Studies On Catalytic Asymmetric Decarboxylative Addition Reactions Of ?-ketoacids With Unsaturated Double Bonds

Constructing new organic compounds with moderate reaction conditions and high efficiency is one of the most important goals for organic chemists.Recently,?-keto acids have attracted much attention due to its low cost and high reactivity,and have made rapid progress in the field of asymmetric catalysis through decarboxylative reactions.Nevertheless,it is still of great significance to develop new types of decarboxylative reactions of?-keto acids.In this dissertation,three works were developed with?-keto acids as nucleophilic substrates.We first developed the asymmetric decarboxylative Michael addition of?-keto acids to dicyanoolefins and disulfonylolefins with excellent results.With systematic optimizing of the reaction conditions,the desired enantioselective decarboxylative Michael adducts were obtained in high yield?up to 99%?and high ee?up to 94%?with the saccharide-derived bifunctional amino thiourea as the best chiral catalyst.We also obtained a monofluorinated ketone after further chemical transformations.In the second part,we developed the enantioselective decarboxylative Aldol reaction of?-keto acids with monohydrate?-oxo aldehydes,which was catalyzed by copper-bisoxazoline complex.A serious of chiral 2-hydroxy-1,4-dicarbonyl compounds were obtained in moderate to high yields?up to 99%?with excellent enantioselectivities?up to 98%ee?.Meanwhile,a variety of aliphatic?-carbonyl aldehyde hydrates were used in the synthesis of 2-hydroxy-1,4-dicarbonyl compounds successfully,realized the asymmetric addition of?-keto acids to C=O bond with high ee.We developed the asymmetric decarboxylative amination of?-keto acids with azodicarboxylates at the third part.Using biscinchona alkaloid?DHQD?₂PYR as the best catalyst,a series of chiral?-amino ketones were obtained in good to high yields?75-99%?and enantioselectivities?57-95%ee?under mild reaction conditions.Moreover,the synthetic potential of this methodology was also demonstrated to access an optically active 1,2-amino alcohol.Simple recrystallization of 1,2-amino alcohol provided the single stereoisomer with excellent optical purity,and its absolute configuration was determined from the X-ray structural analysis.