Title : Eco-friendly strategies for N-arylation of pyrrolidines and related frameworks
Abstract:
Nitrogen-containing heterocycles are central to medicinal chemistry because of their broad therapeutic potential. Among them, N-arylated pyrrolidines have emerged as valuable scaffolds, where aryl substitution at the nitrogen atom enhances structural diversity and biological activity. These compounds occur in numerous bioactive molecules and display effects such as anti-Alzheimer, antihypoxic, anticancer, analgesic, plant activator, and anti-hepatitis C activity. The growing importance of this framework has stimulated extensive research on efficient and reliable methods for its synthesis. In particular, advances reported in the last decade reveal a broad spectrum of strategies, including both transition-metal-catalyzed and transition-metal-free approaches. Notable methodologies encompass decarboxylation reactions, reductive amination, nucleophilic cyclization, Ullmann-Goldberg amidation, Buchwald-Hartwig amination, Chan-Evans-Lam coupling, additions to benzyne, rearrangement reactions, multistep sequences, and multicomponent reactions, with a variety of green synthetic protocols. Collectively, these strategies illustrate the adaptability of synthetic chemistry in providing access to N-aryl pyrrolidines with high efficiency and structural diversity. Special attention has been directed toward sustainable protocols that emphasize atom economy, operational simplicity, reduced energy input, and the use of environmentally benign conditions. This review consolidates these developments, underscoring how the chemistry of N-arylated pyrrolidines has advanced in parallel with the principles of green chemistry. Ultimately, these compounds serve not only as valuable therapeutic candidates but also as model scaffolds demonstrating how modern synthetic methods can contribute to the broader goal of sustainable development.
Keywords: N-arylation, pyrrolidines, heterocycles, green synthesis, drug discovery
