Organocatalysis for the Asymmetric Michael Addition of Cycloketones and alpha, beta-Unsaturated Nitroalkenes

Abstract

Michael addition is one of the most important carbon-carbon bond formation reactions. In this study, an (R, R)-1,2-diphenylethylenediamine (DPEN)-based thiourea organocatalyst was applied to the asymmetric Michael addition of nitroalkenes and cycloketones to produce a chiral product. The primary amine moiety in DPEN reacts with the ketone to form an enamine and is activated through the hydrogen bond formation between the nitro group in the alpha, beta-unsaturated nitroalkene and thiourea. Here, the aim was to obtain an asymmetric Michael product through the 1,4-addition of the enamine to an alkene to form a new carbon-carbon bond. As a result, the primary amine of the chiral diamine was converted into an enamine. The reaction proceeded with a relatively high level of enantioselectivity achieved using double activation through the hydrogen bonding of the nitro group and thiourea. Michael products with high levels of enantioselectivity (76-99% syn ee) and diastereoselectivity (syn/anti = 9/1) were obtained with yields in the range of 88-99% depending on the ketone.