Page 91 - Advanced Organic Chemistry Part B - Reactions & Synthesis

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Reactions of Carbon

Nucleophiles with Carbonyl

Compounds

Introduction

The reactions described in this chapter include some of the most useful methods
for carbon-carbon bond formation: the aldol reaction, the Robinson annulation, the
Claisen condensation and other carbon acylation methods, and the Wittig reaction and
other olefination methods. All of these reactions begin with the addition of a stabilized
carbon nucleophile to a carbonyl group. The product that is isolated depends on the
nature of the stabilizing substituent (Z) on the carbon nucleophile, the substituents
(A and B) at the carbonyl group, and the ways in which A, B, and Z interact to
complete the reaction pathway from the addition intermediate to the product. Four
fundamental processes are outlined below. Aldol addition and condensation lead to
-hydroxyalkyl or -alkylidene derivatives of the carbon nucleophile (Pathway A).
The acylation reactions follow Pathway B, in which a group leaves from the carbonyl
electrophile. In the Wittig and related olefination reactions, the oxygen in the adduct
reacts with the group Z to give an elimination product (Pathway C). Finally, if the
enolate has an -substituent that is a leaving group, cyclization can occur, as in
Pathway D. This is observed, for example, with enolates of -haloesters. The funda-
mental mechanistic concepts underlying these reactions were introduced in Chapter 7
of Part A. Here we emphasize the scope, stereochemistry, and synthetic utility of these
reactions.

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