Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters

Wang, Peng-Fei1,2; Yu, Jiao2; Guo, Kai-Xin2,3; Jiang, Sheng-Peng2; Chen, Ji-Jun2; Gu, Qiang-Shuai1,3; Liu, Ji-Ren4; Hong, Xin4; Li, Zhong-Liang3; Liu, Xin-Yuan1,2

2022-04-13

10.1021/jacs.2c00957

Journal of the American Chemical Society   影响因子和分区

0002-7863

1520-5126

The enantioconvergent radical C(sp3)-C(sp2) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.

;

The enantioconvergent radical C(sp3)-C(sp2) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.

SCI ; EI

英语

NI论文

第一 ; 共同第一 ; 通讯

National Natural Science Foundation of China[22025103,21831002] ; Guangdong Innovative Program[2019BT02Y335] ; Guangdong Provincial Key Laboratory of Catalysis[2020B121201002] ; Guangdong Basic and Applied Basic Research Foundation[2019A1515110308] ; Shenzhen Special Funds[JCYJ20200109141001789] ; Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis[ZDSYS20190902093215877] ; Shenzhen Nobel Prize Scientists Laboratory Project[C17783101]

Chemistry

Chemistry, Multidisciplinary

WOS:000790698300035

AMER CHEMICAL SOC

20221611973514

Copper ; Ligands

Copper:544.1 ; Physical Chemistry:801.4 ; Organic Compounds:804.1

2-s2.0-85128186936

Scopus

正式出版

1.Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis,Southern University of Science and Technology,Shenzhen,518055,China
2.Shenzhen Grubbs Institute and Department of Chemistry,Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,518055,China
3.Academy for Advanced Interdisciplinary Studies and Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China
4.Department of Chemistry,Zhejiang University,Hangzhou,38 Zheda Road,310027,China

Wang, Peng-Fei,Yu, Jiao,Guo, Kai-Xin,et al. Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters[J]. Journal of the American Chemical Society,2022,144(14):6442-6452.

Wang, Peng-Fei.,Yu, Jiao.,Guo, Kai-Xin.,Jiang, Sheng-Peng.,Chen, Ji-Jun.,...&Liu, Xin-Yuan.(2022).Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters.Journal of the American Chemical Society,144(14),6442-6452.

Wang, Peng-Fei,et al."Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters".Journal of the American Chemical Society 144.14(2022):6442-6452.