Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis

Harrison, Wesley; Jiang, Guangde; Zhang, Zhengyi; Li, Maolin; Chen, Haoyu; Zhao, Huimin

doi:10.1021/jacs.4c00620

Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis

Journal Article · Fri Apr 05 00:00:00 EDT 2024 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.4c00620· OSTI ID:2377396

Harrison, Wesley ^[1]; Jiang, Guangde ^[2]; Zhang, Zhengyi ^[2]; Li, Maolin ^[2]; ^[2]; ^[2]

University of Illinois at Urbana−Champaign, IL (United States); University of Illinois Urbana-Champaign
University of Illinois at Urbana−Champaign, IL (United States)

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derive nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination. In this reaction, the flavin-dependent ene-reductase photocatalytically generates the aminium radical cation from the corresponding hydroxylamine and catalyzes the asymmetric intermolecular hydroamination to furnish the enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated hydrogen atom transfer. Furthermore, this work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a long-standing challenge in chemical synthesis.

View Accepted Manuscript (DOE)

Research Organization:: Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0018420

OSTI ID:: 2377396

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 15 Vol. 146; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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