Alkenylation And Asymmetric Addition To Allenamides Of Pyrazolones

Carbon-carbon double bonds are one of the most common functional groups in organic chemical reactions,which can be used to carry out multiple reactions such as electrophilic addition,free radical addition,oxidation reaction and catalytic hydrogenation.Therefore,the introduction of carbon-carbon double bonds in compounds plays an important role in the construction and modification of compounds.Pyrazolone structure is a very important class of compound skeletons.It is widely found in natural products and drug molecule and has obvious biological activities.Therefore,the synthesis and construction of various compounds with pyrazolone skeletons have important applications and value.Herein,we report two different methods to introduce carbon-carbon double bonds at the C-4 position of the 4-position monosubstituted pyrazolones.The carbon-carbon double bonds were used to derivatize and convert and many disubstituted pyrazolones were synthesized which greatly expands the methods of pyrazolone building and has important significance for the construction of pyrazolone compounds.The specific reactions mainly include the following two aspects:（1）The oxidative dehydrogenation coupling reaction of the 4-position monosubstituted pyrazolones and the simple olefins was directly carried out under the mediation of iodine.Through the screening of catalyst,oxidant,solvent,temperatur and other influencing factors,the best reaction conditions were determined.26 different pyrazolones with alpha-alkenyl groups were obtained in good yields（up to 91%yield）.The structures of products were confirmed by ¹H-NMR,¹³C-NMR,HRMS.（2）Asymmetric nucleophilic addition of 4-position monosubstituted pyrazolones to allenamines was carried out.By screening the influencing factors such as catalyst,solvent and temperature,the best reaction conditions were determined.19 differentα-allyl pyrazolones were obtained with excellent yields and enantioselectivities（up to 98%yield and up to 90%ee）,and when the reaction was scaled up to gram,both yield and enantioselectivity were maintained.The structures of products were confirmed by ¹H-NMR,¹³C-NMR,HRMS.