An Alternative Synthesis of Chiral (S)‐Proline Derivatives that Contain a Thiohydantoin Moiety and Their Application as Organocatalysts in the Asymmetric Michael Addition Reaction under Solvent‐Free Conditions.

Abstract

AbstractA convenient synthetic procedure for the preparation of chiral thiohydantoins derived from natural α‐amino acids is reported. Salient features of this method include ready availability of the starting materials, mild reaction conditions, and high yields of the desired products. The prepared thiohydantoins were tested as organocatalysts in asymmetric Michael addition reactions, under solvent‐free reaction conditions. Thiohydantoin 10 d turned out to be the most efficient catalyst, and its catalytic activity can be significantly enhanced by the use of an equimolar amount of salicylic acid as additive. Furthermore, highest diastereo‐ and enantioselectivity is achieved when the reaction is carried out at −5.5 °C, without detriment of the reaction rate. Regarding the reaction’s scope, the asymmetric Michael reaction catalyzed by 10 d was found to maintain its efficiency with various Michael acceptors.