Zn(II)-Catalyzed Selective N-Alkylation of Amines with Alcohols Using Redox Noninnocent Azo-Aromatic Ligand as Electron and Hydrogen Reservoir

Abstract

We report a sustainable and eco-friendly approach for selective Nalkylation of various amines by alcohols, catalyzed by a well-defined Zn(II)-catalyst, Zn(L a )Cl 2 (1a), bearing a tridentate arylazo scaffold. A total of 57 N-alkylated amines were prepared in good to excellent yields, out of which 17 examples are new. The Zn(II)catalyst shows wide functional group tolerance, is compatible with the synthesis of dialkylated amines via double N-alkylation of diamines, and produces the precursors in high yields for the marketed drugs tripelennamine and thonzonium bromide in gramscale reactions. Control reactions and DFT studies indicate that electron transfer events occur at the azo-chromophore throughout the catalytic process, which shuttles between neutral azo, one-electron reduced azo-anion radical, and two-electron reduced hydrazo forms acting both as electron and hydrogen reservoir, enabling the Zn(II)-catalyst for Nalkylation reaction.

C3-Functionalization of indoles with α-heteroaryl-substituted methyl alcohols

“…Recently, several reports described a metal-mediated synthesis of functionalized indoles from 2-aminophenylethyl alcohols through an HA approach. 15 Unfortunately, such a conversion under our standard conditions using 2-aminophenylethyl alcohol as the starting material resulted in a complex reaction mixture and only 14% of 13a was isolated. We suspect that the oxidation of the homoallylic alcohol was inefficient, and future work will address the optimization of this one-pot indole formation/C3-alkylation protocol.…”

Electron transfer catalysis mediated by 3d complexes of redox non-innocent ligands possessing an azo function: a perspective

“…In this work 57 N -alkylated amines were reported to be prepared in good to very good yields. 137 The reaction pathway has been well investigated and as expected, the electron transfer during the catalysis is associated with the azo-chromophore, and it may commute between azo-anion mono-radical and two-electron reduced hydrazo function (Scheme 45). In this regard, the azo function may be thought to act as a reservoir for both the electron and well as hydrogen with the redox innocent Zn( ii )-centre serving as a template for the catalytic transformation.…”

Metal–organic framework-derived CoNx nanoparticles on N-doped carbon for selective N-alkylation of aniline

“…1). The C 1s XPS was tted into ve peaks for: sp 2 hybridised carbon of C]C (284.7 eV), sp 3 hybridised carbon C-C bond (284.9 eV), C]N (285.9 eV), C-N (287.6 eV), and COOH (290.1 eV). 57 The ratio of the graphitic carbon to other carbon is determined to be 1.62, which closely matches with the Raman data.…”

“…2 Additionally, the amine and nitrogen moieties play a key role in drug molecules. 3 Due to their high signicance, numerous methods have been developed for the selective formation of C-N bonds. [1][2][3][4] In general, secondary amines have been prepared by both oxidative and reductive methods.…”

“…3 Due to their high signicance, numerous methods have been developed for the selective formation of C-N bonds. [1][2][3][4] In general, secondary amines have been prepared by both oxidative and reductive methods. 5,6 In the reductive process, the carbonyl compound reacts with primary amines in the presence of a suitable catalyst and stoichiometric amounts of reducing agents (borohydride/formic acid/ammonium/formate/silanes).…”