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Accessing Difluoromethylated and Trifluoromethylated cis ‐Cycloalkanes and Saturated Heterocycles: Preferential Hydrogen Addition to the Substitution Sites for Dearomatization
Author(s) -
Zhang Xue,
Ling Liang,
Luo Meiming,
Zeng Xiaoming
Publication year - 2019
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.201907457
Subject(s) - chemistry , carbene , trifluoromethyl , alkyl , catalysis , hydrogen , substitution (logic) , medicinal chemistry , organic chemistry , computer science , programming language
Reported here is a straightforward process in which a cyclic (alkyl)(amino)carbene/Rh catalyst system facilitates the preferential addition of hydrogen to the substitution sites of difluoromethylated and trifluoromethylated arenes and heteroarenes, leading to dearomative reduction. This strategy enables the diastereoselective synthesis of cis ‐difluoromethylated and cis ‐trifluoromethylated cycloalkanes and saturated heterocycles, and even allows formation of all‐ cis multi‐trifluoromethylated cyclic products with a defined equatorial orientation of the di‐ and trifluoromethyl groups. Deuterium‐labeling studies indicate that hydrogen preferentially attacks the substitution sites of planar arenes, resulting in dearomatization, possibly with heterogeneous Rh as the reactive species, followed by either reversible or irreversible hydrogen addition to the nonsubstitution sites.