Infrared Investigation of Acid Activation by PyBOP in Polystyrene/Divinylbenzene Supported Solid-Phase Synthesis

Abstract

The infrared technology presented in this paper provides a mechanism for the detailed study of PyBOP [(1H-benzotriazole-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate] ester activation in a solid-phase supported chemical system. Prior to this work, formation of the alkoxyphosphonium salt had been postulated as a necessary reactive intermediate for formation of the triazole-activated ester in the PyBOP activation process; however, observation of the alkoxyphosphonium salt has not been reported at room temperature. The present work not only confirms the presence of the salt but further demonstrates it to be the primary activated species for couplings performed on the solid phase at room temperature. More important than the specific identification of the PyBOP activation method is the general introduction of a set of infrared analytical tools for analysis of solid-phase reaction mechanisms and kinetics.