Synthesis 2019; 51(09): 1969-1979
DOI: 10.1055/s-0037-1612089
paper
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of Vicinally Bis(trifluoromethyl)-Substituted 3,3′-Pyrrolidinyl Spirooxindoles via Organocatalytic 1,3-Dipolar Cycloaddition Reactions

Wen-Run Zhu §
a   College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Zhen-Wei Zhang §
a   College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Wei-Hua Huang
b   Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P. R. of China   Email: lugui@mail.sysu.edu.cn
,
Ning Lin  *
a   College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Qing Chen*
a   College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Kai-Bin Chen
a   College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Bi-Chuan Wang
a   College of Pharmacy, Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P. R. of China   Email: linning@gxtcmu.edu.cn   Email: chenqing@gxtcmu.edu.cn
,
Jiang Weng
b   Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P. R. of China   Email: lugui@mail.sysu.edu.cn
,
Gui Lu*
b   Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P. R. of China   Email: lugui@mail.sysu.edu.cn
› Author Affiliations
We are grateful for grants from the National Natural Science Foundation of China (Nos. 21262008, 21502240 and 21861009), the Natural Science Foundation of Guangxi Province (Nos. 2018GXNSFAA281317, 2016GXNSFAA380178 and 2018GXNSFBA138032) and the Guangxi University of Chinese Medicine Research Foundation for introduced PhD (No. XB017027).
Further Information

Publication History

Received: 21 October 2018

Accepted after revision: 28 December 2018

Publication Date:
19 February 2019 (online)


§ These two authors contributed equally to this work.

Abstract

Under bifunctional squaramide and thiourea organocatalysis, a series of vicinally bis(trifluoromethyl)-substituted 3,3′-pyrrolidinyl spirooxindoles were successfully synthesized via 1,3-dipolar cycloaddition reactions of 3-(trifluoroethylidene)oxindoles with diethyl 2-((2,2,2-trifluoroethyl)imino)malonate and N-(2,2,2-trifluoroethyl)isatin ketimines. The highlight of this protocol is the efficient construction of the vicinally bis(trifluoromethyl)-substituted pyrrolidine unit of spirooxindoles, including multiple contiguous stereogenic centres, in excellent yields and stereoselectivities.

Supporting Information