Page 33 - Advanced Organic Chemistry Part B - Reactions & Synthesis

−
B−H C K a C−H 5
K = =
C−H B K
−
SECTION 1.1
a B−H
Generation and
If we consider the case of a simple alkyl ketone in a protic solvent, for example, Properties of Enolates
we see that hydroxide ion or primary alkoxide ions will convert only a fraction of a and Other
Stabilized Carbanions
ketone to its anion.
O O –
RCCH + RCH O – RC CH 2 + RCH OH K < 1
2
3
2
The slightly more basic tertiary alkoxides are comparable to the enolates in basicity,
and a more favorable equilibrium will be established with such bases.

O O –
RCCH 3 + R 3 CO – RC CH + R COH K ~ 1
3
2
Note also that dialkyl ketones such as acetone and 3-pentanone are slightly more acidic
than the simple alcohols in DMSO. Use of alkoxide bases in DMSO favors enolate
formation. For the amide bases, K a B−H << K a C−H , and complete formation of the
enolate occurs.

O O –
+ R N – RC CH + R NH K >> 1
RCCH 3 2 2 2

It is important to keep the position of the equilibria in mind as we consider reactions of
carbanions. The base and solvent used determine the extent of deprotonation. Another
important physical characteristic that has to be kept in mind is the degree of aggregation
of the carbanion. Both the solvent and the cation influence the state of aggregation.
This topic is discussed further in Section 1.1.3.

1.1.2. Regioselectivity and Stereoselectivity in Enolate Formation
from Ketones and Esters

Deprotonation of the corresponding carbonyl compound is a fundamental method
for the generation of enolates, and we discuss it here for ketones and esters. An
unsymmetrical dialkyl ketone can form two regioisomeric enolates on deprotonation.

O O – O –
B –
R CHCCH R' R 2 C CCH R' or R CHC CHR'
2
2
2
2
Full exploitation of the synthetic potential of enolates requires control over the regio-
selectivity of their formation. Although it may not be possible to direct deprotonation so
as to form one enolate to the exclusion of the other, experimental conditions can often
be chosen to favor one of the regioisomers. The composition of an enolate mixture
can be governed by kinetic or thermodynamic factors. The enolate ratio is governed