PyBroP | CAS 132705-51-2 | ≥98%

PyBrOP — bromotripyrrolidinophosphonium hexafluorophosphate — is a halogenophosphonium peptide-coupling reagent of the BOP/PyBOP family, carrying bromide in place of the benzotriazol-1-yloxy group of PyBOP. In the presence of a tertiary amine base, it activates carboxylic acids through an acyloxyphosphonium intermediate to highly reactive acylating species, including oxazolone and/or symmetrical-anhydride intermediates, which are rapidly aminolysed. Unlike the benzotriazolyl active ester formed by PyBOP — poorly reactive toward N-methyl amino esters — these intermediates readily acylate hindered, slow-reacting amines, which makes PyBrOP a powerful reagent for the difficult coupling of N-methyl and α,α-dialkyl amino acids. As a phosphonium salt, PyBrOP avoids the N-terminal guanidinylation/end-capping side reaction associated with uronium/aminium reagents such as HBTU and HATU, so excess reagent can be used without blocking the free amine terminus. PyBrOP is supplied as a white to off-white crystalline powder, soluble in common peptide-coupling solvents such as DMF and NMP; store cold and dry.

Common Scientific Applications

• Carboxyl activation: with a tertiary amine base such as DIPEA, PyBrOP activates carboxylic acids to highly reactive acylating species for amide bond formation.
• N-methyl amino-acid coupling: often gives better results than phosphonium/HOBt reagents for the difficult coupling of N-methyl amino acids, where BOP and HOBt-based reagents are inefficient. Little epimerisation is reported for this coupling, although racemisation is not fully suppressed in principle, since the reagent carries no auxiliary nucleophile; a weaker base such as collidine is used for racemisation-sensitive or prolonged couplings.
• α,α-Dialkyl and hindered residues: effective for sterically demanding couplings, including α,α-disubstituted amino acids such as Aib; the most hindered cases are run with added DMAP.
• Advantage over uronium and BOP reagents: unlike HBTU and other uronium/aminium salts it forms no guanidinylated end-capping by-product at the amine, and unlike BOP it generates no HMPA by-product.
• Activation of phenols and hydroxy-heterocycles: beyond peptide coupling, PyBrOP is used in phosphonium-coupling chemistry to activate phenols, enols and tautomerisable hydroxy-heterocycles as O-phosphonium electrophiles for nucleophilic substitution or transition-metal cross-coupling.
• Azine N-oxide activation: PyBrOP activates pyridine and related azine N-oxides for regioselective nucleophilic 2-substitution under mild conditions, providing an N-oxide activation route to substituted azines.

Further Reading

For guidance on selecting between carbodiimides, aminium/uronium salts, phosphonium salts and other reagent classes for amide and peptide bond formation, see NorrChemica's Lab Journal guide: Choosing a Coupling Reagent for Amide and Peptide Bond Formation.