Science of Synthesis

Rodriguez, J.; Bonne, D.; Coquerel, Y.; Constantieux, T., Science of Synthesis: Multicomponent Reactions, (2014) 2, 1.

General Introduction

Since the first condensation of diethyl malonate with ethyl cinnamate, reported more than 120 years ago, the archetypal 1,4-conjugate addition of nucleophiles, nowadays referred to as the Michael addition, has constituted one of the most popular, reliable, and efficient methods for the formation of a C—C bond.[‌1‌] Despite the importance of this reaction and its intrinsic atom economy, the Michael addition came to be of interest for multicomponent reactions only recently.[‌2‌] It is now established as a key transformation for synthetic applications in multicomponent reactions with a great potential for heterocycle synthesis.[‌3‌] In this chapter the reader will find a selection of multicomponent reactions for the synthesis of diverse families of valuable acyclic, carbocyclic, and heterocyclic scaffolds, in which the Michael addition is either the initiating step or, less often, a late event of the domino sequence. All the examples concern transformations in which each component is present at the beginning of the reaction, thus excluding multicomponent reactions in which the α,β-unsaturated electrophilic component is formed in situ. The main sections have been organized to present first achiral and racemic reactions, then diastereoselective reactions, and finally enantioselective reactions, with each subsection first discussing carba-Michael additions and then, when applicable, hetero-Michael additions.

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