Asymmetric Synthesis Of ?-butenolides Catalyzed By Chiral Imidodiphosphoric Acid

?-Butenolides are common structures extensively existed in natural products,medicinal and biological chemistry.Functional and chiral?-Butenolides exhibit various biological activities.The asymmetric vinylogous Mannich?AVM?reaction is an important approach to synthesize?-butenolides bearing amine groups and multiple stereocenters.Based on the important application value of chiral?-butenolides compounds,organic chemists have been working on exploring new synthesis strategies and methods,including using different substrates aldimine and vinylogous nucleophilic reagents,or developing new catalysts to catalyze this reaction.In recent years,the application of organocatalysis to AVM reactions has also attracted considerable attention.However,when the AVM reaction of aldimine with 2-?trimethyl-siloxyl?furan was catalyzed by organocatalysis,the ortho-position of the substrate aldimine required hydroxyl to assist in controlling the stereoselectivity of the reaction.In this paper,an AVM reaction of aromatic aldehyde aromatic amine with 2-?trimethylosiloxyl?furan by using a chiral imidodiphosphoric acids catalyst was studied,solved the problem of limited substrates,the effects of hydroxyl at different positions of the substrate aldimine on the reaction were also investigated.Specific research contents and results are as follows:First,a chiral phosphoric acid catalyst and ten chiral phosphoimide catalysts were synthesized and applied to the AVM reaction of aromatic aldehyde aromatic amine 1 and 2-?trimethyl-siloxyl?furan 2.The optimum reaction conditions were obtained by screening the structure and dosage of the catalyst,solvent,reaction temperature,substrate ratio and additive type:At-40^oC,aromatic aldehyde aromatic amines 1 and 2-?trimethyl-siloxyl?furan 2 molar ratio of 1:3,5 mol%VAPOL skeletons with biaxial chiral phosphanyimionic acid?Cat.4?as catalyst and toluene as solvent,adding 40 mg/mmol HP-?-CD as additive.Under this optimal condition,24substrates 1 with different substituent structures were expanded,and a good yield?the highest 98%?and enantioselectivity?the highest 97%ee?were obtained,and an AVM reaction in the form of three components was attempted using chiral imidodiphosphoric acid catalyst.All the catalytic products were characterized by melting point,optical rotation,¹H NMR,¹³C NMR,HRMS,X-Ray and HPLC.In addition,we applied 11 chiral imidodiphosphoric catalysts to the AVM reaction of salicylaldehyde aromatic amine 4 and furan 2?trimethyl-siloxyl?.After the initial screening of the conditions,the chiral phosphanyimide?Cat.4?of VAPOL skeleton was selected as the optimal catalyst and the optimal catalyst dosage was determined to be 5 mol%.Mesitylene was determined to be the best reaction solvent and the best reaction temperature was-10^oC.Under this condition,the product 5a is obtained with 90%yield,58%ee and 71%ee enantioselectivity.In addition,we also extended 11 kinds of salicylaldehyde aromatic amine substrates 4a-k,the preliminary research results have been obtained.