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Organocatalytic Enantioselective Functionalization of Unactivated Indole C(sp 3 )−H Bonds
Author(s) -
Ma Dengke,
Zhang Zhihan,
Chen Min,
Lin Zhenyang,
Sun Jianwei
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201909397
Subject(s) - enantioselective synthesis , organocatalysis , chemistry , catalysis , surface modification , indole test , substrate (aquarium) , phosphoric acid , alkyl , combinatorial chemistry , intermolecular force , organic chemistry , molecule , oceanography , geology
Described here is a direct catalytic asymmetric functionalization of unactivated alkyl indoles using organocatalysis. In the presence of an effective chiral urea catalyst and a phosphoric acid additive, the intermolecular C−C bond formation between alkyl indoles and trifluoropyruvates proceeded with high efficiency and enantiocontrol. Unlike previous asymmetric C(sp 3 −H) functionalizations of α‐azaarenes, this process does not require the use of either a strong base or an electron‐deficient substrate. The excellent enantiocontrol is particularly noteworthy in view of the severe background reaction as well as the complete inability of other types of catalysts evaluated. Control experiments, kinetic studies, and DFT calculations provided important insights into the mechanism.