Synthesis Of Trisubstituted Trifunctional Dihydrobenzofuran Derivatives Through Pd/NBE Strategy

The dihydrobenzofuran compound skeleton is a very important class of drug molecular skeleton.Its unique structure,diverse biological activities and huge medicinal value have long been attracting people's attention since 1909.More than 20,000 dihydrobenzofuran compounds have been discovered or synthesized after the first reports of dihydrobenzofuran compounds.The limited sources of dihydrobenzofuran compounds in nature have severely restricted the development and utilization of the biological activity and medicinal value of these compounds,it is necessary to find a new synthetic routes.Based on the concept of green chemistry,the Catellani reaction strategy catalyzed by transition metals to synthesize this compound has aroused the interest of our research group.This paper summarizes the outstanding contributions made by the predecessors in exploring the field of Catellani reaction,and on the basis of it,the palladium/norbornene co-catalyzed tri-substituted trifunctional triaryl reaction of aryl iodide is catalyzed by this method Dihydrobenzofuran compounds containing many different substituents were synthesized.The specific content of the thesis is divided into the following two chapters:In the first chapter,mainly summarizes the discovery and development process of Catellani reaction.Taking the different ortho substituents of aryl halides as ideas,it summarizes o-arylation,o-alkylation,o-acylation and o-amination Catellani type reaction.Also introduced the ortho-alkane(nitrogen)oxycarbonylation and the synthesis of disilane/digermane compounds that have only been developed in recent years.In the second chapter,described the synthesis of trisubstituted trifunctional dihydrobenzofuran derivatives using Pd/NBE co-catalytic strategy.The reaction was initiated with Pd0,and under the synergy of norbornene,a continuous three-substitution reaction of ortho and home positions for aryl iodide was realized.Three chemical bonds were constructed in one step,and an unprecedented three-substitution trifunctionalization reaction was realized.Under a series of optimized reaction conditions,the reaction has high chemical selectivity and the substrate functional group is well tolerated,not only compatible with ortho-acylation reagents but also compatible with ortho-position amination reagents.Finally,some optical properties of the ortho-aminated dihydrobenzofuran compounds were studied,and a reasonable reaction mechanism was proposed.