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

• Published in: Journal of organic chemistry Vol. 85; no. 23; pp. 15488 - 15501
• Main Authors: Reddy, G. Surendra, Reddy, L. Mallikarjuna, Kumar, A. Suresh, Ramachary, Dhevalapally B
• Format: Journal Article
• Language: English
• Published: American Chemical Society 04.12.2020
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.0c02247

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.