Synthesis of Spirocyclic Piperidines from N-Arylisonicotinamides

Significance

Reported is a method for the synthesis of spirocyclic piperidines by Tf₂O-induced dearomatizing intramolecular coupling of N-arylisonicotinamides. Nucleophilic dearomatizing addition of arenes to N-triflyl pyridinium salts is known to result in 4-aryl-1,4-dihydropyridines (E. J. Corey, Y. Tian Org. Lett. 2005, 7, 5535). The extension of this approach on intramolecular coupling of pyridine-containing structures leads to target spirocyclic piperidines in poor to excellent yields. Mechanistically interesting is the fact that, under the conditions described for N-arylamide isonicotinamides, the corresponding amides of nicotinic and picolinic acids do not form spiro­materials but lead to structures A and B, respectively. Rationalization or experimental proof of these results, e.g., the involvement of spiro intermediate for the formation of A, was not provided.