title: Intermolecular carbene S-H insertion catalysed by engineered myoglobin-based catalysts†.
abstract: The first example of a biocatalytic strategy for the synthesis of thioethers via an intermolecular carbene S-H insertion reaction is reported. Engineered variants of sperm whale myoglobin were found to efficiently catalyze this C-S bond forming transformation across a diverse set of aryl and alkyl mercaptan substrates and α-diazoester carbene donors, providing high conversions (60-99%) and high numbers of catalytic turnovers (1,100-5,400). Furthermore, the enantioselectivity of these biocatalysts could be tuned through mutation of amino acid residues within the distal pocket of the hemoprotein, leading to myoglobin variants capable of supporting asymmetric S-H insertions with up to 49%ee. Rearrangement experiments support a mechanism involving the formation of a sulfonium ylide generated upon attack of the thiol substrate to a heme-bound carbene intermediate.
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Rd, Rochester, New York 14627, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Tyagi
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Rd, Rochester, New York 14627, USA.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Bonn
authors.affiliation: Department of Chemistry, University of Rochester, 120 Trustee Rd, Rochester, New York 14627, USA.
authors.forename: Rudi
authors.initials: R
authors.lastname: Fasan