Studies Of Ketone Cyanosilylation With Bifunctional Cyanating Reagents

The asymmetric ketone cyanosilylation is one of the most important C-C bond forming reactions,because the resulting cyanohydrins bearing a oxygen-containing quaternary stereocenter are versatile synthons to pharmaceuticals and agrochemicals.This thesis focuses on applying bifunctional cyanating reagents to asymmetric ketone cyanosilylation.A kinetic resolution of racemic branched ketones were achieved via diastereo-and enantioselective cyanosilylation using Me₂（CH₂Cl）SiCN.And a new bifunctional cyanating reagent,Me₂（CH₂=CH）SiCN,is developed and applied to tandem reactions based on the ketone cyanosilylation,affording valuable cyclohexenyl ketones andβ-cyano ketones.This thesis has finished the following work:1)By using the three-component catalyst system consisting of（salen）AlCl complex,phosphorane and HMPA,the highly stereoselectivity asymmetric cyanosilylation and kinetic resolution of acyclicα-branched ketones were achieved using Me₂（CH₂Cl）SiCN as cyanating reagent.This process not only represented the first highly selective kinetic resolution ofα-branched ketones,but also the first diastereo-and enantioselective ketone cyanosilylation reaction to construct C^α-tetrasubstituted cyanohydrins bearing two adjacent stereocenters.¹³C NMR studies showed that HMPA functioned as a Lewis base to effectively activate Me₂（CH₂Cl）SiCN,forming a more sterically hindered cyanide reagent.This is beneficial for the control of stereoselectivity.Furthermore,two novel diversifying reactions of the resulting cyanohydrins were developed by taking advantage of the chloromethyl group.The thus obtained chiralα-branched ketone was further used to synthesize the key intermediate of taranabant,which is an anti-obesity agent.2)A series of chiral phosphorus ylide ligands were designed and synthesized.Under the catalysis of chiral（salen）AlCl complex activated by chiral phosphorus ylides,the kinetic resolution ofβ-allyl ketones was developed.And a chiral matching effect was observed.Moreover,the asymmetric addition reactions of Me₂（CH₂Cl）SiCN to a simple ketone or a nitroolefin were attempted,by using chiral phosphorus ylides and achiral（salen）AlCl complex.3)We developed a new bifunctional cyanating reagent Me₂（CH₂=CH）SiCN.A novel one pot tandem Wittig/cyanosilylation/Diels-Alder/retro-cyanosilylation reaction based onα,β-unsaturated aldehydes,phosphorus ylides and Me₂（CH₂=CH）SiCN is developed,providing a new entry to construct cyclohexenyl ketones with diversified structure.In addition,β-cyano ketones were also accessible with high yield and diastereoselectivity by changing the reaction conditions.