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Photoenzymatic Hydrogenation of Heteroaromatic Olefins using ‘Ene’-Reductases with Photoredox Catalysts

Nakano, Yuji and Black, Michael J. and Meichan, Andrew J. and Sandoval, Braddock A. and Chung, Megan M. and Biegasiewicz, Kyle F. and Zhu, Tianyu and Hyster, Todd K. (2020) Photoenzymatic Hydrogenation of Heteroaromatic Olefins using ‘Ene’-Reductases with Photoredox Catalysts. Angewandte Chemie International Edition, 59 (26). pp. 10484-10488. ISSN 1433-7851.

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Flavin‐dependent ‘ene’‐reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be “dynamically stable”, suggesting it is sufficiently long lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic paradigms.

Item Type:Article
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URLURL TypeDescription
Zhu, Tianyu0000-0003-2061-3237
Hyster, Todd K.0000-0003-3560-355X
Additional Information:© 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Accepted manuscript online: 17 March 2020; Manuscript accepted: 17 March 2020; Manuscript revised: 13 March 2020; Manuscript received: 29 February 2020. Version of Record online: 15 April 2020. Financial support provided by NSF (1846861), Searle Scholar Program, Sloan Scholar Program, and Princeton University. YN thanks the Australian Government for an Endeavour Postdoctoral Fellowship. We thank Phil Jeffrey for assistance with X‐ray structure determination and the NSLS‐II AMX (17‐ID‐1) beam line staff for assistance with X‐ray data collection. This research used NSLS‐II AMX (17‐ID‐1), a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under contract No. DE‐SC0012704. The authors declare no conflict of interest.
Funding AgencyGrant Number
Searle Scholars ProgramUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Princeton UniversityUNSPECIFIED
Department of Education, Skills and Employment (Australia) UNSPECIFIED
Department of Energy (DOE)DE-SC0012704
Subject Keywords:biocatalysisl Photoredox catalysisl asymmetric catalysis; Pyridine; hydrogen atom transfer
Issue or Number:26
Record Number:CaltechAUTHORS:20200323-092845496
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Official Citation:Y. Nakano, M. J. Black, A. J. Meichan, B. A. Sandoval, M. M. Chung, K. F. Biegasiewicz, T. Zhu, T. K. Hyster, Angew. Chem. Int. Ed. 2020 , 59 , 10484.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102041
Deposited By: Tony Diaz
Deposited On:23 Mar 2020 17:22
Last Modified:23 Jun 2020 21:17

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