Stereoselective synthesis of 2,6--4-oxopiperidines using an acid-mediated 6- cyclisation

• Published in: Organic & biomolecular chemistry 2018-09, Vol.16 (35), p.641-6422
• Main Authors: Bell, Jonathan D, Harkiss, Alexander H, Wellaway, Christopher R, Sutherland, Andrew
• Format: Article
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c8ob01363b

An acid-mediated 6- endo-trig cyclisation of amine-substituted enones has been developed for the stereoselective synthesis of trans -6-alkyl-2-methyl-4-oxopiperidines. Performed under conditions that prevent removal of the Boc-protecting group or acetal formation, the key cyclisation was found to generate cleanly the 4-oxopiperidine products in high overall yields from a wide range of alkyl substituted enones. The synthetic utility of the trans -6-alkyl-2-methyl-4-oxopiperidines formed from this process was demonstrated with the total synthesis of the quinolizidine alkaloid, (+)-myrtine and the piperidine alkaloid, (−)-solenopsin A. An acid-mediated 6- endo-trig cyclisation has been developed for the synthesis of trans -6-alkyl-2-methyl-4-oxopiperidines and used for the stereoselective preparation of quinolizidine alkaloid, (+)-myrtine and the piperidine alkaloid, (−)-solenopsin A.