Enantioselective Intramolecular Crossed Rauhut-Currier Reactions through Cooperative Nucleophilic Activation and Hydrogen-Bonding Catalysis: Scope and Mechanistic Insight

A highly efficient and enantioselective intramolecular crossed Rauhut–Currier (RC) reaction of nitroolefins with tethered enonates has been developed through cooperative nucleophilic activation and a hydrogen‐bonding catalytic strategy (≤98 % ee and 98 % yield). The reaction features simple experimental procedures and is completely chemoselective and atom‐economic in character. The potential synthetic applications have been demonstrated by the conversion of the RC reaction products into biologically and pharmaceutically valuable compounds with highly diastereoselectivity. In addition, computational investigations were employed to support the proposed mechanism and to obtain a good understanding of the origin of the stereoselectivity in RC reactions. Working together: Cooperative nucleophilic activation and hydrogen‐bonding catalysis allow a highly efficient and enantioselective intramolecular crossed Rauhut–Currier (RC) reaction of nitroolefins with tethered enonates (≤98 % ee, 98 % yield; see scheme). Computational investigations indicate that the stereoselectivity of the RC reaction is determined by the intramolecular Michael addition and the rate‐determining step is a retro‐aza‐Michael addition reaction.