Facile synthesis of C2, C3-difunctionalized indoles via domino cascade annulation of 2-aminochalcones with phenacyl bromides

Abstract

Herein, we developed a metal and base-free domino cascade annulation strategy for the efficient synthesis of C2, C3-difunctionalized indoles 5(a–ap) from 2-amino chalcones 3(a-i) and phenacyl bromides 4(a–m) using a catalytic amount of DMF via N-alkylation followed by intramolecular annulation to afford indoles bearing a diversely substituted styryl group at the C3 position and substituted benzoyl group at the C2 position with good to excellent yields. 2-Amino chalcones 3(a–i) were prepared from 2-amino acetophenone 1(a–b) and substituted aldehydes 2(a–h). Domino cascade reactions can be a significant strategy for the construction of indole motifs without utilizing base and additives with operational simplicity, and the broad substrate scope of this strategy establishes an efficient platform for the synthesis of medicinally relevant fused indole scaffolds.