Direct Enantioselective C(sp3)–H Acylation for the Synthesis of α‑Amino Ketones

A direct enantioselective acylation of α-amino C­(sp3)–H bonds with carboxylic acids has been achieved via the merger of transition metal and photoredox catalysis. This straightforward protocol enables cross-coupling of a wide range of carboxylic acids, one class of feedstock chemicals, with readily...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2020-11, Vol.142 (45), p.19058-19064
Main Authors: Shu, Xiaomin, Huan, Leitao, Huang, Qian, Huo, Haohua
Format: Article
Language:English
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Summary:A direct enantioselective acylation of α-amino C­(sp3)–H bonds with carboxylic acids has been achieved via the merger of transition metal and photoredox catalysis. This straightforward protocol enables cross-coupling of a wide range of carboxylic acids, one class of feedstock chemicals, with readily available N-alkyl benzamides to produce highly valuable α-amino ketones in high enantioselectivities under mild conditions. The synthetic utility of this method is further demonstrated by gram scale synthesis and application to late-stage functionalization. This method provides an unprecedented solution to address the challenging stereocontrol in metallaphotoredox catalysis and C­(sp3)–H functionalization. Mechanistic studies suggest the α-C­(sp3)–H bond of the benzamide coupling partner is cleavage by photocatalytically generated bromine radicals to form α-amino alkyl radicals, which subsequently engages in nickel-catalyzed asymmetric acylation.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.0c10471