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TiCl<sub>4</sub>‐Mediated [2+2] Cycloaddition for Synthesis of Isolable CF<sub>3</sub>‐Substituted 2‐Azetines

Shunya Hara, Shigekazu Ito

2021Asian Journal of Organic Chemistry12 citationsDOI

Abstract

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.

Topics & Concepts

CycloadditionChemistryRegioselectivityCatalysisMedicinal chemistryLewis acids and basesTitanium tetrachlorideArylHydrideRing (chemistry)StereochemistryOrganic chemistryMetalAlkylCatalytic C–H Functionalization MethodsFluorine in Organic ChemistrySynthesis and Catalytic Reactions
TiCl<sub>4</sub>‐Mediated [2+2] Cycloaddition for Synthesis of Isolable CF<sub>3</sub>‐Substituted 2‐Azetines | Litcius