Synthesis of Symmetric and Unsymmetric Secondary Amines from the Ligand-Promoted Ruthenium-Catalyzed Deaminative Coupling Reaction of Primary Amines

The
catalytic system generated in situ from the tetranuclear Ru–H
complex with a catechol ligand (1/L1) was
found to be effective for the direct deaminative coupling of two primary
amines to form secondary amines. The catalyst 1/L1 was highly chemoselective for promoting the coupling of
two different primary amines to afford unsymmetric secondary amines.
The analogous coupling of aniline with primary amines formed aryl-substituted
secondary amines. The treatment of aniline-d7 with 4-methoxybenzylamine led to the coupling product with
significant deuterium incorporation on CH2 (18% D). The
most pronounced carbon isotope effect was observed on the α-carbon
of the product isolated from the coupling reaction of 4-methoxybenzylamine
(C(1) = 1.015(2)). A Hammett plot was constructed from measuring the
rates of the coupling reaction of 4-methoxyaniline with a series of para-substituted benzylamines 4-X-C6H4CH2NH2 (X = OMe, Me, H, F, CF3)
(ρ = −0.79 ± 0.1). A plausible mechanistic scheme
has been proposed for the coupling reaction on the basis of these
results. The catalytic coupling method provides an operationally simple
and chemoselective synthesis of secondary amine products without using
any reactive reagents or forming wasteful byproducts.