Thiophosphates, oxygen chiral, configurational

F. Configurational Analysis of Oxygen Chiral Thiophosphate Monoesters. 112... 

Methods for Syntheses and Configurational Analyses of Oxygen Chiral Phosphate and Thiophosphate Esters... 

Given the inability to implicate free metaphosphate anion in these studies, Cullis and Rous examined the stereochemical consequence of an alcoholysis reaction (55). When [ 0, 0, 0]P -0-ethyl-P -thiopyrophosphate is treated with methyl iodide in ethanol, the S-methyl derivative rapidly decomposes to form 0-ethyl-S-methyl thiophosphate and ethyl [ 0, 0, 0]phosphate this reaction is thought to proceed via a mechanism involving metaphosphate anion, but, as would be expected on the basis of the observations by Knowles, the stereochemical consequence is nearly quantitative inversion of configuration. In dichloromethane solution, the decomposition of the oxygen chiral substrate yields ethyl [ 0, 0, 0]phosphate that has suffered extensive racemization (approximately 70%). This stereochemical result can be rationalized by the intermediacy of free metaphosphate anion in the absence of nucleophile acceptors. 

Two new techniques have been introduced that are especially useful when no stable intermediate can be isolated. Thiophosphates or phosphates with isotopically labeled oxygen atoms are chiral and can thus be us to probe the stereochemistry of the phosphoryl transfer event (Eckstein, 1979 Knowles, 1980). One in-line displacement leads to an inversion of configuration on the phosphorus atom. If one covalent intermediate is involved, retention of configuration should result from the double-displacement reaction. Using this technique, the existence of the acetate kinase acyl phosphate intermediate has been challenged (Knowles, 1980), whereas others (Spector, 1980) have interpreted the same results as being indicative of a triple-displacement mechanism. 

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