Phosphinic carboxylic mixed anhydrides

With these considerations in mind it was decided to investigate phosphinic-carboxylic mixed anhydrides in peptide methodology. .Mechanistic consideration of the reactants (2) and (3) and products shown above would suggest regiospecific nucleophilic attack by the amine component due to the formation of an amide bond with concomitant generation of a new P-0 bond.As in the study of phosophinamidates discussed above,a series of phosphinic acids were selected for preparation of the mixed anhydrides (2) because of the intimate steric and electronic... 

A comparison of the dimethyl derivatives of phosphinic chloride (MeaPOCl) and phosphochloridate [(MeO)2POCl] indicated that the latter was less reactive toward oxygen nucleophiles than dimethylphosphinic chloride, which suggests that phosphinic chloride derivatives should react with carboxylate anions to form mixed anhydrides more rapidly than phosphoro-chloridates [119]. Fast formation of mixed anhydrides is an important consideration in coupling reactions. A further advantage of the use of phosphinic carboxylic mixed anhydrides is the elimination of the potential substitution... 

The phosphinic isocyanates (116) and isothiocyanates (117) react with oxygen, nitrogen, and phosphorus nucleophiles by attack at carbon rather than phosphorus. Phenyl phosphonodichloridate has been recommended as a useful reagent for the activation (presumably by mixed anhydride formation) of carboxylic acids for conversion to amides and hydrazides. ... 

Mixed anhydrides between phosphoric, phosphonic, and phosphinic acids on one side and sulfonic or carboxylic acids on the other are conveniently prepared via phosphor-azolides.[150]... 

FIGURE 8.21 Proposed mechanism for the BOP-Cl-mediated reaction of a carboxylate anion with a methylamino group. Formation of a mixed anhydride is followed by aminolysis that is facilitated by anchimeric assistance provided by the oxygen atom of the ring carbonyl.101 (van der Auwera Anteunis, 1987). BOP-C1 = fcw(2-oxo-3-oxazolidino)phosphinic chloride. 

Other less commonly used coupling reagents include EEDQ (formation of mixed carboxylic carbonic anhydrides), Bop-Cl (formation of mixed carboxylic phosphinic anhydrides [52,53]), DPPA (formation of acyl azides), DECP (formation of acyl cyanides), MSNT (formation of mixed carboxylic sulfonic anhydrides), and benzisoxazo-lium salts (generation of phenyl esters [54]). 

Derivatives of phosphinic acids have been used by Ramage and coworkers [116,117] in both solution and solid-phase approaches. The mechanism of the coupling was postulated to involve a carboxylic-iphosphinic mixed anhydride [116]. An advantage to these mixed anhydride intermediates in comparison with the biscarboxylic derivatives is regioselectivity. Bis-... 

Other organo-phosphorous reagents are based on the mixed carboxylic-phosphoric or phosphinic anhydrides. Initially used to convert carboxylic acids into acyl azides, DPPA 12 has been introduced as a one-pot coupling reagent for peptide chemistry (32), and it was adapted later to solid-phase chemistry (81). The driving force of these reactions is the formation of the phosphoric or phosphinic acids and their salts. Later DPP-Cl 49 (82) and FDPP 50 were introduced. FDPP 50 has been used successfully in macro cyclizations (83). Examples of... 

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