Synthesis of Epibatidine Analogues by Pyrrole Diels–Alder Reactions: Rapid Access to Azabicyclo2.2.1heptane and 3,8‐Diazabicyclo3.2.1octane Scaffolds for Library Synthesis

Analogues of the nicotinic acetylcholine antagonist epibatidine, suitable for diversification, were synthesized by application of a pyrrole Diels–Alder strategy, allowing rapid generation of azabicyclo2.2.1heptane bicyclic cores. Further molecular complexity could be accessed by using intramolecular Diels–Alder reactions, or ring expansion by ozonolysis–reductive amination chemistry. Scaffolds were designed such that they could be orthogonally deprotected, yielding three points of diversity for library synthesis, exemplified by 24 compounds synthesized from four cores.