The Eschenmoser Coupling Reaction

Abstract

The Eschenmoser coupling reaction represents a versatile and efficient method to prepare vinylogous amides and urethanes by alkylation of a secondary or tertiary thioamide with an appropriate electrophilic component followed by elimination of sulfur (equation 1). This coupling, which in essence condenses an enolizable carbon with an amide carbonyl, can be formally considered a variant of the Claisen condensation. An extension of this process through alkylation of thiocarboxylic acids leads to direct synthesis of 1,3-dicarbonyl compounds (equation 2). Vinylogous amides and carbamates along with their hydrolysis products, the 1,3-dicarbonyl compounds, are important synthetic intermediates; their value is attested by the numerous methods available for their synthesis.1,2 The Eschenmoser reaction provides an alternative approach to prepare these compounds that offers several distinct advantages. The unambiguous formation of a particular vinylogous amide or carbamate or a substituted 1,3-dicarbonyl compound can be achieved. Since the reaction conditions are sufficiently mild, incorporation of various functional groups and preservation of base-sensitive stereocenters are possible. The reacting centers also are relatively insensitive to the steric environment. In addition, the range of applications now available to the reaction has been broadened significantly through modifications and extensions on the original studies.