Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Botanic Garden, Howrah 711103, India.
J Org Chem. 2023 May 5;88(9):5944-5961. doi: 10.1021/acs.joc.3c00313. Epub 2023 Apr 13.
A Ru(II)-catalyzed efficient and selective -alkylation of amines by C1-C10 aliphatic alcohols is reported. The catalyst [Ru(L)(PPh)Cl] () bearing a tridentate redox-active azo-aromatic pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline () is air-stable, easy to prepare, and showed wide functional group tolerance requiring only 1.0 mol % (for -methylation and -ethylation) and 0.1 mol % of catalyst loading for -alkylation with C3-C10 alcohols. A wide array of -methylated, -ethylated, and -alkylated amines were prepared in moderate to good yields via direct coupling of amines and alcohols. efficiently catalyzes the -alkylation of diamines selectively. It is even suitable for synthesizing -alkylated diamines using (aliphatic) diols producing the tumor-active drug molecule MSX-122 in moderate yield. showed excellent chemo-selectivity during the -alkylation using oleyl alcohol and monoterpenoid β-citronellol. Control experiments and mechanistic investigations revealed that the -catalyzed -alkylation reactions proceed via a borrowing hydrogen transfer pathway where the hydrogen removed from the alcohol during the dehydrogenation step is stored in the ligand backbone of , which in the subsequent steps transferred to the in situ formed imine intermediate to produce the -alkylated amines.
报道了一种 Ru(II) 催化的、高效的、对胺的 C1-C10 脂肪醇选择性 -烷基化反应。催化剂 [Ru(L)(PPh)Cl] () 含有一个三齿氧化还原活性的偶氮芳基夹持配体 2-((4-氯苯基)偶氮基)-1,10-菲咯啉 ()，它具有空气稳定性，易于制备，并且对官能团具有广泛的耐受性，只需 1.0 mol %（用于 -甲基化和 -乙基化）和 0.1 mol %的催化剂负载量即可用于 C3-C10 醇的 -烷基化反应。通过胺和醇的直接偶联，制备了一系列中等至良好收率的 -甲基化、-乙基化和 -烷基化胺。 高效地选择性催化二胺的 -烷基化。即使使用（脂肪族）二醇，它也适用于合成 -烷基化二胺，以中等产率得到肿瘤活性药物分子 MSX-122。 在使用油醇和单萜 β-香茅醇的 -烷基化反应中，表现出优异的化学选择性。控制实验和机理研究表明， -催化的 -烷基化反应通过氢转移途径进行，其中醇在脱氢步骤中脱除的氢储存在配体骨架中，随后在后续步骤中转移到原位形成的亚胺中间体，生成 -烷基化胺。
