Efficient Ruthenium-Catalyzed N-Methylation of Amines Using Methanol

Abstract

An in situ-generated complex from [RuCp*Cl 2 ] 2 and dpePhos ligand is reported as an efficient catalyst in the presence of 5 mol % of LiOtBu for the N-methylation of amines using methanol as the methylating agent at moderate conditions, following hydrogen borrowing strategy. This simple catalyst system provides selective N-monomethylation of substituted primary anilines and sulfonamides as well as N,Ndimethylation of primary aliphatic amines in excellent yields at 40−100°C with good tolerance to reducible functional groups. The catalytic intermediate Cp*Ru(dpePhos)H was isolated and was shown to be active for methylation in the absence of base.

Efficient Cobalt‐Catalyzed Methylation of Amines Using Methanol

“…[13] Other aromatic amines all produced monomethylated products in the optimized catalytic system. For the methylation of aniline (1 n), only monomethylated product Nmethylaniline (2 n) was obtained in a yield of 95% without dimethylated product under the optimized conditions.…”

“…[1,5] N-methylation of amines using methanol is a promising green and sustainable method for synthesis of N-methylamines with H 2 O as the only byproduct. [12] Up to now, methylation of amines with methanol has been achieved over expensive and rare second/third-row transition-metal catalysts such as homogeneous Ru [13][14][15] and Ir [16][17] complex, and heterogeneous Lewis acid catalysts under harsh reaction conditions (> 240 8C). [11] Apparently, the energy barrier to the activation of smaller alcohols appeared to be too uphill.…”

“…Co ( [11][12][13][14][15][16]. The yield of 2 a was decreased from > 99% to 77% when Na 3 PO 4 was used in stead of K 3 PO 4 , probably owing to the decreased basicity (entry 6 vs. 11).…”

“…[13,29] Notably, the formation of formaldehyde was detected using dimedone solution (for experimental details, see SI). In the methylation/formylation reaction with methanol catalyzed by Ru or Ir complexes, formaldehyde was detected as an intermediate, which was formed through the dehydrogenation of methanol.…”

“…This is a classical borrowing hydrogen strategy, [13,30] during which only one hydrogen atom is abstracted. Taking secondary amine as an example, firstly, a Comethoxy complex (II) is formed in the presence of base after coordination of Co species with PP 3 (I), which then transforms into Co-hydride (III) intermediate through b-hydride abstraction, releasing formaldehyde.…”