Page 613 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

interfere with effective solvation of the developing negative charge on oxygen, the rate 595
of proton abstraction is reduced. The observed activation energies parallel the rates. 45
Structural effects on the rates of deprotonation of ketones have also been studied SECTION 6.3
using very strong bases under conditions where complete conversion to the enolate Carbanions Stabilized by
Functional Groups
occurs. In solvents such as THF or DME, bases such as LDA and KHMDS give
solutions of the enolates that reflect the relative rates of removal of the different protons
in the carbonyl compound (kinetic control). The least hindered proton is removed most
rapidly under these conditions, so for unsymmetrical ketones the major enolate is the
less-substituted one. Scheme 6.1 shows some representative data. Note that for many
ketones, both E- and Z-enolates can be formed.
The equilibrium ratios of enolates for several ketone-enolate systems are also
shown in Scheme 6.1. Equilibrium among the various enolates of a ketone can be
established by the presence of an excess of the ketone, which permits reversible
proton transfer. Equilibration is also favored by the presence of dissociating additives
such as HMPA. As illustrated by most of the examples in Scheme 6.1, the kinetic
enolate is formed by removal of the least hindered hydrogen. The composition of
the equilibrium enolate mixture is usually more closely balanced than for kinetically

Scheme 6.1. Composition of Enolate Mixtures Formed under Kinetic and Thermody-
namic Control a
1 – O –
O –
O O 6 – –
Kinetic CH 3 CH 3 O O O
CH 3 CH 2 CH 2 CH 3
(LDA 0 °C)
CH 3 CH 2 CCH 3 CH 3 CH 3 CH 3
CH 3
71% 13% 16%
2 O – Kinetic
O – O CH 3 (LDA, 0 °C) 99% 1%
CH 3
(CH 3 ) 2 CHCCH 3 (CH 3 ) 2 CH Thermodynamic 26% 74%
CH 2 (NaH)
CH 3
Kinetic
(KHMDS, –78 °C) 99% 1% 7 O O – O –
Thermodynamic 88% 12% CH(CH 3 ) 2 CHCH 3 ) 2 CH(CH 3 ) 2
(KH)
3 O –
O O – O – Kinetic
CH 3 (CH 2 ) 3 100% 0%
CH 3 (Ph 3 CLi)
CH 3 (CH 2 ) 3 CCH 3 CH 3
CH 3 (CH 2 ) 3 CH 2
Thermodynamic
CH 3 (CH 2 ) 3 35% 65%
(Ph 3 CK)
Kinetic
(LDA – 78 °C) 100% 0% 0%
Thermodynamic 42% 46% 12% 8 O O – O –
(KH, 20 °C)
4b – O O
O – O
CH 3
CH 3 CH 3 CH 3
CH 2 CH 3 CH 3
(CH 3 ) 2 CHCCH 2 CH 3 (CH 3 ) 2 CH (CH 3 ) 2 CH
CH 3 Kinetic
CH 3 82% 18%
(Ph 3 CLi)
E Z
Kinetic 40% 60% 0% Thermodynamic 52% 48%
LDA (Ph 3 CK)
LiTMP 32% 68% 0%
LiHMDS 2% 98% 0% 9 – –
2% 98 % 0 O O O
LiNHC 6 H 2 Cl 3
5 O O – O –
PhCH
PhCH 2 CCH 3 CH 3
PhCH 2 CH 2
Kinetic
E,Z – combined (LDA) 98% 2%
Kinetic
(LDA 0 °C) 14% 86% Thermodynamic 50% 50%
(NaH)
Thermodynamic
(NaH) 2% 98%
a. Selected from a more complete compilation by D. Caine, in Carbon-Carbon Bond Formation, R. L. Augustine,
ed., Marcel Dekker, New York, 1979.
b. C. H. Heathcock, C. T. Buse, W. A. Kleschick, M. C. Pirrung, J. E. Sohn, and J. Lampe, J. Org. Chem., 45, 1066
(1980); L. Xie, K van Landeghem, K. M. Isenberger, and C. Bernier, J. Org. Chem., 68, 641 (2003).
45
T. Niiya, M. Yukawa, H. Morishita, H. Ikeda, and Y. Goto, Chem. Pharm. Bull., 39, 2475 (1991).