| Pyridine and tetrahydrothiophene derivatives are two common heterocyclic skeletons in natural products, which are widely used in medicines, pesticides, and a variety of functional materials. Therefore, for a long time, much attention is paid to the synthesis of pyridines and tetrahydrothiophenes. In this article, pyridine and tetrahydrothiophene derivatives were seperatively synthetized by reaction of 1,2,4-triazines and methyl ketones or D-A cyclopropanes and β-oxodithioesters through [4+2] or [3+2]-cycloaddition. The reaction between D-A cyclopropanes and isocyanides was also studied. Details are as follows:In the first section, we summarized different protocols of preparing pyridines and tetrahydrothiophenes as well as their important applications in pesticide, medicines, and the application of functional materials were also introduced.In the second section, a new route to prepare pyridine derivatives based on inverse electron demand Diels-Alder/retro-Diels-Alder reaction of methyl ketones with 1,2,4-triazines was reported. Firstly, we summarized the functionalization and utilization of of methyl ketones. By comparing the impacts on the reaction, different kinds of bases and solvents were introduced. The optimum reaction condition was in refluxing ethanol using NaOH (1.5 equiv) as the base. In addition, the effects of different substituents on the reaction time and the yield of the products were also explored. It is the first time using methyl ketones directly as a dienophile to react with 1,2,4-triazines without enamine intermediates, which is complementary to the classical Boger reaction (the reaction of 1,2,4-triazines and enamines to synthesis pyridine derivatives).Considering that enaminones contain the enamine motif, we next attempted to use enaminones as dienophiles to react with 1,2,4-triazines directly expecting to obtain products containing acyloxy. Surprisingly, the decarbonylated products were obtained instead of the desired products. The control experiments revealed an unprecedented phenomenon that enaminones could easily convert to the corresponding ketones under alkaline conditions. To our knowledge, this retro-aldol type conversion under alkaline conditions has never been reported.In the third section, we have developed a simple and efficient protocol for synthesis of tetrahydrothiophenes via reaction of D-A cyclopropanes and β-oxodithioesters in a domino fashion, and to our knowledge, this [3+2]-annulations reaction had never been reported so far.The fascinating properties of D-A cyclopropanes and β-oxodithioesters as building blocks in heterocyclic frameworks were introduced. And the best results were obtained when reactions were carried out in refluxing 1,2-DCE with 5 mol% Yb(OTf)3 as the catalyst. The methodology is amenable to a broad array of functional groups and heterocycles and mostly afforded good to excellent yields. The experiment revealed that the reactions proceed in a highly regioselectivity manner under catalyst dose of lewis acid through β-oxodithioesters to replace toxic sulfur source, which provide a new way for the synthesis of tetrahydrothiophenes.In the fourth section, we explored an approach to synthesize a new kind of cyclopentene derivatives. The best reaction conditions were:10 mol% Yb (OTf) 3 as catalyst under solvent-free at 80℃. And a possible mechanism was also proposed. The characteristic of this topic is:the reaction between D-A cyclopropanes and isonitrilers reported in literatures was AB2 type, while the reaction of D-A cyclopropanes with isocyanides in this thesis was A2B2 type.The structures of all the synthesized compounds were characterized by IR,1H NMR,13C NMR, and HRMS. Furthermore, single crystals of compounds 4d,14e and 14j were cultured and their precise spatial configurations were determined. |
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