Concise and scalable asymmetric synthesis of 5-(1-amino-2,2,2-trifluoroethyl)thiazolo[3,2-b][1,2,4]triazoles

Abstract

This study describes asymmetric Mannich-type additions between C-5 lithiated thiazolo[3,2-b][1,2,4]triazoles and enantiomerically pure (S_S)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine. Under the optimized conditions, these reactions proceed with good (up to 78%) chemical yields and virtually complete (98 : 2 to >99 : 1 dr) diastereoselectivity. The same stereochemical outcome was obtained using 1.05 g scale of the starting (3,3,3)-trifluoroacetaldimine. The method developed in this work provides concise and generalized access to thiazolo[3,2-b][1,2,4]triazoles containing a chiral (trifluoro)ethylamine group.