Biocatalytic, Intermolecular C-H Bond Functionalization for the Synthesis of Enantioenriched Amides.

Autor: Athavale SV; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California, 91125, USA., Gao S; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California, 91125, USA., Liu Z; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California, 91125, USA., Mallojjala SC; Department of Chemistry, Binghamton University, Binghamton, New York, 13902, USA., Hirschi JS; Department of Chemistry, Binghamton University, Binghamton, New York, 13902, USA., Arnold FH; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California, 91125, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Nov 15; Vol. 60 (47), pp. 24864-24869. Date of Electronic Publication: 2021 Oct 13.
DOI: 10.1002/anie.202110873
Abstrakt: Directed evolution of heme proteins has opened access to new-to-nature enzymatic activity that can be harnessed to tackle synthetic challenges. Among these, reactions resulting from active site iron-nitrenoid intermediates present a powerful strategy to forge C-N bonds with high site- and stereoselectivity. Here we report a biocatalytic, intermolecular benzylic C-H amidation reaction operating at mild and scalable conditions. With hydroxamate esters as nitrene precursors, feedstock aromatic compounds can be converted to chiral amides with excellent enantioselectivity (up to >99 % ee) and high yields (up to 87 %). Kinetic and computational analysis of the enzymatic reaction reveals rate-determining nitrenoid formation followed by stepwise hydrogen atom transfer-mediated C-H functionalization.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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