Synthesis of C7-Functionalized Indoles through an Aromaticity Destruction–Reconstruction Process

Abstract

A process for the synthesis of C7-functionalized indoles using para-substituted 2-alkynylanilines as starting materials was reported. The process involves a dearomatization, an 1,2addition by organic lithium or Grignard reagents, an aromatizationdriven allylic rearrangement, and a cyclization. A variety of groups including alkyl, aryl, alkenyl, or alkynyl groups were selectively installed at the C7 site of indoles leading to the formation of 2,5,7trisubstituted indoles.

One-pot synthesis of 4-(imidazol-1-yl)indole derivatives through a sequential dearomatization and Ag-catalyzed cyclization/Cs2CO3-mediated addition/aromatization reaction

“…8,13 In this context and to continue our recent interest in exploring new atom-and step-economical methods for the synthesis of N-heterocycles, 14 herein we developed an expedient synthesis of 4-(imidazol-1-yl)indole derivatives from N-sulfonyl o-alkynylanilines and imidazoles through two-step sequential reactions involving a dearomatization and a Ag(I)-catalyzed cyclization/ cesium carbonate-mediated conjugate addition/aromatization cascade process (Scheme 1, eqn (5)). As an important compensation of the previously reported addition/cyclization/aromatization reactions of o-phenylethynyl cyclohexadienimines, 8,13,15 the present work indicates that the combined use of a Lewis acid and cesium carbonate plays a significant role in the relevant domino transformation.…”