中国科学院上海有机化学研究所刘国生团队报道了铜催化自由基中继对等位基因sp2 C–H的位点选择性氰化。相关研究成果于2023年11月27日发表于国际顶尖学术期刊《美国化学会杂志》。

与广泛报道的sp3 C–H处的氢原子转移（HAT）相比，在sp2碳处提取氢原子的情况极为罕见。

该文中，研究人员使用铜催化的自由基中继策略来传达等位基因的sp2 C–H键的位点选择性氰化。该反应直接由简单的烯类化合物制备出各种烯基腈，在温和的条件下具有广泛的底物范围和显著的官能团相容性。这些反应对sp2 C–H表现出优异的位点选择性，这是由于铜结合的氮中心自由基产生的独特口袋。sp2 C–H上有利的HAT是由于键合到Cu（II）中心的氟化物和烯丙基位置的氢原子之间的关键氢键。这些特征使得含有等位基因基序的类药物生物活性分子能够进行后期功能化。

附：英文原文

Title: Site-Selective sp2 C–H Cyanation of Allenes via Copper-Catalyzed Radical Relay

Author: Zhongming Cheng, Tilong Yang, Can Li, Yunshun Deng, Fangjia Zhang, Pinhong Chen, Zhenyang Lin, Shengming Ma, Guosheng Liu

Issue&Volume: November 27, 2023

Abstract: Compared with the extensively reported hydrogen atom transfer (HAT) at sp3 C–H, abstraction of hydrogen atoms at the sp2 carbon is extremely rare. Here, we communicate the site-selective cyanation of the sp2 C–H bond of allenes using the strategy of copper-catalyzed radical relay. The reactions afford various allenyl nitriles directly from simple allenes with a broad substrate scope and a remarkable functional group compatibility under mild conditions. These reactions exhibit excellent site-selectivity toward sp2 C–H, which can be attributed to the unique pocket created by the Cu-bound nitrogen-centered radical. The favorable HAT on sp2 C–H is due to crucial hydrogen bonding between the fluoride bonded to the Cu(II) center and the hydrogen atom at the allylic position. These features enable the late-stage functionalization of druglike bioactive molecules containing an allene motif.

DOI: 10.1021/jacs.3c11368

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.3c11368