Metal-catalyzed Novel Labeling Reactions Study Of α-Substituted Vinyl Azide

Vinyl azide is a special olefin compound formed by the direct connection of the two functional groups of carbon carbon double bond and azide.Because of the conjugated structure formed by the two groups,the vinyl azide has high reactivity and multiple reaction sites.As one of the most important members,α-substituted vinyl azide has developed a variety of reaction types due to the electron-rich properties of olefin:Schmitt rearrangement reaction,Michael addition reaction,free radical addition reaction,metal reduction reaction and can be used as free radical receptor reaction.Aza-Wittig reaction,Schmitt rearrangement,click-click reaction,Staudinger junction and a series of reactions can also occur in azide.However,new organic labeling reactions based on the easily availableα-substituted vinyl azide still need to be further explored,among many drugs used in labeling reactions,sodium trifluoromethanesulfinate has the advantages of stability,cheap and easy to obtain,and the trifluoromethyl functional groups contained in it can be divided into different reaction types:bifunctional group reaction,aromatic trifluoromethylation reaction,trifluoromethyl sulfide reaction,trifluoromethyl sulfonylation reaction,etc.,and based on the above reaction types,a variety of drugs with different effects have been developed.However,there is no relevant research on the reaction between vinyl azide and sodium trifluoromethanesulfinate,so how to use vinyl azide to develop a new trifluoromethyl labeling reaction has become a challenging problem.In addition,deuterium-labeled compounds are also widely used in medicine.As an isotope of hydrogen,deuterium can be used in biological field to locate deuterium more accurately,which is conducive to rapid and effective analysis of deuterium.Moreover,drugs containing deuterium are more easily absorbed by the human body,which can prolong the half-life and improve the efficacy of drugs.Some typical deuterium drugs,such as deuterium paroxetine,have entered the clinical trial stage.In conclusion,based on the high reactivity ofα-substituted vinyl azide,the use of trifluoromethyl compounds and deuterium labelled compounds to react withα-substituted vinyl azide will further promote the wide application of vinyl azide intermediates in the preparation of important organic compounds and biomarkers.Therefore,the research contents of this paper are described as follows:1)Palladium-catalyzed novel trifluorosulfination ofα-substituted vinyl azide:We developed a palladium catalytic Schmidt rearrangement reaction between low-cost availableα-phenylvinyl azide and sodium trifluoromethanesulfinate.Introducing the novel trifluorosulfinyl functional group intoα-vinyl azide with high selectivity,and a series of amides substituted by trifluorosulfinyl group were constructed.At the same time,the new application of trifluoromethyl as a marker in the field of organic chemistry and pharmacology has been expanded,providing a new method and strategy for the simple,efficient and regionally selective synthesis of trifluoromethyl sulfinyl compounds.2)Palladium-catalyzed novel tandem labeling ofα-substituted vinyl azide,alkynes and sodium borodeuteride:Based on vinyl azide selectivity rupture ofβchemical bond,we developed a palladium catalytic tandem labeling reaction betweenα-substituted vinyl azide,alkynes and sodium borodeuteride,which expands theα-substituted reaction type,as well as introduces a new method of labeling deuterium atom into organic compounds.It also provides a new way for the simple and efficient synthesis of N~1-[(3-deuterium)-propenyl]-1,2,3-triazole derivatives.