Bioinspired Oxidative Aromatizations: One-Pot Syntheses of 2-Substituted Benzothiazoles and Pyridines by Aerobic Organocatalysis

Heteroaromatic structures are abundant in bioactive natural products, medicines, and other functional materials. Oxidative aromatization is a common method for preparing heteroaromatic species from simple building blocks. A bioinspired method was developed using robust flavin mimics as organocatalysts that perform O 2 -fueled oxidations of 1,4-dihydropyridines to pyridines and benzothiazolines to benzothiazoles in high yields (>95%) and purity at ambient temperature in methanol. The efficient oxidative aromatizations facilitated one-pot multicomponent syntheses of pyridines (from various aldehydes, dicarbonyl compounds, and ammonium acetate, in yields ranging from 35 to 95%) and benzothiazoles (from 2-aminothiophenol and various aldehydes, in 78–95% yield) without metals or reactive stoichiometric oxidants. For most substrates, neutral conditions were effective. Hindered 4-substituted dihydropyridines that oxidized slowly were accelerated by selection of more electrophilic flavin catalysts and the addition of various acids in a manner inversely proportional to p K a .