One-Pot Synthesis of 3‑Azido- and 3‑Aminopiperidines by Intramolecular Cyclization of Unsaturated Amines

• Published in: Journal of organic chemistry Vol. 79; no. 2; pp. 571 - 581
• Main Authors: Ortiz, Gerardo X, Kang, Bora, Wang, Qiu
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-01-2014
• Subjects: Amines - chemistry; Cyclization; Molecular Structure; Piperidines - chemical synthesis; Piperidines - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo4022666

A highly efficient one-pot synthesis of 3-azidopiperidines has been achieved by an intramolecular cyclization of unsaturated amines that allows for the nucleophilic installation of an azide moiety. This method unlocks the versatile employment of the azide functionality in the preparation and biological studies of piperidine-containing structures. This strategy has been expanded for the direct incorporation of a variety of nitrogen nucleophiles, and thus it provides a rapid and modular synthesis of 3-amino and 3-amidopiperidines of important pharmaceutical and biological relevance. Particularly noteworthy is that the regioselectivity of this transformation enables the formation of the anti-Markovnikov-type adduct, complementing Markovnikov-based olefin amino functionalization methods.