Nature Communications (Sep 2024)

Cooperative chemoenzymatic and biocatalytic cascades to access chiral sulfur compounds bearing C(sp3)–S stereocentres

  • Fei Zhao,
  • Ariane Mattana,
  • Ruqaiya Alam,
  • Sarah L. Montgomery,
  • Akash Pandya,
  • Fabrizio Manetti,
  • Beatriz Dominguez,
  • Daniele Castagnolo

DOI
https://doi.org/10.1038/s41467-024-52608-8
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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Abstract Biocatalysis has been widely employed for the generation of carbon-carbon/heteroatom stereocentres, yet its application in chiral C(sp3)–S bond construction is rare and limited to enzymatic kinetic resolutions. Herein, we describe the enantioselective construction of chiral C(sp3)–S bonds through ene-reductase biocatalyzed conjugate reduction of prochiral vinyl sulfides. A series of cooperative sequential/concurrent chemoenzymatic and biocatalytic cascades have been developed to access a broad range of chiral sulfides, including valuable β-hydroxysulfides bearing two adjacent C(sp3)–S and C(sp3)–O stereocentres, in a stereoconvergent manner with good to excellent yields (up to 96%) and enantioselectivities (up to >99% ee). Notably, this biocatalytic strategy allows to overcome the long-standing shortcomings of catalyst poisoning and C(sp2)/C(sp3)–S bond cleavage faced in transition-metal-catalyzed hydrogenation of vinyl sulfides. Finally, the potential of this methodology is also exemplified by its broader application in the stereoconvergent assembly of chiral C(sp3)–N/O/Se bonds with good to excellent enantioselctivities.