Cyclization Reactions Of Oximes In Nitrogen-containing Heterocyclic Compounds Synthesis

Nitrogen-containing heterocyclic compounds are abundant in natural products, pharmaceutical molecules and materials that are widely used in the fields of medicine, pesticide, and material science. Oxime and its derivatives are versatile building blocks for the synthesis of structurally diverse and biologically active N-heterocycles, such as pyrroles, pyridines, isoquinolines, isoxazoles and imidazoles. The cyclization reactions of oximes are a simple and straightforward route to constructing N-containing heterocycles. However, many of the existing methods suffer from the limited substrate scope, harsh conditions, multistep procedures and/or unsatisfactory regioselectivity. Therefore, a general, efficient method for the synthesis of N-heterocycles is still in high demand.Carboamination of alkenes represents a powerful and straightforward tool for the one-step introduction of both C-N and C-C bonds that possesses significantly synthetic utility in the synthesis of nitrogen-containing molecules. Despite significant progress in the field, approaches of the alkene carboamination are much less abundant and remain a great challenge: The majority of available transformations are restricted to the intramolecular carboamination or the two component reactions, which have a disadvantage of the limited carboamination agents. In addition, Most of the alkene carboamination reactionsrely on the same principle that need one step of intramolecular intramolecular amination. Further, to our knowledge, three-component examples of the alkene carboamination via C-H functionalization have not been reported.On the basis of these, this dissertation mainly focuses onthe construction of nitrogen-containing heterocyclic compounds through the cyclization of oximes and iron-catalyzed intermolecular 1,2-carboamination of alkenes with alkyl nitriles and amines. This dissertation includes five parts:In chapter 1, two parts on the construction of nitrogen-containing molecules have been described in this chapter, including:(i) Recent advances in the annulation of oximes for the synthesis of nitrogen-containing heterocyclic compounds, such as pyrroles, pyridines, isoquinolines, phenanthridines, isoxazoles, and(ii) recent progress in the carboamination of alkenes.In chapter 2, a new highly regioselective silver-catalyzed oxyfluorination of unactivated alkenes using commercially available Selectfluor as the fluorine source and the oxidant was developed. This method provided a new access to 5-(fluoromethyl)-4,5-dihydroisoxazoles from,!-unsaturated ketoximes. Moreover, a iminoxyl radical process was supported by some control experiments. Most importantly, this work provides a new access to the introduction of a fluorine atom into the isoxazoline framework, thereby making the isoxazolines more accessible for agrochemicals, pharmaceuticals and materials due to the unique electronic properties of fluorine.In chapter 3, a novel route to producing functionalized isoxazolines was presented via silver-mediated radical cyclization of a-halo ketoximes with 1,3-dicarbonyl compounds. This radical cyclization reaction was triggered by silver salts"and afforded the desired products in good to excellent yields under mild and simple conditions. Further mechanism investigation suggested that this tandem method is realized through sequential nucleophilic replacement and radical cyclization. Meanwhile, the recovery experiment of silver salts could dramatically reduce the cost and waste, which would allow for a large range of applications in the organic synthesis.In chapter 4, anovelasimple, and efficient protocol for 3-aminopyrroles synthesis by copper-catalyzed annulation of O-acyl oximes with "-amino carbonyl compounds was established. The optimized conditions were approved as 10 mol% of Cu(OAc)2 in DMSO at 80 oC for 12 h under argon. This protocol features several advantages, including diversified and poly-functionalized products, an inexpensive catalyst, mild and easily handling conditions, green byproducts(HOAc and H2O), oximes serving as an internal oxidant to avoid the use of external oxidants.In chapter 5, a new iron-catalyzed intermolecular 1,2-carboamination of alkenes with alkyl nitriles and amines involving C(sp3)-H oxidative radical functionalization was established. This method enabled one-step formation of two new chemical bonds, a C-C bond and a C-N bond, to selectively produce γ-amino alkyl nitriles, and represented the first example of alkene carboamination initiated by C(sp3)-H oxidative radical functionalization. This protocol features simple manipulation, basic and cheap starting materials and a broad substrate scope. The cyanomethyl radical mechanism was also discussed according to the control experiments. In addition, applications of the products, γ-amino alkyl nitriles, to prepare γ-amino acid, γ-amino amide and 1,4-diamine have been examined.