A recent example involves the conversion of 187 to 1 8 8 (68% y i e l d ) . Similar ex­ periments with lupanoic acid amides 189 gives mainly the corresponding 2 7 9

322

^CONH

2

LTA/I /hv_ 2

c H 8

1

7

^o^o

benzene

(-cf>) \

187

CH e

/

17

(ref. 322)

ΚΟΗ

EtOH/H 0 2

C H C0CH(CH C0 H) 8

CONH.

17

2

188 <

(ref. 323)

3 2 0 3 2 1 3 2 2

S. S. Simons, Jr., 7. Org. Chem. 38, 414 (1973). S. S. Simons, Jr., J. Am. Chem. Soc. 96, 6492 (1974). W. L. Parker and F. Johnson, J. Org. Chem. 38, 2489 (1973).

2

2

100

GEORGE Μ. RUBOTTOM

isocyanates. Cyclization was also observed in the L T A oxidation of 190 324,324a j ^ electron-withdrawing substituents inhibited ring formation and increased the a m o u n t of dimeric products 191 p r o d u c e d . 323

n

§

c a s e

3 2 4

PhCH 0—NHCONH 2

190

^0

3CH Ph

LTA

2

CHClg

•N \ OCH Ph

R

+

(ArNHCO—N4? 191

9

(ref. 324)

A novel ring contraction occurs when 1 9 2 is treated with L T A . Product 193 may well arise from an intramolecular acetyl transfer involving 194. 3 2 5

rr"Y 192

™, (FRY

COXOMel

-co

2

/ Ν \ COMe 193 (86%)

194

(ref. 325)

Finally, oxidation of a series of bicyclic secondary amides 1 9 5 gives products consistent with the formation of the highly strained 1 9 6 . 3 2 6

(CH ) 2

n

Sulfonamides can also undergo nitrenoid reactions when treated with LTA. The examples presented below are t y p i c a l . ' ' Failure of 3 2 7

3 2 8

3 2 8 0

J. Protiva and A. Vystroil, Collect. Czech. Chem. Commun. 41, 1200 (1976). J. H. Cooley and P. T. Jacobs, J. Org. Chem. 40, 552 (1975). A. R. Forrester, Ε. M. Johansson, and R. H. Thomson, J. Chem. Soc. Perkin Trans. 1, 1112(1979). C. W. Rees and A. A. Sale, J. Chem. Soc. Perkin Trans. 1, 545 (1973). M. Toda, H. Niwa, K. Ienaga, Y. Hirata, and S. Yamamura, Tetrahedron Lett., 335 (1972). M. Okahara, K. Matsunaga, and S. Komori, Synthesis, 203 (1972). 328 ' ' T. Ohashi, K. Matsunaga, M. Okahara, and S. Komori, Synthesis, 96 (1971). T. A. Chaudri, Pak. J. Sci. Ind. Res. 18, 1 (1976). 3 2 3

3 2 4

3 2 4 a

3 2 5

3 2 6

3 2 7

1

/. Oxidations

with Lead I TA

R R ' N — S 0 N H + SMe ^ 2

ArS0 N=SRR'

2

2

101

RR'N—S0 —N=S(Me) Ο

2

2

A r S 0 N H + LTA

2

Tetraacetate

ArS0 N=S(Me)

2

2

2

(ref. 327)

2

(refs. 328,328a)

alkenes to trap intermediates is taken as negative evidence for free nitrene formation. The same conclusion was reached from the observation that the arsinimines 1 9 7 produced by L T A oxidation of sulfonamides in the presence of triphenylarsine actually arise from nitrogen attack on inter­ mediate 1 9 8 . * The same considerations are thought to apply to the 3 2 8 3

3 2 9

3 3 0

I TA

RS0 NH + P h A s ^ Ph As=NS0 R 2

2

3

3

(refs. 329,330)

2

(197) (Ph As(OAc) ) 3

2

198

reactions of sulfonamides with L T A and sulfides noted above. In this case 199 is proposed as a likely i n t e r m e d i a t e . Analogous oxidations have also been reported to give the tellurium derivatives 2 0 0 . The bis-sulfonamide 329

3 3 1

R S(OAc) 2

2

(ref. 329)

R Te(OAc) 2

199

2

(ref. 331)

200

201 gives a 9 3 % yield of ( £ / Z ) - 2 0 2 when allowed to react with L T A in acetic a c i d . 3 3 2

(ref. 332) SO Ph z

202 (93%)

C. HYDRAZINES AND RELATED COMPOUNDS

The reaction of hydrazines with L T A generally produces azo c o m p o u n d s or diazines, depending u p o n substitution pattern and this behavior has been reviewed. With hydrazine, treatment with two equivalents of L T A 2 7 9 , 3 3 3

3 2 9 3 3 0 3 3 1 3 3 2 3 3 3

J. I. G. Cadogan and I. Gosney, J. Chem. Soc. Perkin Trans. 1, 466 (1974). J. I. G. Cadogan and I. Gosney, J. Chem. Soc. Chem. Commun., 586 (1973). B. C. Pant, Tetrahedron Lett., 4779 (1972). A. G. Pinkus and J. Tsuji J. Org. Chem. 39, 497 (1974). D. M. Lemal, in "Nitrenes" (W. Lwowski, ed.), p. 345. Wiley (Interscience), New York, 1970.

102

GEORGE Μ. RUBOTTOM

gives a quantitative yield of N in a reaction that has been used to detect small a m o u n t s of hydrazine using coulometric t e c h n i q u e s . Oxidation of thiadiazolidines produces excellent yields of the corresponding thiadiazolines as part of a high-yield method for the synthesis of symmetrically substituted alkenes. Systems 2 0 3 and 2 0 4 are typical. 2

3 3 4 , 3 3 5

3 3 6

Η

Η

stV R > T

R

3 3 7

">0

pet. ether

R

S

"H ""* »• " 33

R

R

(ref. 336)

R

(ref. 337) 204 (85%)

203 (69%)

The reaction of benzylhydrazine with L T A is reported to afford benzyldiimide which then reacts further to give benzyl acetate with a second molar equivalent of L T A . Since the production of benzyl acetate predominates in the presence of excess methanol, it is proposed that this c o m p o u n d arises via the intramolecular reaction of 2 0 5 . The diimide initially formed from 3 3 8

PhH C—Ν 2

AcO^fvN Pt> AcO^ OAc 205

2 0 6 cyclizes to give 2 0 7 in low yield Ο

339

Q

C0 Et 2

Me.„>k

/N—NHCO.Et

LTA

Μ θ

NHCO Et

-Ν

EtOH

Et. I Me

a

(ref. 339)

2

206

207 (19%)

Diacylhydrazides are readily oxidized to the corresponding diacyldiimides by L T A , " and in the presence of 1,3-dienes, high yields of [4 + 2]cycloaddition products are o b t a i n e d . " 3 3 8 , 3 4 0

3 4 2

3 4 0

3 4 3

/. Oxidations

with Lead Tetraacetate

103

Τ. J. Pastor, V. J. Vajgand, V. V. Vojka, and V. Antonijevic, Mikrochim. Acta, 131 (1978). M. R. Mahmoud, M. S. El-Meligy, and I. M. Issa, Indian J. Chem. 54, 872 (1977). A. P. Schaap and G. R. Faler, J. Org. Chem. 38, 3061 (1973). L. K. Bee, J. Beeby, J. W. Everett, and P. J. Garratt, J. Org. Chem. 40, 2212 (1975). R. O. C. Norman, R. Purchase, C. B. Thomas, and J. B. Aylward, J. Chem. Soc. Perkin Trans. 1, 1692(1972). E. C. Taylor and F. Sowinski, J. Org. Chem. 40, 2321 (1975). D. W. Whitman and Β. K. Carpenter, J. Am. Chem. Soc. 102, 4272 (1980). S. F. Nelsen, W. C. Hollinsed, L. A. Grezzo, and W. P. Parmelee, J. Am. Chem. Soc. 101, 7347 (1979). 340b j j chem. 34, 3181 (1969). Μ. E. Jung and J. A. Lowe, J. Org. Chem. 42, 2371 (1977). R. J. Cremlyn, M. J. Frearson, and D. R. Milnes, J. Chem. Soc. Chem. Commun., 319 (1974). R. J. Weinkam and Β. T. Gillis, J. Org. Chem. 37, 1696 (1970).

3 3 4 3 3 5

3 3 6 3 3 7 3 3 8

3 3 9

3 4 0

3 4 0 a

B

3 4 1

3 4 2

3 4 3

G i n i s

a n d

R

A

I z y d o r e 5

0

r

g

104

GEORGE Μ. RUBOTTOM

(MePhN) P—NHNHCO-Et 2

+

Ο

LTA CC1

ΊΡ— (NPhMe)

4

(?)

2

(ref. 342)

(ref. 343)

(88%)

The formation of azo c o m p o u n d s has also been noted from the deacylation of certain hydrazine d e r i v a t i v e s , and in this regard N,iV-diisopropyl3 3 8 , 3 4 4

Ο Μ

6

- Ν ^ γ

Η Ν

^ 0

/ 2

οΛΛΛ Me

Η

Ε 1

M H

°

Ο

e

\

K

Ο

\

N

Ο^ΑΛο/

A C

\

Me

Η

/

0

^Α>Αθ Me (66%) (ref. 344)

E. C. Taylor and F. Sowinski, J. Org. Chem. 40, 2329 (1975).

/. Oxidations with Lead

Tetraacetate

105

hydrazine has been used as an easily removed protecting group for carboxylic acids. Λ^Ν-Dialkylhydrazides ' and N 7V-dialkylhydrazines can 3 4 5

338

346

338

3

LTA

^T^

RCO-N—NH

I

•

Py

RC0 H

^ N=N

+

2

\

(-100%)

(ref. 345)

f—

(not isolated)

also generate dipoles such as 2 0 8 when treated with L T A . A series of diMe COCH Ph co \ / Ν—Ν Ν—Ν 2

PhCH=CHj + Me N—NHCOCHaPh

LTA

a

*Ph

(ref. 346)

. (15%) (H C=N—N—COCHjjPh) Me +

2

208

aziridines 2 0 9 was cleaved with L T A to give 2 1 0 and 2 1 1 Η

347

OAc L

*^CHR R l

T

A

»

R ^ i — N = N — C R R O A c + R R CH-N=N—CR R OAc s

4

1

2

210

e

s

4

211 (ref. 347)

209

W h e n the 1,1-disubstituted hydrazine is incorporated into a ring system, a n u m b e r of products arise which probably come from an intermediate diazine (nitrene). F o r instance, the formation of a tetrazene and the ap­ propriate amine derivative can occur from the oxidation or fragmentation of the initially formed 2 1 2 . Several other examples of the latter process 3 4 8 , 3 4 9

Z—N=N—Ζ '[oxidation] LTA Z-NH,

C H > C 1 >

Ζ =

»» [ Ζ — N H - N H - Z ] 212

^[fragmentation] Ζ—Η 3 4 5

3 4 6

(ref. 348)

D. H. R. Barton, M. Girijavallabhan, and P. G. Sammes, J. Chem. Soc. Perkin Trans. /, 929 (1972). W. Oppolzer and H. P. Weber, Tetrahedron Lett., 1711 (1972).

GEORGE Μ. RUBOTTOM

106 are a v a i l a b l e .

In systems where nitrogen extrusion can take place,

3 5 0 , 3 5 1

fragmentation occurs in high y i e l d .

3 5 0

'

""

3 5 2

Similar products are also

3 5 5

observed from the L T A oxidation of substituted Ν—Ν

LTA

2 R—CN

benzene R

Ν

+

N

1,2-diaminobenzenes.

2

(refs. 350, 354, 355)

(88-90%)

R

356

NH

2

LTA

N—NH

benzene

9

(ref. 352)

(81%) Ring expansion has also been observed a n d used as a high-yield m e t h o d for the synthesis of b o t h 1,2,3-benzotriazines a n d 1 , 2 , 4 - b e n z o t r i a z i n e s . 357

N—NH

/

\

or

2

NH Ν II / N - N H Ν

358,359

LTA/CaO

T

(ref. 357)

2

2

R

LTA CH C1 2

m

2

^

VV ^ As.iL 1

(refs. 358, 359)

(48-95%)

3 4 7 3 4 8 3 4 9 3 5 0 3 5 1 3 5 2 3 5 3 3 5 4 3 5 5

3 5 6 3 5 7

3 5 8 3 5 9

V. N. Yandovskii, P. M. Adrov, and L. B. Koroleva, Zh. Org. Khim. 11, 156 (1975). L. Hoesch and A. S. Dreiding, Helv. Chim. Acta 58, 980 (1975). D. J. Anderson, T. L. Gilchrist, and C. W. Rees, J. Chem. Soc. Chem. Commun., 800 (1971). K. Sakai and J.-P. Anselme, Tetrahedron Lett., 3851 (1970). K. Sakai and J.-P. Anselme, J. Org. Chem. 37, 2351 (1972). J. W. Barton and A. R. Grinham, J. Chem. Soc. Perkin Trans. 1, 634 (1972). T. L. Gilchrist, G. E. Gymer, and C. W. Rees, / . Chem. Soc. Perkin Trans. 1, 1747 (1975). Κ. K. Mayer, F. Schroppel, and J. Sauer, Tetrahedron Lett., 2899 (1972). F. Schroppel and J. Sauer, Tetrahedron Lett., 2945 (1974). L. S. Kobrina, Ν. V. Akulenko, and G. G. Yakobson, Zh. Org. Khim. 8, 2375 (1972). Β. M. Adger, S. Bradbury, M. Keating, C. W. Rees, R. C. Storr, and Μ. T. Williams, J. Chem. Soc. Perkin Trans. 1, 31 (1975). Α. V. Zeiger and Μ. M. Joullie, J. Org. Chem. 42, 542 (1977). Α. V. Zeiger and Μ. M. Joullie, Synth. Commun. 6, 457 (1976).

/. Oxidations

with Lead

Tetraacetate

107

When 1 -aminopyridinium, 1 -aminoquinolinium, 1 -aminoisoquinolinium, or certain 2-aminoimidazo[l,5-fl]pyridinium b r o m i d e s are treated with LTA, the corresponding acylated cyclic hydrazides result in moderate to excellent yield. The sequence shown portrays the postulated mechanism for the pyridine d e r i v a t i v e . 360

360

3 6 0

3 6 0 3

360

HNCOMe

Treatment of 1-aminobenzotriazole with L T A affords a mild, high-yield method for the generation of b e n z y n e . The procedure, carried out in the presence of suitable 1,3-dienes gives products derived from [4 + 2]cycloaddition. Benzyne produced by the above method also reacts with C S 361

3 6 2 - 3 6 4

2

NH

2

(ref. 362)

3 6 0 3 6 0 a 3 6 1 3 6 2 3 6 3

3 6 4

J. T. Boyers and Ε. E. Glover, J. Chem. Soc. Perkin Trans. 7, 1960 (1977). Ε. E. Glover, L. W. Peck, and D. G. Doughty, J. Chem. Soc. Perkin Trans. 7, 1833 (1979). C. D. Campbell and C. W. Rees, J. Chem. Soc. C, 742 (1969). T. Irie and H. Tanida, J. Org. Chem. 43, 3274 (1978). H. Kato, S. Nakazawa, T. Kiyosawa, and K. Hirakawa, J. Chem. Soc. Perkin Trans. 1, 672 (1976). T. J. Barton, A. J. Nelson, and J. Clardy, J. Org. Chem. 37, 895 (1972).

108

GEORGE Μ. RUBOTTOM

to give good yields of 213 or 214 depending u p o n the solvent e m p l o y e d .

365

/. Oxidations

with Lead

109

Tetraacetate

The lifetime of an aryne can be lengthened dramatically by immobilizing the system on carboxylated polystyrene resin. The persistence of 2 1 5 for 70 seconds has been r e p o r t e d . 3 6 6

0-

( ? ) — COOCH CH

COOCHXHL

2

k^AV

CH C1 2

s

(ref. 366) 2

215

NH,

In the absence of an " a r y n e t r a p , " the formation of biphenylenes becomes important, and in several instances crossed aryne couplings have been demonstrated. T h e typical [4 + 2] adducts obtained from L T A treatment 3 6 7

352

(31%)

(15%) (ref. 352)

of 2 1 6 or 2 1 7 in the presence of dienes are indicative of the fact that nonbenzenoid arynes are accessible by the method too. 3 5 3

3 6 8

N or N -isomer x

(ref. 353)

217

3

(ref. 368)

Generation of double as well as triple bonds in nonaromatic systems is also feasible as noted by the synthesis of the interesting c o m p o u n d s 2 1 8 , 219, 220, and 2 2 1 . The triazene derivative 2 2 2 loses nitrogen on 3 6 9

3 6 9

3 6 5 3 6 6 3 6 7

3 6 8 3 6 9

3 7 0 3 7 1

3 7 0

3 7 1

J. Nakayama, J. Chem. Soc. Perkin Trans. 1, 525 (1975). P. Jayalekshmy and S. Mazur, J. Am. Chem. Soc. 98, 6710 (1976). C. F. Wilcox, Jr., J. P. Uetrecht, G. D. Grantham, and K. G. Grohmann, J. Am. Chem. Soc. 97, 1914(1975). D. Christophe, R. Promel, and M. Maeck, Tetrahedron Lett., 4435 (1978). R. L. Viavattene, F. D. Greene, L. D. Chueng, R. Majeste, and L. M. Trefonas, J. Am. Chem. Soc. 96, 4342(1974). T. Nakazawa and I. Murata, Angew. Chem., Int. Ed. Engl. 14, 711 (1975). C. W. Rees and D. E. West, J. Chem. Soc. C, 583 (1970).

110

GEORGE Μ. RUBOTTOM

(ref. 369)

"Bis-#-aminotriazoline"

(ref. 369)

(ref. 370)

(ref. 371)

treatment with L T A to afford 223, or the equivalent, which gives 1,3- as well as 1,2- and 1,4-adducts when trapped with a number of 1 , 3 - d i e n e s . ' 372

J. Meinwald and G. W. Gruber, J. Am. Chem. Soc. 93, 3802 (1971). J. Meinwald, L. V. Dunkerton, and G. W. Gruber, /. Am. Chem. Soc. 97, 681 (1975).

373

/. Oxidations

with Lead

Tetraacetate

111

222

(44%)

223

(72%)

(ref. 372)

(ref. 373)

Diazenes which d o not undergo the fragmentation reactions noted above afford high yields of aziridines by cycloaddition to alkenes. Stereochemical studies ' " indicate stereospecific addition which implicates singlet 3 5 5

3 7 4

3 7 6

LTA

RgNNHg-

(R,N-N)

Η

^N—NR

2

nitrene as the reactive intermediate, and I N D O calculations even favor a preferred singlet g r o u n d - s t a t e . Systems 2 2 4 - 2 3 0 have all been used successfully and even 2 3 0 , which fragments readily in the absence of alkene, gives aziridines when alkenes are p r e s e n t . ' When the diazene generated from 2 3 0 was trapped with a series of aryl substituted styrenes it was found that electron-donating groups in the styrene p r o m o t e aziridine formation 293

3 5 4

EtO C a

P h ^

N

ι

^ P h

NH

3 7 5 3 7 6

a

M e ^ ^ M e NH,

2

224 (ref. 354) 3 7 4

CO Et

225 (ref. 354)

3 5 5

/ Ν—Ν

Ph

Me NH

ii NH

2

2

226 (ref. 354)

227 (ref. 374)

D. J. Anderson, T. L. Gilchrist, D. C. Horwell, and C. W. Rees, J. Chem. Soc. C, 576 (1970). H. Person, C. Fayat, F. Tonnard, and A. Foucaud, Bull. Soc. Chim. Fr., 635 (1974). H. Person, F. Tonnard, A. Foucaud, and C. Fayat, Tetrahedron Lett., 2495 (1973).

112

GEORGE Μ. RUBOTTOM

^N

r^"V"^

/ N H 2

i

Ι π

N^Me

Ν—Ν

1 \

ι

^ / ^ Ν ^ Ο

Ph^N^Ph

I

I

NH

NH

2

228 (ref. 374)

2

229 (ref. 374)

230 (refs. 354, 355)

at the expense of f r a g m e n t a t i o n . The fact that diazenes might have some nucleophilic character due to tervalent nitrogen lone pair d e r e a l i z a t i o n should enhance the reactivity of the nitrene toward electrophilic alkenes. 355

R N—S

R N =N" +

2

2

This behavior has been o b s e r v e d . " The effect of substituents on b o t h the nitrene and alkene have also been discussed in terms of frontier orbital theory. ' A large n u m b e r of aziridines have been synthesized using iV-aminophthalimide as the nitrene precursor. The examples given in Table VIII are i l l u s t r a t i v e . 3 7 4

3 7 5

3 7 6

3 7 6

3 7 4 - 3 8 3

T A B L E VIII LTA-PROMOTED AZIRIDINE FORMATION WITH 7V-AMINOPHTHALIMIDE IN METHYLENE CHLORIDE

Substrate

Product

% Yield

Reference

O. R = —Ν Ο R \

R

1

/ R

R \

3

1

/

c=c

c

\

/ \ R

2

R

4

/

c

3

R

4

\

Ν

2

R /

I

R R C H ί-Bu Me Me Η CI CI 1

6

R Η Η Η Η Me Η CI 2

5

R Η Me Η Me Me Η Η 3

R Η Me Me Η Me CI CI 4

42 61 36 19 57 60 90

374 374 374 374 375 374 374

/. Oxidations with Lead

Tetraacetate

113

TABLE VIII (cont.) Substrate

R

1

\ R

2

Product

/

R

3

R

4

; Yield

Reference

/ C=C

R

\

R

1

C0 Me C0 Et COaMe C0 Me COMe COHS /?-C1COH4 /7-N0 C H m-MeOC H CoHs />-ClC H />-N0 C H /?-MeOC H m-MeOC H COHS />-ClC H /7-N0 C H /7-MeOC H COHS /7-ClC6H /?-N0 C H /?-MeOC H CeHs /7-ClC H /?-N0 C H COHS /?-N0 C H /7-N0 C H /?-MeOC H COHS COHS COHS 2

2

2

2

6

2

4

6

4

6

4

6

4

6

4

6

4

6

2

6

4

4

6

4

4

2

6

4

6

4

6

4

2

6

4

2

6

4

2

6

4

6

4

2

Η Η Me Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η Η

R

3

Η Η Η Η Me CN CN CN CN CN CN CN C0 Et C0 Et C0 Et C0 Et C0 Et Et Et Et Et Me Me Me Me CN CN CN CN CN Η Η 2

2

2

2

2

R

4

Η C0 Et Η Me Me C0 Me C0 Me C0 Me CONH CONH CONH CONH C0 Et C0 Et C0 Et C0 Et C0 Et N0 N0 N0 N0 N0 N0 N0 N0 PO(OEt) PO(OEt) Ts CeHs CeHs C0 Me COC H 2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2 2

2

6

5

73 20 100 90 88 73 83 95 74 81 90 83 40 40 48 51 96 50 50 62 70 66 58 80 85 18 50 20 25 43 75 70

374 374 374 374 374 375, 3 7 6 375,376 375,376 375, 3 7 6 375,376 375,376 375,376 375,376 375 375 375 375, 3 7 6 375, 376 375,376 375,376 375,376 375 375 375 375 375, 3 7 6 375,376 375,376 376 376 375, 3 7 6 375, 376 (cont.)

114

GEORGE Μ. RUBOTTOM TABLE VIII (cont.) Substrate

Product

; Yield

Reference

[I

R = -N

6 R

1

\ R

2

/

R

3

R

4

R

/ C=C

R

\

R

R

1

2

2

1

\

C

/

R

/

C

\

Ν

/

R

3

R

4

\

R

3

4

C6H5

Η

Η

CHO

50

375, 376

COHS

Η

Η

CN

35

375,376

OEt

Η

Η

Η

95

375,376

COHS Η

Η

50

377

Η

32

378

Η COHS

C6H5

Ν—R

30-40

374, 375, 376

42

379

Ν—R

R'

V R"

Ν—R

R"

C0 Me Η

Η 35 Η 22

380

Η

CI 12

381

2

R'

18

381

382

endo/exo mixture

Η Ν—R

22

382

endo/exo mixture

Η

a?

R OAc

89

383

/. Oxidations

with Lead

Tetraacetate

115

Phthalomidonitrene generated from L T A treatment of N-aminophthalimide reacts with 1,3-dimethoxybenzene to give 2 8 - 3 7 % of 2 3 1 along with a trace of azepine 2 3 2 . Pyrolysis of 2 3 3 affords a 2 to 1 mixture rich in 3 8 4

(ref. 384) OMe 231 (28-37%)

232 (trace)

1.5 233

azepine. The difference in product ratios is attributed to acetic acid present in the L T A reaction. In one interesting extension of the method, N-aminophthalimide was oxidized in the presence of alkynes in an attempt to generate the antiaromatic

3 7 7 3 7 8 3 7 9 3 8 0 3 8 1 3 8 2 3 8 3 3 8 4

L. A. Carpino and R. K. Kirkley, J. Am. Chem. Soc. 92, 1784 (1970). R. Annunziata, R. Fornasier, and F. Montanari, J. Org. Chem. 39, 3195 (1974). G. C. Tustin, C. E. Monken, and W. H. Okamura, J. Am. Chem. Soc. 94, 5112 (1972). G. R. Meyer and J. Stavinoha, Jr., J. Heterocycl. Chem. 12, 1085 (1975). A. G. Anderson, Jr. and D. R. Fagerburg, Tetrahedron 29, 2973 (1973). A. Ruttimann and D. Ginsburg, Tetrahedron 32, 1009 (1976). D. W. Jones, J. Chem. Soc. Chem. Commun., 884 (1972). D. W. Jones, J. Chem. Soc. Chem. Commun., 67 (1973).

116

GEORGE Μ. RUBOTTOM

l//-azirine system. However, the only product isolated was the 2//-azirine, derived perhaps from rearrangement of the transiently stable 1//-system 234.

3 8 5

N—NH,

(ref. 385)

Diazenes can also be trapped by allyl aryl sulfides to give 2 3 5 which subsequently afford 2 3 6 by a [2,3] sigmatropic s h i f t . Trapping with 386

R-N +

R'CH=CH \Ή Ar — S

Ar\

c

2

235

236 (54-64%)

II > + •

(ref. 386)

sulfoxides gives high yields of the corresponding s u l f o x i m i d e s ' reaction that occurs with retention of configuration at s u l f u r . 3 5 4

3 8 7 , 3 8 8

3 8 8 a , 3 8 8 b

15

16 17

in a The

D. J. Anderson, T. L. Gilchrist, G. E. Gymer, and C. W. Rees, /. Chem. Soc. Perkin Trans. 7, 550 (1973). R. S. Atkinson and S. B. Awad, J. Chem. Soc. Perkin Trans. 7, 651 (1975). T. L. Gilchrist, C. W. Rees, and E. Stanton, J. Chem. Soc. Chem. Commun., 801 (1971).

/. Oxidations

with Lead

Tetraacetate

117

formation of 2 3 7 is one interesting application of the p r o c e s s .

38815

Pyrolysis

p©

S—f"\/

LTA/RNH, ^

1-N^/\

CH CI 2

2

C0 R'

I

|"~ ~\S

L_ ^y\ N

C0 R'

2

2

237 (76%)

(ref. 388b)

of 2 3 8 at low pressure has been shown to give benzocyclobutene-1,2dione whereas photolysis of 2 3 8 in the presence of cyclohexene affords aziridine 2 3 9 . Thermal decomposition of the readily available 3 8 7 , 3 8 8

3 8 8

(ref. 388) (35%)

Ο

(refs. 387, 388)

239 (20%)

3-amino-2-oxazolidone system 2 4 0 results in concomitant loss of N • Ν » . -Ν Ο

\ II N = SMe

2

•N \ :N:

+ N + C0 2

and

2

2

240

3 8 8

3 8 8 a 3 8 8 b

D. J. Anderson, D. C. Horwell, E. Stanton, T. L. Gilchrist, and C. W. Rees, J. Chem. Soc. Perkin Trans. J, 1317 (1972). S. Colonna and C. J. M. Stirling, J. Chem. Soc. Perkin Trans. 7, 2120 (1974). J. E. G. Kemp, M. D. Closier, and Μ. H. Stefaniak, Tetrahedron Lett., 3785 (1979).

118

GEORGE Μ. RUBOTTOM

C 0 from an intermediate diazene to afford excellent yields of a l k e n e . ' This predominantly syn-elimination allows the preparation of interesting strained alkenes such as 2 4 1 and 2 4 2 . ' 3 8 9

3 9 0

2

3 8 9

241

3 8 9

3 9 0

242

(ref. 389)

(refs. 389,390)

D. AZOMETHINES

The chemistry of the oxidation of azomethines ( 2 4 3 ) with L T A has been studied extensively. T w o excellent comprehensive reviews on the subject have

ζ / RR'C=N 243

appeared ' along with several specific reviews dealing with oxidation of oximes, substituted h y d r a z o n e s , heteroallylic s y s t e m s , and oxida­ tive cyclization of carbonyl d e r i v a t i v e s . The depth of coverage of this interesting area of L T A chemistry noted above precludes further discussion except to note several recent reports. Hydrazone 2 4 4 is cyclized in good y i e l d , while treatment of 2 4 5 with 9

3 9 1

392

393

394

395

396

^Y^N N ^ N 244

NH

LTA 2

λ

benzene *

fy^\

N^L/^ (60%)

L T A in the presence of acrylonitrile gives 2 4 6 . U n d e r the same con­ ditions, 2 4 7 affords the corresponding t r i a z o l o p y r i d i n e . Both 2 4 8 and 3 9 7

397

19 10 (1 12 ,3 4 15

6 17 , 7 a

M. Kim and J. D. White, J. Am. Chem. Soc. 99, 1172 (1977). M. Kim and J. D. White, J. Am. Chem. Soc. 97, 451 (1975). R. N. Butler, F. L. Scott, and T. A. F. O'Mahony, Chem. Rev. 73, 93 (1973). R. N. Butler, Chem. Ind. (London), 523 (1972). R. N. Butler, Chem. Ind. (London), 437 (1968). R. N. Butler, Chem. Ind. (London), 499 (1976). J. Warkentin, Synthesis, 279 (1970). G. Maury, J.-P. Paugam, and R. Pougam, J. Heterocycl. Chem. 15, 1041 (1978). B. Stanovnik and M. Tisler, Croat. Chem. Acta 49, 135 (1977). T. Tsuchiya and J. Kurita, / . Chem. Soc. Chem. Commun., 803 (1979).

3 9 7 a

/. Oxidations

with Lead

245

Tetraacetate

119

246

(ref. 397)

H

I

gj with L T A . 249397b

v e

interesting ring-contracted products when allowed to react R

(ref. 397a)

(60-65%)

249

1.4

(25%)

:

1

( f. 397b) re

Studies on the reaction of L T A with a series of aliphatic aldehyde phenylhydrazones 250 containing o r t h o substituents in the 7V-phenyl ring indicate that formation of 251 is favored by both the ortho substituent on the N-phenyl ring and an alkyl group (R) on the methine carbon of 250. P r o ­ duction of 252 is enhanced by replacement of alkyl with aryl or by increased 3 9 7 b

J. B. Press, Ν. H. Eudy, F. M. Lovell, and N. A. Perkinson, Tetrahedron Lett., 1705 (1980).

120

GEORGE Μ. RUBOTTOM

complexity in the alkyl group. A partitioning of 2 5 3 accounts for both products. ' The acyl hydrazone 2 5 4 is oxidized by L T A to afford 3 9 8

C=N— Ν Η

i

w

3 9 8 3

//

LTA

NO

/ =

a

N

" p v \

//

NO

a

(AcO) Pb 3

250

(refs. 398, 398a)

253

OAc I RHC—N=N—Ar R

251

_ =N-N-Ar C

H

°

A

C

Ac I RCONH—N—Ar 252

stereoselective ring f o r m a t i o n .

39815

(ref. 398b)

NNHAc

OH LTA CH C1 2

HO*

2

AcO* (63%)

254

Oxime 2 5 5 gives a mixture of nitrosoacetates upon treatment with L T A , while oximes 2 5 6 produce mixtures of nitrosoacetates and nitroacetates in moderate y i e l d s . A series of dioximes were found to give mainly 3 9 9

3 9 9 3

N—OH

LTA (78%)

NO OAc

+

OAc "NO (ref. 399)

255

8 8 a 8 b 9 9 a 0 0 a

R. N. Butler and W. B. King, J. Chem. Soc. Perkin Trans. 1, 282 (1977). R. N. Butler and A. M. O'Donohue, Tetrahedron Lett. 4583 (1979). I. R. McDermott and C. H. Robinson, J. Chem. Soc. Chem. Commun., 28 (1979). T. Bosch, G. Kresze, and J. Winkler, Liebigs Ann. Chem., 1009 (1975). D. Shafiullah and H. Ali, Synthesis, 124 (1979). A. Ohsawa, H. Arai, and H. Igeta, Heterocycles 9, 1367 (1978). H. Arai, A. Ohsawa, and H. Igeta, Heterocycles 12, 204 (1979).

/. Oxidations

with Lead

Tetraacetate

(ref. 399a)

PA NO

N—OH

AcO/ Ή N0

AcO (15-18%)

256

121

2

(18-22%)

257, but the analogous bis-hydrazones give mainly b u t a d i e n e s when treated with L T A in methylene chloride. 4 0 0

4 0 0 b

N—OH

t

LTA

„ / R—(v

HO-N

, \ _ /)—R

Ο

40015

^

+

257

(refs. 400-400b)

Me NNHAr

LTA CH Cl a

ArNHN

(ref. 400b)

ArN=N

Me

The oxidation of b i s - t o s y l h y d r a z o n e s ' and b i s - s e m i c a r b a z o n e s ' with L T A gives rise to the cyclization noted. The process is favored when X in 2 5 8 is a good leaving group. T h e proposed diazo intermediate 2 5 9 ( Y = 0 ) can be isolated when 2 5 8 ( Y = 0 ) is oxidized using methylene c h l o r i d e triethylamine as solvent. Subsequent treatment of 2 5 9 ( Y = 0 ) with acetic 401

LTA HOAc

Ar—C=N—NHX I Y= C—Ar

402

- Ar—C=N=NJ Ar—C=Y^

403

404

Y= NR Ar^N

259

258

Y = Ο HOAc CONH Ts Ts CONH

4 0 1

2

NNHCONH NNHTs Ο Ο

2

Refs.

OAc I ArCHCOAr (refs. 401,404,405)

NHCONH NHTs

2

403, 404 401,402

Qhsawa, H. Arai, H. Igeta, T. Akimoto, A. Tsuji, and Y. Iitaka, J. Org. Chem. 44, 3524 (1979). R. N. Butler, A. B. Hanahoe, and W. B. King, /. Chem. Soc. Perkin Trans. 1, 881 (1978). R. N. Butler and A. B. Hanahoe, J. Chem. Soc. Chem. Commun., 622 (1977).

4oob

4 0 2

2

A

122

GEORGE Μ. RUBOTTOM

acid gives O - a c e t y l b e n z o i n . treatment with L T A . ' 4 0 6

4 0 1 , 4 0 4 , 4 0 5

Systems of type 2 6 0 also cyclize upon

4 0 7

^R N"

3

A-

LTA Y = NR

3

R R C=NNHCNHR 1

2

260

3

LTA Υ = Ο or Y = °> R3 = N=CR R 1

(ref. 406)

A 2

R

1

(refs. 406, 407)

IV. LTA Reactions with Hydrocarbons A. ALKANES

Acetoxylation of saturated hydrocarbons by L T A received little attention prior to 1 9 7 0 . It was reported that oxidation of polycyclic alkanes such as a d a m a n t a n e was complicated by further reaction of primary p r o d u c t s . Further, it has been shown that regioselectivity is not particularly high with adamantyl d e r i v a t i v e s . ' ' However, recent studies have discovered that 122

4 0 8

1 7

1 8

4 0 9

1. LTA/TFA LiCl/CH Cl 2. 10% NaOH 2

2

(88-92%)

1. LTA/TFA LiCl/CH Cl 2. 10% NaOH 2

1. LTA/TFA LiCl/CH Cl 2

OH

2

(ref. 409)

2

2. 10% NaOH OH (88%)

/. Oxidations

with Lead

Tetraacetate

123

the use of L T A / T F A in the presence of chloride ion gives excellent yields of trifluoroacetoxylated polycyclic hydrocarbons isolated as the corresponding alcohols. The reaction was less successful with methylcyclohexane and 3-methylhexane, but with 261, a regioisomer and a product with rearranged carbon skeleton were i s o l a t e d . A very useful extension of the reaction 409

409

LTA/TFA LiCl/CH Cl 2

2

2. 10% NaOH (18%) 26

261

24

(ref. 409)

involves sequential treatment of hydrocarbon with L T A / T F A and then with a nucleophile. In this manner, a n u m b e r of bridgehead functionalized hydro­ carbons are obtained in excellent y i e l d . The identity of the oxidizing 4 0 9 , 4 1 0

1. LTA/TFA 2. nucleophile

Ζ

% yield

—NHCOMe —NHCHO —C H OMe-p -C H OH-/> —CH(C0 Et)COMe

85 82 64 81 87 97

6

6

4

4

2

—S-H-BU

(ref. 410) 1. LTA/TFA 2. CHaCN/H**" H0 2

NHCOMe (78%)

agent in the L T A / T F A / L i C l reaction is not clear, but mechanistic studies have shown that oxidation does not occur via radical-cation intermediates.

4 0 3 4 0 4

4 0 5 4 0 6 4 0 7 4 0 8 4 0 9 4 1 0

Ν. E. Alexandrou and S. Adamopoulos, Synthesis, 482 (1976). R. N. Butler, A. B. Hanahoe, and A. M. O'Donohue, J. Chem. Soc. Perkin Trans. 1, 1246 (1979). R. N. Butler and A. B. Hanahoe, Chem. Ind. (London), 39 (1978). L. M. Cabelkova-Taguchi and J. Warkentin, Can. J. Chem. 56, 2194 (1978). K. Ramakrishnan, J. B. Fulton, and J. Warkentin, Tetrahedron 32, 2685 (1976). W. H. W. Lunn, / . Chem. Soc. C, 2124 (1970). S. R. Jones and J. M. Mellor, J. Chem. Soc. Perkin Trans. 1, 2576 (1976). S. R. Jones and J. M. Mellor, Synthesis, 32 (1976).

124

GEORGE Μ. RUBOTTOM

At this point, a mechanism proceeding by electrophilic attack at the c a r b o n hydrogen bond is f a v o r e d . ' The L T A acetoxylation of hydrocarbons, as noted above, is not par­ ticularly useful as a synthetic technique. Acetoxylation of the benzylic position of aromatic hydrocarbons, however, is frequently e m p l o y e d . The reaction of 2 6 2 with L T A is t y p i c a l . The reaction of toluene with 4 1 1

4 1 2

122

413

(ref. 413) (82%)

262

L T A has been rationalized by a free-radical mechanism in which the radicals have a slight positive c h a r a c t e r . ' The fact that cumene reacts twice as fast as toluene with L T A is taken as supportive e v i d e n c e , as is the iso­ lation of products resulting from ring substitution by methyl and carboxymethyl r a d i c a l s . Both short-lived r a d i c a l s and concerted c a r b o n lead bond f o r m a t i o n have been suggested in the acetoxylation of fluorene derivatives with L T A . A mechanistic change occurs, however, in aromatic systems with low ionization potentials. In these systems an electron-transfer process per­ tains. Thus, 2 6 3 is initially oxidized to 2 6 4 followed by production of 2 6 5 ; with excess L T A 2 6 6 is o b t a i n e d . 4 1 4

4 1 5

416

414

415

4 1 6 3

4 1 7

418

(ref. 418)

266 (50%) 4 1 1

265 (37%)

S. R. Jones and J. M. Mellor, J. Chem. Soc. Perkin Trans. 2 , 511 (1977).

/. Oxidations with Lead

Tetraacetate

125

A similar process may be occurring in the L T A oxidations of b o t h 7-methyl- and 1 2 - m e t h y l b e n z ( a ) a n t h r a c e n e . A very useful a d a p t a t i o n of the electron-transfer pathway occurs with the oxidation of methoxy-substituted alkyl benzenes. D u e to the shift in mecha­ nism away from the radical route, 2 6 7 reacts in preference to 2 6 8 as shown 419

0CH3

0CH3

Φ 9 CH

3

267

HC(CH3)

2

268

by a competition experiment. Therefore, methyl functionalization by L T A is possible in the presence of tertiary benzylic hydrogen with oxygenated aromatics. 420

(ref. 420)

(60%)

4 1 2 4 1 3 4 1 4 4 1 5

4 1 6 4 1 6 a

4 1 7

4 1 8 4 1 9 4 2 0

S. R. Jones and-J. M. Mellor, J. Chem. Soc. Chem. Commun., 385 (1976). H. Yagi and D. M. Jerina, / . Am. Chem. Soc. 97, 3185 (1975). Ε. I. Heiba, R. M. Dessau, and W. J. Koehl, Jr., J. Am. Chem. Soc. 90, 1082 (1968). P. S. Radhakrishnamurti and S. N. Mahapatro, Indian J. Chem. Sect. A 14, 478 (1976). Ε. I. Heiba, R. M. Dessau, and W. J. Koehl, Jr., J. Am. Chem. Soc. 91, 6830 (1969). S. Narasimhan and N. Venkatasubramanian, Indian J. Chem. Sect. Β 17, 143 (1979). Ε. I. Heiba, R. M. Dessau, and W. J. Koehl, Jr., J. Am. Chem. Soc. 91, 138 (1969). J. Pataki and R. Balick, Tetrahedron Lett., 3447 (1974). P. Jacquignon and M. Croisy-Delcey, C. R. Acad. Sci. Ser. C 276, 955 (1973). V. V. Dhekne and A. S. Rao, Synth. Commun. 8, 135 (1978).

126

GEORGE Μ. RUBOTTOM

The oxidation reaction of benzylic methyl groups with L T A has also been applied to p y r r o l e s . Use of 2 molar equivalents of L T A with 269 4 2 1 , 4 2 1 3 , 4 2 2

w f\

R

3

R

w

R

2

LTA

^

M e ^ N > - C 0 R ^ HOAc/Ac 0 2

2

^

AcO

N

3

A

Η

C

R

2

0 R^

(refs. 421, 421a, 422)

2

(53-

yields large a m o u n t s of the corresponding aldehydes upon h y d r o l y s i s . In a manner analogous to pyrrole oxidation, indoles can also be transformed 422

Me

Me

Me

W

Me

l.LTA/HOAc,

Me-^N^CO^

Δ

'

W Π Τ ί Γ ^ Nχ τ Α , CO R OHCT

z U

X

(ref. 422)

X

z

I

Η

Η 269

(57-8

into the corresponding acetoxy derivatives by treatment with L T A . Attempts at bis-acetoxylation were unsuccessful.

LTA HOAc

MeO

R

R'

% yield

OMe OMe Me Me Me

CN CHO CHO CN C0 Me

76 65 — — —

2

Dehydrogenation was observed when 270 was treated with L T A , MeO

4 2 2 a

4 2 3

and

MeO LTA benzene

(ref. 423)

OMe 270 11 l a

2 2 a 3

(30%)

A. H. Jackson, G. W. Kenner, Κ. M. Smith, and C. J. Suckling, Tetrahedron 32,2757 (1976). L. Diaz, G. Buldain, and B. Frydman, / . Org. Chem. 44, 973 (1979). J. B. Paine III, R. B. Woodward, and D. Dolphin, / . Org. Chem. 41, 2826 (1976). K. Takahashi and T. Kametani, Heterocycles 13, 411 (1979). P. J. M. Gunning, P. J. Kavanagh, M. J. Meegan, and D. Μ. X. Donnelly, / . Chem. Soc. Perkin Trans. 7, 691 (1977).

/. Oxidations

with Lead

Tetraacetate

127

the interesting b r o m o derivative 2 7 1 was obtained when 2 7 2 was allowed to react with L T A / N B S . In the latter case, no product of benzylic oxida­ tion was isolated. 4 2 4

271 (10%)

272

In rare instances, L T A cleavage of c a r b o n - c a r b o n σ-bonds has been observed for the most p a r t in systems containing cyclopropyl r i n g s . ' 4 2 5

4 2 6

(ref. 425) OAc (61%)

c

\^Pb(OAc)j

LTA HOAc \

Ν

r

OAc

ηΔ, OAc

(ref. 426)

(72%)

Mechanistic studies on a series of substituted arylcyclopropanes reveal that the strained ring is attacked by L T A and not by ( A c O ) P b A c O ~ . A con­ certed mechanism involving coordination of the cyclopropane with lead as acetate ion departs is f a v o r e d . Lead(IV) diacetate difluoride also cleaves phenylcyclopropane in a m a n n e r analogous to L T A . +

3

427

4 2 8

B. AROMATIC HYDROCARBONS

Reactive polynuclear aromatics and aromatic c o m p o u n d s containing electron-donating groups can undergo nuclear acetoxylation with L T A . 4 2 4

4 2 5 4 2 6 4 2 7 4 2 8

B. Talapatra, S. K. Mukhopadhyay, Μ. K. Chaudhuri, and S. K. Talapatra, Indian J. Chem. Sect. Β 14, 129 (1976). L. T. Scott and W. R. Brunsvold, J. Am. Chem. Soc. 100, 4320 (1978). D. F. Covey and Alex Nickon, J. Org. Chem. 42, 794 (1977). R. J. Ouellette, D. Miller, A. South, Jr., and R. D. Robins, J. Am. Chem. Soc. 91,971 (1969). J. Borastein and L. Skarlos, J. Chem. Soc. Chem. Commun., 796 (1971).

128

GEORGE Μ. RUBOTTOM

When benzylic oxidation is not a competitive process, yields of this type product are m o d e r a t e . The synthesis of 273 is an e x a m p l e . 1 2 2

4 2 9

OAc

(ref. 429)

Br

Br 273 (40%)

L T A oxidation of anthracene in benzene, benzene-pyridine, b e n z e n e cyclohexane, or chloroform gives a mixture containing approximately equal amounts of cis- and / r u f / t ^ J O - d i a c e t o x y ^ J O - d i h y d r o a n t h r a c e n e . When b e n z e n e - m e t h a n o l is used as solvent, the corresponding dimethoxy deriva­ tives are formed showing a preference for formation of the trans-isomev 274. In the former case, products are believed to arise from a carbonium ion intermediate, while in the latter, concerted methoxy transfer from a methoxylated lead species to afford 2 7 5 is followed by S 2 displacement of lead to give 2 7 4 . Results consistent with this second pathway were also 430

N

4 3 0

OMe

OMe

275

274

(ref. 430)

obtained in the L T A / b e n z e n e - m e t h a n o l oxidation of a c e n a p h t h y l e n e . The bis-acetoxylation referred to above is also observed with furan deriva­ tives as illustrated by the conversions of 2 7 6 and 2 7 7 . 431

4 3 2

4 3 2 a

(ref. 432)

276

/. Oxidations

with Lead

Tetraacetate

129

AcO

(ref. 432a)

(90%)

277

The L T A oxidation of methoxy-substituted benzenes has proven to be a complex reaction. In general, methoxy-substituted benzenes react with L T A via S 2 plumbylation to afford aryl lead c o m p o u n d s which either homolyze or h e t e r o l y z e . ' Alternatively, electron transfer occurs to afford a radical cation that is intercepted by a nucleophile. The radical thus formed is oxidized further to give p r o d u c t s . ' Radical initiators such as Perkadox enhance the latter process, whereas monomethyl oxalate facilitates both types of r e a c t i o n s . The use of acetic acid as solvent in the oxidation of anisole increases the a m o u n t s of nuclear acetoxylated products observed at the expense of ring methylation, acetoxymethylation, and attack of the alkyl methyl g r o u p . ' Oxidation studies using lead t e t r a b e n z o a t e and a series of naphthalene e t h e r s have also been carried out. A n interesting synthetic application of the reaction of methoxylated aromatics with L T A involves the oxidative cyclization of diarylidene succinic anhydrides into 1-phenylnaphthalenes. The reaction occurs in yields of over 60% and can be illustrated by the conversion of 278 into 2 7 9 . E

4 3 3

4 3 4

4 3 3

4 3 5

4 3 5

436

4 3 4

4 3 5

437

4 3 7 a

4 3 8

4 2 9 4 3 0 4 3 1 4 3 2 4 3 2 a

4 3 3 4 3 4

4 3 5

4 3 6

4 3 7

4 3 7 a 4 3 8

R. G. Harvey and H. Cho, J. Chem. Soc. Chem. Commun., 373 (1975). B. Rindone and C. Scolastico, J. Chem. Soc. C, 3983 (1971). B. Rindone and C. Scolastico, Tetrahedron Lett., 1479 (1973). Τ. M. Cresp and F. Sondheimer, J. Am. Chem. Soc. 97, 4412 (1975). H. Akita, T. Naito, and T. Oishi, Chem. Lett., 1365 (1979). R. O. C. Norman and C. B. Thomas, J. Chem. Soc. B, 421 (1970). L. C. Willemsens, D. de Vos, J. Spierenburg, and J. Wolters, /. Organomet. Chem. 39, C61 (1972). R. A. McClelland, R. O. C. Norman, and C. B. Thomas, J. Chem. Soc. Perkin Trans. 1, 562 (1972). R. A. McClelland, R. O. C. Norman, and C. B. Thomas, J. Chem. Soc. Perkin Trans. 1, 578 (1972). R. A. McClelland, R. O. C. Norman, and C. B. Thomas, J. Chem. Soc. Perkin Trans. 1, 570(1972). E. R. Cole, G. Crank, and B. J. Stapleton, Aust. J. Chem. 32, 1749 (1979). A. S. R. Anjaneyulu, V. K. Rao, P. Satyanarayana, and L. R. Row, Indian J. Chem. 11, 203 (1973).

130

GEORGE Μ. RUBOTTOM Ο

MeO

v

Ο

ί

MeO' Brv

LTA HOAc

ο

?

(ref. 438)

^OMe

OMe 278 As with alkanes, the oxidation of aromatic hydrocarbons is facilitated by the use of either L T A / T F A or lead tetrakistrifluoroacetate ( L T T F A ) in T F A . Both electrophilic p l u m b y l a t i o n ' ' and electron-transfer p r o 439,442 are thought to occur. Plumbylation affords 2 8 0 which then cesses converts to 2 8 1 in a reaction thought to involve aryl c a t i o n s . ' Since 281 is readily hydrolyzed, the sequence represents a high yield phenol s y n t h e s i s . Intermediates such as 2 8 0 can also be conveniently prepared via metathesis involving T F A and the corresponding aryl lead t r i a c e t a t e s . 4 3 9

4 4 0

4 4 1

4 3 9

4 4 3

443

443

Ar—Η + LTTFA -

ArPb(OCOCF ) 3

3

280 ,ArPb(OCOCF ) 3

Pb(OCOCF ) 3

ArOCOCF

TFA 3

*

+

Ar

3

2 A

+

>rPb(OCOCF ) + TFA

2

(ref. 443)

HOCOCF,

2

281

The proposed intermediate, A r P b ( O C O C F ) is also trapped by reactive a r o ­ matic compounds to afford high yields of biphenyl d e r i v a t i v e s . ' Com­ binations of TFA/polymethylbenzenes and A1C1 or [ A l ( O C O C F ) ]/ benzene or toluene give the best r e s u l t s . ' 3

2

4 4 4

3

4 4 4

OMe

4 4 4 3

n

2 n + 1

3

4 4 4 3

MeO. TFA (ref. 444)

Pb(OAc)

3

(84%) 4 3 9 4 4 0 4 4 1 4 4 2

R. O. C. Norman, C. B. Thomas, and J. S. Willson, J. Chem. Soc. B, 518 (1971). J. R. Campbell, J. R. Kalman, J. T. Pinhey, and S. Sternhell, Tetrahedron Lett., 1763 (1972). D. de Vos, J. Wolters, and A. van der Gen, Reel. Trav. Chim. Pays-Bas 92, 701 (1973). R. O. C. Norman, C. B. Thomas, and J. S. Willson, J. Chem. Soc. Perkin Trans. 1,325 (1973).

L Oxidations

with Lead

Tetraacetate

131

Plumbylation also occurs readily with L T A in the presence of m o n o halogenoacetic a c i d s , dichloroacetic a c i d , and trichloroacetic acid. ' A wide range of aryl lead triacetates can therefore be pre­ pared by using the appropriate combination of aromatic substrate, L T A , and halogenated acetic acid followed by metathesis with acetic a c i d . 4 4 5

4 3 9

4 4 3 , 4 4 6

4 4 3 , 4 4 6

4 4 3

C. ALKENES 1. ACYCLIC ALKENES

Oxidation of acyclic alkenes by L T A is believed to occur via the sequence shown in Scheme 4 . Recent studies using methanol serve to confirm this 5 2

1 2

= (

+

/=\

LTA

Η

—) (OAc) Pb 3

AcO" AcO'

+

Pb(OAc)

2

+

AcO

OAc

~) ^~

\ . I

(+ +

AcO

OAc

/ ., X \

(OAc) Pb* s

SCHEME 4

premise, ' and evidence has been presented favoring the decomposition of the organometallic adduct 2 8 2 with concomitant formation of an acetoxonium ion 2 8 3 . The presence of water then gives high yields of 2 8 4 and 2 8 5 . With internal alkenes evidence is presented which implicates 2 8 6 4 4 7

4 4 8

4 4 7

OAc

OH

C H -eH-CH 1 3

6

2

Pb(OAc) 282

3

9Ο /

+

pΡ

H l s C e

283

OAc

^C ++ *-CHH CH—CH CH—CH OAc e e

1 31 3

22

284

ΟΑ,ΟΗ—fH, CeH^CH-CH, OH 285

(ref. 447)

H. C. Bell, J. R. Kalman, J. T. Pinhey, and S. Sternhell, Tetrahedron Lett., 853 (1974). H. C. Bell, J. R. Kalman, J. T. Pinhey, and S. Sternhell, Tetrahedron Lett., 857 (1974). H. C. Bell, J. R. Kalman, G. L. May, J. T. Pinhey, and S. Sternhell, Aust. J. Chem. 32,1531 (1979). D. de Vos, J. Spierenburg, and J. Wolters, Reel. Trav. Chim. Pays-Bas 91, 1465 (1972). D. de Vos, F. Ε. H. Boschman, J. Wolters, and A. van der Gen, Reel. Trav. Chim. Pays-Bas 92, 467(1973). A. Lethbridge, R. O. C. Norman, C. B. Thomas, and W. J. E. Parr, J. Chem. Soc. Perkin Trans. 7,231 (1975).

a

132

GEORGE Μ. RUBOTTOM

R

Ή 286

as the source of at least part of the diacetates f o r m e d . Ally lie products arise from homolytic p a t h w a y s . When L T A / T F A is used in the oxidation of a series of styrene-related c o m p o u n d s , preparatively worthwhile yields of carbonyl c o m p o u n d s are formed, and a similar transformation was observed with 1 - o c t e n e . 4 4 7

4 4 7

4 4 9 , 4 5 0

447

^

^

1. LTA/TFA

If

2. H 0

J>

2

~Ο

(refs. 449,450)

(98%)

1. LTA/TFA 0 ΓΓ 2

2. H 0 2

^

0

J<^J>

2

N ^ ^ ^

(ref. 449)

Ο

(91%)

The generalized mechanism for the reaction is illustrated for the conversion of 2 8 7 to 2 8 8 . ' Similar mechanistic considerations would seem to apply in the reaction of L T A / H F with 1,2-diphenylethylene. 4 4 9

4 5 0

451

ArCR=CHR'

L T A / T F A

>

ArCR—CHR' I

287

CF COO 3

I

Pb(OCOCF ) 3

\ ^

3

(refs. 449, 450)

+

TFA CR—CHR'Ar Ji^(CF COO) CR—CHR'Ar^" | RCOCHR'Ar OCOCF 3

2

3

288

The reaction of biallyl with L T A leads to a partitioning of the initially formed 2 8 9 to give b o t h 2 9 0 and 2 9 1 . Allenes react with L T A in acetic 4 5 2

8

9 10 1 12

A. Lethbridge, R. O. C. Norman, and C. B. Thomas, J. Chem. Soc. Perkin Trans. 7, 1929 (1974). A. Lethbridge, R. O. C. Norman, and C. B. Thomas, J. Chem. Soc. Perkin Trans. 7,35 (1973). D. Westphal and E. Zbiral, Monatsh. Chem. 106, 679 (1975). D. D. Tanner and P. Van Bostelen, J. Am. Chem. Soc. 94, 3187 (1972). I. Tabushi and R. Oda, Tetrahedron Lett., 2487 (1966).

/. Oxidations

with Lead A c 0

Tetraacetate

133

^y-oAc 290

Pb(OAc)

3

LTA HOAc ~

„

+

^

<

r e f 4 5 2

)

289 AcO OAc 291

acid to give the corresponding 3 - a c e t o x y a l k y n e . ' Use of optically active allene reveals that the addition of L T A occurs predominantly by a suprafacial pathway. The reaction of (£)-( +)-l,3-dimethylallene to give (S)-( + )-4-acetoxy-2-pentyne is i l l u s t r a t i v e and similar results pertain with 1,2-cyclononadiene. 454 453

454

453

(OAc) Pb 3

Μ θ

\ / )C-C=C

LTA

V

Η (S)

MG

N Η

/Pb(OAc) C=C^ ! C^ Η

3

A

c

0

-

Me

"

| OAc ~ - "

M E

(ref. 453)

2. CYCLIC ALKENES

The oxidation of cyclic alkenes with L T A has been widely s t u d i e d . In general, products can be rationalized by invoking 2 9 2 which can lead to 2 9 3 and 2 9 4 . Intermediate 2 9 3 can also arise from syn addition of L T A to 52

4 5 3

4 5 4

R. D. Bach, R. N. Brummel, and J. W. Holubka, J. Org. Chem. 40, 2559 (1975). R. D. Bach, U. Mazur, R. N. Brummel, and L.-H. Lin, J. Am. Chem. Soc. 93, 7120 (1971).

134

GEORGE Μ. RUBOTTOM

a

+:Pb(OAc)

Pb(OAc) 294

LA

3

292

3

Pb(OAc)

3

OAc

293

products

products

the a l k e n e , and 2 9 3 and 2 9 4 can undergo homolysis of the l e a d - c a r b o n bond followed either by product formation from the ensuing radical or by oxidation to the corresponding carbonium ion which then gives p r o d u c t s . When the reaction is applied to strained alkenes or alkenes capable of carbonium ion rearrangement, novel results often occur. F o r example, treat­ ment of 1,3,3-trimethylcyclopropene with L T A affords 2 9 5 and 2 9 6 in yields of 40% and 5% r e s p e c t i v e l y . The interesting intermediate 2 9 7 is 4 5 5

52

456,457

(AcO) HC

LTA

2

CH C1 2

2

295 (40%)

296 (5%)

(refs. 456, 457) (OAc) Pb 3

(OAc) Pb s

297

postulated to account for the formation of 295. In a related case, the series 2 9 8 reacts with L T A to selectively produce 2 9 9 . The selectivity is explained by invoking 3 0 0 . M o r e remote cyclopropyl functionality can remain 4 5 8

R

1

R

RN 2

R R 298

4 5 5 4 5 6 4 5 7 4 5 8

3

4

LTA

AcO

1

R -A 2

R

4

HOAc ^-Pb(OAc)„ 300

R

OAc

1

"R

4

R

2

R

3

(ref. 458)

299

D. D. Tanner, P. B. Van Bostelen, and M. Lai, Can. J. Chem. 54, 2004 (1976). T. Shirafuji and H. Nozaki, Tetrahedron 29, 77 (1973). T. Shirafuji, Y. Yamamoto, and H. Nozaki, Tetrahedron Lett., 4713 (1971). R. Noyori, Y. Tsuda, and H. Takaya, J. Chem. Soc. Chem. Commun., 1181 (1970).

/. Oxidations

with Lead

Tetraacetate

135

intact during oxidation, as in the preparation of 301 and 3 0 2 from 3 0 3 . This behavior is in contrast to the oxidation of 4-carene by LTA/benzene in 4 5 9

303

301 (60-65%)

302 (16-20%) (ref. 459)

which a n u m b e r of products were isolated which are consistent with h o m o allylic rearrangement of the three-membered r i n g . With 3-carene, the major product of L T A oxidation was 3 0 4 . 4 6 0

4 6 1

(ref. 461) OAc 304

Ring contraction was observed when 3 0 5 or the corresponding anhydride was treated with LTA, and the intermediate 3 0 6 is implicated in the rea r r a n g e m e n t . Analogous to the reaction of 4-carene with L T A mentioned 462

(OAc) HC 2

(ref. 462)

C0 Me 2

306 4 5 9 4 6 0

4 6 1 4 6 2

H. Sekizaki, M. Ito, and S. Inoue, Bull Chem. Soc. Jpn. 51, 3663 (1978). B. A. Arbuzov, V. V. Ratner, Z. G. Isaeva, and M. G. Belyaeva, Dokl Akad. Nauk SSSR 204, 1115 (1972). B. A. Arbuzov, V. V. Ratner, and Z. G. Isaeva, Izv. Akad. Nauk SSSR, Ser Khim, 45 (1973). T. Sasaki, K. Kanematsu, A.Kondo, and K. Okada, J. Org. Chem. 41, 2231 (1976).

136

GEORGE Μ. RUBOTTOM

above, /J-pinene affords products involving participation of the neighboring four-membered r i n g . ' With 3 0 7 , a mixture containing the diacetate 3 0 8 and allylic acetate 3 0 9 was f o r m e d . T h e results are less straightforward with alkenes containing 5 2

4 6 3

4 6 4

(ref. 464) 307

308

309

a double bond exocyclic to a five-membered ring. The oxidation of 3 1 0 is a case in p o i n t . A pronounced solvent effect has been reported for the 4 6 5

(ref. 465)

(10%)

(7%)

(50%)

oxidation of both longifolene, 3 1 1 , and camphene, 3 1 2 . In each case, the use of acetic acid as solvent results in ring expansion whereas the use of 4 6 6

(ref. 466)

' H. Ohue, M. Matsushita, T. Ikeda, and H. Miki, Osaka Kogyo Daigaku Kiyo Rikohen 22, 175 (1978). V. Balogh, J.-C. Beloeil, and M. Fetizon, Tetrahedron 33, 1321 (1977). G. Ortar and I. Torrini, Tetrahedron 33, 859 (1977). S. N. Suryawanshi, P. K. Jadhav, and U. R. Nayak, Indian J. Chem. Sect. Β 16, 446 (1978). 3

4

5

6

/. Oxidations

with Lead

Tetraacetate

LTA

LTA

HOAc

benzene

137

OAc

OAc

(ref. 466)

Η 312

(66%)

(59%) /Ζ-mixture

Ε

benzene gives the corresponding aldehyde enol acetate. This dramatic change in product composition is attributed to the dielectric constant of the solvent used. Solvent effects also play a role in the oxidation of both norbornadiene and norbornene, a fact alluded to in some detail in reference 52. N o r b o r n e n e was originally reported to give an 85% yield of 3 1 3 upon treatment with L T A in acetic a c i d . However, improved techniques of product analysis have re4 6 7

OAc OAc

313

vealed a much more complex set of p r o d u c t s . ' The m o d e of formation of 3 1 3 is an area of some c o n t r o v e r s y . A recent comparison of the behavior of n o r b o r n e n e and benzobicyclo[2.2.2]octatriene toward both L T A and L T A / H F has resulted in the formulation of a mechanism involving initial syn-addition of L T A to the alkene in question. Displacement of lead then gives a cation 3 1 4 , which then results in the production of 3 1 3 . 5 2

4 6 8

52

4 5 1

455

4 5 1 , 4 5 5

OAc

LTA HOAc

^\X~Fb(OAc)

3

314

^OAc

313

The L T A / H F oxidant and P b F ( O A c ) both have been used to fluorinate cyclohexene rings contained in steroids, and a spectrum of products is 2

4 6 7

4 6 8

2

K. Alder, F. H. Flock, and H. Wirtz, Chem. Ber. 91, 609 (1958). J. Kagan, Helv. Chim. Acta 55, 2356 (1972).

138

GEORGE Μ. RUBOTTOM

obtained. L T T F A in methylene chloride-nitromethane reacts with steroidal cyclohexenes to yield products arising from 1,2-ditrifluoroacetoxylation and allylic trifluoroacetoxylation. Analogous to the reaction of conjugated dienes with L T A , L T T F A reacts with both 1,3-cyclohexadiene and cyclopentadiene to give products of 1 , 4 - a d d i t i o n . 4 6 9 , 4 7 0

450

5 2

450

ο

CFXOO

OCOCF,

LTTFA Et O

(ref. 450)

a

(33%)

Extensive studies have been carried out concerning the reactions of lead(IV) acetate azides [ P b ( O A c ) _ „ ( N ) J with alkenes and much of the work in this area has been r e v i e w e d . F o r the reaction run at low temper­ atures (—20°C), a mechanism involving addition of "positive azide" to the alkene has been postulated. Products then arise from the carbonium ion thus formed. Alternatively, products might evolve from a sequence in­ volving the cyclo addition of azide to the double bond to give 315 which then reacts f u r t h e r . A n interesting and typical example of the synthetic 4

3

471

4 7 1 , 4 7 2

4 7 2 , 4 7 3

N// Ν Ν

I

Ζ—Pb Ζ = OAc or N

3

315

use of the reaction occurs when lead(IV) acetate azide and norbornene interact to give 316 in a yield of 7 5 % . A series of A -steroidal alkenes has 4 7 4

Pb(OAc) _ (N ) 4

n

CH C1 2

3

5

OAc

n

(ref. 474)

2

316 (75%)

4 6 9 4 7 0 4 7 1 4 7 2 4 7 3 4 7 4

M. Ephritikhine and J. Levisalles, Bull. Soc. Chim. Fr., 339 (1975). M. Ephritikhine and J. Levisalles, / . Chem. Soc. Chem. Commun., 429 (1974). E. Zbiral, Synthesis, 285 (1972). E. Zbiral and A. Stutz, Monatsh. Chem. 104, 249 (1973). A. Stutz and E. Zbiral, Liebigs Ann. Chem. 765, 34 (1972). E. Zbiral and A. Stutz, Tetrahedron 27, 4953 (1971).

/. Oxidations with Lead

Tetraacetate

139

been found to fragment when treated with lead(IV) acetate a z i d e , ' whereas steroidal alkenes unsubstituted at the double bond in question, afford α-azido k e t o n e s . ' In the former case, temperature is crucial 4 7 1

4 7 1

4 7 5

4 7 6

(ref. 475)

(ref. 476)

(50%)

since allyl a z i d e s and other oxidation p r o d u c t s arise when the reaction is carried out at + 2 0 ° C . Dienes react with lead(IV) acetate azide to give 4 7 5

4 7 7

COMe

COMe

(ref. 475)

(45%)

mixtures resulting from both 1,2- and 1,4-addition of the reagent as well as products resulting from r e a r r a n g e m e n t . ' ' In the presence of L T A / T F A , alkenes react with disulfides to afford high yields of the corresponding /?-trifluoroacetoxysulfides that are converted by treatment with base to /J-hydroxy s u l f i d e s . The cleavage of /J-hydroxy sulfides with L T A has been mentioned in Section ΙΙ,Β. T h e use of diselenides in place of disulfides also results in alkene addition when employed in con­ junction with L T A . 4 7 1

4 7 8

4 7 9

118

4 7 9 a

5 6 7 8 9 9 a

H. Hugl and E. Zbiral, Tetrahedron 29, 759 (1973). E. Zbiral and G. Nestler, Tetrahedron 27, 2293 (1971). E. Zbiral and H. Hugl, Tetrahedron 29, 769 (1973). A. Wolloch, E. Zbiral, and E. Haslinger, Liebigs Ann. Chem., 2339 (1975). H. Hugl and E. Zbiral, Tetrahedron 29, 753 (1973). N. Miyoshi, Y. Ohno, K. Kondo, S. Murai, and N. Sonoda, Chem. Lett., 1309 (1979).

140

GEORGE Μ. RUBOTTOM

PhS—SPh

.SPh

1. LTA/TFA

+

2. base

-

k ^ H ^

(ref. 118)

(74%)

PhSe-SePh

cc

o

+

SePh (ref. 479a)

OAc

(70%)

V. LTA Reactions with Organometallics Interest in the reactions of organometallics with L T A has led to the development of a number of useful synthetic procedures. Oxidation of trialkylboranes with L T A gives moderate yields of the corresponding alkyl acetates. With mixed trialkylboranes containing both primary and 480

R B + LTA

3ROAc

3

(ref. 480)

secondary alkyl groups on boron, preferential formation of secondary alkyl acetate occurs. The reaction has also been extended to the oxidation of 1-bromo-l-alkenyl dialkyl boranes as a means of obtaining the correspond­ ing l-bromo-l,2-dialkylethenes. In this case, alkyl migration occurs instead of acetate f o r m a t i o n . Use of low temperature ( —50°C) and C H C 1 as 481

2

Br

R'

\

RB

/

C=C

\

2

Br LTA

/

R'

\

/

Η

2

/ c

=

=

c

R

\

(ref. 481) Η

solvent favors production of the Z-isomer while ^-isomer formation occurs at 0°C in benzene-hexane mixtures. Hydroalumination of 1-alkenes with L A H by T i C l catalysis followed by L T A treatment provides another excellent method for the preparation of primary alkyl a c e t a t e s . The use of 3 1 7 is crucial since organoaluminates 4

482

2RCH=CH + LAH 2

LiAl(CH CH R) H ^ 2

2

2

2

2AcOCH CH R

317 4 8 0

4 8 1

482

Y. Masuda and A. Arase, Bull. Chem. Soc. Jpn. 51, 901 (1978). Y. Masuda, A. Arase, and A. Suzuki, Chem. Lett., 665 (1978). F. Sato, Y. Mori, and M. Sato, Tetrahedron Lett., 1405 (1979).

2

2

( f. 482) re

/. Oxidations with Lead

141

Tetraacetate

of the type L i A l R lose only two of the R-groups in the L T A reaction. The selective monohydroalumination of unconjugated dienes also allows for the preparation of unsaturated a c e t a t e s . 4

482

1. L A H / T i C l THF

OAc 4

(ref. 482)

2. L T A

(64%)

Both arylthallium d i t r i f l u o r o a c e t a t e s and diarylthallium trifluoroacetates react with L T A - t r i p h e n y l p h o s p h i n e in T F A to give excellent yields of aryl trifluoroacetates. Subsequent alkaline hydrolysis leads to the p r o ­ duction of the corresponding phenols. The aryllead tri(trifluoroacetate) 3 1 8 is proposed as a likely i n t e r m e d i a t e . 483

4 8 4

484

ArTl(OCOCF ) 3

2

1. L T A / T F A

ArOCOCF

" °> ArOH 39-78%

(ref. 483)

^ " ° > ArOH 21-69%

(ref. 484)

Na 3

c

3

Ar T!OCOCF 2

1. L T A / T F A 3

°

H/ H

2

c

2

2. P h P

2ArOCOCF

Ν 3

2. P h P

2

2

3

2

2

(ArPb(OCOCF ) ) 3

3

318

W h e n arylthallium ditrifluoroacetates are treated with L T T F A in T F A , formation of 3 1 8 is actually observed, with subsequent decomposition to the corresponding aryl t r i f l u o r o a c e t a t e s . A n extension of the reaction allows preparation of 3 1 9 from both arylmercury(II) trifluoroacetates and 443,485

SiMe

LTTFA

LTTFA

TFA

TFA Pb(OCOCF )

3

3

319

CFoCOO

3

HgOCOCFg

142

GEORGE Μ. RUBOTTOM

arylsilicon c o m p o u n d s . ' ' In each case, m e t a l - m e t a l exchange and not protonation followed by plumbylation p r e v a i l s . ' A number of organotin c o m p o u n d s containing S n — H , S n — C , S n — S n , and S n — Ο groups are effectively acetoxylated with L T A , and dialkyldiarylstannanes give 7 0 - 9 0 % yields of diacetoxydiarylplumbanes along with the corresponding diacetoxyldialkylstannanes. £-l-Alkenyl-fl-butylstannanes are converted smoothly into terminal alkynes upon treatment with 4 4 3

4 8 5

4 8 5 3

4 8 5

4 8 5 3

4 8 6

487

R

2SnAr

L T A 2

HO ? 8

A C ) 2

a

L T A in a c e t o n i t r i l e . is proposed.

488

'

R Sn(OAc) + Ar Pb(OAc) (70-90%) 2

2

2

2

(ref. 487)

Intermediate 320 leading to 321 and thus the alkyne

LTA Sn(Bu)

CH CN a

3

(ref. 488) LTA CH-CN I Η

Sn(Bu)

3

(64%) Bu.Sn

Bu Sn 3

C=C

\

^ R

HC—CHR — (OAc) PbCH=CHR / + Pb(OAc) Bu SnOAc 3

3

320 ί 3

14 15

15a 6

17 18

HC=C—R

3

321

E. C. Taylor, H. W. Altland, R. H. Danforth, G. McGillivray, and A. McKillop, J. Am. Chem. Soc. 92, 3520(1970). E. C. Taylor, H. W. Altland, and A. McKillop, J. Org. Chem. 40, 2351 (1975). J. R. Kalman, J. T. Pinhey, and S. Sternhell, Tetrahedron Lett., 5369 (1972). H. C. Bell, J. R. Kalman, J. T. Pinhey, and S. Sternhell, Aust. J. Chem. 32, 1521 (1979). U. Christen and W. P. Neumann, J. Organomet. Chem. 39, C58 (1972). O. P. Syutkina, Ε. M. Panov, and K. A. Kocheshkov, Zh. Obshch. Khim. 43, 1322 (1973). E. J. Corey and R. H. Wollenberg, J. Am. Chem. Soc. 96, 5581 (1974).

/. Oxidations

with Lead

Tetraacetate

143

Allylic mercuric acetates are transformed into mixtures of allylic acetates by LTA. The major reaction pathway is thought to involve S ' (probably S i') formation of a σ-allylic lead derivative which then d e m e t a l a t e s . With the dimeric π-complex 3 2 2 direct attack by L T A is p o s t u l a t e d . Oxidation of E

E

489

489

'>m< c

H

3

C

/y^S

\

Pd J

HOAc

CH —CH—CH=CH 3

2

(ref. 489)

OAc

AcO I O/OAc Pb Q^^ OAc

major product

b

A c

322

cycloocta-l,5-diene with L T A / P d C l gives a 70% yield of 3 2 3 , and arylbutenylacetates are formed in high yield from the reaction of aryl4 9 0

2

LTA/PdCl HOAc

,

2

1

^ ^

x

(ref. 490)

x

mercuric salts, butadiene, and L T A in the presence of a catalytic a m o u n t of palladium a c e t a t e . 491

_ PhHgOAc

^

+

LTA Pd(OAc) H CN

C

3

2

»

^ l^jl

ι

Γ Τ L

^

.

(ref. 491)

(78%)

A series of jS-aminopalladium c o m p o u n d s 3 2 4 were treated with L T A to afford the corresponding jS-aminoacetates. Hydrolysis or L A H reduction gives β - a m i n o a l c o h o l s . Stereochemical studies show that /?-aminoacetate 492

4 8 9

4 9 0

4 9 1 4 9 2

W. Kitching, T. Sakakiyama, Z. Rappoport, P. D. Sleezer, S. Winstein, and W. G. Young, J. Am. Chem. Soc. 94, 2329 (1972). P. M. Henry, M. Davies, G. Ferguson, S. Phillips, and R. Restivo, J. Chem. Soc. Chem. Commun., 112(1974). R. F. Heck, J. Am. Chem. Soc. 90, 5542 (1968). J.-E. Backvall, Tetrahedron Lett., 2225 (1975).

144

GEORGE Μ. RUBOTTOM NMe

NMe

2

RCH—CHR

I

Yfi?

NMe

2

OH

-

I

or L A H

RCH—CHR

PdCl

2

(ref. 492)

RCH—CHR

I

OAc

OH

324

formation occurs with inversion at the site containing palladium. Alkyl transfer to lead with retention, followed by acetate ion attack with inversion, accounts for the observed r e s u l t s . 492

Me

R—

LTA

crPdCl

-R-6^

Me

Pb(OAc)

AcO 3

OAc I R—C-»'H Me

(ref. 492)

The reaction of L T A in pyridine to free cyclobutadiene from cyclobutadieneiron tricarbonyl is a method which complements the use of eerie a m m o n i u m nitrate ( C A N ) for the same p u r p o s e . " L T A is especially useful in systems where acidic conditions can be deleterious. The examples given are illustrative. 4 9 3

LTA py Fe(CO)

4 9 5

(ref. 493)

ο

3

(40-44%)

EtO,

EtO

OEt

OEt

LTA

(ref. 494)

py Fe(CO)

3

(ref. 495) C0 R / 22

/

RO,C Fe(CO) 3 4 5

N=N

LTA

.CO R

py CO R a

3

% yield

a

—C ~"CH CH-j 2

L. Brener, J. S. McKennis, and R. Pettit, Org. Synth. 55, 43 (1976). J. C. Barborak and R. Pettit, J. Am. Chem. Soc. 89, 3080 (1967). S. Masamune, N. Nakamura, and J. Spadaro, J. Am. Chem. Soc. 97, 918 (1975).

45 50-60

/. Oxidations with Lead

Tetraacetate

145

Benzocyclobutadiene is generated by the L T A oxidation of 3 2 5 and when 3 2 5 is used in conjunction with cyclobutadieneiron tricarbonyl and L T A the mixed adduct 3 2 6 is obtained in 75% y i e l d . The latter intriguing result stems from the fact that oxidation of 3 2 5 and cyclobutadieneiron tricarbonyl 496

(ref. 496)

occurs at comparable rates. This being the case, the benzocyclobutadiene thus produced can only function in the role of dienophile in the subsequent [4 + 2]cycloaddition with c y c l o b u t a d i e n e . 496

LTA py Fe(CO)

3

Fe(CO)

326 (75%)

3

325

(ref. 496)

(100%)

ACKNOWLEDGMENT

The author gratefully acknowledges H. D. Juve, Jr., D. K. Heckendorn, W. D. Boyce, and L. A . Rubottom for their help in preparing the manuscript, and Professor J. H. Cooley for his most useful comments.

W. Merk and R. Pettit, J. Am. Chem. Soc. 89, 4787 (1967).