Page 483 - Advanced Organic Chemistry Part B - Reactions & Synthesis

456 questions of both regiochemistry and stereochemistry arise. 1-Octene is the exclusive
product from 2-octanone. 288
CHAPTER 5
C H SO NHN
Reduction of 7 7 2
Carbon-Carbon Multiple 2 LiNR 2
3
2 5
2 5
Bonds, Carbonyl CH C(CH ) CH 3 CH 2 CH(CH ) CH 3
Groups, and Other
Functional Groups
This regiospecificity has been shown to depend on the stereochemistry of the C=N
bond in the starting hydrazone. There is evidently a strong preference for abstracting
the proton syn to the arenesulfonyl group, probably because this permits chelation with
the lithium ion.
N –
ArSO 2
N –
ArSO 2 +
N H
N Li
CH 2 CHCH R
2
CH 2 CCH 2 R
CH CCH R
3
2
The Shapiro reaction converts the p-toluenesulfonylhydrazones of -unsaturated
ketones to dienes (see Entries 3 to 5 in Scheme 5.15). 289
The vinyl lithium reagents generated in the Shapiro reaction can be used in
tandem reactions. In the reaction shown below, a hydroxymethyl group was added by
formylation followed by reduction.
CH 3 1) n-BuLi, TMEDA CH 3
2) DMF
3) NaBH 4
NNHSO C H CH OH
2
2 7 7
In another example, a sequence of methylation-elimination-hydroxymethylation was
used to install the functionality pattern found in the A-ring of taxol. The hydrazone
dianion was generated and methylated at low temperature. The hydrazone was
then deprotonated again using excess n-butyllithium and allowed to warm to room
temperature, at which point formation of the vinyllithium occurred. Reaction with
paraformaldehyde generated the desired product. 290
1) 4.0. equiv n-BuLi
CH 1) 2.2. equiv n-BuLi CH CH 3 CH CH CH 3 CH 3
CH 3 3 CH 3 –55°C 3 O 3 –50°C 3 O
ArSO HNN O CH 3 ArSO 2 HNN CH 3 then 25°C HOCH 2 CH 3
2
O O 2) CH O O
2) 2.5 equiv CH I 2 CH
3 CH 3
3
62%
Ar = 2,4,6-trimethylphenyl
Scheme 5.15 shows some examples of the Shapiro reaction. Entry 1 is an example
of the standard procedure, as documented in Organic Syntheses. Entry 2 illustrates
the preference for the formation of the less-substituted double bond. Entries 3, 4, and
5 involve tosylhydrazone of -unsaturated ketones. The reactions proceed by -

deprotonation. Entry 6 illustrates the applicability of the reaction to a highly strained
system.

288
K. J. Kolonko and R. H. Shapiro, J. Org. Chem., 43, 1404 (1978).
289 W. G. Dauben, G. T. Rivers, and W. T. Zimmerman, J. Am. Chem. Soc., 99, 3414 (1977).
290
O. P. Tormakangas, R. J. Toivola, E. K. Karvinen, and A. M. P. Koskinen, Tetrahedron, 58, 2175
(2002).