The Study On Asymmetric Catalytic Reactions Of Quinone Methides

As a vital class of active intermediates,the quinone methides?QMs?have shown high reactivity and competent synthetic potential in organic synthesis benefiting from their driving force to rapidly rearomatize.Particularly in recent years,with the continual advancement in asymmetric catalytic synthesis,the asymmetric conjugate addition reactions and[4+n]cyclization of quinone methides have shown prominent advantages in the construction of chiral diaryl methanes and phenoxyheterocyclic molecules and maken remarkable achievements.This dissertation mainly studies the asymmetric catalytic reactions of the QMs intermediates and their application in organic synthesis,including five parts as follows:Firstly,advances in the studies of QMs in asymmetric catalytic reactions were briefly summarized.Secondly,based on bifunctional chiral tertiary amine-squaramide catalysis,the asymmetric conjugated addition of 4-subsitituded pyrazolin-5-ones to in situ generated ortho-quinomethanes?o-QMs?was developed in excellent yields?up to 96%?and stereoselectivities?up to 99:1 dr,99%ee?,providing a highly stereoselective organocatalytic approach to constructing the important pyrazolin-5-ones bearing adjacent all-carbon quaternary and tertiary stereocenters and extending the application of in situ generated o-QMs in organic asymmetric synthesis.In the third part,based on bifunctional chiral tertiary amine-squaramide catalysis,we established an asymmetric[4+1]annulation of in situ generated o-QMs with 4-halo pyrazolones.This reaction was realized through the cascade conjugate addition/nucleophilic substitution sequence,affording a series of chiral4-spiropyrazolone derivatives featuring oxygen incorporated stereocenters.More importantly,controlling the diastereodivergent switch by the leaving group of C1synthons could be realized in this work,which indicated that the present protocol provided an arbitrary access to all four possible stereoisomers of the 4-spiropyrazolone via an appropriate choice of C1 synthons and chiral catalysts.In the fourth part,based on bifunctional chiral tertiary amine-squaramide catalysis,a regio-and enantioselective Friedel-Crafts benzhydrylation of indoles in carbocyclic ring was developed,and 1.5 mol%catalyst enabled the reation to afford a series of novel chiral diarylindolylmethanes derivatives in excellent yields?up to 95%?and stereoselectivities?up to 99%ee?.In this transformation,the hydroxyl group could guide and activate the reaction,and switching the position of hydroxy group in the hydroxyindoles allowed the asymmetric functionalization at the C4,C5,and C6positions of indoles.Moreover,the reaction was still highly efficient in scale-up experiment.In the fifth part,based on chiral diphenylamine-linked bis?oxazoline?-Cu?OTf?₂complexes catalysis,an asymmetric 1,6-conjugate addition of cyclic?-keto esters to in situ generated p-QMs was developed with good yields and stereoselectivities,delivering the?-ketoester skeleton bearing adjacent all-carbon quaternary and tertiary stereocenters in high efficiency.The strategy of generating p-QMs in situ can overcome the structural limitation of pre-synthesized p-QMs requiring bulky electron-donating substituents,while at present,the compatible asymmetric catalytic systems are limited to chiral phosphoric acid and phase transfer catalyst.In this work,we firstly reported the asymmetric 1,6-conjugated addition reaction between in situ p-QMs with1.3-dicarbonyl compounds and realized the application of the in situ generated p-QMs in transition metal catalytic asymmetric organic synthesis.