Transition-metal Carbene For The Stereoselective Synthesis Of 3-phosphoindoles

In recent years,a large number of studies have shown that compounds containing P-substituents exhibit special bioactivities and chemical characteristics,which makes it widely used in pharmaceutical chemistry,materials chemistry and organic synthesis.Furthermore,indole frameworks are the basic backbone of many natural products with significant drug value and biological activity.Thus,3-phosphoindole derivatives has been reported play important role as biological drugs.The diazo compound is a compound capable of efficiently constructing a carbon-heteroatom(C-X)bond.However,compared with the insertion reaction with a significant study of the heteroatom-hydrogen(X-H)bond,due to the high coordination of the phosphine element,the metal catalyst is usually susceptible to poisoning the organophosphorus compound,and the organophosphorus compound is difficult to control the stereoselectivity of the participating reaction,leading to a slow progress in the P-H insertion reaction.The research work of this paper is divided into two parts:one is the development of a-imino indole diazo compounds and phosphine hydrides synthesis of 3-phosphonoindole derivatives synthesis method;the second is the use of optical pure(1S,2S,5R)--menthoxylphenylphosphinate as a chiral auxiliary in the stereoselective synthesis.In the first part of the paper,we formation of a-imide copper carbene by a-imino indole diazo compounds catalyzed by metal copper.The reaction conditions were optimized and screened.Finally,3-phosphoindole derivatives can be obtained in a yield of 48%to 88%.It's a effective way to construction of C(sp2)-P bonds.In the second part of the thesis,we used the optically pure(IS,2S,5R)-(-)-menthoxylphenylphosphinate as the object of P-H insertion reaction,the first attempt to a-imine metal carbene P-H insertion reaction of the stereoselectivity synthetic research.We finally verify the reaction has good stereoselectivity deteramined by 31P NMR with high dr value,which proved that the synthesis method has high efficiency and stereoselectivity and proved a new synthetic strategies for organic compounds containing chiral phosphine centers.