Ag(I)-Mediated Annulation of 2-(2-Enynyl)pyridines and Propargyl Amines to Access 1-(2H-Pyrrol-3-yl)indolizines

Abstract

An effective Ag(I)-mediated annulation of 2-(2enynyl)pyridines and propargyl amines was developed, unexpectedly affording a broad range of functionalized 1-(2H-pyrrol-3yl)indolizines in moderate to excellent yields. The developed method is characterized by operational simplicity, ready availability of starting materials, high regioselectivity, and broad substrate scope under mild reaction conditions. The Ag(I)-promoted cyclization of 2-(2-enynyl)pyridines and propargyl amines possibly results in the formation of the spiroindolizine, the ring-opening rearrangement of which may give the 1-(2H-pyrrol-3-yl)indolizine. Furthermore, a gram-scale reaction and synthetic transformations are also studied.

Silver(I)-Promoted [3 + 3]-Cycloaddition of 2-(2-Enynyl)quinolines with N′-(2-Alkynylbenzylidene)hydrazides

“…Based on the above experimental results and previous reports, − a plausible mechanism for the synthesis of aza-polycyclic products 3 from 2-(2-enynyl)quinolines 1 and N’ -(2-alkynylbenzylidene)hydrazides 2 was proposed in Scheme . First, as a π-Lewis acid, the Ag(I) catalyst can activate the alkyne of 2-(2-enynyl)quinolines 1 , and which promotes the nucleophilic attack by the quinoline nitrogen toward the carbon–carbon triple bond of 2 .…”

“…Single-crystal X-ray diffraction intensity data were collected using a Bruker D8 VENTURE. The known substrates 1 were prepared according to the previous literature. − The known substrates 2 were prepared according to the previous literature …”

“…Furthermore, a palladium-mediated three-component tandem reaction has been demonstrated by Jia et al to afford 1,2,3-trisubstituted indolizines . More recently, we have reported an interesting protocol to synthesize 1-(2 H -pyrrol-3-yl)indolizines via the Ag(I)-promoted tandem rearrangement cyclization of 2-(2-enynyl)pyridines and propargyl amines . However, 2-(2-enynyl)pyridines react with an active dipole, containing nucleophilic and electrophilic centers, to construct fused polycyclic indolizines, which had rarely been demonstrated.…”