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Updated: May 20, 2026
14:11
Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
Published on: June 10, 2021
Recent Advances in Intramolecular C─N Bond Formation for Pyrrolidine Synthesis
Rasma Kroņkalne1, Māris Turks1
1Institute of Chemistry and Chemical Technology, Faculty of Natural Sciences and Technology, Riga Technical University, Riga, Latvia.
Chemistryopen
|May 19, 2026
Summary
This review details advances in synthesizing pyrrolidines through intramolecular C─N bond formation, a key strategy for pharmaceuticals and materials. It covers various cyclization methods for efficient pyrrolidine framework construction.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Materials Science
Background:
- Pyrrolidines are vital nitrogen heterocycles found in numerous pharmaceuticals, bioactive molecules, and functional materials.
- Efficient synthetic strategies for pyrrolidine construction are continuously sought after.
- Intramolecular C─N bond formation is a fundamental and versatile approach for building pyrrolidine frameworks.
Purpose of the Study:
- To provide a systematic overview of pyrrolidine synthesis via intramolecular C─N bond formation.
- To summarize key advances in the field from 2013 to 2025.
- To focus on cyclization mechanisms involving a polar N: → C(+/δ+) step.
Main Methods:
- Review of transition-metal-catalyzed and metal-free cyclizations of alkenyl and alkynyl amines.
- Analysis of tandem annulation processes.
- Examination of intramolecular nucleophilic additions to carbonyls, nucleophilic substitutions, and C(sp³)-H activation.
Main Results:
- Comprehensive summary of recent (2013-2025) pyrrolidine synthesis methods.
- Detailed discussion of mechanistic features, substrate scope, and synthetic utility.
- Inclusion of Hofmann-Löffler-Freytag-type transformations.
Conclusions:
- The review offers a practical reference for designing novel pyrrolidine syntheses.
- It highlights the importance and versatility of intramolecular C─N bond formation.
- Advances discussed facilitate the creation of diverse pyrrolidine-containing compounds.
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