Organocatalysis for the Asymmetric Michael Addition of Cycloketones and <i>α</i>, <i>β</i>-Unsaturated Nitroalkenes

• Main Authors: Jae Ho Shim, Byung Kook Ahn, Ji Yeon Lee, Hyeon Soo Kim, Deok-Chan Ha
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Catalysts
• Subjects: organocatalyst; enantioselectivity; cycloketone; thiourea catalyst; asymmetric synthesis; Michael addition
• Online Access: https://www.mdpi.com/2073-4344/11/8/1004

Michael addition is one of the most important carbon–carbon bond formation reactions. In this study, an (<i>R</i>, <i>R</i>)-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 <i>α</i>, <i>β</i>-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% <i>syn</i> ee) and diastereoselectivity (<i>syn</i>/<i>anti</i> = 9/1) were obtained with yields in the range of 88–99% depending on the ketone.