Page 29 - Advanced Organic Chemistry Part B - Reactions & Synthesis

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Alkylation of Enolates

and Other Carbon

Nucleophiles

Introduction

Carbon-carbon bond formation is the basis for the construction of the molecular
framework of organic molecules by synthesis. One of the fundamental processes for
carbon-carbon bond formation is a reaction between a nucleophilic and an electrophilic
carbon. The focus in this chapter is on enolates, imine anions, and enamines, which
are carbon nucleophiles, and their reactions with alkylating agents. Mechanistically,
these are usually S 2 reactions in which the carbon nucleophile displaces a halide or
N
other leaving group with inversion of configuration at the alkylating group. Efficient
carbon-carbon bond formation requires that the S 2 alkylation be the dominant
N
reaction. The crucial factors that must be considered include: (1) the conditions
for generation of the carbon nucleophile; (2) the effect of the reaction conditions
on the structure and reactivity of the nucleophile; and (3) the regio- and stereo-
selectivity of the alkylation reaction. The reaction can be applied to various carbonyl
compounds, including ketones, esters, and amides.

O – O
H + R'CH X
Z 2 Z R'
R R
Z = R, RO, R N enolate alkylation
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These reactions introduce a new substituent to the carbonyl group and constitute an
important method for this transformation. In the retrosynthetic sense, the disconnection
is between the -carbon and a potential alkylating agent.
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