Synthesis Of Phthalides From Aryl Amides And Paraformaldehyde Via Ru(?)-Catalyzed And Research Of Novel Chiral Cp Ligand

Phthalide is an important bioactive molecule,which is the intermediate of synthetic medicine molecule.Phthalide with excellent biological activity are widely found in nature plants,where more than 180 phthalides have been isolated.These plants have long been used as traditional medicines,dietary supplements and food flavorings.Although phthalide compounds have been the ingredients of traditional medicines for a long time,the diversity of their therapeutic effects has not been appreciated by scientists until recently.In addition to treating circulatory and heart disease,phthalides are also common synthons in organic synthesis.Form a synthetic point of view,the chemical synthesis methods of phthalide compounds have been explored by chemists from 1980.But the traditional strategies are cumbersome,complicated and require the pre-functionalization substrates.Therefore,how to synthesize such compounds by simple,efficient and green methods has become the main content of chemists'continuous research.In this paper,aryl amides react with paraformaldehyde or other aldehydes as C sources via Ru(II)catalyzed C-H activation,through the ortho-hydroxyl methylation reaction and then lactonization into a variety of phthalides.Products were detected by¹H NMR,¹³C NMR and MS to characterize their structure.Then a large scale reaction was conducted and a series of experiments were carried out to explored the mechanism.Finally,the proposed mechanism was put forward.In addition,in order to realize asymmetric catalysis of this reaction through chiral induction,the synthesis and optimization of novel chiral cp ligands were also carried out.In the initial path,the target enyne ether was synthesized by propylene alcohol and 3-bromopropargyne,and then,after the ether bond was broken,it was coupled with binaphthol to generate benzoyl and monosaturated ketone.Finally,the chiral cp ligand was obtained through a series of transformations.However,the reaction was difficult,so the Diels-Alder reaction between cyclopentadiene and butylenic acid was used to synthesize norbornedienedioic acid.After dehydration,it was coupled with binaphthol,and then the target ligand was generated by reverse Diels-Alder reaction.This method shortens the reaction steps and avoids the PK reaction and the open-loop reaction with a low middle rate in the initial route.