Nucleophilic Addition/oxa-Michael Tandem Reaction Of O-formylchalcone With Dimethyl Diazomethylphosphonate

Seyferth-Gilbert homologation is the strong base-promoted reaction of dimethyl(diazomethyl)phosphonate with aldehydes and aryl ketones at low temperatures,which provides an efficient method for the synthesis of alkynes.Dimethyl(diazomethyl)phosphonate(Seyferth-Gilbert reagent)has been proven an efficient and popular reagent for transforming aldehydes and aryl ketones into alkynes through the Seyferth-Gilbert homologation.Herein,we reported a novel base-promoted tandem reaction between ortho-formyl chalcones and dimethyl(diazomethyl)phosphonate for the construction of a series of phosphine-containing 1,3-dihydroisobenzofuran derivatives with up to 99% yields.This reaction was amenable to scale up to 1 mmol with a 90% yield.The alkyne,which was well-known as the product of Seyferth-Gilbert homologation,was not detected in this reaction.In addition,the enantioselective version of this reaction was also tested,the product was obtained with higher enantioselectivity(89% ee),moderate diastereoselectivity(78:22 dr)and yield(38% yield).In order to explore possible mechanisms,the product of the first step reaction(nucleophilic addition)was isolated and ee value was determined.The results showed that chirality mainly originates from the second step reaction(oxa-Michael).