Pyrrolidide formation as a side reaction during activation of carboxylic acids by phosphonium salt coupling reagents

Pyrrolidide derivatives are observed as unwanted by-products from slow reactions of activated carboxylates with nucleophilic amines, as mediated by phosphonium salt coupling reagents (PyAOP, PyBOP, PyBroP). This side reaction is attributed to the presence of small amounts (e.g., 0.5%, w/w) of pyrrolidine as a contaminant to commercial phosphonium salts, and does not occur when the reagents are crystallized before their use in coupling reactions.