Alkylations of Enols and Enolates

Enolate alkylation, the nucleophilic substitution of electrophilic alkylating reagents by carbon nucleophiles generated from the adeprotonation of carbonyl compounds, is one among the most fundamental and important methods for the construction of carbon–carbon bonds adjacent to a carbonyl group. Over the past fifty years, this methodology has evolved into a highly selective, efficient, and essential technique integral to the practitioners of pharmaceutical industry, chemical biology, and academic organic synthesis. Since the previous publication of Comprehensive Organic Synthesis in 1991, a field-wide explosion of interest in catalysis has sparked the development of numerous metal and metal-free catalytic alkylation methods. These advances have introduced new methods for enolate formation, expanded substrate scope, and enabled highly stereoselective α-alkylations. New techniques allow elaboration of a diverse array of small molecules and have made enolate alkylation one of the most important methods for asymmetric carbon–carbon bond formation. Owing to the overwhelming wealth of literature on carbonyl chemistry, attempt has been made to narrowly define ‘enolate alkylation’ to encompass only the reactions of enolates with sp^3-hybridized carbon electrophiles. Aldol reactions, conjugate additions, arylations, and functionalizations of enamines and metalloenamines will be addressed in other chapters of this compendium