Coulombic effects on the traceless Staudinger ligation in water.

The traceless Staudinger ligation can be mediated by phosphinothiols under physiological conditions. Proximal positive charges are necessary to achieve that transformation, presumably because those charges discourage protonation of the key iminophosphorane intermediate. Here, a series of cationic phosphinothiols is used to probe Coulombic effects on the traceless Staudinger ligation in aqueous buffers. The reagent bis(m-N,N-dimethylaminomethylphenyl)phosphinomethanethiol (3) is found to be superior to others, both in its ability to mediate the traceless Staudinger ligation in water and in the efficiency of its synthesis.