Wu Xiuli, Song Xiangyu, Xia Ying
West China School of Public Health and West China Fourth Hospital, West China-PUMC C.C. Chen Institute of Health, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China.
Adv Sci (Weinh). 2024 May;11(18):e2401243. doi: 10.1002/advs.202401243. Epub 2024 Mar 9.
Transition-metal (TM) catalyzed reaction of gem-difluorinated cyclopropanes (gem-DFCPs) has drawn much attention recently. The reaction generally occurs via the activation of the distal C─C bond in gem-DFCPs by a low-valent TM through oxidative addition, eventually producing mono-fluoro olefins as the coupling products. However, achieving regioselective activation of the proximal C─C bond in gem-DFCPs that overcomes the intrinsic reactivity via TM catalysis remains elusive. Here, a new reaction mode of gem-DFCPs enabled by high-valent copper catalysis, which allows exclusive activation of the congested proximal C─C bond is presented. The reaction that achieves fluoroarylation of gem-DFCPs uses NFSI (N-fluorobenzenesulfonimide) as electrophilic fluoro reagent and arenes as the C─H nucleophiles, enabling the synthesis of diverse CF-containing scaffolds. It is proposed that a high-valent copper species plays an important role in the regioselective activation of the proximal C─C bond possibly via a σ-bond metathesis.
过渡金属（TM）催化的偕二氟环丙烷（gem-DFCPs）反应近来备受关注。该反应通常通过低价态过渡金属经氧化加成活化gem-DFCPs中远端的碳-碳键来进行，最终生成单氟烯烃作为偶联产物。然而，通过过渡金属催化实现gem-DFCPs中近端碳-碳键的区域选择性活化以克服其固有反应活性仍然难以实现。在此，报道了一种由高价铜催化实现的gem-DFCPs新反应模式，该模式能够专一性活化拥挤的近端碳-碳键。实现gem-DFCPs氟芳基化的反应使用NFSI（N-氟苯磺酰亚胺）作为亲电氟试剂，芳烃作为碳-氢键亲核试剂，从而能够合成多种含CF的骨架结构。据推测，高价铜物种可能通过σ键复分解在近端碳-碳键的区域选择性活化中发挥重要作用。
