J. Am. Chem. Soc. 1996, 118, 2289-2290
2289
Scheme 1
The Catalytic Shapiro Reaction
Keiji Maruoka,† Masataka Oishi, and Hisashi Yamamoto*
School of Engineering, Nagoya UniVersity
Chikusa, Nagoya 464-01, Japan
ReceiVed May 2, 1995
The alkyllithium-mediated decomposition of ketone arene-
sulfonylhydrazones (i.e., the Shapiro reaction) is certainly one
of the most powerful methods for regioselective preparation of
alkenes via alkenyllithium reagents.1 In all cases, however, the
procedures require stoichiometric or even excess amounts of
the bases to generate the alkenyllithium reagents. Accordingly,
development of an efficient catalytic method in the Shapiro
reaction constitutes a veritable challenge in organic synthesis.
Herein we wish to disclose a first example of excellent regio-
and stereoselectivity obtained using the combination of ketone
phenylaziridinylhydrazones 1 as arenesulfonylhydrazone equiva-
lents2,3 with a catalytic amount of lithium amides.
Similarly, the (E)-hydrazone 1 (R1 ) octyl, R2 ) Me) was
transformed to cis-2-undecene (2, R1 ) octyl, R2 ) Me) almost
exclusively in 98% yield (entry 9). These results clearly support
regioselective deprotonation with amide base by preferential
abstraction of the R-methylene hydrogen syn to the phenylaziri-
dyl moiety in 1 and subsequent decomposition of the resulting
3 to furnish, with extrusion of styrene and nitrogen, alkenyl-
lithium 4, which abstracts the amine proton, producing alkene
product 2 in regeneration of lithium amide for further use in
the catalytic cycle for cis-alkene formation (Scheme 1). The
excellent cis selectivity is also explainable by the internal
chelation structure 3.
The requisite phenylaziridinylhydrazone 1 (R1 ) pentyl, R2
) Bu) was prepared from the condensation of 6-undecanone
with 1-amino-2-phenylaziridine.4 Treatment of 6-undecanone
phenylaziridinylhydrazone 1 (R1 ) pentyl, R2 ) Bu) in ether
with catalytic LDA (0.3 equiv) at -20 °C for 1 h and at 0 °C
for 3 h resulted in the smooth extrusion of styrene and nitrogen
to furnish 5-undecene 2 (R1 ) pentyl, R2 ) Bu) in 84% yield.
Utilization of optically active 1-amino-2-phenylaziridine for
the present methodology allows the facile synthesis of optically
active alkenes. For example, condensation of 4-methyl-4-p-
tolylcyclohexanone with optically pure 1-amino-2-phenylaziri-
dine (>99% ee),6 followed by separation of diastereomeric
hydrazones by column chromatography, afforded (R,R)-hydra-
zone 5 and (S,R)-hydrazone 6. Individual treatment of 5 and 6
in ether with catalytic LDA (0.1 equiv) at 0 °C for 1 h gave
rise to (R)- and (S)-3-methyl-3-p-tolyl-cyclohexene (7, 94% ee,
and 8, 92% ee, respectively) in high yield. Ozonolysis of 7 in
MeOH/CH2Cl2 and further oxidation by PDC in dry DMF in
the presence of MeOH gave the known diester 9 in 61% yield,
which is a chiral key intermediate of (+)-R-cuparenone.7
The cis/trans ratio was determined to be 99.4:0.6 by capillary
GLC analysis after conversion to the corresponding epoxides
with MCPBA. The amount of LDA can be decreased to 0.05
equiv without affecting the yield and cis/trans ratio of the olefin
product in the 30 mmol scale reaction. Lithium 2,2,6,6-
tetramethylpiperidide (LiTMP) is equally employable, but use
of LiNEt2 and LiN(SiMe3)2 gave less satisfactory results.
Other selected examples are listed in Table 1. Virtually
complete stereoselectivity is observed for butyl cyclohexyl
ketone phenylaziridinylhydrazone 1 (R1 ) cyclohexyl, R2 )
Pr) (entry 6). This selectivity is in marked contrast to the normal
Shapiro reaction of the corresponding tosylhydrazone with BuLi/
TMEDA (cis/trans ) 75:25). Stereoselective diene synthesis
appears feasible (entry 7). In the case of unsymmetrical
3-undecanone, a mixture of (Z)-hydrazone 1 (R1 ) Et, R2 )
heptyl) and (E)-hydrazone 1 (R1 ) octyl, R2 ) Me) was formed
in ∼1:1 ratio, which was easily separated by column chroma-
tography on silica gel.5 Reaction of the (Z)-hydrazone 1 (R1 )
Et, R2 ) heptyl) with catalytic LDA (0.1 equiv) at 0 °C for 1
h yielded cis-3-undecene 2 (R1 ) Et, R2 ) heptyl) in 88% yield
with exceedingly high regio- and stereoselectivity (entry 8).
† Present address: Department of Chemistry, Graduate School of Science,
Hokkaido University, Sapporo 060, Japan.
(1) Reviews: (a) Shapiro, R. H. Org. React. 1976, 23, 405. (b) Adlington,
R. M.; Barrett, A. G. M. Acc. Chem. Res. 1983, 16, 55. (c) Chamberlin, A.
R.; Bloom, S. H. Org. React. 1990, 39, 1.
(2) Bamford-Stevens reaction of ketone phenylaziridinylhydrazones: (a)
Mohamadi, F.; Collum, D. B. Tetrahedron Lett. 1984, 25, 271. (b) Sarkar,
T. K.; Ghorai, B. K. J. Chem. Soc., Chem. Commun. 1992, 1184.
(3) Shapiro reaction of ketone phenylaziridinylhydrazones with excess
base: Evans, D. A.; Nelson, J. V. J. Am. Chem. Soc. 1980, 102, 774.
(4) Muller, R. K.; Joos, R.; Felix, D.; Schreiber, J.; Wintner, C.;
Eschenmoser, A. Organic Syntheses; Wiley: New York, 1988; Collect. Vol.
VI, p 56.
The application of the present method in natural product
synthesis is illustrated in Scheme 2 by a simple route to
(6) Prepared from optically pure (R)-1-phenyl-1,2-ethanediol and purified
by recrystallization of 1-amino-2-phenylaziridinium acetate according to
the procedure in ref 4.
(7) The enantioselectivity of 7 and 8 was determined by HPLC analysis,
and the absolute configuration was correlated to the known diester 9 {70%
ee, [R]D -20.0° (c ) 1.3, CHCl3)}: Honda, T.; Kimura, N.; Tsubuki, M.
Tetrahedron: Asymmetry 1993, 4, 21.
(5) The regiochemical assignments of (E)- and (Z)-isomers were made
by 13C NMR analysis: Bunnell, C. A.; Fuchs, P. L. J. Org. Chem. 1977,
42, 2614.
0002-7863/96/1518-2289$12.00/0 © 1996 American Chemical Society