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Enhancement of Neighbouring‐Group Participation in Cu 0 ‐Promoted Cross‐Coupling gem ‐Difluoromethylenation of Aryl/Alkenyl Halides with 1,3‐Azolic Difluoromethyl Bromides
Author(s) -
Jiang Haizhen,
Lu Wenjun,
Yang Kun,
Ma Guobin,
Xu Minjun,
Li Jian,
Yao Jianhua,
Wan Wen,
Deng Hongmei,
Wu Shaoxiong,
Zhu Shizheng,
Hao Jian
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201402205
Subject(s) - oxazoline , aryl , moiety , halide , chemistry , bromide , conjugated system , coupling reaction , molecule , combinatorial chemistry , medicinal chemistry , functional group , group (periodic table) , stereochemistry , organic chemistry , catalysis , alkyl , polymer
A copper(0)‐promoted direct reductive gem ‐difluoromethylenation of unactivated aryl or alkenyl halides with benzo‐1,3‐azolic (oxa‐, thia‐ or aza‐) difluoromethyl bromides or 2‐bromodifluoromethyl‐1,3‐oxazoline has been developed for the construction of pharmaceutically important gem ‐difluoromethylene‐linked twin molecules. The unique π‐conjugated aryl‐fused 1,3‐azolic moiety in difluoromethyl bromide substrates could stabilise the reaction intermediates, which promotes the reactivities, providing facile access to the cross‐coupling products in good to excellent yields, and allowing significant functional group tolerance. The reaction exhibits an enhanced neighbouring‐group‐participation effect. This method could provide a new strategy for the construction of gem ‐difluoromethylene‐linked identical or nonidentical twin drugs through further functionalisation of 1,3‐azolic skeletons.