Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins
Abstract
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.
- Authors:
-
[1];
[1];
[1];
[1];
[1];
[1]
- 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)
- Publication Date:
- Research Org.:
- Princeton Univ., NJ (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division
- OSTI Identifier:
- 1756844
- Grant/Contract Number:
- SC0019370
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of the American Chemical Society
- Additional Journal Information:
- Journal Volume: 143; Journal Issue: 1; Journal ID: ISSN 0002-7863
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Hydrocarbons; Flavins; Peptides and proteins; Stereoselectivity; Chemical reactions
Citation Formats
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., and Hyster, Todd K. Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins. United States: N. p., 2020.
Web. doi:10.1021/jacs.0c11462.
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. Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins. United States. https://doi.org/10.1021/jacs.0c11462
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., and Hyster, Todd K. Mon .
"Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins". United States. https://doi.org/10.1021/jacs.0c11462. https://www.osti.gov/servlets/purl/1756844.
@article{osti_1756844,
title = {Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins},
author = {Page, Claire G. and Cooper, Simon J. and DeHovitz, Jacob S. and Oblinsky, Daniel G. and Biegasiewicz, Kyle F. and Antropow, Alyssa H. and Armbrust, Kurt W. and Ellis, J. Michael and Hamann, Lawrence G. and Horn, Evan J. and Oberg, Kevin M. and Scholes, Gregory D. and Hyster, Todd K.},
abstractNote = {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.},
doi = {10.1021/jacs.0c11462},
journal = {Journal of the American Chemical Society},
number = 1,
volume = 143,
place = {United States},
year = {Mon Dec 28 00:00:00 EST 2020},
month = {Mon Dec 28 00:00:00 EST 2020}
}
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