Enantioselective Nazarov cyclization of indole enones cooperatively catalyzed by Lewis acids and chiral Brønsted acids

Chemical Science
Guo-Peng WangQi-Lin Zhou

Abstract

Enantioselective control of the chirality of a tertiary α-carbon in the products of a Nazarov cyclization of enones is challenging because the reaction involves an enantioselective proton transfer process. We herein report the use of cooperative catalysis using Lewis acids and chiral Brønsted acids to control the stereochemistry of the tertiary α-carbon in the products of this reaction. Specifically, with ZnCl2 and a chiral spiro phosphoric acid as catalysts, we realized the first enantioselective construction of cyclopenta[b]indoles with chiral tertiary α-carbons via Nazarov cyclization of indole enone substrates with only one coordinating site. Mechanistic studies revealed that the chiral spiro phosphoric acid acts as a multifunctional catalyst: it co-catalyzes the cyclization of the dienone and enantioselectively catalyzes a proton transfer reaction of the enol intermediate. This new strategy of enantioselective control by means of cooperative catalysis may show utility for other challenging asymmetric cyclization reactions.

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Citations

Apr 11, 2018·Organic & Biomolecular Chemistry·Yuan-Yuan RenQi-Lin Zhou
Jan 18, 2020·Chemistry : a European Journal·Xiong SunCongqing Zhu
Aug 30, 2019·Topics in Current Chemistry·Gui-Chun FangXin-Yuan Liu
Sep 3, 2019·Chemical & Pharmaceutical Bulletin·Kenji SugimotoYuji Matsuya
Aug 14, 2020·Organic & Biomolecular Chemistry·Balakrishna AegurlaRama Krishna Peddinti
Apr 29, 2021·Journal of the American Chemical Society·Jin CaoQi-Lin Zhou
Feb 16, 2019·Journal of the American Chemical Society·Jie OuyangBenjamin List
Sep 26, 2019·The Journal of Organic Chemistry·Mariam ZakyD Jean Burnell
Jun 13, 2019·The Journal of Organic Chemistry·Jonas J KoenigMartin Breugst
Mar 23, 2019·Journal of the American Chemical Society·Connor HoltAlison J Frontier

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