Page 107 - Advanced Organic Chemistry Part B - Reactions & Synthesis

control the stereoselectivity of enolate formation from esters. For simple esters such 79
as ethyl propanoate, the E-enolate is preferred under kinetic conditions using a strong
base such as LDA in THF solution. Inclusion of a strong cation-solvating cosolvent, SECTION 2.1
such as HMPA or DMPU, favors the Z-enolate. 36 These enolates can be trapped and Aldol Addition and
Condensation Reactions
analyzed as the corresponding silyl ketene acetals. The relationships are similar to
those discussed for formation of ketone enolates in Section 1.1.2.

LDA TMSCl H OSi(CH )
3 3
CH CH CO C H E-silyl ketene acetal
3
2
2 2 5
THF OC H
CH 3 2 5
CH
LDA TMSCl 3 OSi(CH )
3 3
CH CH CO C H Z-silyl ketene acetal
2 2 5
3
2
THF, HMPA OC H
H 2 5
These observations are explained in terms of a chairlike TS for the LDA/THF condi-
tions and a more open TS in the presence of an aprotic dipolar solvent.
O OR′
– O R H –
Li R OR′ O
R N H O OR′ R OR′
2
H
R H
E-enolate –
H :B Z-enolate
Despite the ability to control ester enolate geometry, the aldol addition reactions
of unhindered ester enolate are not very stereoselective. 37
OH OH
O
CH 3 1) LDA RO C + RO C
2
2
RO 2) R′CH=O R′ R′
CH 3 CH 3
R R′ syn:anti
CH 3 (CH ) CH 45:55
3 2
Ph 45:55
CH 3
(CH ) C Ph 49:51
3 3

This stereoselectivity can be improved by use of a very bulky group. 2,6-
Dimethylphenyl esters give E-enolates and anti aldol adducts. 38

36
R. E. Ireland and A. K. Willard, Tetrahedron Lett., 3975 (1975); R. E. Ireland, R. H. Mueller, and
A. K. Willard, J. Am. Chem. Soc., 98, 2868 (1976); R. E. Ireland, P. Wipf, and J. D. Armstrong, III,
J. Org. Chem., 56, 650 (1991).
37 A. I. Meyers and P. J. Reider, J. Am. Chem. Soc., 101, 2501 (1979); C. H. Heathcock, C. T. Buse,
W. A. Kleschick, M. C. Pirrung, J. E. Sohn, and J. Lampe, J. Org. Chem., 45, 1066 (1980).
38
M. C. Pirrung and C. H. Heathcock, J. Org. Chem., 45, 1728 (1980).