Synthesis Of Thianthrene Onium Salt And Its Application In Heck Cross-coupling Reaction

Transition metal-catalyzed cross-coupling reactions have important research significance for the development of bioactive drugs and the synthesis of natural products.At present,the realization of regioselective functionalization of site-specific transformation still needs the assistance of guiding groups(amino acid residues,heterocycles,etc.)or special substituents(boronic esters or halogens and their equivalents,etc.),otherwise it will lead to the production of multiple isomers.However,the introduction of these guiding groups will also be incompatible with subsequent functionalization reactions,or there may be regioselectivities of the introduction of substituents.These factors will greatly limit its application potential.Therefore,it is an urgent problem to develop a method that can realize the activation of the aryl C-H bond with high selectivity without using a guiding group.The reaction produces stable thianthrene cation radicals through thianthrene onium salts(Ar-TFT+/Ar-TT+),which then forms dicationic adducts with a variety of complex aromatic hydrocarbons,and finally deprotonates to form thianthrene products.Thianthrene-based onium salts participate in the coupling reaction,and its regioselectivity is higher than that of conventional brominated reagents or boron reagents.This work has developed simple aromatic hydrocarbon thianthracene onium salts,complex aromatic hydrocarbon thianthracene onium salts that can tolerate multiple functional groups,heterocyclic thianthracene onium salts,alkene thiaxanthrene onium salts,and alkyne thianthracene onium salts.Onium salt and so on.Based on the characteristics of these thianthenium salts,their application in cross-coupling reactions catalyzed by eight palladium as catalyst precursors(Suzuki reaction,Sonogashira reaction,Negishi reaction,Heck reaction,Kumada reaction,Stille reaction,Ullmann reaction,Hiyama reaction),and the preliminary experiment was completed.The results showed that the target product was obtained in excellent separation yield in 5 mol%Pd(OAc)₂/Ant Phos system.In this work,46 thianthenium salts were firstly developed.Secondly,based on Heck reaction,they have been widely used in the total synthesis of a variety of natural products and drugs,which has great application potential.Therefore,in the follow-up research,the application potential of thiaanthene-like onium salts in the classical Heck reaction was deeply explored,and the classical Heck reaction was completed at 60?with a low catalyst amount(1 mol%Pd(OAc)₂/Ant Phos).A total of 35 olefins were synthesized.On this basis,we have further explored the preparation of stilbene compounds on a gram scale with one-thousandth catalyst and solvent-free reactions,and the three-step rapid synthesis of Resveratrol,a natural product with antioxidant and anti-cancer activity,with thianthenium salts as substrates was successfully realized.The products were characterized by Nuclear Magnetic Resonance(¹H NMR,¹³C NMR)and high resolution Mass Spectrometry(MS).In summary,this work realized the synthesis of thianthracene onium salt and its application in cross-coupling reaction.It not only synthesized many types of thianthracene onium salt,but also explored its application effect and application potential in Heck reaction,and broadened.The synthetic scope of thianthracene onium salts has also been explored for its application prospects in the synthesis of natural products and drugs.This work helped the development of thianthrene reagents,and at the same time,it is expected that thianthrene reagents will be applied in more fields.