Phosphoramides, protonation

The phosphoramidic chloride (11) has been employed to phosphorylate phenols and alcohols, including carbohydrates.16 Other activity in phosphorylation chemistry has been mostly concentrated in two main areas. In the first of these, Japanese workers have continued their studies on the use of 2-substituted-4-nitrophenyl-phosphoric acids. The 7V-protonated form of the 2-dimethylamino-compound (12 R = Me) is a better phosphorylating agent than the corresponding 2-diethylamino-compound. The reaction of (12) with hydroxy-amines results in selective O-phos-... 

The role of phosphoramidates and phosphazenes as 7V,0-ambident nucleophiles has been considered.79 Thus in the reaction of (EtO)3P=NCOPh with hydrogen chloride it appears that nitrogen rather than oxygen undergoes protonation ... 

Thereafter, Yamamoto reported the first metal-free Bronsted add catalyzed asymmetric protonahon reachons of silyl enol ethers using chiral Bronsted acid 13c in the presence of achiral Bronsted add media (Scheme 5.34) [61]. Importantly, replacement of sulfur and selenium into the N-triflyl phosphoramide increases both reactivihes and enanhoselectivihes for the protonation reaction. 

T0 prepare models of TA, the corresponding cyclic alkylene phosphoric acids cannot be directly polymerized because the presence of acidic protons of the phosphate group makes the ionic polymerization impossible. Thus, cyclic phosphorus compounds with blocked third functions have to be used. These are phosphates., phosphoramidates and phosphites. After polymerization the obtained polymer is converted by deblocking into the polyalkylene phosphate, e.g. polysalt or polyacid form. 

Acid-catalysed solvolysis of N-aryl phosphoramidates is characterised by the negative value of the reaction constant (p = -1.2).These inversed substituent effects illustrate two points discussed before. First, if the N-protonated form repre -sents the reactive intermediate in solvolysis of (2), much stronger dependence of the protonation preequilibrium on the effect of N-substitution is expected. Secondly, if the resonance effects are poorly transmitted to the P atom through the -NH- bridge, structural variation in the N-aryl substituent should have weak effect upon the ability of phosphorus to accept a nucleophile. 

Hydrolysis of phosphoramidic acid (NH2-P03H2) has been studied " in the acidity range pH 2-8, in aqueous solution and in some mixed solvents. Reaction appears to occur through the mono-anion, the neutral molecule and through a protonated species (rate equation (1) and Table 13). 

The novel dinucleotide phosphoramidate (78) has been obtained from the phosphoramidite dimer (79) upon reaction with methoxymethylene ethanolamine in the presence of tetrazole, followed by iodine oxidation in the presence of the same amine. Since the two amino substituents are identical it is envisaged that in aqueous solution, rapid proton transfer between the two phosphoramido moieties will render the molecule achiral at phosphorus. 

Monoanions of A -substituted phosphoramidic acids (30) show an interesting solvolytic rate dependence on the basicity of the amine. For amines of pK, 8.0 the rate is independent of basicity, and for these cases it was suggested that the fraction of AT-protonated species became rate limiting. From a comparison of the Bronsted j8 values associated with the entering and leaving groups it was proposed that quinquecovalent intermediates are not involved in the solvolysis of (30) or in the solvolysis... 

The gas-phase protonation reactions of a number of phosphine oxides and phospho-ramides have also been studied. In these instances protonation occurs at oxygen to form stable quasiphosphonium ions. Oxygen protonation is thermodynamically favoured over nitrogen protonation for phosphoramides. It has been suggested that this is due to the fact that the quasiphosphonium ion thus formed can be stabilized via n back-donation to the d orbitals of phosphorus. 

Polyammonium macrocycles are successful mimics of a variety of phosphoryl transfer enzymes. These simple compounds are noted for their capability to bind to a number of anions, including the simple phosphate and polyphosphates as well as more complex nucleotides. "Large" polyazacycloalkanes in their protonated forms have been found to exhibit ATP binding as well as ATPase activity. A general accepted mechanism for ATP hydrolysis catalyzed by polyaza macrocycles involve the formation of a ATP-receptor complex, held by electrostatic interaction and hydrogen bonds, followed by the formation of a covalent intermediate macrocyclic-phosphoramidate species, which is subsequently hydrolyzed (see Figure 2)P... 

One of the central amines of the bridges is not protonated at neutral pH and performs the nucleophilic attack to the terminal phosphorous atom (P ) of ATP to form the phosphoramidate transient species (steps A and B in Figure 19). The electrostatic and hydrogen-bonding interactions of the phosphate chain of the nucleotide with the... 

Presumably, this transformation proceeds via initial protonation of divinylketone 49 by phosphoramide 50, resulting in the formation of adduct 53, which consists of a cyclopentadienyl cation and a phosphoramide anion. Subsequent conrotatory 4n electrocyclization leads to an oxyal-lyl cation 54 that, through the elimination of a proton, forms 55. Subsequent protonation results in the formation of cyclopentenone 51 or 52, regenerating Br0nsted acid catalyst 50 (Figure 8). 

Denmark has described several chiral bis-phosphoramides as Lewis base activators of weak Lewis acid SiCL and demonstrated their ability to mediate an enantioselective Passerini-type reaction. Catalytic bis-phosphoramide 36 and stoichiometric SiCU, in the presence of a proton scavenger (Htinig s base), promoted the formation of a-hydroxyamides with remarkably good enantioselectivity and yield. A variety of aromatic and unsaturated aldehydes and aryl, alkyl, and functionalized alkyl isocyanides proved to be useful and effective starting materials. High yields of Passerini products were attributed to the production of imidoyl chloride 37, which reduced the prevalence of the nitrilium intermediate and prevented the addition of a second equivalent of isonitrile. 

---