Palladium/norbornene catalysis for selective aromatic functionalization via C-H activation

The subject of this PhD thesis is the study of new processes in homogeneous catalysis for the synthesis of selectively substituted compounds containing the biaryl unit. The methodology, discovered in our laboratory, utilizes simple and readily available starting materials to form complex molecular structures under mild conditions. It takes advantage of the catalytic system based on palladium and norbornene. The metal, the strained olefin and an aryl halide work in a cooperative way to build up an arylnorbornylmetallacycle through C--H activation. This key intermediate is able to drive selective transformations on either the aryl or the norbornyl side of the palladacycle. A biaryl unit can be formed by oxidative addition of a second aryl halide on the palladacycle and subsequent Csp2-Csp2 coupling by reductive elimination. The removal of norbornene from the organometallic complex affords a biarylpalladium species. which can close the catalytic cycle in several ways, each leading to different synthetic pathways. In the course of my PhD work various termination steps have been studied. Intermolecular couplings have been obtained by C--heteroatom reductive elimination and condensed cyclic structures have been achieved by nucleophilic attack of the biarylpalladium intermediate to a carbonyl group present in the same biaryl fragment. Moreover, a different type of reactivity, that leads to the functionalization of the norbornyl side of the palladacycle with retention of the norbornyl moiety in the final organic product, has been studied. A straightforward and general methodology has thus been developed for the synthesis of dibenzoazepine derivatives. In all cases, target compounds can be of interest for the fine chemicals and pharmaceutical industry.