Radical deoxygenation of 3-azatricyclo[2.2.1.02,6]heptan-5-ols to 2-azabicyclo[2.2.1]hept-5-enes and 1,2-dihydropyridines

Selective Carbon–Carbon Bond Cleavage of Cyclopropylamine Derivatives

“…249 In certain cases, alternate pathways can predominate; for example, pyridine derivative 332 was generated from thiocarbonate 330 (Scheme 79C). 250 This process likely involves a nonradical-based rearrangement to give 1,2-dihydropyridine aldehyde 331 as an intermediate.…”

“…This methodology has been used to transform 327 to 328 , which is a precursor en route to epibatidine analogue 329 (Scheme B). , A related rearrangement strategy was developed for the synthesis of kainoid amino acids . In certain cases, alternate pathways can predominate; for example, pyridine derivative 332 was generated from thiocarbonate 330 (Scheme C) . This process likely involves a nonradical-based rearrangement to give 1,2-dihydropyridine aldehyde 331 as an intermediate.…”

Ring-opening, cycloaddition and rearrangement reactions of nitrogen-substituted cyclopropane derivatives

“…151 The group of D. Hodgson has extensively studied the radical chemistry of a particular family 156 In that case, the reaction is believed to proceed along an ionic pathway, where…”

“…Cyclopropane ringopening takes place under typical radical deoxygenation conditions to generate the radical 76, stabilised by the nitrogen atom. Two main types of reactivity are eventually observed: either direct trapping by Bu 3 SnH to produce 2-azabicyclo[2.2.1]hept-5-enes or a further β-fragmentation to produce the radical 77, which finally abstracts a hydrogen atom from Bu 3 SnH to give a dihydropyridine compound(Scheme 50, top) 152,153,154,155,156. The latter reaction pathway operates only when the starting radical precursor bears a radical-stabilising group R 1 (e.g.…”

Synthesis, utility and medicinal importance of 1,2- & 1,4-dihydropyridines

“…Hodgson, et al 15 have developed a new methodology of radical deoxygenation process on 3-azatricyclo[2.2.1.0 2,6 ] heptan-5-ols 53 using tributyltin hydride to afford the 1,2-dihydropyridines. 3-Azatricyclo[2.2.1.0 2,6 ]heptan-5-ols 54a-b were synthesized from the corresponding epoxide 52 (readily available from cycloaddition of the N-Boc pyrrole and tosyl ethyne, followed by the epoxidation of the resulting bicyclic diene), which on radical deoxygenation (via the xanthate) using Bu 3 SnH (2.0 equiv.)…”