Room Temperature Construction of Vicinal Amino Alcohols via Electroreductive Cross-Coupling of N-Heteroarenes and Carbonyls

Abstract

Despite the widespread applications of α-hydroxyalkyl cyclic amines, direct and diverse access to such a class of unique vicinal amino alcohols still remains, to date, a challenge. Here, through a strategy of electroreductive α-hydroxyalkylation of inactive N-heteroarenes with ketones or electron-rich arylaldehydes, we describe a room temperature approach for the direct construction of α-hydroxyalkyl cyclic amines, which features a broad substrate scope, operational simplicity, high chemoselectivity, and no need for pressurized H 2 gas and transition metal catalysts. The zinc ion generated from anode oxidation plays a crucial role in the activation of both reactants by decreasing their reduction potentials. The strategy of electroreduction in combination with substrate activation by Lewis acids in this work is anticipated to develop more useful transformations.

Diastereoselective construction of carbo-bridged polyheterocycles by a three-component tandem annulation reaction

“…Interestingly, in addition to quinoline-based reactants, other N -heteroarenium salts arising from 1,8-naphthyridines and 1,10-phenanthroline were also amenable for the transformation ( C 18 –C 22 ), which shows the potential of the developed chemistry in structural modification of N-ligands (Scheme 2). 14…”

Reductive Functionalization of Pyridine-Fused N-Heteroarenes

“…Recently, we developed an electroreductive cross-coupling of N-heteroarenes 4-a and carbonyls 13 (Figure 7a). 4 We used an undivided cell for the efficient transformation of various Nheteroarenes with carbonyls into N-heterocycle-based vicinal amino alcohols (Figure 7c). The in situ-generated zinc ions via anodic oxidation serve as Lewis acids to coordinate with both reactants and decrease their reduction potentials.…”

Electrochemical nickel-catalysed defluoroalkylation ofgem-difluoroalkenes with alkyl halides

“…In recent years, electrochemical methods have attracted a great deal of interest due to their operationally simple and environmentally friendly properties that avoid the use of stoichiometric amounts of redox reagents. 7,8 In the past few decades, the electrochemical strategy has been widely used in numerous organic research fields, such as C–H activations, 9 reductive coupling, 10 alkene difunctionalizations, 11 carboxylation reactions 12 and others. 13 Electrochemical reduction is becoming an attractive topic to fix the cost and waste problems faced in traditional chemical methods.…”