Enhancement of Neighbouring-Group Participation in Cu0-Promoted Cross-Coupling gem-Difluoromethylenation of Aryl/Alkenyl Halides with 1,3-Azolic Difluoromethyl Bromides
Enhancement of Neighbouring-Group Participation in Cu0-Promoted Cross-Coupling gem-Difluoromethylenation of Aryl/Alkenyl Halides with 1,3-Azolic Difluoromethyl Bromides
复制标题
DOI：
10.1002/chem.201402205
复制
发表时间：
2014-08-04
影响因子：
4.3
通讯作者：
Hao, Jian
中科院分区：
文献类型：
--
作者：
Jiang, Haizhen;Lu, Wenjun;Hao, Jian
铜（0）促进的未活化芳基或烯基卤化物与苯并-1,3-偶氮（氧杂-、硫杂-或氮杂-）二氟甲基溴或2-溴二氟甲基-1,3-恶唑啉的直接还原偕二氟亚甲基化已被开发用于构建药学上重要的偕二氟亚甲基连接的双分子。二氟甲基溴底物中独特的对位共轭芳基稠合 1,3-偶氮部分可以稳定反应中间体，从而促进反应活性，以良好至优异的产率轻松获得交叉偶联产物，并允许显着的官能团耐受性。该反应表现出增强的邻近基团参与效应。该方法可以为通过1,3-偶氮骨架的进一步功能化来构建偕二氟亚甲基连接的相同或不同孪生药物提供新策略。
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 p-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.