Research On Asymmetric Reactions Of Chiral Fluorine-Containing Tert-butanesulfinyl Imines

Of potential drug activity,chiral amines are present in many biologically active molecules.They are widely applied in asymmetric synthesis chemistry as chiral intermediates,chiral ligands and small molecular catalysts.The introduction of fluorine into biologically active compounds generally leads to an improved molecular drug activity and higher stability toward oxidative degradation.Fluorine-containing chiral amines have also attracted wide attention from synthetic chemists and pharmaceutical chemists.In this thesis,we focus on ?-CF3-N-tert-butylsulfinylaldimine,N-tert-butylsulfinyl-phosphoryl difluoro-imine and N-tert-butylsulfinyl-(perfluoro)benzald-imine.We explore their asymmetric addition reactions and prepare a series of optically pure chiral amines.The thesis is mainly divided into the following three parts:In the first part,we mainly studied that the addition reactions between(S)-and(R)-N-t-butylsulfinyl-3,3,3-trifluoro-acetaldimine and tertiary enolates derived from a-thiocyanate ketones.We demonstrate that the addition reactions show unusual regiodivergence as a function of the reaction conditions.We found that the direct Mannich addition products was achieved with application of NaOAc as a base and THF as the solvent and the products of tandem Mannich-cyclization reactions was got with application of Na2CO3 as a base and DMF as the solvent.The reactions show wide structural generality and allowed the preparation of biologically relevant fluorine-containing compounds.The observed mechanism of reactivity and stereochemistry were explained.In the second part,we studied the reaction of chiral sulfinyl-derived difluoro(phos-phoryl)aldimines with properly protected glycinates(Schiff base,alkyl/aryl ester).This reaction was operationally simple and provided the ?-amino-y,y-difluoro-?-phosphor in good(60-80%)yields with excellent(99:1)diastereoselectivity.This Mannich addition process provides a novel type of biologically interesting molecules containing carboxylic acid,?,?-diamino acid and phosphonic acid structural features.The absolute configuration of the predominant configuration was determined by culturing single crystals,and the results of reactivity and stereoselectivity were explained.In the third part,we explored the design and synthesis of N-tert-butylsulfinyl-(perfluoro)benzaldimine.We study Mannich addition reactions of this new chiral and indolinone derived tertiary enolates generated in situ led to quaternary ?-perfluorophen yl-?-amino-indolin-2-ones in good yields with excellent diastereoselectivity.The new chiral show excellent reactivity and can be a better chiral auxiliary for the synthesis of perfluorophenyl compounds.Through the cultivation and analysis of the product single crystal,the absolute configuration of the product was determined and explained.