Oxa-(4+4)-Cycloaddition Entry to Oxazocine Scaffolds

A Palladium-Catalyzed Oxa-(4+4)-Cycloaddition Strategy Towards Oxazocine Scaffolds: A. Scuiller, X. Liu, M. Cordier, J. Garrec, A. Archambeau
Synlett 2021, 32, 981–986

Nitrogen-containing eight-membered heterocycles are important motifs in organic and medicinal chemistry, sometimes endowed with interesting biological activities. For example, oxazocine heterocyclic compounds have been reported to be active against CNS disorders, besides being used for the treatment of pain and inflammation. Recently, the group of Professors Julian Garrec and Alexis Archambeau from the Ecole Polytechnique (Palaiseau, France) have reported a versatile and straightforward entry to mono and polycyclic 1,5-oxazocines, based on a novel oxa-(4+4)-cycloaddition strategy.

Professor Archambeau said: “We have developed a Pd-catalyzed (4+4)-cycloaddition pathway towards nitrogenated eight-membered heterocycles using azadienes as electrophiles. We were pleased to discover that linear 1-azadienes derived from cheap chalcones could also lead to monocyclic adducts and DFT calculations allowed us to rationalize this peculiar finding.”

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