N-Heterocyclic Carbene-Supported Nickel-Catalyzed Selective (Un)Symmetrical N-Alkylation of Aromatic Diamines with Alcohols

Abstract

The "borrowing hydrogen" (BH) approach for the N-alkylation of phenylenediamines using alcohols as coupling partners is highly challenging due to the selectivity issue of the generated products. Furthermore, the development of base-metal systems that can potentially substitute precious metals with competitive activity is a major challenge in BH catalysis. We present herein an efficient protocol for the N,N′-di-alkylation of aromatic diamines using an in situ-generated Ni−NHC complex from NiCl 2 and the ligand L1, which gave access to a wide range of N,N′-di-alkylated orthophenylene diamines (rather than the generally observed benzimidazole derivatives), meta-and paraphenylene diamines along with 2,6-diamino pyridine derivatives in good to excellent yields. Moreover, the catalyst system was also successful in the derivatization of a clinically important drug molecule, Dapsone. Notably, the present protocol could be applied effectively to synthesize unsymmetrically substituted N,N′-di-alkylated diamines via sequential alkylation and is the first report in the base-metal system to the best of our knowledge. Diverse control experiments including the deuterium incorporation studies suggest that the present protocol proceeds via a BH sequence.

N-Heterocyclic carbene supported zinc catalysed N-formylation of diverse N–H functionalities with carbon dioxide under ambient conditions

“…In order to identify the key intermediates and to probe the reaction mechanism, various control experiments were conducted (Scheme 4) to mechanistic pathway. First of all, we observed a drastic decrease in the product (3a) formation in the presence of a stoichiometric amount of trityl cation w.r.t catalyst (Scheme 4a), 17 which suggests the involvement of a Zn-H species in the mechanistic cycle. Further, the addition of a radical scavenger like TEMPO, BHT, and CuCl 2 to our standard reaction did not affect the formylation of 2a implying that the present catalytic cycle does not follow a radical pathway.…”

Heteroditopic NHC Ligand Supported Manganese(I) Complexes: Synthesis, Characterization, and Activity as Non‐bifunctional Phosphine‐Free Catalyst for the α‐Alkylation of Nitriles

“…Further, all our attempts to detect a Mn−H intermediate through spectroscopic means were failed which might be due to either thermodynamic instability or the higher reactivity of generated hydride species under the present reaction conditions. However, suppression of the catalytic activity was observed in presence of a stoichiometric amount of trityl cation (acts as a hydride quencher), [22b–c] which possibly suggests the involvement of a Mn−H species in the catalytic cycle (eq. 5).…”

Development of a Mild and Efficient Process for Ir-Catalyzed N-Alkylation of 4-Bromopyridin-2-amine with a Primary Alcohol via Borrowing Hydrogen

“…This reaction typically proceeds by conversion of an alcohol to a carbonyl functionality via transition-metal-catalyzed oxidative dehydrogenation followed by condensation with an amine to form an imine intermediate and subsequent reduction of the imine with metal-hydride to form an N -alkylated product. Since the pioneering work by Watanabe et al and Grigg et al, several reports have been published for N -alkylation of amines with primary alcohols using Co, Fe, Ir, Mn, Ni, and Ru catalysts. Most of these reaction conditions are characterized by the use of specialized ligands ( N -heterocyclic carbene, pincer, etc.…”