Photoenzymatic enantioselective intermolecular radical hydroalkylation

Huang, Xiaoqiang; Wang, Binju; Wang, Yajie; Jiang, Guangde; Feng, Jianqiang; Zhao, Huimin

doi:10.1038/s41586-020-2406-6

Photoenzymatic enantioselective intermolecular radical hydroalkylation

Journal Article · Mon Jun 08 00:00:00 EDT 2020 · Nature (London)

DOI:https://doi.org/10.1038/s41586-020-2406-6· OSTI ID:1632290

^[1]; Wang, Binju ^[2]; Wang, Yajie ^[3]; Jiang, Guangde ^[3]; Feng, Jianqiang ^[2]; ^[3]

Univ. of Illinois at Urbana-Champaign, IL (United States); CABBI
Xiamen Univ. (China)
Univ. of Illinois at Urbana-Champaign, IL (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States); Univ. of Illinois at Urbana-Champaign, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: SC0018420

OSTI ID:: 1632290

Journal Information:: Nature (London), Journal Name: Nature (London) Vol. 584; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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