Rhodium-catalyzed Branch-selectivity Asymmetric ??allylic Alkylation Of Simple Ketones With Alkynes

As an important class of intermediates in organic synthesis,chiral allylic compounds has drawn extensive attention from the synthetic community in recent years.Transition metal-catalyzed asymmetric allylic alkylation reaction is one of the most important and powerful methods for the construction of allyl compounds with stereocenters,and has developed rapidly in recent years.Among them,the asymmetric a-allylic alkylation of ketones is an important research area in this field.Cooperative catalysis refers to a catalytic strategy in which two different catalysts cooperate with each other and activate two different substrates without interfering with each other.Using this strategy can reduce the activation energy of the reaction and achieve a chemical conversion that cannot be achieved with single catalyst.Among them,the concerted catalytic system of metal and organic small molecule combination is one of the most widely used strategiesIn this thesis,we have developed a new type of asymmetric a-allylic alkylation of ketones by utilizing transition metal and organo cooperative catalysis with alkyne as an atom-economic allyl precursor.With this method,a series of ?,?-unsaturated ketones are formed in moderate to excellent yields with high enantioselectivity.In the presence of a secondary amine catalyst,the ketone substrate was in situ converted into a more nucleophilic enamine intermediate,which attacks the metal-?-allyl intermediate formed from rhodium catalyst and alkyne.This strategy has the advantages of mild reaction conditions,no need to add a strong base,no pre-activation of the substrate,and no equivalent by-products.It is a new type of atomically economical allylation strategyUnder optimized reaction conditions,when the substrate is cyclopentanone,a series of target products with branch selectivity were obtained in moderate to good yields.when the substrate is non-cyclic ketone,the reaction activity is reduced,and the product is obtained in 26-65%yield through further optimization of conditions.In addition,the allylation of cholestanone derivatives was achieved by this method Based on the screening of chiral ligands,using the BIPHEP series of chiral ligands,the asymmetric catalytic control of the reaction was achieved,giving the allylic product in up to 95%yield and 96:4/96:4 enantioselectivities.The generated?,?-unsaturated ketones can be further elaborated into useful structures.