Substituent-Controlled Annuloselectivity and Stereoselectivity in the Sulfa-Staudinger Cycloadditions

In the sulfa-Staudinger cycloadditions of imines and sulfonyl chlorides, the annuloselectivity is mainly controlled by the electronic effect of the α-substituents of sulfonyl chlorides and the nucleophilicity of imines. Sulfonyl chlorides with weakly electron-donating and withdrawing substituents prefer the [2s+2i] annulation, giving a mixture of cis- and trans-β-sultams. Sulfonyl chlorides bearing strongly electron-withdrawing α-substituents show different annuloselectivity depending upon the nucleophilicity of imines as following: (1) weakly nucleophilic imines with sterically larger substituents than the methyl group undergo only [2s+2i] annulation to produce trans-β-sultams; (2) strongly nucleophilic imines with the N-methyl substituent take place both [2s+2i] and [2s+2i+2i] annulations generally, delivering trans-β-sultams and rel(3S,5S,6R)-1,2,4-thiadiazinane 1,1-dioxides composed of one molecule of the sulfenes and two molecules of imines; (3) more strongly nucleophilic cyclic (Z)-imines give predominately [2s+2i+2i] annulations, resulting in a pair of diastereomeric [2s+2i+2i] annuladducts 1,2,4-thiadiazinane 1,1-dioxides. In the second case, the electronic and steric effects of the C-substituents of the N-methyl imines also affect the annuloselectivity. The stereochemistry and stereoselectivities of the [2s+2i] and [2s+2i+2i] annuladducts were investigated systematically and mechanistically rationalized.