Catalytic Asymmetric Synthesis of Atropisomeric N-Aryl 1,2,4-Triazoles.

Abstract

The atroposelective synthesis of N-aryl 1,2,4-triazoles was developed. A cyclodehydration reaction was rendered asymmetric with the use of a chiral phosphoric acid catalyst to afford atropisomeric N-aryl 1,2,4-triazoles in up to 91:9 er. Recrystallization of the isolated heterocycle further enriched the atropisomeric ratio of several analogs to 99:1 er or greater. A divergent and substrate-dependent reaction pathway yielding a different heterocyclic product is also disclosed.