Stereochemistry and mechanistic insights in the [2^t + 2ⁱ + 2ⁱ] annulations of thioketenes and imines

Stereochemical models and mechanistic insights are proposed for [2^t + 2ⁱ + 2ⁱ] annulations of thioketenes and imines on the basis of experimental and computational investigations. In the [2^t + 2ⁱ + 2ⁱ] annulations involving cyclic imines, the zwitterionic intermediates generated from monosubstituted thioketenes and the cyclic imines undergo a stepwise nucleophilic endo-addition/Si-face attack pathway with a second imines molecule, giving initially (2,4)-cis-(4,5)-cis-[2^t + 2ⁱ + 2ⁱ] annuladducts, which completely epimerize into the corresponding (2,4)-cis-(4,5)-trans-annuladducts under basic reaction conditions. The annuloselectivity of thio-Staudinger cycloadditions is dependent on the substituents of both thioketenes and imines. The reactivities and annuloselectivities of Staudinger, thio-Staudinger, and sulfa-Staudinger intermediates are compared.