Buchwald-Hartwig amination of the chloro substituted benzobicyclo[3.2.1]octadiene skeleton using primary benzylic amines

Abstract

Promising test results on biological activity of our previously described benzobicyclo[3.2.1]octadienes, obtained by intramolecular photochemical cycloaddition of o-vinylphenyl substituted butadienes, prompted us to continue with the further functionalization of this basic skeleton. Synthesis was extended to amino substituted benzobicyclo[3.2.1] octadienes starting from the chloro derivative. Novel benzobicyclo[3.2.1]octadiene benzylamines were prepared for the first time by Buchwald-Hartwig amination from the photoproduct obtained by highly efficient continuous flow-photochemistry setup. The novel amino substituted benzobicyclo[3.2.1]octadienes are especially interesting because of their methano-bridged junction of the three aromatic units at defined geometries as this gives them potential as molecular clips with very promising ADME properties due to the amino functional group. This is the first example of the Buchwald-Hartwig amination reaction on a rigid non-planar system.