Studies On Synthesis Of Heterocyclic Compounds Via Iridium-Catalyzed Asymmetric Allyl Amination Or Etherification

Chiral heterocyclic compounds are the basic structural units of many natural products,pharmaceutical and bioactive molecules.The development of efficient and concise methodologies for the synthesis of chiral heterocyclic compounds is favored by organic and medicinal chemists.Asymmetric allylation catalyzed through transition metal is an important method to synthesize chiral compounds.At present,many transition metal complexes(Pd,Ir,Rh,Ru,Co,Cu,etc.)have been applied to the reaction.Among them,palladium and iridium complexes are the most efficient catalysts.Compared to the palladium complex,the iridium complex-catalyzed allyl substitution reaction usually results in branched chain products.Although iridium-catalyzed asymmetric allylation has been widely used in the synthesis of heterocyclic compounds,it is urgent to develop in the construction of a wide range of chiral heterocyclic compounds.This paper mainly focused on the asymmetric synthesis of heterocyclic compounds via iridium-catalyzed intramolecular and intermolecular allyl heteroatom reactions.Chapter 1 Asymmetric allyl substitution catalyzed by iridium complexes isreviewed.It mainly includes studies on the mechanism of allylation reaction and the catalytic asymmetric allyl substitution reaction involving the nucleophile of the“carbon”source and the nucleophile of the“heteroatom”source.Chapter 2 We have developed an efficient iridium-catalyzed enantioselectiveintramolecular allylic substitution reaction of 2-tosylhydrazono or hydroxyimino carbonates.Functionalized chiral pyrazoline and isoxazoline derivatives were synthesized in high yield(up to 99%)with high enantioselectivity(up to 98%ee).This reaction can be well applied to the synthesis of chiral hexadic and seven-membered heterocyclic compounds containing N-N and N-O bonds.At the same time,various chemical transformations were carried out.Chapter 3 The iridium-catalyzed intramolecular allyl substitution reaction has been developed to achieve enantioselective desymmetrization of 1,3-diol and1,3-diamine derivatives.Functionalized tetrahydrofuran and tetrahydropyrrole derivatives with quaternary carbon stereocenter were afforded in high yield,diastereo-with excellent enantioselectivity and the reaction is capable of relizing scale-up synthesis.In addition,the products containing the-OH,-NH and double bonds can be transformed to some extent.This is the first successful example of iridium-catalyzed asymmetric desymmetrization of intramolecular allyl heteroatom(oxygen and nitrogen atoms)reaction.Chapter 4 We have developed the first iridium-catalyzed enantioselective formal[5+1]annulation of allyl carbonate derived from phenylacetaldehyde with primary amine using in situ generated enylamine as N-nucleophile.A series of functionalized tetrahydropyridine and dihydropyrrole derivatives were synthesized with moderate to good yields(up to 86%)and excellent enantioselectivity(up to 97%ee).The reaction mechanism was investigated by control experiments and~1H NMR in situ.The products can achieve chemical transformation,and enantioselective synthesis of the compound with potential antidepressant activity using this reaction as a key step.Chapter 5 The palladium-catalyzed intramolecular allyl substitution reaction of(E)-(5-(3-substituted-2-oxo-indolin-1-yl)pent-2-en-1-yl)tert-butyl carbonate has been developed for the first time.A series of novel(Z)-2,3,6,7-tetrahydro-1,7-methanobenz-o[b]azonin-12-one derivatives were afforded in good yields.The reaction has the advantages of wide substrate applicability,mild conditions and simple operation.Furthermore,a new method for the synthesis of 1,7-methyloxabenzene[b]acridonazin derivatives was developed and the asymmetric catalytic reaction was also investigated and the desired(Z)-7-phenyl-2,3,6,7-tetrahydro-1,7-methanobenzo[b]azonin-12-one product was obtained in 40%yield and 80%ee.