Synthesis Of Aporphine Analogues Via Palladium Catalyzed Intramolecular Aryl-aryl Dehydrogenative Coupling

Biaryl compounds are widely found in natural products,medicines,ligands,pesticides,and have a wide range of uses in the fields of chemical engineering,medicine,and food.The construction of biaryl skeleton structure is a hot area in organic chemistry research and has been attracted the concern of many scientific researchers.The intramolecular aryl-aryl cross-coupling reaction is one of the most efficient methods to construct the biaryl skeleton.The breakthroughs have been made in recent years.This article reviews the recent work of constructing biaryl compounds through intramolecular oxidative coupling reactions from two aspects,First,the oxidative coupling reaction of intramolecular aryl halide and aryl C-H;second,the direct dehydrogenation coupling reaction of intramolecular aryl（heteroaryl）C-H/C-H.Aporphine compounds are a class of naturally occurring alkaloids,which are widely used in biomedicine and synthetic chemistry.At present,although many methods have been used to synthesize such compounds,there are still some shortcomings,such as complicated steps,prefunctional groups of substrates,etc.In this paper,the biaryl compounds-aporphines was successfully constructed by palladium-catalyzed intramolecular dehydrogenation coupling of two aryl C-H groups under the induction of guide group for the first time.Using Pd（TFA）₂as catalyst,Ag TFA as oxidant,HFIP/HOAC（1:1）as solvent,aporphine compounds were successfully synthesized at 80℃.This method has good functional group tolerance,wide substrate range and high atomic utilization.We also applied this method to the synthesis of natural products,and successfully realized the total synthesis of natural products Aporphine and Zenkerine.