Synthesis Of Heterocyclic Boronic Acid Compounds Containing Difluoromethyl

Difluoromethyl compounds are an important class of organic compounds.In addition to exhibiting the biochemical properties of fluorine atoms,these compounds also have the property of improving the biological activity of compounds.The introduction of difluoromethyl into the drug molecule can adjust the activity of the drug and the lipophilicity of the molecule,increase the activity of the drug and thus enhance the utility of the drug,which has important research significance.This project was commissioned by a partner company to use different types of heterocycles as the substrate skeleton,use difluorocarbene reagent to introduce difluoromethyl groups to prepare difluoromethyl compounds,and then synthesize new difluoromethyl heterocycles by boronization.Cycloboronic acid compounds provide methods for the preparation of such compounds.The research on the synthesis of such compounds can also lay the foundation for the research and development of fine chemicals such as related new medicines and pesticides.According to the structural characteristics of heterocyclic substrates,this topic uses different methods to synthesize the target compounds.Use different difluorocarbene reagents to introduce difluoromethyl groups to synthesize target compounds containing-OCF2H,-CF2H,-SCF2H and other groups,and compare and optimize the process to reduce by-products and improve The yield of the target compound is shown.For the boronation reaction,the main selection of high-efficiency palladium catalysis and iridium catalysis methods were carried out in terms of catalyst type,catalyst dosage,feed ratio,reaction solvent and reaction time,etc.,and a better preparation containing difluoromethyl was obtained.The laboratory method of heterocyclic boronic acid(boronic acid or boric acid ester)compounds has laid the foundation for the pilot test.15 compounds containing difluoromethyl heterocyclic boronic acid were synthesized in this subject,and the structure of the target product was verified by ~1H NMR and HRMS.Among the 15 target products synthesized,12 are new compounds with no synthetic routes reported,and 3 are reported with synthetic routes but their routes need to be optimized.Among the synthesized target products,the heterocyclic substrates containing halogen groups are boronylated,and the palladium catalyst method is selected,while the iridium catalyst method is selected for those without halogen groups,and the boronic acid is directly activated by C-H activation and bond breaking Group.