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Regioselective Arene C−H Alkylation Enabled by Organic Photoredox Catalysis
Author(s) -
HolmbergDouglas Natalie,
Onuska Nicholas P. R.,
Nicewicz David A.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202000684
Subject(s) - regioselectivity , chemistry , photoredox catalysis , combinatorial chemistry , reactivity (psychology) , alkylation , catalysis , diazo , surface modification , carbene , organic synthesis , molecule , transition metal , organocatalysis , enantioselective synthesis , photochemistry , organic chemistry , photocatalysis , medicine , alternative medicine , pathology
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.