Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States.
J Am Chem Soc. 2023 Apr 12;145(14):7736-7742. doi: 10.1021/jacs.3c01488. Epub 2023 Mar 28.
Alcohols are commercially abundant and structurally diverse reservoirs of sp-hybridized chemical space. However, the direct utilization of alcohols in C-C bond-forming cross-couplings remains underexplored. Herein we report an N-heterocyclic carbene (NHC)-mediated deoxygenative alkylation of alcohols and alkyl bromides via nickel-metallaphotoredox catalysis. This C(sp)-C(sp) cross-coupling exhibits a broad scope and is capable of forming bonds between two secondary carbon centers, a longstanding challenge in the field. Highly strained three-dimensional systems such as spirocycles, bicycles, and fused rings were excellent substrates, enabling the synthesis of new molecular frameworks. Linkages between pharmacophoric saturated ring systems were readily forged, representing a three-dimensional alternative to traditional biaryl formation. The utility of this cross-coupling technology is highlighted with the expedited synthesis of bioactive molecules.
醇类是商业上丰富且结构多样的 sp 杂化化学空间储库。然而，醇类在 C-C 键形成交叉偶联中的直接利用仍未得到充分探索。在此，我们报告了通过镍金属光氧化还原催化的 N-杂环卡宾 (NHC) 介导的醇和烷基溴化物的脱氧烷基化反应。这种 C(sp)-C(sp) 交叉偶联具有广泛的适用范围，能够在两个次级碳原子中心之间形成键，这是该领域长期存在的挑战。高度应变的三维系统，如螺环、二环和稠环，是极好的底物，能够合成新的分子框架。药效饱和环系统之间的键很容易形成，代表了传统联苯形成的三维替代方案。通过快速合成生物活性分子，突出了这种交叉偶联技术的实用性。
