Cleavage of P-O-bonds

Phosphoesters are ubiquitous in biochemistry and serve several functions [5L Genetic information is stored in DNA and RNA. In cellular control mechanisms, phosphorylation of proteins is an important mechanism for regulating protein activities161. Phosphorylation can activate metabolites or change solubility properties. Enzyme-catalyzed formation and cleavage of P-O bonds are central to the cellular energy balance171. Biosynthesis depends heavily on phosphorylated intermediates. 

Finally, heterophosphonium salts are reduced with cleavage of the phosphorus-heteroatom bond optically active aminophosphonium compounds are usefully reduced to phosphines with retention of configuration747. Methyltrineopentoxyphosphonium trifluoromethanesulphonate gave the quantitative formation of dineopentylmethyl phos-phonite, which is indicative of P—O bond cleavage748 (reaction 223)... 

Converging lines of evidence have led to a general acceptance of the monomeric metaphosphate mechanism for the hydrolysis of phosphate monoester monoanions. The pH rate profile for aryl and alkyl phosphate monoester hydrolyses commonly exhibits a rate maximum near pH 4. where the concentration of the monoanion is at a maximum. The proposed mechanism is based on these principal points of evidence (a) a general observation of P-O bond cleavage (b) the entropies of activation for a series of monoester monoanions are all close to zero, which is consistent with a unimolecular rather than a bi-molecular solvolysis where entropies of activation are usually more negative by 20 eu7 (c) the molar product composition (methyl phosphate inorganic phosphate) arising from the solvolysis of the monoester monoanion in a mixed methanol-water solvent usually approximates the molar ratio of methanol ... 

J. L. Chiara, C. Destable, P. Gallego, and J. Marco-Contelles, Cleavage of N—O bonds promoted by samarium diiodide Reduction of free or N-acylated O-alkylhydroxylamines, /. Org. Chem., 61 (1996) 359-360. 

The ditertiary phosphine l,2-bis(diphenylphosphinomethyl)ethene (88) was conveniently prepared in 68% yield from Ph2PNa and 3-chloro-2-chloromethylprop-l-ene,190 whilst (89) (6(P) —23 ppm m.p. 137-138 °C) was synthesized from the bismesylate and Ph2PLi.191 The synthesis of the methoxy-functionalized ditertiary phosphine (90) has recently been described and involves P—C bond cleavage of P(o-OMeC6H4)3 with sodium in ammonia and quenching with 1,2-dichloroethane.192... 

CNDO-MO calculations suggest that the Wittig olefin synthesis proceeds via 1,2-oxaphosphetans, which undergo P—C bond cleavage considerably in advance of P—O bond cleavage. 

In vivo, cleavage of P-0 bonds are performed by enzymes such as phosphatases, phosphodiesterases, phosphohydrolases, nucleases, DNases and RNases (see Section 13.1.1). In vitro, cleavage of a P- O bond is often a trivial synthetic step. Even for an easy step, enzymes attract increasing attention. The enzymatic reactions are preferred when regio- or stereoselectivity is required, and when the substrates are temperature or pH sensitive. Many phosphate analogs have been tested as substrates of enzymes that hydrolyze phosphoryl groups. These analogs are often accepted as substrates for the enzymes, and such reactions could be synthetically valuable. Typical examples are presented in the tables. 

A similar transformation of P—-O bonded compounds at a metal center is seen in the reaction of [PtCl2(dppm)] with aqueous sodium hydroxide to yield [(Ph2MeP) Ph2P(=0) Pt(/Li-0H)2Pt(Ph2MeP) Ph2P(=0) ]. The key step in the reaction is thought to involve nucleophilic attack by hydroxide with cleavage of a P—C bond as shown in Eq. (6). 

The catalytic reaction of the Mn + form of the native bacteriophage k phosphatase and the H67N mutant have been studied with the substrate p-nitrophenyl phosphate using heavy-atom isotope effects and pH-dependent rate studies. The results indicate that the chemical step of P—O bond cleavage is rate-limiting, the first metallophos-phatase for which this has been shown to be the case. The isotope effects are very similar to those measured for reactions of protein-tyrosine phosphatases, indicating that the families of the enzymes share similar dissociative transition states. 

Direct attack of a sterically hindered phosphine at the metal center is unlikely. likely mechanism involves attack on the oxygen atom, possibly at a vacant 7C -orbital on the Mo=0 fragment, and a concerted two-electron transfer to Mo, followed by Mo-O bond cleavage and P-O bond formation. Elimination of OPR3 and rearrangement to the square-pyramidal... 

---