Regioselective Arene C−H Alkylation Enabled by Organic Photoredox Catalysis

Journal Article · 17 March 2020 · Angewandte Chemie

DOI: https://doi.org/10.1002/ange.202000684 · OSTI ID:1605039

Holmberg‐Douglas, Natalie ^[1]; Onuska, Nicholas P. R. ^[1]; Nicewicz, David A.  ^[1]

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1. Department of Chemistry University of North Carolina at Chapel Hill Chapel Hill NC 27599-3290 USA

Abstract Expanding the toolbox of C−H functionalization reactions applicable to the late‐stage modification of complex molecules is of interest in medicinal chemistry, wherein the preparation of structural variants of known pharmacophores is a key strategy for drug development. One manifold for the functionalization of aromatic molecules utilizes diazo compounds and a transition‐metal catalyst to generate a metallocarbene species, which is capable of direct insertion into an aromatic C−H bond. However, these high‐energy intermediates can often require directing groups or a large excess of substrate to achieve efficient and selective reactivity. Herein, we report that arene cation radicals generated by organic photoredox catalysis engage in formal C−H functionalization reactions with diazoacetate derivatives, furnishing sp ² –sp ³ coupled products with moderate‐to‐good regioselectivity. In contrast to previous methods utilizing metallocarbene intermediates, this transformation does not proceed via a carbene intermediate, nor does it require the presence of a transition‐metal catalyst.

• Sponsoring Organization: USDOE
• OSTI ID: 1605039
• Journal Information: Angewandte Chemie, Journal Name: Angewandte Chemie Vol. 132 Journal Issue: 19; ISSN 0044-8249
• Publisher: Wiley Blackwell (John Wiley & Sons)Copyright Statement
• Country of Publication: Germany
• Language: English