Catalytic Cyclophanes. Part IX. A Thiazolio‐cyclophane as Model for Pyruvate Oxidase and One‐Pot Synthesis of Aromatic Esters by Electrochemical Oxidation of Aldehydes Mediated by Bis(coenzyme) Catalysis

Abstract

AbstractMacrocycle 3 with a hydrophobic cavity and an appended thiazolium ring is prepared following a novel synthetic sequence to monofunctionalized cyclophanes. Although the thiazolium ring of 3 prefers to be located in the cyclophane cavity, it could be displaced with low energetic costs by benzene and naphthalene guests which form stable 1:1 inclusion complexes with 3 in protic solvents. Initial rate studies show that 3 is a pyruvate‐oxidase mimic and catalyzes the oxidation of aromatic aldehydes to carboxylic acids in aqueous solution. Cyclophane 3 also catalyzes the conversion of aromatic aldehydes to the corresponding esters in alcoholic solvents. The supramolecular catalyst 3 exhibits enzyme‐like saturation kinetics, large turnover numbers, as well as high reaction and substrate selectivity, and it is far superior to the non‐macrocyclic catalysts 4 and 5 which lack a substrate binding site. Following cyclic voltammetric investigations of the redox behavior and stability of thiazolium ions, a new one‐pot electrochemical synthesis of aromatic esters is developed: Aromatic esters are prepared efficiently by indirect electrochemical oxidation of the corresponding aldehydes in alcoholic solvents, mediated by two coenzymes, the thiazolium ions 3 or 5 and flavin 21. At the extraordinarily low working electrode potential of −300 mV (vs. Ag/AgCl), high yields of the esters are obtained with high current efficiencies and high turnovers of the catalysts which are stable under the reaction conditions. The origin of the substrate and reaction selectivity, which is particularly pronounced in the supramolecular reactions catalyzed by 3, is analyzed.