Diastereoselective Synthesis of Pyrroloindolines by Palladium-Dihydroxyterphenylphosphine-Catalyzed C3-Dearomative Arylation/Cyclization of Substituted Tryptamines.

Abstract

Pyrroloindolines are promising compounds, yet reports on their syntheses remain scarce. Herein, we report the diastereoselective synthesis of C3a-arylated pyrroloindolines bearing substituents on the pyrrolidine ring by a facile palladium-dihydroxyterphenylphosphine-catalyzed C3-dearomative arylation of substituted tryptamine derivatives, followed by the intramolecular cyclization of the resulting indolenine. The reaction with various tryptamine derivatives showed that the position and bulkiness of the substituents on the aminoethyl chain of the tryptamines strongly influenced the site- and diastereoselectivity of the arylation. The steric hindrance of the arylating agents also determined the reactivity and diastereoselectivity. This study presents an efficient diastereoselective method to synthesize pyrroloindolines with C3a-aryl groups from widely available substituted tryptamine derivatives.