Clinical Pharmacy of The First Affiliated Hospital, School of clinical pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, P. R. China.
School of Materials Science & Engineering, PCFM Lab, School of Chemistry, Sun Yat-sen University, Guangzhou 510275, P. R. China.
Org Biomol Chem. 2021 Apr 26;19(15):3451-3461. doi: 10.1039/d1ob00362c.
Metal hydride complexes are key intermediates for N-alkylation of amines with alcohols by the borrowing hydrogen/hydrogen autotransfer (BH/HA) strategy. Reactivity tuning of metal hydride complexes could adjust the dehydrogenation of alcohols and the hydrogenation of imines. Herein we report ruthenium(ii) complexes with hetero-bidentate N-heterocyclic carbene (NHC)-phosphine ligands, which realize smart pathway selection in the N-alkylated reaction via reactivity tuning of [Ru-H] species by hetero-bidentate ligands. In particular, complex 6cb with a phenyl wingtip group and BArF- counter anion, is shown to be one of the most efficient pre-catalysts for this transformation (temperature is as low as 70 °C, neat conditions and catalyst loading is as low as 0.25 mol%). A large variety of (hetero)aromatic amines and primary alcohols were efficiently converted into mono-N-alkylated amines in good to excellent isolated yields. Notably, aliphatic amines, challenging methanol and diamines could also be transformed into the desired products. Detailed control experiments and density functional theory (DFT) calculations provide insights to understand the mechanism and the smart pathway selection via [Ru-H] species in this process.
金属氢化物配合物是通过借氢/氢自转移（BH/HA）策略实现胺与醇的 N-烷基化的关键中间体。金属氢化物配合物的反应性调变可以调节醇的脱氢和亚胺的加氢。本文报道了具有杂双齿 N-杂环卡宾（NHC）-膦配体的钌（ii）配合物，通过杂双齿配体对[Ru-H]物种的反应性调变，实现了 N-烷基化反应中智能途径选择。特别是具有苯基翼尖基团和 BArF-抗衡阴离子的配合物 6cb，被证明是该转化最有效的预催化剂之一（温度低至 70°C，在 neat 条件下，催化剂负载量低至 0.25mol%）。大量（杂）芳族胺和伯醇可以有效地转化为单 N-烷基化胺，产率良好至优秀。值得注意的是，脂肪族胺、甲醇和二胺也可以转化为所需产物。详细的控制实验和密度泛函理论（DFT）计算提供了对该过程中通过[Ru-H]物种进行机制和智能途径选择的理解。
