Staudinger ligation is a metal-free catalytic click reaction between organic azide and phosphine and it belongs to a bio-orthogonal reaction. It has the following three elements: the reaction must occur in aqueous solution, the catalyst or reactant involved in the reaction is non-toxic, the two functional groups do not exist in the biological system and do not cross react with any functional group in the biological system.
In the Staudinger reduction reaction, the reaction of azide and triphenylphosphine (TPP) firstly releases nitrogen to generate intermediate phosphine imine, and then spontaneously hydrolyzes in an aqueous solution to generate primary amine and stable triphenylphosphine oxide (TPPO). The reaction mechanism of Staudinger ligation is different from the classical reduction reaction. After improvement, TPP is constructed by using the ester located in the ortho position of the phosphine atom in the reactant through intramolecular cyclization reaction as an electrophilic trapping agent, which can capture the nucleophilic azalactium salt intermediate as an amide under the condition of the aqueous solution, thus realizing the covalent "binding" of the two molecules. Traceless Staudinger ligation is a further improvement on the basis of Staudinger ligation. Its "traceless" is reflected in the formation of amide bonds in the hydrolysis step and the removal of TPPO from the final product[1].
