Department of Chemistry, Columbia University, New York, New York 10027, United States.
J Am Chem Soc. 2023 Feb 15;145(6):3294-3300. doi: 10.1021/jacs.2c12767. Epub 2023 Feb 1.
-Demethylation of trialkylamines is a useful transformation, but typically requires harsh reaction conditions and stepwise procedures, as well as judicious protection of labile functional groups. Herein we report a mild, catalytic approach for the demethylation of trialkylamines by utilizing photoinduced nickel catalysis wherein C(sp)-bromides serve as hydrogen-atom transfer (HAT) reagents. This method achieves direct demethylation of trialkylamines with wide functional group compatibility, making it highly suitable for late-stage derivatization of complex molecules. Mechanistic investigations provide evidence that C(sp) radicals generated via photoinduced Ni-C(sp) bond homolysis are involved in hydrogen atom abstraction from trialkylamines. Utilizing steric control of the C(sp)-bromides, our HAT approach achieves demethylation with excellent site selectivity in the presence of benzyl-substituted amines, which is complementary to the selectivity of classical approaches that afford debenzylation product instead.
三烷基胺的脱甲基化是一种有用的转化反应，但通常需要苛刻的反应条件和逐步的程序，以及对不稳定官能团的谨慎保护。在此，我们报告了一种温和的、催化的方法，通过光诱导镍催化，利用 C(sp)-溴化物作为氢原子转移 (HAT) 试剂，来实现三烷基胺的脱甲基化。该方法可实现三烷基胺的直接脱甲基化，具有广泛的官能团兼容性，非常适合复杂分子的后期衍生化。机理研究提供了证据，证明通过光诱导 Ni-C(sp)键均裂产生的 C(sp)自由基参与了从三烷基胺中提取氢原子。利用 C(sp)-溴化物的空间位阻控制，我们的 HAT 方法在存在苄基取代胺的情况下，以优异的位点选择性实现脱甲基化，这与经典方法的选择性互补，经典方法得到的是脱苄基产物。
