title: Enhancement of neighbouring-group participation in Cu0-promoted cross-coupling gem-difluoromethylenation of aryl/alkenyl halides with 1,3-azolic difluoromethyl bromides.
abstract: 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.
authors.affiliation: Department of Chemistry, Shanghai University, Shanghai, 200444 (P.R. China); Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032 (P.R. China). hzjiang@shu.edu.cn.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Jiang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Lu
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Guobin
authors.initials: G
authors.lastname: Ma
authors.forename: Minjun
authors.initials: M
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yao
authors.forename: Wen
authors.initials: W
authors.lastname: Wan
authors.forename: Hongmei
authors.initials: H
authors.lastname: Deng
authors.forename: Shaoxiong
authors.initials: S
authors.lastname: Wu
authors.forename: Shizheng
authors.initials: S
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Hao
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001555:Benzene Derivatives / Q000737:chemistry*; D001965:Bromides / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D054879:Halogenation; D008745:Methylation; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D000475:Alkenes; D001555:Benzene Derivatives; D001965:Bromides; D010080:Oxazoles; D003300:Copper
keywords: copper; cross-coupling; drug design; fluorine; neighboring-group effects