Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions

Chen，Ji Jun1,2; Zhang，Jia Yong2,3; Fang，Jia Heng2; Du，Xuan Yi2; Xia，Hai Dong2; Cheng，Bin3; Li，Nan2; Yu，Zhang Long2; Bian，Jun Qian2; Wang，Fu Li2; Zheng，Jing Jing2; Liu，Wei Long2; Gu，Qiang Shuai4; Li，Zhong Liang1,4; Liu，Xin Yuan1,2

2023-07-12

10.1021/jacs.3c02387

Journal of the American Chemical Society   Impact Factor & Quartile

0002-7863

1520-5126

The enantioconvergent C(sp)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N-alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp)-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex. Thus, this kind of ligand could not only enhance the reducing capability of a copper catalyst to provide an enantioconvergent radical pathway but also avoid the coordination with other coordinating heteroatoms, thereby overcoming catalyst poisoning and/or chiral ligand displacement. This protocol covers a wide range of coupling partners (89 examples for activated racemic secondary/tertiary alkyl bromides/chlorides and (hetero)aromatic amines) with high functional group compatibility. When allied with follow-up transformations, it provides a highly flexible platform to access synthetically useful enantioenriched amine building blocks.

SCI ; IC ; CCR

English

NI Journal Papers ; NI论文

First

National Key Ramp;D Program of China["2021YFF0701604","2021YFF0701704"] ; National Natural Science Foundation of China["22025103","92256301","21831002","22271133"] ; Guangdong Innovative Program[2019BT02Y335] ; Natural Science Foundation of Guangdong Province of China[2023A1515010728] ; Shenzhen Key Laboratory of Cross-Coupling Reactions[ZDSYS20220328104200001] ; Shenzhen Science and Technology Program["KQTD20210811090112004","JCYJ20200109141001789","JCYJ20220818100600001","JCYJ202205300115409020"]

Chemistry

Chemistry, Multidisciplinary

WOS:001018800900001

AMER CHEMICAL SOC

2-s2.0-85164293599

Scopus

1.Shenzhen Key Laboratory of Cross-Coupling Reactions,Southern University of Science and Technology,Shenzhen,518055,China
2.Shenzhen Grubbs Institute and Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China
3.Institute of Marine Biomedicine/Postdoctoral Innovation Practice Base,Shenzhen Polytechnic,Shenzhen,518055,China
4.Academy for Advanced Interdisciplinary Studies and Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China

Chen，Ji Jun,Zhang，Jia Yong,Fang，Jia Heng,et al. Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions[J]. Journal of the American Chemical Society,2023,145(27):14686-14696.

Chen，Ji Jun.,Zhang，Jia Yong.,Fang，Jia Heng.,Du，Xuan Yi.,Xia，Hai Dong.,...&Liu，Xin Yuan.(2023).Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions.Journal of the American Chemical Society,145(27),14686-14696.

Chen，Ji Jun,et al."Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions".Journal of the American Chemical Society 145.27(2023):14686-14696.