Transformation Of Alkynes Into Fluorinated Alkyl Azides By An One-pot Two-step Procedure

Alkyl azide compounds are a very important class of organic synthesis intermediates,which have great applications in the fields of materials chemistry,medicine and chemical biology.The azide group can be further transformed to obtain compounds such as amines and triazoles.Based on the important role of alkyl azides in organic synthesis,it is valuable to explore new synthetic strategies of these compounds.Pharmaceutical compounds with one or more fluorine atoms have become popular.The presence of fluorine atoms in bioactive molecules can greatly increase their fat solubility,metabolic stability,degree of bioavailability,and rate of bioavailability.Given the importance of fluorine functionalization,new practical methods that allow access to a more diverse range of medicinally relevant fluorinated building blocks are of particular importance.β-Fluoroalkyl amines are a class of fluorinated compounds that are very attractive elements in drug candidates.In particular,β-difluorinated alkyl amines are found in a variety of medicinally relevant bioactive molecules and constitute important synthetic motifs in the design of anticancer,anticholinergic,and anti-inflammatory drugs.Moreover,the geminal difluoromethylene group in these molecules shows valuable properties as a chemically and metabolically inert isostere of a variety of polar functional groups.From a synthetic perspective,the available approaches to access β-difluorinated alkyl amines require tedious multistep transformations.Therefore,it is necessary to explore the methods of simple synthesis of these compounds.In this thesis,gem-difluoroalkyl azide compounds were obtained by an one-pot two-step process(hydroazide / fluoroalkylation).This process is accompanied by 1,2-azide migration or 1,2-aryl migration.The mode of migration depends mainly on the electronic properties of the substrate alkyne.Considering the importance of geminal difluoro group and the rich chemical properties of alkyl azides,this strategy will be widely used in organic synthesis.