Synthesis Of C1-phosphonated Tetrahydroisoquinoline Derivatives And N-benzyl Dihydroisoquinolones

Tetrahydroisoquinoline derivatives are a class of alkaloids and widely exist in nature.Derivatives with tetrahydroisoquinoline as a structural unit have a wide range of biological activities,such as antibacterial,antiviral,anti-inflammatory,anti-tumor,and important role in bronchiectasis and central nervous system,and that has attracted widespread attention.In this dissertation,two different tetrahydroisoquinoline derivatives have been synthesized using tetrahydroisoquinoline as framework material through different synthesis methods.The reaction conditions of this experimental protocol are mild and the raw materials are relatively inexpensive.1.The silver-catalyzed three-component reaction of tetrahydroisoquinolines,aromatic aldehydes and phosphite triesters catalyzed by silver acetate was studied.In this reaction,a C1-phosphonated tetrahydroisoquinoline derivative was synthesized by a one-pot method under nitrogen protection at a reaction temperature of 120?.We investigated the universality of the substrate and confirmed the structures of the target compounds using nuclear magnetic resonance spectroscopy,carbon spectroscopy,and high-resolution mass spectrometry.The target compounds with yields ranging from 51% to 90% were obtained.The product yields of the electron-withdrawing groups on the aryl aldehyde are higher than that of the electron-donating groups.The reaction conditions of this experimental scheme are relatively mild,the product structures are novel,and the raw materials are relatively inexpensive.2.The copper-catalyzed two-component reaction of tetrahydroisoquinolines and aromatic aldehydes was studied.This reaction uses oxygen as the source of oxygen to synthesize a series of N-benzyl dihydroisoquinolinone compounds.We have expanded the reaction substrate,and the obtained product structures were confirmed by nuclear magnetic resonance spectroscopy,carbon spectroscopy,and high-resolution mass spectrometry.The target compounds with a yield ranging from 22% to 91% can be obtained.The method is green and environment-friendly,the reaction is highly efficient,the operation is simple,the raw materials do not need to be prepared in advance,and the economic performance is good.Therefore,it is expected to be practically applied in organic synthesis.