Radical and Anionic Response of N-(Bromomethanesulfonyl)-Substituted α,α‘-Bridged Piperidine Substrates

• Published in: Journal of organic chemistry 2000-10, Vol.65 (21), p.7119-7123
• Main Authors: Schloss, Jeffrey D, Leit, Silvana M, Paquette, Leo A
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo000873b

The N-(bromomethanesulfonyl) azabicyclic ketones 2a−c and their ex o-methylene analogues 1a−c were prepared. Our examination of the radical-induced behavior of the latter triad provided experimental evidence for the propensity of the b and c systems to engage in 7-endo cyclization. For 1a, only reductive debromination was observed. In no instance was ring closure by the 6-exo radical mode seen. As concerns ketones 2a−c, all three showed a remarkable facility for engaging in intramolecular SN2 displacement in the presence of KHMDS. Yields at the mid-80% level were realized irrespective of the value of n. Molecular mechanics calculations of the Monte Carlo type were performed on several conformational isomers and product classes in an effort to provide support for the explanatory conclusions offered as rationale for the collective experimental observations.