Organocatalysis For Highly Steroselective Conjugated Addition Of N,N'-Dialylbarbituric Acids To Enones

In recent years,organocatalysis is highly valued by contemporary chemists.The reactions with organocatalysis are mild,easy to operate and environmental friendly.Therefore,they are considered as promising research areas in organic chemistry and pharmaceutical chemistry.Barbituric acids,a class of organic compounds based on acyclic malonamide skeleton,are widely distributed in various biologically relevant molecules.The conjugate addition reaction of barbituric acid as active methylene compound was rarely reported.In this paper,conjugate addition reaction of barbituric acid and enones under the catalysis of small organic molecules has been studied.A series of barbituric acid derivatives with high selectivity,especially high stereoselectivity,were synthesized through the regulation of small organic catalyst in reaction.1.Highly Enantioselective Michael Additions of N,N'-Dialkylbarbituric Acids to Enones using a Cinchona Alkaloid Squaramide OrganocatalystFirstly,using cinchona alkaloid-based bifunctional squaramide as an organocatalyst,the conjugate reaction of N,N'-di-tert-butylbarbituric acid with various enones features a highly enantioselective(91–99% ee)and highly yield(49-99%)affording the corresponding optically active 5-substituted barbituric acid derivatives.A variety of enones bearing different substituents,including aryl,heteroaryl and alkyl groups,were found to be suitable.The transformations of the product 4a were realized in two ways,deprotection to remove the N-tert-butyl group and alkylation to produce 5,5-disubstituted barbituric acid derivatives2.Selectivity Single and Double Conjugate Addition Reaction of N,N'-Dialkylbarbituric Acids to Enones using Tertiary Smines or Boron Fluoride Ethyl EtherThe selectivity single and double conjugate addition of N,N'-di-tert-butylbarbituric acid with enones was studied.The chemical selectivity of the reaction system can be effectively controlled by changing different catalysis,and the trans product was obtained in the cyclization reaction caused by the double conjugated addition.Tetramethylguanidine as a catalyst gave double addition products with good yield(52-95%),and boron trifluoride etherate as a catalyst gave single addition products with moderate yield(51-81%).This study extends the scope of the catalytic michael addition with interesting biologically active molecules,providing novel and efficient method to stereoselective and chemical selective synthesis of a series of optically active barbituric acid derivatives.