Regio- and stereo-control of chemical reactions is a central theme in modern synthetic chemistry. Among different strategies, organocatalysis is one of the main branches of enantioselective synthesis. Although moderate success has been found for monofunctional organocatalysts, bifunctional structures lead to promising and efficient asymmetric transformations. However, little is known about how bifunctional moieties synergistically work to achieve the activation of both nucleophiles and electrophiles. In addition, the limits of reaction landscape catalyzed by these structures are far from being determined. Herein, we report a detailed study combining experiments and theory that unravels how a novel reaction is able to show both regio- and enantioselectivity, as a result of the cooperation of a squaramide moiety and an amine group in a bifunctional asymmetric catalyst. In particular, we describe the first asymmetric 1,3 addition of silyl-dienol ethers to nitroalkenes. The reaction can be carried out in good yields and excellent enantioselecivities. The process takes place under smooth conditions, compatible with the use of a large variety of nitroalkenes, and different silyl-dienol ethers to give aldehydes, ketones, esters and amides. This unusual regioselectivity, provides access to chiral Rauhut-Currier type products bearing either tri- or tetra-substituted double bonds, which are difficult to obtain by the existing methods. Only 1,3 regioselectivity is observed, even though the activation of the most reactive site of the silyl-dienol ether (C5) should result in the 1,5 isomer.

Asymmetric synthesis of Rauhut-Currier type products by a regioselective Mukaiyama reaction under bifunctional catalysis

253rd National Meeting (2017)

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