[133894-48-1] · C12H24ClF6N3P2 · (421)
(reagent for carboxylic acid activation, coupling agent in peptide synthesis)
Alternate Name: PyCloP.
Physical Data: mp 150-151 °C.1
Solubility: soluble in CH2Cl2, CHCl3, DMF, DMSO, NMP, acetone.
Form Supplied in: colorless crystals.
Analysis of Reagent Purity: 31P NMR, HPLC.
Preparative Methods: addition of chlorine to a diethyl ether solution of tripyrrolidinophosphine, then addition of KPF6 in water.2 Addition of tripyrrolidinophosphine oxide to a DCM solution of phosphoryl trichloride, then addition of KPF6 in water.1-3
Purification: recrystallization (CH2Cl2/Et2O).
Handling, Storage, and Precautions: the toxicological properties of this reagent have not been investigated and no special instructions for storage and handling are mentioned in the literature.
Treatment of a carboxylic acid with PyCloP in the presence of base produces the unstable acylphosphonium intermediate. This species directly reacts with a nucleophile or decomposes into a different activated form (e.g. carboxylic anhydride). This reagent gives results that are comparable to those obtained with PyBroP (bromotripyrrolidinophosphonium hexafluorophosphate).1
Compared with hydroxybenzotriazol-based activators like BOP, PyBOP, HBTU, or DCC/HOBT, which produce moderately activated benzotriazolyl esters from carboxylic acids, PyCloP is highly recommended for coupling N-methylated amino acids, as illustrated by the difficult coupling of NMeVal (eq
Using different phosphorus reagents for activation of a monothiocarboxylic acid, the observed oxygen/sulfur selectivities correlate with the hardness/softness of the reaction center. Compared with the soft leaving bromine atom in PyBroP (S selective) or the hard oxygen atom in PyBOP (O selective), the PyCloP is borderline in O/S (25:47) selectivity (eq
PyBOP, a related phosphonium coupling reagent for peptide synthesis, has been prepared from PyCloP,2 and several analogs of PyBOP have also been prepared as reagents for thioacylation of monothiocarboxylic acid 3 (eq
PyBroP, bromotripyrrolidinophosphonium hexafluorophosphate;
CNRS-UPR9023, Montpellier, France