A New Type Of P-Chiral 1-Phosphanorbornene Ligands:Synthesis And Application

Chiral phosphine have been widely developed in the past decades.They are widely used as ligands or catalysts in asymmetric metal catalysis,organocatalysis,and the synthesis of natural products,drugs and pesticides.But most of the studies on chiral phosphine focus on the design of the chiral framework(Such as ferrocene,binaphthyl,biphenyl,spiro and so on).Because of the difficulty of their synthesis,and P-stereogenic easily racemized,the development of P-stereogenic ligands is relatively hysteretic.However,the chiral sites of P-stereogenic ligands directly coordinated to the metal center,which made P-stereogenic center closer to the reaction site,increasing the possibility of chiral induction and transmission.Taking the “chirality of phosphorus closer to the catalytic center” as starting point,we designed a series of P-stereogenic ligands,which were been applied to asymmetric catalytic 1,3-dipolar cycloadditions and organic catalytic reactions.In the first chapter,the applications of P-stereogenic ligands in asymmetric metal catalysis are reviewed.In the second chapter,We combined 1-phosphanorbornes bearing a special bridge ring skeleton with chiral sulfinamide.Applying to the cheap and readily available 2H-phosphole,the 1-phosphanorborne was obtained through Diels-Alder reaction of 2H-phosphole with alkynes,Then the(R)-2-methylpropane-2-sulfinamide motif was combined with 1-phosphanorborne derivatives and reacted with different metal reagents,a series of P-stereogenic ligands(Ganphos)were obtained by column chromatography.In the third chapter,because of the unique medicinal value and biological activity,as well as small molecular mass leading to easily modified,the chiral spirocyclic bis-pyrrole compounds were important intermediates in pharmaceuticals.In this chapter,we use the P-stereogenic ligands(Ganphos)designed by our research group,coordinating with copper salt to form organic-metal catalyst,the cycloaddition reaction of azomethine ylides with N-phenyl-itacamides smoothly carried out,producing the spirocyclic dipyrrolidine compounds high stereoselectivity.The reaction has good substrate universality and high enantioselectivity and diastereoselectivity.At the same time,a pair of P-stereogenic ligands worked as pseudoenantiomers to tune the enantioenantioselective 1,3-dipolar cycloaddition,and providing a pair of enantiomeric pure pyrrolidines,respectively.In the fourth chapter,we developed a 1,3-dipolar cycloaddition reaction of electron-deficient 2-arylmethylidene benzocyclohexanones with azomethine ylides catalyzed by using Cu/Ganphos catalyst,giving a series of spiropyrrolidine-phenyl cyclohexanone derivatives.These compounds had good enantioselectivity and diastereoselectivity.Remarkably,aliphatic iminoester could participate in the [3+2] cycloaddition to afford corresponding product in good yields and enantioselectivity.In the last chapter,functional six-membered ring was an important intermediate in organic synthesis.We had developed tertiary phosphorus-catalyzed cyclization of conjugated dienes with γ-substituted allenoates.It is noteworthy that nucleophilic addition of β,γ-unsaturated α-ketoester usually occured at more electrophilic α or γ site in previous works.And we developed a nucleophilic addition site at β’ site,producing a series of multifunctional cyclohexenes.This greatly enriched the six-membered ring types.