Reductive Asymmetric Aza-Mislow-Evans Rearrangement by 1,3,2-Diazaphospholene Catalysis

Abstract

1,3,2-diazaphospholene hydrides (DAP-H) enable smooth conjugate reduction of polarized double bonds. The transiently formed phosphorus-enolate provides a potential platform for reductive α-functionalizations. In this respect, asymmetric C-heteroatom bond forming processes are synthetically appealing but remain elusive. We report a 1,3,2-diazaphospholene-catalyzed three-step cascade reaction of N-sulfinyl acrylamides comprised of conjugate reduction, [2,3]-sigmatropic aza-Mislow-Evans rearrangement and subsequent S-O bond cleavage. The obtained enantio-enriched α-hydroxy amides are formed in good yields and excellent enantiospecificity. The stereo-defined P-bound N,O-ketene aminal ensures an excellent transfer of chirality from the sulfur stereocenter to α-carbon. The transformation operates under mild conditions at ambient temperature. Moreover, DAP-H is a competent reductant for the cleavage of formed sulfenate ester, eliminating the extra step in traditional Mislow-Evans processes.

Keywords: Asymmetric Synthesis; Diazaphospholenes; Main Group Catalysis; Phosphorous; Sigmatropic Rearrangement.