The traceless Staudinger ligation of azides and phosphines is an effective method to produce an amide bond. In this work, density functional theory (DFT) calculations were carried out to investigate the mechanism of the traceless Staudinger ligation, which suggested that its rate-limiting step was the attack of azide on phosphine leading to the formation of phosphazide. After the formation of iminophosphorane intermediate, competition between acyl transfer followed by hydrolysis and direct hydrolysis determined different product distributions. The traceless Staudinger ligations mediated by different coupling reagents were then computed. The results were consistent with the experiments.

Key words: traceless Staudinger ligation, density functional theory, acyl transfer, hydrolysis