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Copper‐Catalyzed C(sp 3 )−H/C(sp 3 )−H Cross‐Dehydrogenative Coupling with Internal Oxidants: Synthesis of 2‐Trifluoromethyl‐Substituted Dihydropyrrol‐2‐ols
Author(s) -
Zhu Chuanle,
Zhu Rui,
Zeng Hao,
Chen Fulin,
Liu Chi,
Wu Wanqing,
Jiang Huanfeng
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201707719
Subject(s) - chemistry , pyridazine , trifluoromethyl , thiophene , catalysis , pyrrole , medicinal chemistry , furan , oxime , catalytic cycle , copper , organic chemistry , alkyl
Abstract The first oxidative C(sp 3 )−H/C(sp 3 )−H cross‐dehydrogenative coupling (CDC) reaction promoted by an internal oxidant is reported. This copper‐catalyzed CDC reaction of oxime acetates and trifluoromethyl ketones provides a simple and efficient approach towards 2‐trifluoromethyldihydropyrrol‐2‐ol derivatives in a highly diastereoselective manner by cascade C(sp 3 )−C(sp 3 ) bond formation and cyclization. These products were further transformed into various significant and useful trifluoromethylated heterocyclic compounds, such as trifluoromethylated furan, thiophene, pyrrole, dihydropyridazine, and pyridazine derivatives. A trifluoromethylated analogue of an Aβ 42 lowering agent was also synthesized smoothly. Preliminary mechanistic studies indicated that this reaction involves a copper(I)/copper(III) catalytic cycle with the oxime acetate acting as an internal oxidant.