Studies On The Synthetic Methodology For Some Nitrogen-or Oxygen-Containing Heterocyclic Compounds Involving Alkynoates

Nitrogen- and oxygen-containing heterocyclic compounds are crucial moieties in a wide range of drug leads. Nitrogen- and oxygen-containing heterocyclic compounds of different ring sizes, with different substitution patterns and embedded in various molecular frameworks constitutes extremely important structure classes in the search for bioactivity. Despite the large availability of methods to construct nitrogen- and oxygen-containing heterocyclic compounds, there is still a strong need to further explore novel and being environmentally friendly synthetic methods to efficiently synthesize novel heterocyclic structures. We aim at the development of novel methodologies and catalysts for the synthesis of nitrogen- and oxygen-containing heterocyclic structural motifs from readily available alkynoates. The main work presented in this dissertation can be divided into six parts:1) We have successfully developed an synthesis of polysubstituted 5,6-dihydro-2H-pyran-2-ones and 2H-pyran-2-ones via the hydroalkylation of electron-deficient of alkynoates with activated methylenes and the transesterification using sodium hydroxide from alkynoates and 1.3-dicarbonyl compounds. This protocol provides several advantages such as mild condition, simple work-up procedure, high yield and compatibility to various substrates.2) A novel and convenient one-pot synthesis of multisubstituted 1,2,3,4-tetrahydropyridines via sodium acetate promoted five-component reactions under mild conditions from alkynoates, malononitrile, primary amine and formaldehyde. This multicomponent reactions (MCRs) offer several advantages such as atom economy and simpler procedures and equipment, time and energy savings, as well as environmental friendliness, and avoid the separation and purification of intermediates to maximize.3) DABCO induced [2+2+2] cycloaddition reaction to synthesize 4-Aryl-4H-pyrans, through reactions of of ethyl propiolate and aromatic aldehydes, is described. Operational simplicity, mild condition, atom economy, use of an economically convenient catalyst and starting materials are the key features of this protocol. Besides, to the best of our knowledge, reports about the synthesis of 4H-pyran derivatives through an oxygen migration process of aldehydes are rather rare, although there are many strategies for their synthesis.4) We have established a facile and efficient method to synthesize polysubstituted furans via tin(II) and copper(I)-involved addition/oxidative cyclization of alkynoates and 1,3-dicarbonyl compounds using DDQ as the oxidant. This methodology, comparing o traditional methods, not only provides a simple new way to construct polysubstituted furan derivatives, but also opens a brand new way to build oxygen-containing vinyl ether compounds through oxidation. To the best of our knowledge, it is the first reports about the synthesis of furans through an oxidative process.5) A facile and highly efficient C-N and C-C bonds formation method to construct pyrrole framework directly via one pot multicomponent reactions using AgBF4 as the catalyst and PIDA as the oxidant. In this protocol, various of amines and alkynes are all compatibility to this novel addition/oxidative cyclization reaction. Up to now, reports about the synthesis of pyrrole derivatives through an oxidative process are rather rare, although there are many strategies for their synthesis. Besides, this strategy provides an alternative way to construct symmetric and asymmetric polysubstituted pyrrole derivatives via controlling the starting materials of alkynoates.