TiCl4‐Mediated [2+2] Cycloaddition for Synthesis of Isolable CF3‐Substituted 2‐Azetines

Abstract We demonstrate the catalytic intermolecular [2+2] cycloaddition of electron‐rich alkynes and a trifluoroiminopyruvate, affording the corresponding CF 3 ‐substituted isolable 2‐azetines. Whereas [4+2] interaction affording acyclic imidates was predominant in the absence of a Lewis acid catalyst, using a catalytic amount of titanium(IV) tetrachloride was quite effective in promoting the desired [2+2] cycloaddition providing 2‐azetines. Electron‐rich aryl‐substituted inner alkynes provided complete regioselectivity, and using a silyl group was effective for inducing the dominant [2+2] cycloaddition pathway. Both [2+2] cycloaddition and formation of γ‐butenolides via a “5‐ exo‐dig type” cyclization pathway were confirmed. Hydride reduction of a 2‐azetine provided the azetine‐substituted primary alcohol, and treatment with potassium t ‐butoxide promoted ring expansion, affording the 6‐membered cyclic sulfonamide.