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Updated: Jun 4, 2026

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Biocatalytic Metal Hydrogen Atom Transfer for Asymmetric Olefin-Olefin Coupling
Rajib Mandal1, Jaicy Vallapurackal1, Aris V Rubio1
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
None:
Metal-mediated hydrogen atom transfer (MHAT) enables versatile radical hydrofunctionalization reactions, yet asymmetric variants, especially for olefin-olefin coupling, remain unknown with small-molecule catalysts. Here we report an enzymatic solution using engineered protoglobins, establishing a biocatalytic platform for asymmetric MHAT-triggered intramolecular cyclization. Directed evolution of a protoglobin furnished a variant that catalyzes 5-exo-trig radical cyclizations to generate 3,4-substituted pyrrolidines in high yields and up to 98:2 e.r. The reaction tolerates diverse donor and acceptor substituents, including esters, amides, nitriles, nitro groups, imines, and ketones. Mechanistic experiments and DFT calculations support a radical pathway with an ultrafast enantiodetermining radical cyclization. These results show that engineered heme proteins can support new-to-nature MHAT chemistry and exert stereocontrol over rapid radical steps, providing a powerful system for asymmetric MHAT reactions.
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