Reaction Method Study On Synthesis Of 3-Hetero Isocoumarins Based On Rhodium Catalyzed

Heterocyclic compounds are widely used as a class of compounds in the world.They play an increasingly important role in the fields of medicine,pesticide,catalyst luminescent materials and dyes.Oxygenated heterocycles,especially those having a benzopyrone structure,are common structural units in many drugs.Because of its very good biological activity,such as antibacterial,anti-inflammatory,anti-cancer,inhibition of protease and weeding and other biological activity,these compounds play a very important role in human life.In addition,Heteroatom substituted isocoumarins in the biomedical,organic synthesis,natural products and other aspects;especially in the anti-tumor drugs play an important role.Due to isocoumarins compounds have varied and signifiant physiological activities,which have attracted an increasing attention most recently.Therefore,it is important to synthesize 3-hetero isocoumarins compounds.In this paper,we studied the synthesis of isocoumarin by heteroatom.The following studies were carried out:(1)We first introduced the application of isocoumarin derivatives in biomedicine,and then introduced the traditional synthesis methods of isocoumarin derivatives and the methods of preparing isocoumarin compounds by cyclization reaction of C-H bond activation under metal catalysis.Finally we establish the research direction and content of this paper.(2)We introduced the synthesis of the substrate:(i)we used the simple structure,and easy to obtain acetylene as the starting material.After bromination,nucleophilic substitution reaction,alkynl phosphonates compounds 2a-21 were been synthesized.(ii)We synthesized alkynyl acetylamine 2m-2p in a convenient way in which the simple structure,inexpensive and easy available Phenyl ethynyl bromide reacted with 2-Oxazolidone through nucleophilic substitution reaction,(iii)And we got acetylene esters compounds 2q-2s in high yiedls by the the esterification reaction with phenylpropyne acid and ethanol as raw materials.(3)We used alkynl phosphonates 2a and benzoic acid(1b)as model substrates to optimize the reaction conditions.The optimal reaction conditions were obtained by optimizing the conditions such as oxidant,catalyst,solvent,temperature and reaction time.Then,under the optimum conditions,we obtianed a series of target products in high yields through cyclization reaction in one step.And some of the target products,which were synthesized,were reported for the first time.At last,The single crystal of 3-(Diethyl phosphoryl)-4-phenyl-6-iodo-lH-2-benzopyran-l-one(3ja)was acquired,and its configuration was identified by X-ray diffraction.(4)According to the mechanism of C-H activation and the structure of the product,a plausible mechanism of the reaction was proposed,and then we give a reasonable explanation.In this paper,all the target compounds synthesized in this paper were confirmed by 1H NMR,13C NMR,31P NMR,El,IR and HRMS.The synthesis method of 3-hetero isocoumarins has the advantages of atom economy,high selectivity of region,simple operation and less by-product and easy separation.Moreover,the target compounds are easy to be separated.The system has a wide range of applicability to different substrates and is generally tolerant to common functional groups,providing a new method for the synthesis of 3-hetero isocoumarins...