Carson William P, Tsymbal Artem V, Pipal Robert W, Edwards Grant A, Martinelli Joseph R, Cabré Albert, MacMillan David W C
Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States.
Lilly Genetic Medicine, Eli Lilly and Company, Cambridge, Massachusetts 02142, United States.
J Am Chem Soc. 2024 Jun 12;146(23):15681-15687. doi: 10.1021/jacs.4c04477. Epub 2024 May 30.
Alcohols are among the most abundant chemical feedstocks, yet they remain vastly underutilized as coupling partners in transition metal catalysis. Herein, we describe a copper metallaphotoredox manifold for the open shell deoxygenative coupling of alcohols with -nucleophiles to forge C()-N bonds, a linkage of high value in pharmaceutical agents that is challenging to access via conventional cross-coupling techniques. -heterocyclic carbene (NHC)-mediated conversion of alcohols into the corresponding alkyl radicals followed by copper-catalyzed C-N coupling renders this platform successful for a broad range of structurally unbiased alcohols and 18 classes of -nucleophiles.
醇类是最为丰富的化学原料之一，但在过渡金属催化中作为偶联伙伴的利用率仍然极低。在此，我们描述了一种铜金属光氧化还原体系，用于醇类与亲核试剂的开壳脱氧偶联以形成C（）-N键，这种键合在药物制剂中具有很高的价值，但通过传统交叉偶联技术很难实现。-杂环卡宾（NHC）介导的醇类转化为相应的烷基自由基，随后进行铜催化的C-N偶联，使得该平台适用于多种结构无偏向的醇类和18类亲核试剂。
