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Title: Enantioselective decarboxylative alkylation using synergistic photoenzymatic catalysis
Photoenzymatic catalysts are attractive for stereoselective radical reactions because the transformation occurs within tunable enzyme active sites. When using flavoproteins for non-natural photoenzymatic reactions, reductive mechanisms are often used for radical initiation. Oxidative mechanisms for radical formation would enable abundant functional groups, such as amines and carboxylic acids, to serve as radical precursors. However, excited state flavin is short-lived in many proteins because of rapid quenching by the protein scaffold. Here we report that adding an exogenous Ru(bpy)3 2+ cofactor to flavin-dependent ‘ene’-reductases enables the redox-neutral decarboxylative coupling of amino acids with vinylpyridines with high yield and enantioselectivity. Additionally, stereo-complementary enzymes are found to provide access to both enantiomers of the product. Mechanistic studies indicate that Ru(bpy)3 2+ binds to the protein, helping to localize radical formation to the enzyme’s active site. This work expands the types of transformation that can be rendered asymmetric using photoenzymatic catalysis and provides an intriguing mechanism of radical initiation.  more » « less
Award ID(s):
2342328
PAR ID:
10507429
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
Nature
Date Published:
Journal Name:
Nature Catalysis
Volume:
7
Issue:
1
ISSN:
2520-1158
Page Range / eLocation ID:
35 to 42
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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