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Direct Acylation of C(sp 3 )−H Bonds Enabled by Nickel and Photoredox Catalysis
Author(s) -
Joe Candice L.,
Doyle Abigail G.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201511438
Subject(s) - catalysis , electrophile , chemistry , nickel , photoredox catalysis , aryl , radical , acylation , alkyl , transition metal , photochemistry , reactivity (psychology) , chelation , combinatorial chemistry , coupling reaction , organic chemistry , photocatalysis , medicine , alternative medicine , pathology
Abstract Using nickel and photoredox catalysis, the direct functionalization of C(sp 3 )−H bonds of N‐aryl amines by acyl electrophiles is described. The method affords a diverse range of α‐amino ketones at room temperature and is amenable to late‐stage coupling of complex and biologically relevant groups. C(sp 3 )−H activation occurs by photoredox‐mediated oxidation to generate α‐amino radicals which are intercepted by nickel in catalytic C(sp 3 )−C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross‐coupling while avoiding limitations commonly associated with transition‐metal‐mediated C(sp 3 )−H activation, including requirements for chelating directing groups and high reaction temperatures.