Synthesis Of Fused And Spiro/Ketals With Gold Catalysis

Ketals are not only widely found in some natural products with biological activity,but also the core backbone of some drugs,such as artemisinin with antimalarial effect,berkelic acid with anticancer effect,and natural product rubromycin.So it is extremely important to construct ketal skeletons.In the past few years,gold-catalyzed reactions have developed rapidly,including the synthesis of ketone compounds catalyzed by gold.In the past few years,homogeneous gold catalysis has the advantages of mild conditions,insensitivity to water and oxygen,and has been rapidly developed.Gold catalysis is also widely used in the synthesis of spirocyclic ketals or cyclic ketals.In this context,this thesis explores the gold-catalyzed controlled selective synthesis of fused/spiroketal ketalsIn this paper,the important role of keta in drug synthesis and natural products and the method of synthesis of ketones are briefly introduced.The second part focuses on the synthesis fused/spirocyclic ketal compounds catalyzed by gold.In the initial research,we found that o-alkynyl benzyl alcohol can react with methylene p-benzoquinone derivatives under the catalysis of JohnphosAuNTf2 to obtain ketals This is due to the cyclization of o-alkynyl benzyl alcohol under the catalysis of gold to obtain the active intermediate electron-rich exocyclic alkenyl ether,followed by cyclization with methylene p-benzoquinone to obtain spiroketal.When we extended the substrate with the best conditions,we accidentally discovered that when 1-ol-4-pentyne is used as the substrate to react with methylene p-benzoquinone,not only the spiro ring product is obtained,but also fused ketal products can be detected.Based on the above findings,we further studied the gold-catalyzed and fused ketal product,and found that in the presence of a small amount of water,the main product obtained by the reaction was a cyclic product.We speculate that the presence of water can induce the isomerization of exocyclic alkenyl ethers to obtain cycloalkenyl ethers,which are then subjected to a cycloaddition reaction with methylene p-benzoquinone to obtain fused products.This discovery allows us to use a gold catalyst to catalyze the reaction to obtain ketal compounds in two configurations,fused/spirocyclic.In this study,the presence and amount of water played a very important role.The last part of the paper describes the synthesis of polysubstituted pyrrole compounds by gold-catalyzed reaction of proacetylbenzyl alcohol with enyl azo compounds.The mechanism was speculated as follows:the electron-rich exocyclic enyl ether was obtained by 5-exo-dig cyclization of O-alkynyl benzyl alcohol under the catalysis of gold,followed[3+2]Cyclization with 1,3-dipoles formed by alkenyl azo to give azaspiral ketal,and finally elimination to obtain polysubstituted pyrrole.