[4+2] Annulation Of Alkyl(Phenyl)Phosphinic Chlorides With Enones

Phosphaheterocycles including δ-phosphinolactones are a class of important organic compounds with wide applications in many fields,such as catalysis,pesticides and pharmaceuticals.In recent years,phosphaheterocycles have received extensive attention because of their biocompatibility.There are various reports on the synthesis of δ-phosphonolactones,especially benzo-δ-phosphonolactones.However,the synthetic strategies for δ-phosphinolactones are limited.In this report,alkyl(phenyl)phosphinic chlorides and α,β-enones were chosen as substrates to obtain δ-phosphinolactones via Michael-like addition and followed by intramolecular substitution.First of all,the conditions were optimized by using benzyl(phenyl)phosphinic chlorides ade chalcones as standard substrates.And then,we extended the scopes of substrates under the optimal conditions.It was found that the reaction could proceed efficiently under mild conditions with good to excellent yields and diastereospecificity.The annulation includes deprotonation of alkyl(phenyl)phosphinic chlorides,the Michael addition with enones,and nucleophilic substitution.Also,in the case of benzyl(phenyl)phosphinic chlorides,electron-donating substituents will decrease the acidity of the benzlic methylene and thus led to a decrease in yield.On the contrary,electron-withdrawing groups facilitated the reaction.While,the larger steric structure was not more favorable for the reaction.However,the annulation can proceed regardless of the substituents,and the steric hindrance of substituent has no significant effect on the reaction.In addition,the reaction is scalable and easily separated and purified by recrystallization rather than column chromatography after the reaction.The products exhibited potential applications by several transformations.Moreover,the scopes of substrates for the annulation of arylmethylphosphonochloridates with dibenzo[b,f][1,4]oxazepines was extended.In conclustion,the annulation of alkyl(phenyl)phosphinic chlorides withα,β-enones was explored in this work,and a new method for the synthesis of δ-phosphinolactones was proposed.It features readily available starting materials,atom-and step-economic,diastereospecific,good to excellent yields,wide substrate scopes,and mild reaction conditions.And,the potential application ofδ-phosphinolactones was demonstrated.Meanwhile,the reaction of arylmethylphosphonochloridates with dibenzo[b,f][1,4]oxazepines with dibenzo[b,f][1,4]oxazepines was improved.