Studies On The Asymmetric Addition Reactions Of Conjugated Double-bond Systems Induced By The Chiral Binaphthyl Ligands

The conjugated double bonds can undergo versatile addition reactions,in which the asymmetric [4+2] cycloaddition reactions of the 1,3-conjugated dienes,the asymmetric 1,4-addition reactions of the conjugated nitro olefins and the asymmetric 1,2-addition reactions of the α,β-unsaturated ketones are significant methods to enantioselectively construct the carbon-carbon bonds and carbon-hetero bonds.Now the weakness,which includes the low enantioselectivities,narrow scopes of substrates,limited types of functional groups,relatively small scales,and limited types of catalysts,still exists in the studies on the asymmetric addition reactions mentioned above.Chiral 1,1’-binaphthyl backbone is a privileged unit which has constructed abundant efficient diphosphine ligands and 1,1’-binaphthyl-2,2’-diol ligands.Since the chiral ligand is a key point to control the reactivity of the central metal and the stereoselectivity of the asymmetric reaction,several important chiral phosphoramidite ligands and a series of novel and efficient chiral ligands featured with spiro-fused oxazoline were synthesized to improve the weakness in these three asymmetric addition reactions.The catalytic properties and characteristics of these chiral ligands were investigated in this dissertation.In the study of the asymmetric [4+2] cycloaddition reaction,initially 6 chiral phosphoramidite ligands were synthesized and the optimal ligand was picked out,which was used to prepare the required chiral rhodium(I)catalyst in the presence of the bis(norbornadiene)rhodium(I)tetrafluoroborate and silver hexafluorosilicate.In the intermolecular [4+2] cycloaddition reactions of 1,3-dienes and dialkyl acetylenedicarboxylates,a series of enantioselective substituted cyclohexa-1,4--dienes were synthesized with up to >99% ee,which improved the asymmetrically synthetic methodology of these products.The scale-up reactions of the 1 gram and10 grams were carried out,giving the enantioselectivities as 99% ee.Additionally,the derivatizations of the products were explored,where the oxidative aromatization and hydrolysis of the products were realized.It was found that the enantioselectivity could be kept as 99% ee when the diester was converted to dicarboxylic acid.On the other hand,the application of the chiral rhodium(I)catalyst in the intramolecular asymmetric [4+2] cycloaddition was explored and the asymmetric synthesis of the substituted piperidine was realized.Lastly,a proposed mechanism was presented,which discussed the coordination with the substrates,oxidative cyclization,suprafacial 1,3-allylic migration and reductive elimination in the catalytic cycle.Since the high atom economy,diversity of the products and considerable practicability were obtained in this asymmetric reaction,it expanded the application of the chiral phosphoramidite ligand in the asymmetric cycloaddition reactions.In the study of the asymmetric 1,4-addition reaction,three novel chiral spiro-fused bisoxazoline were synthesized firstly via nine steps and the optimal ligand was screened out,which was utilized to prepare the required chiral nickel(II)catalyst in the presence of nickel(II)perchlorate hexahydrate.The asymmetric 1,4-addition reactions of indole derivatives and β,β-disubstituted nitroalkenes were realized in the presence of the optimal catalyst,where the β-substituted groups include the trifluoromethyl,difluoromethyl,ester and methyl.When β-substituted group was trifluoromethyl or difluoromethyl,a series of indole derivates bearing an all-carbon quaternary stereocenter were asymmetrically synthesized with up to >99.9% ee,providing a new protocol for the highly enantioselective synthesis of these compounds.By using this catalyst,the 1,4-addition reaction of pyrrole and(E)-(3,3,3-trifluoro-1-nitroprop-1-en-2-yl)benzene was also realized,affording98% ee.By comparing the specific rotations between the products and the known products,the absolute configurations of fifteen products were confirmed.Lastly,a model of deep chiral pocket was established to reveal the controlled mechanism of the chiral ligand for controlling the reactivity and stereoselectivity.This research enriched the types of the chiral bisoxazoline ligands and expanded the application of the chiral spiro-fused bisoxazoline ligands in the asymmetric 1,4-addition reactions.In the study of the asymmetric 1,2-addition reaction,initially thirteen chiral spiro-fused oxazoline-pyridine-type ligands were synthesized via 7 to 11 steps,in which ten ligands have not been reported before.By screening the chiral ligands,the optimal ligand was picked out and the required chiral nickel(0)catalyst was prepared though the complexation of the optimal ligand and bis(1,5-cyclooctadiene)nickel(0).The 1,2-addition reactions of the α,β-unsaturated ketones and pinacolborane were catalyzed by the chiral nickel(0)catalyst,providing the corresponding boric acid esters.By quenching the boric acid esters with ammonium fluoride,a series of optically active allyl alcohols were synthesized with up to 99% yield and 96% ee.When trifluoromethyl,cyano,fluoro,chloro,bromo,methoxyl and cyclopropyl were introduced into the substrates,the asymmetric reactions showed good compatibility with them.The absolute configurations of eleven products were confirmed through comparing the specific rotations between the products and the known products.A mechanism was proposed to demonstrated the catalytic cycle,which suffered from the coordination with the pinacolborane,coordination with the substrate,hydride transfer and s-bond metathesis.In the expanding studies,the cobalt catalyzed asymmetric addition of the cyclic N-sulfonyl ketimine with phenylsilane in presence of the chiral spiro-fused oxazoline-pyridine-type ligands,providing the product with up to 72% yield and35% ee.These studies increased the types of the chiral oxazoline-pyridine-type ligands and extended the applications of the chiral spiro-fused oxazoline-pyridine-type ligands in the asymmetric 1,2-addition reactions.