-Alkylation of Amines by C1-C10 Aliphatic Alcohols Using A Well-Defined Ru(II)-Catalyst. A Metal-Ligand Cooperative Approach.

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.