Multicomponent synthesis of novel dihydropyrano-dioxine fused-bicyclic systems as a potentially new class of heterocyclic atropisomers

A new series of dihydropyrano-dioxine products were synthesized via one-pot combination of 2,2-dimethyl-1,3-dioxan-5-one with aromatic aldehydes and malononitrile. The first step occurs rapidly in an aqueous alcoholic medium at reflux, followed by nucleophilic addition of malononitrile to the olefinic site of the intermediate and iodine induced oxidation to the final products, which directly precipitate in the vessel, avoiding time consuming and expensive chromatographic separations. The structure of the products was elucidated based on their NMR data and verified by X-ray crystallography. In the case of α-substituted derivatives, rotational barrier caused by the bulk of the ortho substituent led to the formation of atropisomeric products. To study this aspect, molecular geometry of 4 g was optimized by ChemDraw professional 20 and then MM2 calculation was performed.