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Exploration of the Synthetic Potential of Electrophilic Trifluoromethylthiolating and Difluoromethylthiolating Reagents
Author(s) -
Zhang Jingjing,
Yang JinDong,
Zheng Hanliang,
Xue XiaoSong,
Mayr Herbert,
Cheng JinPei
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201805859
Subject(s) - electrophile , reagent , chemistry , nucleophile , carbanion , heterolysis , gibbs free energy , computational chemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , thermodynamics , catalysis , physics
Abstract The electrophilicity parameters (E) of some trifluoromethylthiolating and difluoromethylthiolating reagents were determined by following the kinetics of their reactions with a series of enamines and carbanions with known nucleophilicity parameters (N, s N ), using the linear free‐energy relationship log k 2 =s N (N+E). The electrophilic reactivities of these reagents cover a range of 17 orders of magnitude, with Shen and Lu's reagent 1 a being the most reactive and Billard's reagent 1 h being the least reactive electrophile. While the observed electrophilic reactivities (E) of the amido‐derived trifluoromethylthiolating reagents correlate well with the calculated Gibbs energies for heterolytic cleavage of the X−SCF 3 bonds (Tt + DA), the cumol‐derived reagents 1 f and 1 g are more reactive than expected from the thermodynamics of the O−S cleavage. The E parameters of the tri/difluoromethylthiolating reagents derived in this work provide an ordering principle for their use in synthesis.