Cooperative chemoenzymatic and biocatalytic cascades to access chiral sulfur compounds bearing C(sp<sup>3</sup>)-S stereocentres.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39333478.
- Also identified by DOI 10.1038/s41467-024-52608-8 and PMC identifier 11436715.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Biocatalysis has been widely employed for the generation of carbon-carbon/heteroatom stereocentres, yet its application in chiral C(sp<sup>3</sup>)-S bond construction is rare and limited to enzymatic kinetic resolutions. Herein, we describe the enantioselective construction of chiral C(sp<sup>3</sup>)-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(sp<sup>3</sup>)-S and C(sp<sup>3</sup>)-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(sp<sup>2</sup>)/C(sp<sup>3</sup>)-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(sp<sup>3</sup>)-N/O/Se bonds with good to excellent enantioselctivities.