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Pentafluorophenol is mostly used to prepare pentafluorophenyl active esters for peptide synthesis, which can promote the formation of peptide bonds, and the reaction is efficient and has no side reactions. Kinetic studies show that, compared to other pentafluorophenyl esters, the relative rate in terms of coupling speed is OPFP>>OPCP>ONp, corresponding to 111:3.4:1, where PFP=pentafluorophenyl, PCP=pentachlorophenyl , Np=nitrobenzene, a large coupling rate is beneficial to reduce or eliminate adverse reactions. Some applications of pentafluorophenol and its derivatives in organic synthesis are introduced below.
Coupling agent for carbon-nitrogen bond formation reaction, peptide synthesis
Fmoc can protect amino groups in peptide synthesis. The problem associated with this group is that the Fmoc group is cleaved by the free amino moiety and acylated, resulting in bisacylation. The main way to avoid this now is to use the Fmoc group in conjunction with highly reactive pentafluorophenyl esters (1), which greatly increases the coupling rate compared to adverse reactions.
Pentafluorophenol derivative pentafluorophenyldiphenylphosphinate (FDPP) can also be used as a coupling reagent without side reactions. FDPP is prepared by mixing equimolar amounts of diphenylphosphonyl chloride, pentafluorophenol and imidazole in dichloromethane (2). FDPP has been used in solid and solution peptide synthesis by mixing FDPP, tertiary amine, amine component and carboxylic acid component in DMF solution to react (3). Analysis shows that its racemization rate is the lowest among commonly used coupling reagents.
A commonly used strategy in peptide synthesis involves a three-step process of protection of the α-amino group, activation of the carboxyl group as a pentafluorophenyl ester, and subsequent coupling with an amino acid. Pentafluorophenyl trifluoroacetate (PFP-O-TFA) was used to simultaneously protect and activate amino acids (4).
Reactions used to form carbon-carbon bonds
The reaction of trimethylaluminum and triethylaluminum with chiral acetal is not stereoselective, and pentafluorophenol is added to the organometallic reagent to form a complex (5) with improved reactivity and selectivity.
for the reduction reaction
Reduction of the corresponding pentafluorophenol ester with sodium borohydride in THF under mild conditions gave the primary alcohol and the chiral protected 2-aminoalcohol (6). The method is fast and compatible with various functional groups such as halides, esters, nitro, benzyl ethers, and thioethers, as well as common N-protecting groups such as CBZ, Boc, and Fmoc.
Diethylaluminum fluoride and pentafluorophenol in a ratio of 1:2 generate an aluminum reagent for the diastereoselective reductive cleavage of chiral acetals to give β-alkoxyketones (7).
For sulfonamide formation reactions
Sulfonamides are usually prepared by reacting sulfonyl chlorides with amines. Sulfonyl chlorides can be difficult to handle and purify, and can easily hydrolyze back to sulfonic acid, limiting their storage properties. As a substitute for sulfonyl chloride, pentafluorophenylsulfonate has better crystal properties and is not easily hydrolyzed. It can be prepared from sulfonyl chloride (8) or directly from the sulfonate (9).
Pentafluorophenol and its derivatives have been widely used in peptide synthesis, and can also be used in the formation of carbon-carbon bonds, reduction reactions, and reactions to form sulfonamides, and are important chemical intermediates. Haofan Bio can provide you with high-quality PFP-OH pentafluorophenol (771-61-9), pentafluorophenol formate (111333-97-2), pentafluorophenol acrylate (71195-85-2), Biotin-PFP pentafluorophenol biotin ester (120550-35-8), pentafluorophenyl trifluoroacetate (14533-84-7), welcome to inquire!