Photoenzymatic enantioselective intermolecular radical hydroalkylation
Abstract
Enzymes are increasingly explored for asymmetric synthesis, but their applications are generally limited by the reactions available to naturally occurring enzymes. Recently, interest in photocatalysis has spurred the discovery of new reactivity from known enzymes. Yet, so far photo-induced enzymatic catalysis has not been used for cross-coupling of two molecules. For instance, intermolecular coupling of alkenes with α-halo carbonyl compounds through a visible-light-induced radical hydroalkylation, which could provide access to important γ-chiral carbonyl compounds, has not yet been achieved by enzymes. The major challenges are the inherent poor photoreactivity of enzymes and the difficulty in stereochemical control of the remote prochiral radical intermediate. Here we show a new-to-nature, visible-light-induced ene-reductase catalysed intermolecular radical hydroalkylation of terminal alkenes with readily available α-halo carbonyl compounds. This method provides an efficient approach to various carbonyl compounds bearing a γ-stereocentre with excellent yields and enantioselectivities (up to 99% yield, 99% enantiomeric excess), which otherwise are difficult to access by chemocatalysis. Mechanistic studies suggest that the substrates/ene-reductase complex formation at the enzyme active site triggers the enantioselective photo-induced radical reaction. Our research further expands the reactivity repertoire of biocatalytic, synthetically-useful asymmetric transformations by the merger of photocatalysis and enzyme catalysis.
- Authors:
-
- Univ. of Illinois at Urbana-Champaign, IL (United States)
- Xiamen Univ. (China)
- Publication Date:
- Research Org.:
- Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States); Univ. of Illinois at Urbana-Champaign, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
- OSTI Identifier:
- 1632290
- Grant/Contract Number:
- SC0018420; S10-RR028833
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature (London)
- Additional Journal Information:
- Journal Name: Nature (London); Journal Volume: 584; Journal ID: ISSN 0028-0836
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Huang, Xiaoqiang, Wang, Binju, Wang, Yajie, Jiang, Guangde, Feng, Jianqiang, and Zhao, Huimin. Photoenzymatic enantioselective intermolecular radical hydroalkylation. United States: N. p., 2020.
Web. doi:10.1038/s41586-020-2406-6.
Huang, Xiaoqiang, Wang, Binju, Wang, Yajie, Jiang, Guangde, Feng, Jianqiang, & Zhao, Huimin. Photoenzymatic enantioselective intermolecular radical hydroalkylation. United States. https://doi.org/10.1038/s41586-020-2406-6
Huang, Xiaoqiang, Wang, Binju, Wang, Yajie, Jiang, Guangde, Feng, Jianqiang, and Zhao, Huimin. Mon .
"Photoenzymatic enantioselective intermolecular radical hydroalkylation". United States. https://doi.org/10.1038/s41586-020-2406-6. https://www.osti.gov/servlets/purl/1632290.
@article{osti_1632290,
title = {Photoenzymatic enantioselective intermolecular radical hydroalkylation},
author = {Huang, Xiaoqiang and Wang, Binju and Wang, Yajie and Jiang, Guangde and Feng, Jianqiang and Zhao, Huimin},
abstractNote = {Enzymes are increasingly explored for asymmetric synthesis, but their applications are generally limited by the reactions available to naturally occurring enzymes. Recently, interest in photocatalysis has spurred the discovery of new reactivity from known enzymes. Yet, so far photo-induced enzymatic catalysis has not been used for cross-coupling of two molecules. For instance, intermolecular coupling of alkenes with α-halo carbonyl compounds through a visible-light-induced radical hydroalkylation, which could provide access to important γ-chiral carbonyl compounds, has not yet been achieved by enzymes. The major challenges are the inherent poor photoreactivity of enzymes and the difficulty in stereochemical control of the remote prochiral radical intermediate. Here we show a new-to-nature, visible-light-induced ene-reductase catalysed intermolecular radical hydroalkylation of terminal alkenes with readily available α-halo carbonyl compounds. This method provides an efficient approach to various carbonyl compounds bearing a γ-stereocentre with excellent yields and enantioselectivities (up to 99% yield, 99% enantiomeric excess), which otherwise are difficult to access by chemocatalysis. Mechanistic studies suggest that the substrates/ene-reductase complex formation at the enzyme active site triggers the enantioselective photo-induced radical reaction. Our research further expands the reactivity repertoire of biocatalytic, synthetically-useful asymmetric transformations by the merger of photocatalysis and enzyme catalysis.},
doi = {10.1038/s41586-020-2406-6},
journal = {Nature (London)},
number = ,
volume = 584,
place = {United States},
year = {Mon Jun 08 00:00:00 EDT 2020},
month = {Mon Jun 08 00:00:00 EDT 2020}
}
Web of Science
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