Strategic Vinyl Sulfone Nucleophile β-Substitution Significantly Impacts Selectivity in Vinylogous Darzens and Aza-Darzens Reactions.

Vinylogous Darzens and aza-Darzens reactions employing a benzothiophene 1,1-dioxide nucleophile are reported. These new [2 + 1] annulation reactions, which proceed under mild reaction conditions, are γ-selective, affording trans-epoxides selectively and favoring trans-aziridines. The reactions are base-dependent, with KOtBu and Cs2CO3 being optimal for aldehyde and imine annulations, respectively. Comparison of the benzothiophene nucleophile to its acyclic counterpart reveals superior performance in the case of aldehydes, while the outcome varies depending on the sulfonamide imine used.