Base‐Promoted Structural Rearrangement of Ynamide and Simultaneous N‐Desulfonylation

Abstract

The strategy of ynamide structural rearrangement is crucial in modern organic synthesis. The distinct carbon atoms in ynamides have different selectivity under various reaction conditions. Herein, we developed a base‐promoted regioselective and chemoselective cascade cyclization, ynamide N–Csp bond cleavage, selective intramolecular 1,3‐migration, and simultaneous N‐desulfonylation strategy for the synthesis of 2‐phenyl‐3‐(phenylethynyl)‐1H‐indole derivatives within a time of 15 min. We observed multiple bond breaking (‐N–Ts, and Csp2–Ts, Csp2–I/Csp2–SePh) from (E)‐3‐(1‐iodo‐2‐phenyl‐2‐tosylvinyl)‐2‐phenyl‐1‐tosyl‐indole/(E)‐2‐phenyl‐3‐(2‐phenyl‐1‐(phenylselanyl)‐2‐tosylvinyl)‐1‐tosyl‐indole derivatives to achieve 2‐phenyl‐3‐(phenylethynyl)‐1H‐indole in 15–60 min using our standard reaction conditions. A gram‐scale experiment and the postsynthetic transformation of the synthesized 2‐phenyl‐3‐(phenylethynyl)‐1H‐indole were conducted to exhibit the advantages of our synthetic methodology. The developed methodology has multiple advantages: a rapid reaction rate, regioselectivity and chemoselectivity, transition metal and acid oxidant free, preventing resource waste and a time‐consuming process in deprotecting steps, broad substrate scope, mild reaction condition, simple setup, ease of handle, gram‐scale experiment, and synthetic product transformations.