Study On The Cascade Synthesis Of Heterocyclic Medicinal Small Molecules Catalyzed By Palladium

Cyclic structures,especially fused ring skeletons containing high tension rings,exist in many natural products and chemically synthesized drugs,and their extensive pharmacological application value has been one of the current research hotspots.The introduction of various functional groups into the cyclic structure,such as boronyl and silicon groups,can effectively improve the activity of molecules.This article introduces the use of readily available palladium catalysts to initiate the synthesis of highly regioselective and stereoselective polyfunctional fused ring compounds from various alkyne compounds,and briefly explores their applications.The synthesis of fused ring compounds with potential pharmaceutical value is mainly described from the following three aspects:1.Using Pd(TFA)2 as catalyst,DCE as solvent,a series of cyclization cyclopropanization reactions of various enynes and silico borate esters were carried out in nitrogen atmosphere with the participation of proton source acetic acid.A variety of complex compounds containing azabicyclic[3.1.0]hexane skeletons have been prepared under mild reaction conditions at 60℃,with high atomic economy and strong reaction universality.Due to the easy separation of the silicon group,this structure can be further transformed into a pure double ring structure,with wide application value.2.Consistent with the use of substrates and reactants in 1,using Pd(dppf)Cl2 as catalyst,DCE as solvent and tBuOH as proton source,a variety of silicified products based on 2,5-dihydropyrrole rings can be obtained by reacting under nitrogen protection at 80℃ for 24 hours.This reaction can obtain compounds with different cyclic structures and different silicon addition sites by adjusting only to a large steric hindrance catalyst based on 1,further demonstrating the strict catalyst requirements for this type of reaction.3.Using Pd(acac)2 as catalyst,DCE as solvent and acetic acid as proton source,the borylative cyclization of B2Pin2 and enynes were carried out at 40℃ and nitrogen atmosphere.Under mild conditions and convenient operation,this reaction has resulted in the synthesis of a series of monovalent cyclic compounds containing cyclopropane structures with high atomic economy.Compared to previous work,the innovation of this method lies in obtaining cyclopropane structures directly without experiencing a carbene process,and realizing polycyclic structures that were originally difficult to synthesize using a one-pot method.Boronic products can further be modified and exhibit certain potential value in the pharmaceutical field.