Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes

Cheng，Xiang1,2; Chang，Xin1,2; Yang，Yuhong3; Zhang，Zongpeng1; Li，Jing1; Li，Yipu1; Zhao，Wenxiao1; Chung，Lung Wa3; Teng，Huailong4; Dong，Xiu Qin1; Wang，Chun Jiang1,2

2023

10.1007/s11426-023-1683-9

Science China Chemistry   Impact Factor & Quartile

1674-7291

1869-1870

Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and β-trifluoromethyl-substituted alkenyl heteroarenes was developed for the first time. A wide range of enantioenriched pyrrolidines containing both heteroarenes and trifluoromethyl group with multiple stereogenic centers could be readily accessible by this method with good to high yields and excellent levels of both stereo- and regioselectivity (up to 99% yield, >20:1 rr, >20:1 dr, and up to 95% ee). Notably, substrate-controlled umpolung-type dipolar cycloaddition was also disclosed in this protocol to achieve regiodivergent synthesis with α-aryl substituted aldimine esters as the dipole precursors. Systematic DFT studies were conducted to explore the origin of the stereo- and regioselectivity of this 1,3-dipolar cycloaddition, and suggest that copper(II) salt utilized in this catalytic system could be reduced in-situ to the active copper(I) species and might be responsible for the observed high stereo- and regioselectivity.

1, 3-dipolar cycloaddition asymmetric catalysis chiral pyrrolidines heteroarene trifluoromethyl group

SCI

English

Corresponding

National Natural Science Foundation of China["22071186","22071187","22073067","22101216","22271226","21933003","22193020","22193023"] ; Natural Science Foundation of Hubei Province[2020CFA036 2021CFA069] ; Fundamental Research Funds for the Central Universities["2042022kf1180","2042022kf1040"] ; Shenzhen Nobel Prize Scientists Laboratory Project[C17783101] ; Guangdong Provincial Key Laboratory of Catalytic Chemistry[2020B121201002]

Chemistry

Chemistry, Multidisciplinary

WOS:001063556600001

SCIENCE PRESS

2-s2.0-85168954319

Scopus

1.College of Chemistry and Molecular Sciences,Wuhan University,Wuhan,430072,China
2.State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Shanghai,230021,China
3.Shenzhen Grubbs Institute,Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,518055,China
4.College of Science,Huazhong Agricultural University,Wuhan,430070,China

Cheng，Xiang,Chang，Xin,Yang，Yuhong,et al. Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes[J]. Science China Chemistry,2023.

Cheng，Xiang.,Chang，Xin.,Yang，Yuhong.,Zhang，Zongpeng.,Li，Jing.,...&Wang，Chun Jiang.(2023).Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes.Science China Chemistry.

Cheng，Xiang,et al."Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes".Science China Chemistry (2023).