Transition Metals And Organocatalysts Cooperatively Catalyzed Asymmetric Allylation Reactions

The combined catalyst system can integrate the catalytic activity of each individual catalyst to enable organic transformations that cannot be or is hardly accomplished by either of the catalysts alone.The cooperation of different transition-metal and organocatalyst has enabled a series of new enantioselective transformations.Transition-metal-catalyzed asymmetric allylic substitution is a convenient and powerful tool for the enantioselective formation of C-C and C-heteroatom bonds and has been widely applied in organic synthesis.This thesis describes several asymmetric allylation reactions using the combined catalytic strategy,which involve the transformations of the π-allyl metal complexes generated from transition-metals and different allylic precursors with the reactive nucleophiles activated by organocatalysts.α-Quaternary amino acids,a class of non-proteinogenic amino acids,are of particular interest in bioorganic and medicinal chemistry.We have developed a new Ir/PTC cooperatively catalyzed asymmetric umpolung addition of simple a-imino esters with allyl acetates to afford a-quaternary amino acid derivatives bearing two vicinal stereocenters in good yields and high stereoselectivities.The products obtained could be readily converted to chiral amino acid salts and quaternary proline analogues with multiple stereogenic centers.By the cooperative catalysis of palladium and amine,we have developed an asymmetric allylation reaction at the benzylic positon of furfural derivatives,which could be easily prepared from 5-hydroxymethylfurfural,an industrial feed stock produced from biomass.A diverse range of synthetically useful chiral furanyl methanol derivatives could be accessed by this method.The synergistic effect of the chiral ligand of palladium catalyst and the chiral amine allowed the reaction to offer high levels of stereoselectivities and suggested a robust strategy for the control of stereoselectivity in asymmetric reactions that are unable to offer high enantioselectivity by chiral organocatalysts,alone.We have established a palladium-catalyzed atom-economic asymmetric a-allylation of aldehydes with alkynes by using a ternary catalyst system of achiral palladium(0)complex,primary amine,and chiral phosphoric acid to integrate enamine and chiral hydridopalladium phosphate catalysis.The protocol enables a wide range of alkynes and enolizable aldehydes to give a diverse spectrum of chiral a-quaternary aldehydes in high yields and with high levels of enantioselectivity.Moreover,the chiral a-quaternary aldehydes can serve as a platform molecule for the synthesis of an array of important synthetic intermediates,which highlight the potential applications in target-oriented synthesis.More importantly,this work suggests a general strategy to create asymmetric allylic alkylation reactions with alkynes by trapping chiral π-allylpalladium phosphates.