Acyloxyphosphonium salts

Similarly, triphenylphosphine dichloride (TPPCI2) can activate aromatic carboxylic acids in pyridine through the formation of acyloxyphosphonium salts (Scheme 2.30).313 A side reaction between tire intermediate acyloxyphosphonium species and a second carboxyl endgroup leading to the formation of anhydrides has been reported.313 This chain-limiting reaction decreases tire molar mass, while the presence of anhydride linkages in tire chains adversely affects the thermal and hydrolytic stability of the final polyester. 

Acyclic dienes, 433 Acylation, Friedel-Crafts, 329 A-Acylimidazoles, 78 Acyloxyphosphonium salts, 79 Adamantane, 354... 

Triaminophosphonium salts, unlike carbodiimides, only react with carboxylic acids under basic conditions, thereby yielding acyloxyphosphonium salts (Figure 13.5). Depending on the counterion X and on the precise reaction conditions, the acyloxyphosphonium salt can either acylate the amine directly or be transformed into the symmetric anhydride or an active ester [2,82], which then acylates the amine. At low... 

This reagent, benzotriazol-l-yl-oxytripyrrolidinophosphonium hexafluorophosphate (14, PyBOP)P l (Scheme 4), was designed in order to avoid the formation of toxic HMPA during acylation. As with BOP, it is assumed that the first step is the carboxylic acid activation which involves formation of an acyloxyphosphonium salt.P This initial salt is then attacked by the benzotriazolyloxy anion to form the benzotriazolyl active ester which then reacts with the amino component. PyBOP can easily replace the BOP reagent and is especially suitable for solid-phase peptide synthesis. It is soluble in a wide range of solvents such as DMF, di-chloromethane, THF, and NMP. PyBOP is more useful in peptide synthesis on solid support than in solution. The byproduct, tris(pyrrolidino)phosphine oxide is partially water-soluble and is easily removed by washing. PyBOP is used under the same experimental conditions as BOP. Note that PyBOP is a white, crystalline and non-hygroscopic solid. It can be kept as a solid, but solutions of PyBOP cannot be stored for more than 24 hours. 

Polymer-supported triphenylphosphine ditriflate (37) has been prepared by treatment of polymer bound (polystyrene-2% divinylbenzene copolymer resin) triphenylphosphine oxide (36) with triflic anhydride in dichloromethane, the structure being confirmed by gel-phase 31P NMR [54, 55] (Scheme 7.12). This reagent is effective in various dehydration reactions such as ester (from primary and secondary alcohols) and amide formation in the presence of diisopropylethylamine as base, the polymer-supported triphenylphosphine oxide being recovered after the coupling reaction and reused. Interestingly, with amide formation, the reactive acyloxyphosphonium salt was preformed by addition of the carboxylic acid to 37 prior to addition of the corresponding amine. This order of addition ensured that the amine did not react competitively with 37 to form the unreactive polymer-sup-ported aminophosphonium triflate. 

Ylides have been implicated in the formation of acylcyclopropanes from the y-acyloxyphosphonium salts (93) as shown, and in the very rapid reaction of the tributylphosphine-carbon disulphide adduct (94) with... 

Polypeptide synthesis. This reagent has been used for polypeptide synthesis, possibly by the mechanism formulated in scheme 1, although there is no conclusive evidence of the involvement of an acyloxyphosphonium salt. This synthesis has the advantage that the coproduct HMPT is water-soluble and easily... 

The biomimetic phosphoric acid mixed anhydride concept stimulated further search for activating reagents that produce derivatives of acylamino acids (and peptides) in more simple ways than the ones mentioned earlier in the Chapter (on p. 78) An interesting attempt in this direction is the so called Bates reagent [47] which on reaction with carboxylic acids yields acyloxyphosphonium salts. 

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