Enantioselective direct aldol reaction: the blossoming of modern organocatalysis

Abstract

The use of simple (S)-proline as catalyst for the intermolecular direct aldol reaction at the beginning of this century became a true milestone in the growth of organocatalysis as a useful synthetic strategy. Since then, a plethora of new organocatalytic systems have been developed allowing to reach extraordinary levels of efficiencies, widening the scope of substrates used. Several modifications have been introduced to overcome some of the initial drawbacks, such as long reaction times, high catalyst loading, excess of reagents, etc., improving the expectations for their use in large scale synthesis. All these achievements would not be possible without a partial understanding of the involved mechanism. The acquired knowledge in this area has allowed the application of this strategy to be used in the synthesis of natural products. Within this review, a comprehensive look of all these aspects will be discussed.