Synthesis of benzobicyclo[2.2.1]heptylimidazoles as conformationally constrained adrenergic receptor antagonists

A facile method for the preparation of conformationally rigid analogues of the adrenergic α-2 receptor antagonist atipamezole and the adrenergic α-2 receptor agonist medetomidine has been developed. The efficient benzyne [4+2] cycloaddition reaction was used to give the core 7-acetylbenzonorbornadiene structure, which was subsequently elaborated to the corresponding imidazole-based syn and anti isomers by means of the classical Bredereck’s method.