Organocatalytic Selective [3 + 2] Cycloadditions: Synthesis of Functionalized 5-Arylthiomethyl-1,2,3-triazoles and 4-Arylthio-1,2,3-triazoles

Abstract

An organocatalytic azide–ketone [3 + 2] cycloaddition (OrgAKC) of a variety of 1-aryl-3-(arylthio)propan-2-ones and 1-alkyl-3-(arylthio)propan-2-ones with different aryl/vinyl/alkyl azides is reported under ambient conditions to furnish the medicinally important 1,4-disubstituted-5-arylthiomethyl-1,2,3-triazoles and 1,5-disubstituted-4-arylthio-1,2,3-triazoles, respectively, in a regioselective manner with high yields/rates. With controlled and online NMR experiments, we proved that the reaction path is following the organocatalytic enolization through selective deprotonation followed by a [1,3]-H shift. Surprisingly, the [3 + 2] cycloaddition of aryl/vinyl/alkyl azides with the in situ-generated equilibrated thermodynamic ↔ kinetic enolates furnished the highly regioselective functionally rich 1,2,3-triazoles by discriminating their reactivities. This is the first report on the investigation of a selective OrgAKC with the regiomers of enolates generated in situ from the unsymmetrical carbonyl compounds. The reaction sustainability is explained with a few controlled experiments, mechanistic studies, and applications.