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Copper‐Catalyzed Enantioconvergent Cross‐Coupling of Racemic Alkyl Bromides with Azole C(sp 2 )−H Bonds
Author(s) -
Su XiaoLong,
Ye Liu,
Chen JiJun,
Liu XiaoDong,
Jiang ShengPeng,
Wang FuLi,
Liu Lin,
Yang ChangJiang,
Chang XiaoYong,
Li ZhongLiang,
Gu QiangShuai,
Liu XinYuan
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202009527
Subject(s) - chemistry , alkyl , azole , racemization , deprotonation , medicinal chemistry , alkylation , ligand (biochemistry) , catalysis , stereochemistry , organic chemistry , combinatorial chemistry , antifungal , medicine , ion , biochemistry , receptor , dermatology
The development of enantioconvergent cross‐coupling of racemic alkyl halides directly with heteroarene C(sp 2 )−H bonds has been impeded by the use of a base at elevated temperature that leads to racemization. We herein report a copper(I)/cinchona‐alkaloid‐derived N , N , P ‐ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp 2 )−H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α‐chiral alkylated azoles, such as 1,3,4‐oxadiazoles, oxazoles, and benzo[ d ]oxazoles as well as 1,3,4‐triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp 2 )−H bond and the involvement of alkyl radical species under the reaction conditions.