A Ru(II)-catalyzed efficient and selective N-alkylation
of amines by C1–C10 aliphatic alcohols is reported. The catalyst
[Ru(L1a)(PPh3)Cl2] (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.