Selective Buchwald–Hartwig arylation of C-amino-1,2,4-triazoles and other coordinating aminoheterocycles enabled by bulky NHC ligands and TPEDO activator

Inorganic Chemistry Frontiers. 2023. Vol. 10. No. 1. P. 218–239.

Astakhov A., Chernenko A., Kutyrev V., S. Ranny G., Minyaev M. E., Chernyshev V., Ananikov V.

C-Amino-1,2,4-triazoles are challenging polynitrogen substrates for metal-catalyzed arylation due to their multidentate character, enhanced coordinating ability and decreased nucleophilicity of the amino group. In the present study, the Buchwald–Hartwig cross-coupling of diverse 3(5)-amino-1,2,4-triazoles with aryl chlorides and bromides delivering (hetero)arylamino-1,2,4-triazoles in good-to-excellent yields under Pd/NHC catalysis was developed. The use of Pd complexes with bulky NHC ligands such as IPr*OMe and TPEDO (1,1,2,2-tetraphenylethane-1,2-diol) as an in situ Pd(II) to Pd(0) reductant enabled the selective arylation of the NH2 group even in acidic NH unprotected substrates and deactivated 1-substituted 5-amino- and 4-substituted 3-amino-1,2,4-triazoles. The reaction mechanism and structure-activity relationships were studied with DFT calculations. A significant effect of the position of the N-substituent in the 1,2,4-triazole ring on the favorable reaction pathways was revealed.

Keywords: DFT calculations, 1,2,4-triazoles, Buchwald–Hartwig arylation, Pd/NHC complexes