Amine-Facilitated Tandem Aerobic Oxidation and Cyclization to Tetrahydro-β-Carbolines

Abstract A tandem oxidation–condensation–cyclization of alcohols with tryptamines was developed under open-air atmosphere. Various harmless and readily available alcohols were used instead of aldehydes for the condensation with amines and subsequent cyclization to afford pharmacologically active tetrahydro-β-carboline products. Mechanistic studies reveal that the base promotes the initial dehydrogenation of alcohols to aldehydes, and the subsequent amine trapping of the reactive aldehydes is the key driving force that shifts the equilibrium, thus allowing the catalytic cycle to proceed continuously to full conversion. A 30 mmol-scale (6.5 g) experiment and the synthesis of two bioactive molecules demonstrated that the method is operationally simple, cost effective, and highly practical.