Rapid Assembly of Saturated Nitrogen Heterocycles in One‐Pot: Diazo‐Heterocycle "Stitching" by N–H Insertion and Cyclization. (28th December 2018)

• Record Type: Journal Article
• Authors: Boddy, Alexander J.; Affron, Dominic P.; Cordier, Christopher J.; Rivers, Emma L.; Spivey, Alan C.; Bull, James A.
• Is Part Of: Angewandte Chemie. Volume 131:Number 5(2019)
• Page Start: 1472
• Page End: 1476
• Publication Date: 2018-12-28
• Subjects: Aminosäuren -- Cyclisierungen -- Fragmentsynthese -- Rhodium-Katalyse -- Stickstoffheterocyclen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201812925
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2, 2‐disubstituted azetidines, pyrrolidines, piperidines, and azepanes bearing ester and diverse aryl substituents. A one‐pot rhodium catalyzed N–H insertion and cyclization sequence uses diazo compounds to stitch together linear 1, m ‐haloamines ( m =2–5) to rapidly assemble 4 ‐, 5 ‐, 6 ‐, and 7 ‐membered saturated nitrogen heterocycles in excellent yields. Over fifty examples are demonstrated, including examples with diazo compounds derived from biologically active compounds. The products can be functionalized to afford α, α‐disubstituted amino acids and applied to fragment synthesis.