Toward Pyridine–Heterocycle Patterns through Prins and Aza‐Prins Cyclisations: Application to a Short Synthesis of (±)‐Anabasine

Abstract

The formation of pyridine‐containing bisheterocycles through a Prins‐type cyclisation is described. Pyridine–tetrahydropyran and pyridine–piperidine conjugates could be efficiently obtained using various carbaldehydes including dicarbaldehydes, and either homoallylic alcohols or a homoallylic amine. Selective partial or complete hydrogenation led to new bisheterocycle combinations. A two‐step sequence involving an aza‐Prins cylisation allowed us to prepare the alkaloid anabasine.

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

“…Thomassigny and co‐workers reported a very short synthesis of the tobacco alkaloid anabasine ( 21 ), in racemic form, as an extension of the method they developed for the aza‐Prins cyclization of pyridinecarbaldehydes . The two‐step sequence involved an In(OTf) 3 ‐promoted aza‐Prins reaction between the homoallylic amine 19 and pyridine‐3‐carbaldehyde ( 18 ), affording a mixture of the two regioisomers of the pyridyl‐dehydropiperidine 20 in 44 % yield.…”

Synthesis of Tricyclic Benzazocines by Aza-Prins Reaction

“…The aza-Prins reaction is an efficient method for the synthesis of piperidines. , The reaction frequently involves the condensation of an homoallylic amine with an aldehyde in the presence of an acid to give an iminium ion, which then undergoes the intramolecular nucleophilic attack by the olefin (Scheme ). The wide applicability and usefulness of the aza-Prins reaction have been demonstrated by the synthesis of a variety of complex natural products …”