Studies On The Catalytic Asymmetric Synthesis Of β-hydroxy Carboxylic Acids And β-hydroxy Acid Allkyl Esters Via Decarboxylative Aldol Reaction

β-hydroxy acids and β-hydroxy acid alkyl esters are key structures of many natural products and drugs,such as statine,Phaitanthrin B,etc.,thus are important synthetic targets.Recently,the asymmetric constructions of such kinds of compounds via decarboxylation aldol reaction between relevant carboxylic acid derivatives and carbonyls attract much attention.Our group has successfully developed a novel asymmetric aldol reaction of Tryptanthrin derivatives,which afforded an efficient access to natural product Phaitanthrin A;based on this result,we developed the asymmetric catalytic decarboxylation aldol reactions to build chiral β-hydroxy acid and β-hydroxy acid alkyl ester compounds by employing either malonic acid or malonic acid half oxyesters(MAHOs)as nucleophilic precursors:We developed efficient asymmetric decarboxylation aldol reactions of MAHOs,in which 2-Pyridinecarboxaldehyde and Tryptanthrin were proved to be good electrophiles in the promotion of chiral metal complex,affording the desired aromatic heterocyclic β-hydroxy carboxylic acid esters,the natural product Phaitanthrin B and its derivatives in moderate to good yields and enantioselectivies;We developed decarboxylation aldol reactions based on the efficient activation of malonic acid,providing an efficient method for the direct synthesis of enantioenriched β-hydroxy acids.In these transformations,Tryptanthrins and isatins were proved to be good reaction partners under the catalysis of the chiral metal salt complexes;the desired β-hydroxy acid products containing a chiral quaternary carbon center were obtained in moderate to good yields and enantioselectivies.The obtained products could be further transformed to optically active natural products Phaitanthrin B and its derivatives in conventional method,which enhanced the importance of this method.The above transformations we developed provided a new platform for the catalytic asymmetric synthesis of chiral β-hydroxy acid alkyl esters and β-hydroxy acids,thus have good theoretical significance and synthetic value.