Flow-photochemical synthesis of the functionalized enzobicyclo [3.2.1]octadiene skeleton

A convenient practical home-made continuous flow-photochemistry setup was evaluated with the aim to enable a more efficient protocol for the synthesis of functionalized benzobicyclo[3.2.1]octadiene skeleton by intramolecular [2+2]-photocycloaddition reaction. Numerous compounds with the bicyclo [3.2.1]-skeleton are proven as potent inhibitors of dopamine and serotonin transporters and also play a crucial role in treatment of central nervous system and Alzheimer's disorders. The yields, reaction times and conversions gained from the flow setup were compared to those obtained from the conventional photoreactor. In comparison to the batch reaction, the flow reaction showed better results, both in increasing the isolated yield and productivity and in lowering the reaction time. This first application of the flow-photochemistry on beta-heteroaryl-o-divinylbenzenes and o-vinylphenyl substituted butadienes proved to be more efficient and less sensitive to oxygen enabling us to scale-up the intramolecular cycloaddition without scaling-up the equipment. Additionally, for all the obtained, potentially bioactive, derivatives promising calculated physico-chemical and absorption, distribution, metabolism, and elimination (ADME) properties were also given. (C) 2018 Elsevier B.V. All rights reserved.