Formal [3 + 2] Cycloaddition of <i>α</i>-Imino Esters with Azo Compounds: Facile Construction of Pentasubstituted 1,2,4-Triazoline Skeletons

Abstract

1,2,4-Triazole and 1,2,4-triazoline are important components of bioactive molecules and catalysts employed in organic synthesis. Therefore, the efficient synthesis of these components has received significant research attention. However, studies on their structural diversity remain lacking. Previously, we developed chiral phase-transfer-catalyzed asymmetric reactions of α-imino carbonyl compounds with α,β-unsaturated carbonyl compounds and haloalkanes. In this study, we demonstrate the formal [3 + 2] cycloaddition reaction of α-imino esters with azo compounds under Brønsted base catalysis, resulting in the corresponding 1,2,4-triazolines in high yields. The results revealed that a wide range of substrates and reactants can be applied, irrespective of their steric and electronic characteristics. The present reaction made the general preparation of 3-aryl pentasubstituted 1,2,4-triazolines possible for the first time. Furthermore, a mechanistic study suggested that the reaction proceeds without isomerization into the aldimine form.

Keywords

• cycloaddition
• <i>α</i>-imino ester
• azo compound
• 1,2,4-triazoline
• 1,2,4-triazole