Base and copper(i) catalyzed Mannich, alkyne hydroamination cascades for the direct synthesis of 2-methylenepyrrolidines

Abstract

An efficient, simple-to-perform, one-pot reaction cascade to 2-methylenepyrrolidines from p-toluenesulfonyl protected imines and propargylated malonates under a combination of base and copper(I) catalysis is reported.

Asymmetric One‐Pot Sequential Organo‐ and Gold Catalysis for the Enantioselective Synthesis of Dihydropyrrole Derivatives

“…[7c-e] Furthermore, Alexakis and co-workers have described a one-pot process consisting of an enantioselective organocatalytic Michael addition to nitroenynes and a subsequent gold-catalyzed acetalization/cyclization for the synthesis of nitro-substituted tetrahydrofuranyl ethers. [8a] In continuation of our research in combining organocatalysis with other chemical concepts, [10] and inspired by the work of Dixon et al [11] who presented a cascade reaction to access racemic 2-methylenepyrrolidines from protected imines and propargylated malonates using base and copper(I) catalysis; we now report a novel approach to highly functionalized optically active 2,3,3,5-tetrasubstituted 2,3-dihydro-1H-pyrroles from imines and propargylated pronucleophiles (Scheme 1).…”

“…[8a] In continuation of our research in combining organocatalysis with other chemical concepts, [10] and inspired by the work of Dixon et al [11] who presented a cascade reaction to access racemic 2-methylenepyrrolidines from protected imines and propargylated malonates using base and copper(I) catalysis; we now report a novel approach to highly functionalized optically active 2,3,3,5-tetrasubstituted 2,3-dihydro-1H-pyrroles from imines and propargylated pronucleophiles (Scheme 1).…”

Base‐ and Copper‐Catalyzed Intramolecular Cyclization for the Direct Synthesis of Dihydrofurans

“…Referring to the related literature, [8] the proposed mechanism for the reaction is shown in Figure 1. First, under base catalysis, the enol anion is rapidly generated from 2.…”

“…[4,5] Although many copper-catalyzed strategies have been successfully applied to the preparation of many heterocyclic compounds, [6] few applications in the synthesis of dihydrofurans were reported. [7] Based on our previous studies, [8] we hypothesize that the direct synthesis of 5-methylene-4,5-dihydrofurans could be achieved by using 2-propynyl-1,3-dicarbonyl compounds as starting materials (Scheme 1). It is anticipated that the rapid enolization of the dicarbonyl compounds under base catalysis followed by an intramolecular nucleophilic addition of the oxygen anion of an enol to a carbon-carbon triple bond activated by a copper salt Scheme 1.…”

Anionen‐induzierte enantioselektive Cyclisierung von Diinamiden zu Pyrrolidinen durch kationische Gold‐Komplexe

“…Die Studien ergaben, dass kationische Gold-Komplexe zur effizienten Bildung der Methylenpyrrolidine führen (Tabelle 1). [15] Durch Verwendung von Katalysatoren mit verschiedenen chiralen Phosphanen wurden die Produkte in Ausbeuten bis 93 % isoliert, jedoch wurden nur sehr niedrige Enantioselektivitäten beobachtet (Tabelle 1, Nr. 4).…”