Designand Synthesis Of Biaryl-based Chiral Catalysts And Their Catalytic Applications In Asymmetric Reactions

Both asymmetric Aldol reaction and Michael addition reaction, two of the mostversatile and powerful approaches for the formation of optically active and highlyfunctionalized chiral compounds, have found many applications in the asymmetricsynthesis of biologically active natural products and chiral drugs. Many kinds ofchiral ligands and organocatalysts have been developed for asymmetric Aldol andMichael addition reactions based on a variety of catalytic mechanisms. Bifunctionalcatalysts, which possess two activation sites and can activate two different types ofreaction substrates, often exhibit excellent catalytic activities and high steroslectivitiesin asymmetric transformations.Based on the Lewis acid-Lewis base dual activation mode and our previous work,in total eleven novel axially-unfixed2,2’-bipyridine-based chiral ligands weredesigned and synthesized using enantiopure α-amino acids as chiral sources. Thereaction conditions were optimized systematically by screening different factorsassociated with chiral induction. It was found that in the presence of waterbifunctional catalyst1-Yb(OTf)3proved to be the best one among the examedcatalysts, and can provide asymmetric Aldol adducts in high chemical yields (up to89%) and excellent stereoselectivities (up to97:3dr and91%ee) in the directasymmetric Aldol reactions between aliphatic ketones and a variety of aromaticaldehydes. The bifunctional mechanism of the examined catalysts was investigated bycarrying out a series of control reactions and examining the1H NMR behaviors ofligand1-metal complexes.Twelve axially-unfixed biaryl-based chiral organocatalysts were designed andsynthesized using enantiopure α-amino acids as chiral sources based on the Br nstedacid-Lewis base bifunctional catalytic mechanism. The reaction conditions wereoptimized fully and，among the biaryl catalysts examed，organocatalyst22and23turned out to be the best ones with regard to catalytic reactivity and stereoselectivity.Under the optimal reaction conditions, organocatalyst23could afford asymmetricMichael products in high chemical yields (up to99%) and excellent stereoselectivities(up to99:1dr and96%ee) in the direct Michael additions of aliphatic ketones andaldehydes to a variety of nitro olefins. The bifunctional nature of organocatalyst22and23was predicted to clarify the stereochemical course of the asymmetric Michaelreactions on the basis of a series of control experiments and the study ofstructure-activity relationships.