Researches On Synthetic Method And Asymmertric Synthesis Of 4H-chromen-4-yl Phosphonate

How many steps to prepare a substance depend on the reactant molecules complexity, which ulteriorly is decided by the number of the formation or fracture of chemical bonds in a reaction. Therefore, the design of a reaction to construct a plurality of chemical bonds is one of the most challenging subjects of economic chemistry. According to the current standard of green chemistry, except of formation of a plurality of chemical bonds and high stereoselection, an ideal reaction should also meet the following requirements:(1) simple operation;(2) easy availability of substrates;(3) resource efficiency(including time, manpower and cost etc.);(4) atom economy;(5) ecological friendly;(6) easy to realize automation. Multicomponent reactions are almost up to specification of the ideal green organic synthesis.Multi-component reaction has a long development history, whereas it only recently attracts chemists' attention. Multi-component reaction(MCR) refers to that three or more different raw materials react in a single reactor, through which complicated molecular structures containing all the material fragments can be obtained.At present, the development of new multicomponent reaction is a very challenging task. It is because that not only the matching of the starting materials should be taken into consideration, but also a thought should be given to how the intermediate molecules generated during the reaction response to matching and compatibility. Multicomponent reaction as a supporting technology, the development and application of it are now an integral part of all units of large pharmaceutical research work. It is worth noting that from the lead compound discovery to the optimization of the production, multicomponent reactions, which greatly predate the combination technology, make a great contribution to drug development.Phosphorus-containing compounds are frequently found in pharmaceuticals, agrochemicals, and natural products. However, up until now, only a few literatures have reported the one-pot synthesis of diethyl(2-amino-3-cyano-4H-chromen-4-yl) phosphonate compounds. Our study is focused on the synthesis of(2-amino-3-cyano-4H-chromen-4-yl) phosphonate derivatives, especially diphenyl(2-amino-3-cyano-4H-chromen-4-yl) phosphonate compounds, including some unreported cases. And unlike a number of methods reported in some literatures, we come up with another tandem reaction, by using diverse substituted salicylaldehyde, malononitrile and diethyl phosphite or diphenyl phosphate as starting materials, as well as anhydrous Lithium Hydroxide, an easy availability and low pollution base. Through optimization of conditions and substrate expansion, we have successfully synthesized the corresponding phosphonate derivatives in good to excellent yields under mild conditions and simple work-up procedures, which enrich the library of phosphorus-containing compounds. At the end of our artwork, a plausible mechanism of this cascade reaction is put forward. At the end of the research work, we propose a reaction mechanism of the reaction. We also use a chiral catalyst, asymmetric synthesis of(2-amino-3-cyano-4H-chromen-4-yl) phosphonate compounds, and determining the measure of its optical purity analysis conditions.Further efforts will be made to testify the mechanism and study the asymmetric domino reaction of salicylaldehyde, malononitrile and triethyl phosphate or triphenyl phosphate.