Chiral Biarylpyridoxal Catalyzed The Asymmetric Michael Addition/cyclization Reaction Of ?,?-unsaturated Ketones At The ? Position Of Glycine Esters

Chiral polysubstituted proline derivatives are key fragments of various biologically active molecules and they have many applications in the fields of organocatalysis,medicinal chemistry and biochemistry.Classic synthetic methods of polysubstituted proline derivatives usually need multiple steps.Thus developrment of highly efficient and new synthetic methods for polysubstituted prllines is highly desirable.Biological reactions are highly efficient.Vitamin B6 can catalyze many transformations as a coenzyme.Inspired by biological aldol reaction of glycine,we developed chiral pyridoxals,which were applied to catalyze Michael addition of a carbon of glycine to ?,?-unsaturated ketones to produce chiral polysubstituted proline derivatives in one step under mild conditions.The research includes the following aspects:(1)A preliminary investigation of the reaction was carried out using a racemic pyridoxal catalyst.(2)A series of chiral pyridoxal catalysts with different amide side chains were developed.Reation conditions were optimized.(3)The substrate was screened under the optimal conditions.A variety of polysubstituted prolines were obtained with up to 95%yield and up to 86%ee.(4)A posssible mechanism has been proposed for the reaction.