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

20 January 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


1,3,2-diazaphospholene hydrides (DAP-H) emerged as a nucleophilic main-group hydride able to promote smooth conjugate reduction of polarized double bonds. The transiently formed phosphorus-bound enolate provides a potential platform for reductive α-functionalizations. In this respect, asymmetric C-heteroatom bond forming processes are synthetically appealing but remain so far elusive. We report a 1,3,2-diazaphospholene-catalyzed three-step cascade transformation of α,β-unsaturated N-sulfinyl acrylamides comprised of a conjugate reduction, [2,3]-sigmatropic aza-Mislow-Evans rearrangement and subsequent S-O bond reductive cleavage. The obtained enantio-enriched α-hydroxyl amides are synthetically highly valuable and 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 atom. The transformation operates under mild conditions at ambient temperature. Moreover, DAP hydrides are found to be competent reductants for the cleavage of the formed sulfenate ester, thus eliminating the required additional step like in traditional Mislow-Evans processes.


Asymmetric Synthesis
Main Group Catalysis
Sigmatropic Rearrangement


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