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

被引：123

作者：

Shu, Xiaomin ^{[1
]}

Huan, Leitao ^{[1
]}

Huang, Qian ^{[1
]}

Huo, Haohua ^{[1
]}

机构：

[1] Xiamen Univ, Coll Chem & Chem Engn, State Key Lab Phys Chem Solid Surfaces, Key Lab Chem Biol Fujian Prov, Xiamen 361005, Peoples R China

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2020年 / 142卷 / 45期

关键词：

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. ©;

D O I：

10.1021/jacs.0c10471

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A direct enantioselective acylation of alpha-amino C(sp(3))-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 alpha-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(sp(3))-H functionalization. Mechanistic studies suggest the alpha-C(sp(3))-H bond of the benzamide coupling partner is cleavage by photocatalytically generated bromine radicals to form a-amino alkyl radicals, which subsequently engages in nickel-catalyzed asymmetric acylation.

引用

页码：19058 / 19064

页数：7