Palladium-Catalyzed Asymmetric Hydrofluoroalkylation Of Conjugated Dienes

The enantioenriched fluoroalkyl moieties exist widely in medicinal and agrochemistry.Thus,it is valuabale to develop methods for stereoselective synthesis of fluoroalkyl skeletons.In the past decade,transition-metal-catalyzed asymmetric hydrofunctionalizations of unsaturated hydrocarbons have received much attention,due to the high atom-economy of these transformations.At present,this strategy has been widely applied to asymmetric hydroamination,hydroalkylation,hydrophosphinylation,hydrosulfonylation,hydrosilylation and hydroalkoxylation,and thus built up a series of valuable allyl moieties.However,related asymmetric hydrofluoroalkylation has not been reported.In this context,this thesis focused on the study of palladium-catalyzed enantioselective hydrofluoroalkylation of conjugated dienes with fluoro-containing nucleophiles to provide a novel access to enantioenriched fluoroalkyl units.First,we explored and realized Pd-catalyzed asymmetric hydrofluoroalkylation of 1,3-dienes and F-containing malonates in high yields and enantioselectivies with a Josiphos ligand.For aryl-sbustituted diene substrates,products with 70-99% yield,92-94% ee and >20:1 rr were generally observed.For dienes bearing unsaturated esters as the electrophiles,the reaction proceeded smoothly with good substrate tolerance and high 1,5-addition efficiency.In addition,gram-scale test was carried out and a series of derivatizations of the products were conducted conveniently.The structure of product was elucidated by X-ray crystal analysis.On the other hand,we have developed the stereoselective hydromonofluoroalkylation of conjugated dienes via synergistic Pd/Cu catalysis to construct skeletons bearing a fully-substituted F-stereogenic center and vicinal tertiary carbon center.The products can be prepared with up to 20:1 dr,>99% ee and >70% yield.The palladium catalyst and copper catalyst can independently dictate the stereoconfiguration of corresponding electrophiles and nucleophiles.By adjusting the absolute configuration of each chiral ligand ligated to the metal,all four stereoisomers of the product were smoothly prepared,highlighting the synthetic value of present method.