Page 166 - Advanced Organic Chemistry Part B - Reactions & Synthesis

138 control is facilitated by use of somewhat more activated enones, such as methyl
1-(trimethylsilyl)vinyl ketone.
CHAPTER 2
O
Reactions of Carbon O
Nucleophiles with CH 3 CCHCH 2 (CH 3 ) 3 Si – OH
Carbonyl Compounds + CH 3 CC CH 2
–
O Si(CH 3 ) 3 O O
O
Si(CH 3 ) 3 + (CH 3 ) 3 SiOH
Ref. 173
The role of the trimethylsilyl group is to stabilize the enolate formed in the conjugate
addition. The silyl group is then removed during the dehydration step. Methyl
1-trimethylsilylvinyl ketone can be used under aprotic conditions that are compatible
with regiospecific methods for enolate generation. The direction of annulation of
unsymmetrical ketones can therefore be controlled by the method of enolate formation.
1) Si(CH )
3 3
CH 3
CH 3 CH 3 CH 2 CCCH 3
CH Li O
3
(CH ) SiO LiO 2) KOH H
3 3
H H O 69%
Ref. 174
Methyl 1-phenylthiovinyl ketones can also be used as enones in kinetically controlled
Robinson annulation reactions, as illustrated by Entry 6. Entry 7 shows a annulation
using silyl enol ether as the enolate equivalent. These reactions are called Mukaiyama-
Michael reactions (see Section 2.6.3).
The Robinson annulation is a valuable method for preparing bicyclic and tricyclic
structures that can serve as starting materials for the preparation of steroids and
terpenes. 175 Reaction with 2-methylcyclohexan-1,3-dione gives a compound called the
Wieland-Miescher ketone.
O O O
O CH 3 O CH 3
CH 3
+ CH
CHCCH 3
CH 2 3
O O O
A similar reaction occurs with 2-methylcyclopentane-1,3-dione, 176 and can be done
enantioselectively by using the amino acid L-proline to form an enamine intermediate.
The (S)-enantiomer of the product is obtained in high enantiomeric excess. 177
O CH 3 O CH O
CH 3 + CO – 3
N 2 +
H
CH CCH CH 2 H H O O
3
2
O OH
O
173 G. Stork and B. Ganem, J. Am. Chem. Soc., 95, 6152 (1973); G. Stork and J. Singh, J. Am. Chem. Soc.,
96, 6181 (1974).
174
R. K. Boeckman, Jr., J. Am. Chem. Soc., 96, 6179 (1974).
175
N. Cohen, Acc. Chem. Res., 9, 412 (1976).
176 Z. G. Hajos and D. R. Parrish, J. Org. Chem., 39, 1615 (1974); U. Eder, G. Sauer, and R. Wiechert,
Angew. Chem. Int. Ed. Engl., 10, 496 (1971); Z. G. Hajos and D. R. Parrish, Org. Synth., 63, 26 (1985).
177
J. Gutzwiller, P. Buchshacher, and A. Furst, Synthesis, 167 (1977); P. Buchshacher and A. Furst, Org.
Synth., 63, 37 (1984); T. Bui and C. F. Barbas, III, Tetrahedron Lett., 41, 6951 (2000).