Work

Synergistic Photoenzymatic Anti-Markovnikov Hydroarylation of Olefins via Heteroaryl Radical Intermediates

Year: 2025

Type: article

Abstract: Heteroaromatic alkylations are indispensable reactions for synthesizing biologically active molecules. The anti-Markovnikov hydroarylation of olefins using heteroaryl halides furnishes the product as a single regioisomer; however, catalytic variants are ineffective at controlling the stereochemical outcome of these reactions. Here, we report a synergistic photoenzymatic hydroarylation of olefins using flavin-dependent "ene"-reductases with ruthenium photoredox catalysts. Enzyme homologues were identified, which provide access to both product enantiomers in greater than 80% yield with up to 99:1 er. This method is effective for styrenyl- and unactivated alkenes, highlighting the generality of this approach. The highest yielding system involves a carboxylated photocatalyst with increased affinity for the enzyme. This work expands the types of radical intermediates that enzymes can use for stereoselective intermolecular coupling reactions.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c01066

Authors: Prasun Mukherjee, Zayed Alassad, Todd K. Hyster

Institution: Princeton University

Language: English

Topic: Radical Photochemical Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Science Foundation, National Institutes of Health, National Institute of General Medical Sciences, Division of Chemistry

Awards: G2400633476, G3933665176, CAREER: BIOCATALYTIC SYNTHESIS OF ENANTIOENRICHED NITROGEN-CONTAINING HETEROCYCLES, Development of Flavoproteins as Catalysts for Asymmetric Radical Reactions