Directed evolution of heme proteins has opened access to new-to-nature enzymatic reactivity. Among these, reactions resulting from active site, iron-nitrene intermediates present a powerful strategy to forge C-N bonds with high site- and stereo-selectivity. Herein, we report the development of a biocatalytic, intermolecular benzylic C-H amidation reaction operating at mild and scalable conditions. With hydroxylamine derivatives as nitrene precursors, feedstock aromatic compounds can be converted to chiral amides with excellent enantioselectivity (upto &gt;99 % ee) and high yields (upto 87 %). Kinetic isotope effect studies combined with active site modeling reveal mechanistic details of the amidation process.

Enantioselective, intermolecular amidation of benzylic C-H bonds with engineered P411 enzymes

ACS Spring Meeting 2021

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