P=N bond, formation

Sekine has reported the synthesis and anticancer activity of Phosmidosine (18) and its demethylated parent (19). The Phosmidosines were obtained by reaction of an appropriately protected 8-oxoadenosine 5 -0-phosphoramidite and N-protected prolinamide in the presence of 5-(3,5-dinitrophenyl)-l//-tetrazole, followed by in situ oxidation with t-BuOOH to form the iV-acyl phosphoramidate linkage. These syntheses required extensive work with regard to the choice of protecting groups on the adenine moiety, as this was crucial for successful P-N bond formation. ... 

The reactions shown in Eqs. 3.43-3.44 are facihtated by two factors. 1) The reactivity of the N-Si and P-Cl bonds towards each other to eliminate Me3SiCl. 2) The spontaneity of the P-N bond formation. The side product Me3SiCl is quite volatile and is therefore easily removed. 

The P-N bond formation between an amide, of the type RC(0)NH2, and a phosphorus(V) site may be performed via a two-stages reaction, which is shown for PCI5 in Scheme 5,... 

One of the most widely used methods for the formation of phosphate esters involves the conversion of a P-N bond of a phosphorus(III) compound to a P-O bond by ROH, catalyzed by l//-tetrazole, followed by oxidation to the phosphorus(V) derivative ... 

As mentioned, stabilization of neutral hexacoordinated phosphorus via nitrogen donation is possible and this topic has been widely studied in the past few years. As P-N bonds are weaker and longer than those of P-C and P-0, chemists have essentially relied on chelation to enforce their formation. Most structures involve five- and six-membered chelating rings and the compounds that have been reported are described in Schemes 7,8, and 9 and Figs. 7 and 8. 

The reaction temperature varies between -40 and 110 °C, depending on the reactivity of both counterparts, amine and chlorophosphane. As usual, aliphatic amino groups react faster than aromatic and heteroaromatic ones due to their greater nucleophilic strength. These differences in reactivity allow chemose-lective phosphinous amide formation, as that represented in Scheme 2 where the P-N bond is formed exclusively at the aliphatic NH2 group of 2 but not at the heteroaromatic NH2, whose lone pair is extensively delocalized in the electron-withdrawing purine ring [35]. 

Formation of the P—N bond has been observed when the cross-coupling of dialkylphosphites (59) with amines (60) proceeds by an iodo cation [I]+-promoted electrooxidation, affording N-substituted dialkylphosphor-amidates (61) (Scheme 22) [76]. Lack of alkali iodide in the electrolysis media results in the formation of only a trace of (61), indicating that the iodide plays an important role in the P—N bond-forming reaction. In contrast, usage of sodium bromide or sodium chloride brings about inferior results since the current drops to zero before the crosscoupling reaction is completed. 

J0rgensen [111] and Vicario [112] independently described the conjugate addition of both triazole and tetrazole based nucleophiles to a,P-unsaturated aldehyde substrates as an alternative method for C-N bond formation. These reactions were catalysed by the diarylprolinol and imidazolidinone scaffolds with equal efficiency showing the complementarity and efficacy of both these catalyst architectures. In addition, Jprgensen has also shown succinimide to be an effective Michael donor (see Sect. 2.3.5 Scheme 49 for further details) [113]. 

The P=N bond of amino(imino)thioxophosphorane 177 is readily cyclopropa-nated even at 0 °C, with formation of phosphaaziridine 178. An intermediate [3 + 2]... 

Bis(trifluoromethyl)-5(2//)-oxazolone undergoes decarboxylation on treatment with trimethyl phosphite. The resulting 1,3-dipole may be trapped by methyl propio-late [171]. The initial P-C bond formation is favored because the alternative mode of reaction would form a weak P-N bond. This counter-Michael addition also generates an a-d-ard system which becomes fragmentable. 

Iodide is used as catalyst for the indirect anodic formation of the P—N bond to generate A-substituted dialkylphosphoramidates from phosphites (Eq. (57) Table 4, No. 36)... 

RGURE 13-5 Hydrolysis of phosphocreatine. Breakage of the P—N bond in phosphocreatine produces creatine, which is stabilized by formation of a resonance hybrid. The other product, Pi, is also resonance stabilized. 

The reaction of (CH3XCF3)3PN(CH3)2 with CS2 proceeds with CS2 insertion into the P-N bond and formation of the (CH3XCF3)3F(Me2Dtc) compound (S90). Very little is known about the chemistry of the xanthate or dithioacid complexes of the Group V elements. The P(EtXant)3 has been reported (410). The IR spectrum of this molecule and those of the corresponding As(III) and Sb(III) compounds show a monotonic decrease of the C—O vibration around 1200 cm 1 (by 7 cm-1 intervals) from P to Bi (635). 

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