The X-ray structures of HOBt-based immonium-type coupling reagents and the rearrangement of benzotriazolyl esters of Nα-protected amino acids or peptides: N- vs. O-substituted forms

Abstract

The crystal structures of HOBt-based immonium salts BOMI and BDMP are reported and show that these compounds crystallize as the N-substituted form rather than as the previously assigned O-substituted form. These unexpected phenomena are explained well by semiempirical PM3 calculations; the crystal structures of other HOBt-based onium salts can also be predicted by these theoretical calculations. The reaction mechanisms for coupling reactions mediated by these HOBt-based immonium salts and the rearrangement of the benzotriazolyl ester intermediate generated during the coupling reactions were studied by both experimental observations and theoretical calculations. The crystal structures of these benzotriazolyl esters were predicted by PM3 calculations and verified by reported X-ray data.