N -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 N -alkylation of amines by C1-C10 aliphatic alcohols is reported. The catalyst [Ru(L 1a )(PPh 3 )Cl 2 ] ( 1a ) bearing a tridentate redox-active azo-aromatic pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline ( L 1a ) is air-stable, easy to prepare, and showed wide functional group tolerance requiring only 1.0 mol % (for N -methylation and N -ethylation) and 0.1 mol % of catalyst loading for N -alkylation with C3-C10 alcohols. A wide array of N -methylated, N -ethylated, and N -alkylated amines were prepared in moderate to good yields via direct coupling of amines and alcohols. 1a efficiently catalyzes the N -alkylation of diamines selectively. It is even suitable for synthesizing N -alkylated diamines using (aliphatic) diols producing the tumor-active drug molecule MSX-122 in moderate yield. 1a showed excellent chemo-selectivity during the N -alkylation using oleyl alcohol and monoterpenoid β-citronellol. Control experiments and mechanistic investigations revealed that the 1a -catalyzed N -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 1a , which in the subsequent steps transferred to the in situ formed imine intermediate to produce the N -alkylated amines.