Studies On The Asymmetric Nucleophilic Reaction Of 2-aryl-1,3-cyclobutanediones

Catalytic desymmetric reactions of prochiral cyclic 1,3-dione shows great potentialin the construction of monocyclic and polycyclic compounds containing chiral quaternary carbon centers.These reactions have been widely used in the total synthesis of natural products and bioactive molecules.However,compared with the numerous reports on desymmetrization of 1,3-cyclohexadione and1,3-cyclopentadione,the studies on the desymmetrization of 1,3-cyclobutadione are relatively limited.Only one case has been reported so far,but it still shows the potential of this strategy in constructing chiral quaternary-carbon-containing cyclobutane derivatives.Therefore,the development of novel desymmetrization reactions of prochiral 1,3-cyclobutanedione could provide a new route for the highly enantioselective construction of chiral cyclobutane compounds,and play a positive role in promoting the related natural products synthesis and drug development.In this thesis,two kinds of desymmetric nucleophilic reactions of 2-aryl-1,3-cyclobutadione were developed:1)Based on the previous work of our group,the asymmetric B-V oxidation reactions of 2-aryl-1,3-cyclobutadione were successfully achieved at-45 ^oC using 10mol%chiral phosphoric acid（R）-8H-TRIP as the chiral catalyst,H₂O₂（30%）as the oxidant and 1,3-dichloropropane as the solvent.The corresponding chiral5-aryl-ketonic acid could be obtained in up to 98%yield and 95%ee value.It is worth noting that this reaction not only tolerates 2-methyl-substituted substrates,but also viable for more steric alkyl substituents,the corresponding products were also achieved with good to excellent ee values.In addition,the reaction could be conducted on the gram scale,with the catalyst loading is halved,without significant impact on the yield and enantioselectivity.2)The first desymmetric allyl reaction of prochiral 2-aryl-1,3-cyclobutadione was achieved using 15 mol%of（R）-3,3’-Ph₂-BINOL as catalyst,1,3-propylene glycol allyl borate as allylation reagent and toluene as solvent at 25 ^oC.The reaction is compatible with a range of alkyl substituted substrates with different steric hindrances,affording chiral cyclobutanone derivatives containing two consecutive four-substituted carbon chiral centers with 76-99%yield and 92-99%ee values.