Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins

Page, Claire G.; Cooper, Simon J.; DeHovitz, Jacob S.; Oblinsky, Daniel G.; Biegasiewicz, Kyle F.; Antropow, Alyssa H.; Armbrust, Kurt W.; Ellis, J. Michael; Hamann, Lawrence G.; Horn, Evan J.; Oberg, Kevin M.; Scholes, Gregory D.; Hyster, Todd K.

doi:10.1021/jacs.0c11462

Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins

Journal Article · Sun Dec 27 23:00:00 EST 2020 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.0c11462· OSTI ID:1756844

Page, Claire G. ^[1]; ^[2]; ^[2]; ^[2]; ^[2]; Antropow, Alyssa H. ^[3]; Armbrust, Kurt W. ^[3]; Ellis, J. Michael ^[3]; Hamann, Lawrence G. ^[4]; Horn, Evan J. ^[5]; Oberg, Kevin M. ^[5]; ^[2]; ^[2]

Princeton Univ., NJ (United States); Princeton University
Princeton Univ., NJ (United States)
Bristol Myers Squibb, Cambridge, MA (United States)
Takeda Pharmaceuticals, Cambridge, MA (United States)
Bristol Myers Squibb, San Diego, CA (United States)

Intermolecular C–C bond-forming reactions are underdeveloped transformations in the field of biocatalysis. Here we report a photoenzymatic intermolecular hydroalkylation of olefins catalyzed by flavin-dependent ‘ene’-reductases. Radical initiation occurs via photoexcitation of a rare high-order enzyme-templated charge-transfer complex that forms between an alkene, α-chloroamide, and flavin hydroquinone. This unique mechanism ensures that radical formation only occurs when both substrates are present within the protein active site. Here, this active site can control the radical terminating hydrogen atom transfer, enabling the synthesis of enantioenriched γ-stereogenic amides. This work highlights the potential for photoenzymatic catalysis to enable new biocatalytic transformations via previously unknown electron transfer mechanisms.

View Accepted Manuscript (DOE)

Research Organization:: Princeton Univ., NJ (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division

Grant/Contract Number:: SC0019370

OSTI ID:: 1756844

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 1 Vol. 143; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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