Phosphines reaction with azides

Diarylphosphinic and diarylphosphoric azides are rapidly hydrolysed by water to diarylphosphinic and diarylphosphoric acids, respectively. Monophosphazenes are obtained by reaction with phosphines (7.225). Methyl phosphonic diazide (7.223c) can be obtained by reacting methylphosphonic dichloride with sodium azide in pyridine (7.226), while phosphoryl triazide is obtainable with... 

The nucleophilic displacement reactions with azide, primary amines, thiols and carboxylatc salts arc reported to be highly efficient giving high (>95%) yields of the displacement product (Table 9.25). The latter two reactions are carried out in the presence of a base (DBU, DABCO). Radical-induced reduction with tin hydrides is quantitative. The displacement reaction with phenolates,61j phosphines,6M and potassium phthalimide608 gives elimination of HBr as a side reaction. 

A similar microwave-assisted cyclization in the presence of ammonium acetate of an a-ketoamide, obtained by acylation of an a-aminoketone, was recently described for the synthesis of the antifungal agent Nortopsedin D [46]. The problem of the instabiUty of the a-amino ketones was successfully resolved by in situ acylation of the amine derived from Staudinger reaction of the azide 50 with a phosphine (Scheme 16). This ketoamide was... 

Hydroxymethyl phosphines are susceptible to oxidation to form the phosphine oxide derivative. Therefore, avoid excess oxygen, oxidizing agents, or azide compounds, which react with phosphines in the Staudinger reaction (Chapter 17, Section 5). In addition, metallic surfaces can be modified via the phosphine group to result in hydroxymethyl group substitutions. 

Early in the last century, the Nobel Prize winning chemist Hermann Staudinger discovered a reaction between phosphines and azides, which became known as the Staudinger reaction (Staudinger and Meyer, 1919). Triphenylphosphine reacts with azides to form an intermediate iminophosphorane with the release of nitrogen gas. This intermediate quickly breaks down in aqueous environments to yield triphenylphosphine oxide and a primary amine (Figure 17.17). 

The methods used for in vivo incorporation of azido-monomers and performing a labeling reaction with live cells are relatively simple. The following protocol is based on the methods of Saxon and Bertozzi (2000), which uses acetylated azidoacetylmannosamine as the azido-monomer source and a biotin-PEG-phosphine compound to biotinylate cell surface glycoproteins at the specific azide-sialic acid incorporation sites (Figure 17.19). 

Figure 18.11 NHS-PEG4-azide can be used to modify an amine-containing molecule to create an amide derivative terminating in azido groups. The azide modifications then can be used in a click chemistry reaction that forms a triazole linkage with an alkyne-containing molecule. Alternatively, the azide derivative can be used in a Staudinger ligation reaction with a phosphine derivative, which results in an amide bond linkage.

The fact that tetrazolo[l,5- ]pyridine reacts with phosphines - via ring opening to the valence bond isomer azide -to give a phosphorane has been long recognized. Some novel applications of this transformation have been published during the recent period. The fused tetrazoles subjected to this reaction, the resulting phosphoranes, and the literature sources are summarized in Table 4. 

Addition reactions of silylphosphines to imines have been reported, 4 as illustrated for diethyl(trimethylsilyl)phosphine (70). Organic azides react with germylphosphines by an insertion pathway,65 as shown for various phenyl(trimethylgermyl)phosphines (71). The initial products (72) isomerize to phosphine imines on heating.66... 

A study of the kinetics and products of the thermolysis of a series of diaryl-phosphinic azides has been reported.119 Diethyl 1-diazomethylphosphonates undergo an aldol-type reaction with aldehydes to give l-diazo-2-hydroxyalkylphosphonates (152).120 Acidification of the diazophosphonates (153) possessing a chiral phosphorus centre yields mixtures of diastereoisomers (154) and epimers at C. For given R1 and R2, the reaction becomes increasingly stereoselective for X= OAc < Cl < OTs. It may be argued that protonation of (153) will yield a mixture of diastereoisomeric di-... 

Routes to phosphazenes involving the reaction of phosphines with carbon tetrachloride in the presence of amines have been reviewed44 and it has been shown45 that this type of reaction does not occurwithdiphosphines.lt was, however, successful with a phosphonite and tosylamine (Scheme 3).46 The same product was also obtained with tosyl azide. 

Diphenyl phosphorszldate can be replaced with diethyl phosphorazidate in the above procedure. Use of other azides such as p-toluenesulfonyl azide, p-methoxybenzyloxycarbonyl azide, diphenylphosphinic azide, or diphenylthio-phosphinic azide is less satisfactory. No reaction occurs when trimethylsilyl azide, dimethylthiophosphinic azide, or alkaline azides are used, while decomposition of formed trimethylsilyldiazomethane seems to occur when... 

The sequence shown in Scheme 11 was more effective if the isothiocyanate was premixed with the azide, rather than added after the phosphine. Aza-Wittig reagents can undergo exchange reactions with carbodiimides ... 

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