Novel Sulfinamide Monophosphine Chiral Ligands:Study On Palladium And Copper Catalytic Asymmetric Reactions

Chiral monophosphine ligands play an important role in the field of asymmetric transition-metal catalysis.Although a lot of privileged chiral monophosphines have been developed,most of their synthesis pose considerable drawbacks,such as using expensive starting materials,long synthetic route,limited structure-diversity,complicated chiral separation and so on.The design and development of effective chiral ligands still have attracted a great deal of attention from both academic and industrial.The main work of this thesis focuses on the modification of chiral monophosphines Ming-Phos and synthesis of novel chiral phosphines Xu-Phos,as well as their applications in asymmetric transition-metal catalysis.The specific research contents include the following three aspects: ?? The design and synthesis of a new type of chiral sulfinamide monophosphine ligandsWe developed a designed new chiral sulfonamide dicyclohexylphosphine ligand(Xu-Phos),which can be easily prepared in a gram-scale from inexpensive commercially available starting materials(1,2-dibromoarene 1,000 CNY/kg)via a 'one-pot' synthesis approach.A series of chiral ligands could be obtained in good yields with high diastereoselectivity and wide structural diversity.In view of the simple structure,air stability,operational simplicity,and wide structural diversity from readily available starting materials,this type of chiral ligands can be expected to find wide applications in the transition metal catalyzed asymmetric reactions.?? Pd-catalyzed asymmetric Heck cascade reactionAlthough a lot of racemic examples of Heck cyclization/nucleophilic trapping of the ?-alkyl-Pd intermediates have been reported,the development of asymmetric versions of these domino reactions has met with less success and still poses a considerable challenge.After systematic study,we found that the Xu-Phos showed the good performance in three types of Pd-catalyzed asymmetric Heck cascade reactions,such as hydroarylation,iodine atom transfer cycloisomerization and Heck/C-H functionalization cascade reaction of unactivated alkenes.?? Cu-catalyzed asymmetric [3+2] cycloaddition reactionWith regard to chiral pyrrolidines bearing a trifluoromethylated quaternary center existing in a number of pharmaceutical and agrochemical compounds,we made much effort to access to these pyrrolidines in highly chemo-and stereoselective manners.Firstly,we reported a copper-catalyzed asymmetric exo-selective dipolar cycloaddition of ?-trifluoromethyl ?,?-disubstituted enones with azomethine ylides,which provides an efficient access to valuable pyrrolidines bearing a trifluoromethylated all-carbon quaternary stereocenter at 3-position.Subsequently,in this reaction,we employed a-trifluoromethyl a,?-unsaturated esters as dipolarophiles to synthesize a series of valuable pyrrolidines bearing a trifluoromethylated all-carbon quaternary stereocenter at 4-position.Finally,highly enantioselective 2,3-dihydropyrroles bearing a trifluoromethylated all-carbon quaternary stereocenter at 3-position also can be achieved by copper-catalyzed [3+2] cycloaddition reaction of a-isocyanoesters with ?,?-disubstituted enones.