Diphenylphosphinic mixed anhydrides

Peptide synthesis. Diphenylphosphinic mixed anhydrides, CBZ—NH-CHRCOOPOfCsHsla, have been used to activate amino acids for formation of peptide bonds. 

Diphenylphosphinic mixed anhydrides have been utilized to form peptide bonds. Peptides are easier to isolate by this method than by employing 1,3-Dicyclohexylcarbodiimide. These anhydrides are the method of choice for the formation of amides of 2-alkenoic acids (eq 1 ). Carbodiimide and acyl carbonate methods proved to be inferior. Primary amines result in better yields than secondary amines. This activation protocol can be employed to form thiol esters (eq 2) p-Amino acids are readily converted to p-lactams with chlorodiphenylphosphine oxide (eq 3). Secondary amines work best. This activation protocol has been utilized to convert acids to amines via a Curtius rearrangement. Phenols have been generated from diene acids, presumably via base-induced elimination of diphenylphosphinic acid from the mixed anhydrides to form ketenes which spontaneously cyclize. Acids have been converted to ketones via activation followed by reaction with organometallic reagents (eq 4)."... 

A New and Efficient Derivative of Pentafluoro-phenol Pentafluorophenol has found many applications in both solution and solid phase peptide syntheses. Diphenylphosphinic mixed anhydrides are also well known in peptide chemistry. A new and efficient reagent has been prepared from these precursors pentafluorophenyl diphenylphosphinate (FDPP 6) which can be used directly as a coupling reagent without side reactions. FDPP is prepared from mixing equimolar amounts of Diphenylphosphinic Chloride, pentafluorophenol (1), and Imidazole in CH2CI2 at room temperature (eq 3). ... 

The mixed anhydrides of diphenylphosphinous acid and heavily substituted alkenoic acids displace one PPh3 ligand from [RhCl(PPh3)3] to form a complex where the anhydride is coordinated through phosphorus. If these products are treated with thaUium(I) or silver(I) salts, the anhydride coordinates additionally through the carbonyl oxygen and the chloro ligand is displaced. 

Kende has demonstrated that the mixed anhydride from carboxylic acids and diphenylphosphinic chloride would acylate Grignard reagents to afford ketones in moderate to good yield. Tertiary carbinols were not observed unless excess Grignard reagent was added. The intermediate anhydrides were generally isolated and made free of triethylamine hydrochloride before addition of the nucleophile. The reaction shown in equation (52) gave improved yields over the simple addition of methyllithium to the carboxylic acid. ... 

Bernasconi, S. Comini, A. Corbella, A. Gariboldi, M. S., Activation of 2-Alkenoic Acids as Mixed Anhydrides with Diphenylphosphinic Acid for the Formation of Carboxamides. Synthesis 1980, 385. 

Amide- and Peptide-bond Fonnation.-Diphenylphosphinic chloride[Ph2P(0)Cl] is reported to be the reagent of choice for the direct mixed anhydride -type... 

Acid Activation. Chlorodiphenylphosphine oxide has been utilized for the activation of acids via in situ formation of the diphenylphosphinic (DPP) mixed anhydrides. These anhydrides are superior to carbon-based mixed anhydrides because they do not suffer from disproportionation to symmetrical anhydrides. Also,... 

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