Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp(3))-H bonds with alkynes

Zhang, Zhen-Hua1,2,3; Dong, Xiao-Yang2,3; Du, Xuan-Yi2,3; Gu, Qiang-Shuai3,4; Li, Zhong-Liang3,4; Liu, Xin-Yuan2,3

2019-12-12

10.1038/s41467-019-13705-1

Nature Communications   影响因子和分区

2041-1723

Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp(3))-C(sp) coupling of unactivated C(sp(3))-H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp(3))-H bond functionalization and the inhibition of readily occurring Glaser homocoupling of terminal alkynes. Here, we report a copper/chiral cinchona alkaloid-based N,N,P-ligand catalyst for asymmetric oxidative cross-coupling of unactivated C(sp(3))-H bonds with terminal alkynes in a highly regio-, chemo-, and enantioselective manner. The use of N-fluoroamide as a mild oxidant is essential to site-selectively generate alkyl radical species while efficiently avoiding Glaser homocoupling. This reaction accommodates a range of (hetero)aryl and alkyl alkynes; (hetero)benzylic and propargylic C(sp(3))-H bonds are all applicable. This process allows expedient access to chiral alkynyl amides/aldehydes. More importantly, it also provides a versatile tool for the construction of chiral C(sp(3))-C(sp), C(sp(3))-C(sp(2)), and C(sp(3))-C (sp(3)) bonds when allied with follow-up transformations.

SCI

英语

NI期刊

通讯

Shandong Provincial Natural Science Foundation[ZR2017BB065]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000502257200001

NATURE PUBLISHING GROUP

Web of Science

1.Linyi Univ, Sch Chem & Chem Engn, Shandong Prov Key Lab Detect Technol Tumor Marker, Linyi 276005, Shandong, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Shenzhen 518055, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Dept Chem, Shenzhen 518055, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Acad Adv Interdisciplinary Studies, Shenzhen 518055, Guangdong, Peoples R China

Zhang, Zhen-Hua,Dong, Xiao-Yang,Du, Xuan-Yi,et al. Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp(3))-H bonds with alkynes[J]. Nature Communications,2019,10.

Zhang, Zhen-Hua,Dong, Xiao-Yang,Du, Xuan-Yi,Gu, Qiang-Shuai,Li, Zhong-Liang,&Liu, Xin-Yuan.(2019).Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp(3))-H bonds with alkynes.Nature Communications,10.

Zhang, Zhen-Hua,et al."Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp(3))-H bonds with alkynes".Nature Communications 10(2019).