Rare Earth Metal-catalyzed Regioselective Reaction Of Azide And Alkene

"Energetic molecules" organic azides are valuable intermediates in organic synthesis.They possess diverse chemical reactivities.Owing to their 1,3-dipole character,they undergo[3 + 2]cycloaddition with unsaturated bonds,such as those in alkenes and alkynes as well as carbonitriles.Organic azides can also be regarded as nitrene equivalents.Accordingly,their reactions with nucleophilic anions,electrophilic cations,and radicals can formally provide the corresponding nitrogen anions,cations,and radicals,respectively.Moreover,the generation of anions,cations,and radicals can result in rapid denitrogenation to deliver the corresponding iminyl species,which can be used in further synthetic transformations.Over the last 15 years,manuscripts and patents on organic azides reported by SciFinder increase considerably,and this class of molecules has been involved in an increasing number of applications.To date,organic azides have been extensively applied to organic synthesis,bioorganic chemistry,pharmaceutical engineering,material science,polymer science,as well as molecular biology.However,less attention has been paid to investigate the rare earth metal-catalyzed[3+2]cycloadditions or cascade reactions of organic azides with alkenes.This dissertation is mainly focused on the selective reactions of organic azides and alkenes catalyzed by rare earth metal,at the same time,the development of novel methodologies that allows the facile synthesis of triazoles,enaminones,enaminonitriles,polysubstituted imidazoles and pyridines from readily available starting materials.(1)In recent years,the use of rare earth metal catalyzed reactions have received significant attention and emerged as a versatile tool for developing syntheses due to their numerous advantages,namely,their relatively high efficiency,water compatibility,mild reaction conditions and eco-friendly catalytic reactions.In this Chapter,we have investigated the rare earth metal-catalyzed[3 + 2]cycloaddition of organic azides with nitroolefins.In the presence of a catalytic amount of Ce(OTf)3,both benzyl and phenyl azides react with a broad range of aryl nitroolefins containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles in good to excellent yields.To the best of our knowledge,this is the first time that a rare earth metal catalyst has been described for[3 + 2]cycloadditions of azides with electron-deficient olefins.(2)A highly regioselective synthesis of ?-aryl enaminones and 1,4,5-trisubstituted 1,2,3-triazoles from chalcones and benzyl azides based on reaction solvent selection is reported.In the presence of a catalytic amount of Ce(OTf)3,reaction of chalcones with benzyl azides in DMF at 100? afforded Z densely substituted ?-aryl enaminones in good to excellent yields(70-92%),The reaction proceeds via a 1,3-dipolar cycloaddition/ring cleavage/1,2-H migration/rearrangement cascade,whereas treatment of chalcones with benzyl azides in toluene at 100 ?selectively produced 1,4,5-trisubstituted 1,2,3-triazoles in excellent yields(77-93%)through 1,3-dipolar cycloaddition and oxidation.Reaction products were determined by the solvent DMF and toluene through the influence on reaction mechanism.Good yields,high regioselectivity,easily available starting materials and experimentally convenient catalytic process make it an attractive alternative to the contemporary synthetic routes.(3)An novel and highly stereoselective synthesis of Z-?-enaminonitriles via reaction of azides with ?,?-unsaturated nitriles mediated by catalytic Sc(OTf)3 has been successfully established.Isotope deuterium labeled cinnamonitrile was used to react with benzyl azide to explore the possible reaction pathway.The reaction proceeds via a 1,3-dipolar cycloaddition—ring cleavage-rearrangement cascade.The assigned structures of all the new compounds were characterized by not only NMR,but also the X-ray crystallography in the case of the products 3aa and 3ba.The reaction was applicable to a variety of azides that tolerated benzyl and alkyl groups as substituents and aryl ?,?-unsaturated nitriles.It also displayed several other merits such as high stereoselectivity,with the Z-form products formed exclusively;good yields,even though a gram-scale synthesis,environment friendly,giving N2 as the only byproduct.(4)We investigated the rare earth metal-catalyzed[2 + 2 + 1]and[4 + 2]annulations of unactivated aromatic alkenes and azidomethyl aromatics.In the presence of a catalytic amount of Sm(OTf)3 and an atmospheric-pressure oxygen,the readily available azidomethyl aromatics were successfully applied as one-or two-nitrogen synthons to prepare fully substituted imidazoles and 2,3,5-trisubstituted pyridines by the reactions with aromatic stilbenes and 1,3-dienes respectively.Mechanistic studies revealed that these transformations might evolve from an initial intermolecular azide-alkene dipolar cycloaddition reaction,affording 1,2,3-triazoline intermediates.The sequential reaction for fully substituted imidazoles is based upon a novel domino process involving 1,3-dipolar cycloaddition/ring cleavage(denitrogenation)/1,2-H migration/rearrangement/aerobic oxidation/1,3-dipolar cycloaddition/ring cleavage(denitrogenation)/aromatization/oxidation,and the construction of pyridine skeleton proceeds through a cascade process of 1,3-dipolar cycloaddition/ring cleavage(denitrogenation)/1,2-aryl migration/rearrangement/aerobic oxidation/6?-electrocyclization/oxidation.Density functional theory(DFT)calculations suggested that the selectivity of 1,2-H and 1,2-aryl migration depends on the structure of alkenes.All reactions are operationally simple providing three types of skeletally distinct N-heterocycles in moderate to good yields.These transformations represent a very useful substrate-controlled bifurcated cascade process for the synthesis of diverse N-heterocycles from azidomethyl aromatics and aromatic alkenes.Notably,the incorporation of two molecules of azidomethyl aromatics into a five-membered-ring product has not been reported,which represents a new application of this versatile class of molecules under rare earth metal catalysis.