Leaving-group controlled N- or C-cyclization of azadienes via domino sequences: synthesis, mechanism, and chemoselectivity

Abstract

The nucleophile-induced N- or C-functionalization is a featured reactivity mode of azadienes, but the rational control of the selectivity has rarely been explored. Herein, we reported a leaving-group controlled N- or C-cyclization of azadienes bearing a benzothiophene moiety with sulfur ylides or α-bromoacetophenones, which produced a variety of benzothiophene fused pyrroles or spiro compounds in high yields. Density functional calculations revealed that the competition of two cyclizations was governed by the nature of the leaving group on the partner, because changing the leaving group from S(Me)₂ to Br altered the preferred steric configuration of the initial intermediate. Furthermore, the azadiene bearing a benzofuran or indene moiety was used as a substrate under the same reaction conditions, which demonstrated the key role of the heteroatom of the azadiene on the reactivity and selectivity.