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

We demonstrate the catalytic intermolecular [2+2] cycloaddition of electron-rich alkynes and a trifluoroiminopyruvate, affording the corresponding CF3-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 gamma-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.

Automated summary

The catalytic intermolecular [2+2] cycloaddition of electron-rich alkynes and trifluoroiminopyruvate was demonstrated, affording the corresponding CF3-substituted isolable 2-azetines. Using titanium(IV) tetrachloride as a catalyst effectively promoted the desired [2+2] cycloaddition, providing 2-azetines. The regioselectivity was complete with electron-rich aryl-substituted inner alkynes, and a silyl group was effective for inducing the dominant [2+2] cycloaddition pathway, leading to the formation of a 6-membered cyclic sulfonamide.