Electrochemical Oxidative Coupling Between Benzylic C(sp³)–H and N–H of Secondary Amines: Rapid Synthesis of α-Amino α-Aryl Esters

Abstract

An intermolecular electrochemical coupling between the benzylic C­(sp3)–H bond and various secondary amines is reported. The electronic behavior of two electronically rich units viz the α-position of α-aryl acetates and amines was engineered electrochemically, thus facilitating their reactivity for the direct access of α-amino esters. A series of acyclic/cyclic secondary amines and α-aryl acetates were tested to furnish the corresponding α-amino esters with high yields (up to 92%) under mild conditions.

Copper (II) bromide/NMO system for α-amination of esters in solvent-free condition

“…Our first attempt was reaction of propiophenone with piperidine in presence of CuBr2 as a catalyst in solvent-free condition (Table 1, entry 1). The desired product 10a was obtained in 41% yield, and characterized by 1 H and 13 C NMR. The presence of a peak at chemical shift value 3.93 (benzylic C-H) in 1 H NMR and peak at 75.1 in 13 C NMR confirms the formation of product.…”

“…The desired product 10a was obtained in 41% yield, and characterized by 1 H and 13 C NMR. The presence of a peak at chemical shift value 3.93 (benzylic C-H) in 1 H NMR and peak at 75.1 in 13 C NMR confirms the formation of product. 28 However, the starting material was not completely consumed, after running the reaction for 24h.…”

Controlled and Predictably Selective Oxidation of Activated and Unactivated C(sp3)–H Bonds Catalyzed by a Molybdenum-Based Metallomicellar Catalyst in Water

“…Commercial aldehyde/ketone production is achieved by chlorination of methylarene followed by saponification, whereas benzoic acid is produced by cobalt-catalyzed liquid-phase oxidation of toluene with O 2 in acetic acid at 165 °C; however, the conversion must be limited to <15% to retain selectivities. − The use of a halogen and acetic acid makes these processes environmentally unfriendly. Recently, a few other protocols for C–H bond oxidation/functionalization catalyzed by transition metal-based catalysts, such as Cr, Mo, Mn, Re, Ru, Os, Rh, Pd, Cu, Au, and Pt, − have been reported (Figure b). Nevertheless, most of the above-mentioned methodologies suffer from the limitations of either toxicity or harsh reaction conditions.…”

Direct Hydroxylarylation of Benzylic Carbon (sp3/sp2/sp) via Radical-involved Paired Electrochemical Cascade Reaction

“…1A), which is also present in many biologically active compounds 23,24 , and nearly 25% of the 200 best-selling drugs contain this structural moiety 25 . Lately, the electrochemical benzylic C(sp 3 )-H activation has been widely used for C-N 26,27,28,29 or C-O 30 coupling. However, to the best of our knowledge, the formation of C-C bond through unactivated benzylic C(sp 3 )-H functionalization is rarely reported.…”