Synthesis Of Heterocycles From 2-electron-withdrawing-group Substituted Acetamides

2-Electron-withdrawing-group substituted acetamides and their derivatives are significant compounds in organic syntheses. Due to their active methylene groups,2-electron-withdrawing-group substituted acetamides can be easily transformed into new active intermediates, such as diazo compounds, aryliodonium ylides, and oximes under the basic conditions. The new formed active intermediates can proceed new transformations and generate new intermediates for medical and natural products. The thesis focuses on methodologies for the syntheses of 1,3,5-cyclohept-trienes,2-acetyloxy-3-cyanoindoles, BF2 complex of 3-carbamoyl-oxindole,3-acyloxindoles and 1,4,2,5-dioxadiazines. All the methods employ 2-electron-withdrawing-group substituted acetamides as starting materials.Firstly, N-benzyl-2-cyanoacetamides were used as starting materials and transferred into two types of carbene precursors, diazo compounds and aryliodonium ylides. Under the catalysis of Cu(II) compounds, chemospecific intramolecular Buchner reactions were taken place, giving 5,7-bycyclic products, fused cyclohepta-1,3,5-triene derivatives. In the previous reports, N-benzyl-2-diazoacetamides with acetyl, alkyloxycarbonyl and hydrogen as a-substituents underwent intramolecular Buchner reactions, affording 5,7-bicyclic products; however, C-H insertion products, such as β-lactam,γ-lactam, and δ-lactam, were often obtained at the meantime. Thus, the reactions exhibited poor chemoselectivity. In the thesis, the cyano group was utilized as a-substituent for the N-benzyl-2-diazoacetamides. Because of the π-π-stacking effects of the cyano group and the aryl ring, relatively small steric hindrance of the cyano group and coplanar effect of the cyano group and the carbenoid, the substrates underwent specific intramolecular Buchner reaction. Cu(Ⅱ) compounds were employed as catalysts, showing excellent catalytic performance. High yields were gained, thus making the reactions economical and practical. The diazo compound method gives higher yields than the iodonium ylide method does, but the ylide method is more green and less toxic. Moreover, the "one-pot" strategy makes the ylide method more practical.Secondly, using 2-cyanodiazoacetanilides as starting materials and Cu(acac)2as catalyst,3-cyanooxindoles were successfully afforded. However, the products were difficult to be isolated due to their strong polar; thus they were transfermed into 2-acetyloxy-3-cyanoindoles in the presence of acetyl chloride and triethylamine. When BF3-OEt2was used as catalyst, the formed 3-cyanooxindoles were transferred into 3-carbamoyl-oxindole in the presence of water, and BF2 complexes of the β-dicarbonyl were generated. Employing the method, a series of polycycilic BF2 complexes of 3-carbamoyl-oxindole was synthesized.Thirdly, a method of aqueous synthesis of 3-alkylideneoxindoles was developed from a-diazo-β-ketoanilides. The 3-alkylideneoxindole is structure motif of antirheumatic drug Tenidap and has been used as significant intermediates of organic synthesis. In the previous reports, precious meta catalysts, such as Rh(Ⅱ), Ru(Ⅱ), Ag(Ⅰ), were employed as catalysts. In addition, toxic solvents, such as benzene and dioxane were used, limiting the application of the reaction. In the thesis, water was applied as solvent and inexpensive Cu(NO3)2·3H2O was applied as catalyst.3-Alkylideneoxindoleswere obtainedwith excellent yields, without formation of the O-H insertion of water products. The reactions were performed without inert gas protection, so the protocol was practical, green, and economical.At last,1,4,2,5-dioxadiazines were synthesized via cascade reactions from nitroacetanilides and acetophenone. The reaction starts with a nitrosation of active methylene in the presence of NaNO2 and H2SO4. The obtained nitrooxime undergoes an intermolecular addition and elimination with the release of two molecules of nitrous acid, generating the products. The previously reported 1,4,2,5-dioxadiazines were obtained via the traditional protocol:dimerization of nitrile oxides, which suffers from drawbacks like tedious step, difficultly-handling and poor chemoselectivity. The method in the thesis employed a domino reaction, so the intermediates can proceed the next reaction step without being isolated. Additionally, the nitroacetanildes were synthesized from anilides and nitroacetic acid in the presence of DCC and DMAP. This approach was also very practical.The methodologies in the thesis display several advantages. Firstly, the starting materials are easily accessible. They can be synthesized from active acetyl derivatives and the corresponding amines. Secondly, high yields were obtained. The highest yields are above 60% for all of the methods. Thirdly, specific chemoselectivity is realized with almost no by-products being formed. Forth, cheap catalysts are employed; thus the methods are all very economical. Finally, the reactions are all easily handled and most of them can be performed without inert gas protection.In summary, efficient, easily-handled, practical, and economical methods approaching fused cyclohepta-1,3,5-triene derivatives, 2-acetyloxy-3-cyanoindoles, BF2 complexes of 3-carbamoyl-oxindoles, 3-acyloxindoles, and 1,4,2,5-dioxadiazines have been developed via intermediates of diazo compounds, phenyliodonium ylides and oximes.