Phosphorazidic acid

DIPHENYL PHOSPHORAZIDATE (Phosphorazidic acid, diphenyl ester)... 

Phosphonic acid, (phthalimidomethyl)-, diethyl ester, 65, 119 Phosphorazidic acid, diphenyl ester (26386-88-9), 68,1 Phosphoric triamide, hexamethyl- (680-31-9), 66, 51, 94 Phosphorodichloridic acid, 2-chloroethyl ester, 65, 68 Phosphorous acid, triethyl ester, 65, 108.119 Phosphorus oxychloride, 66,173, 176 67,1 68, 41,162 Phosphorus tribromide (7789-60-8), 67, 210 Phthalimide, N-(bromoethyl)-, 65, 119 Phthalimide, N-(hydroxymethyl)-, 65,119 Pig liver esterase, 69, 20... 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

The vinyl azide method has been employed to prepare heterospirocyclic 3-amino-277-azirines, which represent useful synthons for heterocyclic amino acids <1997HCA1528>. Diphenyl phosphorazidate (DPPA) was used as the azide... 

Ikota N, Shioiri T, Yamada S, Tachibana S. Amino acids and peptides. XXXI. Phosphorus in organic synthesis. XVIII. Synthesis of porcine motilin by the solid-phase method us- 41. ing diphenyl phosphorazidate (DPPA) and diethyl phosphoro-cyanidate (DEPC). Chem. Pharm. Bull. 1980 28 3347-5336. 

In a direct route from carboxylic acids to acyl azides diphenyl phosphorazidate is used probably the reaction passes through a cyclic transition state (Scheme 41). With aromatic and heteroaromatic educts, yields as high as 75% may be obtained. If aliphatic acids are treated under the same conditions, the corresponding azides are, however, immediately transformed into urethanes via isocyanates. Aroyl azides can also be obtained in excellent yields by reaction of carboxylic acids with NaNa and phenyl di-chlorophosphate in the presence of tetrabutylammonium bromide or pyridine (Scheme 41). ... 

One of the most useful variants of the Curtius reaction is the reaction of carboxylic acids with diphenyl phosphorazidate (DPPA (Ph0)2P(0)N3) in the presence of base, such as triethylamine (equation 2). " ... 

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