Asymmetric Mannich Reaction Of Glycine Imino Esters With Phosphonyl Imines

The ?,?-diamino acid ester motif is widely distributed in natural products and medicines,and thus has made its synthesis a highly persued research topic in the area of asymmetric synthesis.The most common strategies to prepare ?,?-diamino acids and their derivatives include the construction of C-N and C-C bonds.For the strategy of C-C bond construction,tremendous efforts have been made to develop efficient methods for asymmetric Mannich reaction of imino esters with imines,and considerable advancements have been achieved with many different catalytic modes being involved.However,efficient methods for Mannich reaction of imino esters with imines with high stereoselectivity and broad application scope remain scarce.In this thesis,we developed a new catalytic system of copper-complexed phosphine-urea ligand,a bifunctional ligand developed earlier in our lab,for the Mannich reaction of glycine imino esters with phosphonyl imines.By an efficient combination of metal catalysis and organocatalysis,excellent diastereo-and enantioselectivities(up to > 99 : 1 diastereomeric ratio,99% enantiomeric excess)as well as good yields have been achieved.A wide range of substitution patterns of both iminoester and imine are tolerated by this catalyst system,especially with the imines possessing aryl groups with electron-withdrawing substituents that are not well-tolerated in the existing methods are proved to be capable substrates.