转自：康龙化成
Free-Radical Deoxygenative Amination of Alcohols via Copper Metallaphotoredox Catalysis
William P. Carson II, Artem V. Tsymbal, Robert W. Pipal, Grant A. Edwards, Joseph R. Martinelli, Albert Cabré, andDavid W. C. MacMillan*
Merck Center for Catalysis at PrincetonUniversity, Princeton, New Jersey 08544, United States;
Lilly Genetic Medicine, Eli Lilly andCompany, Cambridge, Massachusetts 02142, United States;
Centrode Investigación Lilly S.A., Madrid 28108, Spain
—J. Am. Chem. Soc., 2024,https://doi.org/10.1021/jacs.4c04477.
Recommended by Murong Xu_MC3
ABSTRACT:Alcoholsare among the most abundant chemical feedstocks, yet they remain vastly underutilized ascoupling partners in transition metal catalysis. Herein, we describe a copper metallaphotoredox manifold for the open shell deoxygenative coupling of alcohols with N-nucleophiles to forge C(sp3)−N bonds, a linkage ofhigh value in pharmaceutical agents that is challenging to access viaconventional cross-coupling techniques. N-heterocyclic carbene (NHC)-mediated conversion of alcohols into the corresponding alkyl radicalsfollowed by copper-catalyzed C−N coupling renders this platform successful fora broad range of structurally unbiased alcohols and 18 classes ofN-nucleophiles.
N-NucleophileScope of the Deoxyamination Reaction
Alcohol Scope of the Deoxyamination Reaction (selected)
Plausible Mechanism for the Deoxyamination Reaction.
Prof. W.C. MacMillan et al havedisclosed an efficient protocol for the copper metallaphotoredox-enabledalkylation of N-nucleophiles with simple alcohols. This transformation wasfound to be amenable to an extensive range of substrates, including nitrogenated heterocycles, anilines, amides, primary and secondary alcohols, diols,monosaccharides, and complex drug-like molecules. Given the importance ofC(sp3)−N linkages in bioactive molecules, we anticipate this reaction will beof value to the medicinal chemistry community.
Prof. W. C. MacMillan 及其工作人员公开了一种有效的方案，使N-亲核试剂与简单醇在金属光氧化还原体系下发生烷基化反应。这种转化可以适用于广泛的底物，包括含氮杂环、苯胺、酰胺、伯醇和仲醇、二醇、单糖和复杂的药物样分子。鉴于C(sp3)−N键在生物活性分子中的重要性，我们预计该反应将对药物化学界有价值。
