Asymmetric Palladium-catalyzed Hydrosilylation To Access Silicon-stereogenic Silylenones And Its Mechanism

Chiral organosilicon compounds have been widely applied in medicinal chemistry,materials science,and organic synthesis due to their special physical and chemical properties.Along with the rapid development of asymmetric catalysis,the desymmetric reactions of dihydrosilanes has become one of the most direct and efficient strategies to construct silicon stereogenic centers with following advantages:easy operation,high efficiency,mild reaction conditions,etc.,Though there are numbers of strategies have been developed for the preparation of carbon stereogenic centers via hydrosilylation reaction over the past few decades,the construction of silicon stereogenic centers through hydrosilylation reaction of dihydrosilane remains sereval challenges,especially the synthesis of optical silane with functional groups,and the compatibility problems have not been well resolved.In this thesis,we would like to develope an asymmertic Pd-catalyzed hydrosilylation reaction of ynones to construct the silicon stereogenic center with high enantioselectivity using desymmetrization strategy.The research contents are summarized as follows:Firstly,a highly enantioselective hydrosilylation reaction of ynones with dihydrosilanes was realized for the first time.Using a palladium catalyst with a chiral binaphthyl phosphoramidite ligand,the desymmetrical hydrosilylation reaction of prochiral diaryldihydrosilane afforded a series of silicon-stereogenic silylenones with up to 94% yield,>20:1 regioselectivity and 98:2 enantioselectivity.This methodology proceed with mild reaction conditions,easy operation,wide substrate universality high chemical selectivity.Secondly,the density functional theory(DFT)calculations clarified that the palladium-catalyzed desymmetrical hydrosilylation reaction of alkynone with dihydrosilane was carried out by a cooperative Chalk-Harrod mechanism,and it was found that the oxidative hydrogenation-migration insertion process was the speed control step of the entire catalytic cycle.Combining the noncovalent interaction(NCI)method to explain the origin of stereoselectivity and regioselectivity,the multiple C-H-p interactions and the stereospecific control of the aromatic cavity between alkyne and hydrosilicates in the chiral catalytic system played a vital influence in the stereoselectivity.In this thesis,the asymmetric hydrosilylation reaction of ynones with dihydrosilanes will be discussed,a series of linear silicon-stereogenic α-silylenones with high enantioselectivity were synthesized for the first time,Moreover,a profounder understanding on the palladium-catalyzed asymmetric hydrosilylation of ynones by theoretical calculation to explain the stereospecific aromatic interaction between the catalyst and the substrate,which has a certain theoretical guiding for the development of new catalytic systems in the furture.