Phosphonothioates configuration

Finally, non-racemic phosphorothioic and phosphonothioic acids 98 were obtained via a PTE-catalysed stereoselective hydrolysis of the prochiral substrates 97 (Equation 48). ° The absolute configurations of the thioacids 98 depended on whether native PTE or its mutants were used. 

Oxidation of the cyclic selenophosphate ester (47) with both dinitrogen tetroxide or nitric acid appears to be very stereoselective, proceeding with retention of configuration, and thus contrasts with the behaviour of similar acyclic phosphorothioates and phosphonothioates with these reagents. Heterocyclic A -oxides and the 1-aminopyridine derivative (48)... 

Recognition that the formation of a phosphonothioic chloride from the acid occurs with inversion of configuration stems partly from a study of the alkaline hydrolysis of the chloride (with inversion), but primarily on the basis of the formation and structures of the... 

As indicated in Section III. A. 1, the evidence for configurational inversion during the formation of phosphonothioic halides is based, at least partly, on the belief that the reverse hydrolysis also occurs with inversion. Mikotajczyk made a special study of the hydrolysis of optically active O-ethyl ethylphosphonochloridothioate. In 2 m KOH-dioxane at room temperature, the (-)-chloride is hydrolysed, with high yield, to the (5)-(-)-acid the acid was found to be at least 97.5% optically pure, which suggested that the hydrolysis was 97% stereospecific, the slight loss in stereospecificity being the result of racemization caused by the presence of chloride anions. Thus, the stepwise conversion of the acid into chloride and back into the acid produced acid of configuration identical with that with which the cycle started, probably by two inversion steps. 

Detailed studies on the use of H2O2 in the phosphonothioic(and selenoic) and phos-phinothioic (and selenoic) acid series (in addition to experiments with derivatives of phos-phorothioic and phosphoroselenoic acids) have been carried out, also by Polish workers. It appears that the stereochemical course of oxidative desulphurization (or deselenation) is the same for all three series of esters (retention of configuration) but differs from the reaction for phosphine sulphides (net inversion), whilst the course of the reaction for phosphine... 

Earlier, attention was drawn to a novel application of the oxidative desulphurization reaction which occurs between sulphoxides and phosphonothioic acid esters. When 1 mol of the thio acid is allowed to remain in contact with 2 mol of a racemic methyl alkyl sulphoxide for 2 weeks at room temperature, the unreacted sulphoxide is found to be optically active, a result which represents asymmetric deoxygenation of the sulphoxide. The chemical course of the reaction is consistent with Scheme 31. Since the appearance of the initial results, corrections have been made to the configurations of the phosphorus-containing substrates, and hence the stereochemical details and mechanistic arguments require reappraisal neverthless, the fact remains that (-t-)-sulphoxides are obtained by the use of the ( S)-(-)-acids, R (R O)P(S)OH , a feature which can be used to determine the chirality of other like acids. Dialkyl and alkyl aryl sulphoxides are also known to form diastereoisomeric complexes with (5)-(-)-/er butylphenylphosphinothioic acid, distinguishable by their NMR spectra, and through such complexation it is possible to assess the enantiomeric composition of the sulphoxide " ... 

In other cases, the course of a simple interaction can be complex, as in, for example, reactions between methoxide and phosphonothioates based an halomethyl phospho-nothioic acids. Inch s group " examined the behaviour of (7 )-(+)-0-ethyl S-methyl (dichloromethyl)phosphonothioate (139) this could be dechlorinated with H2-Pd/C in a stepwise fashion, and so eventually correlated with the methylphosphonothioate diester of identical configuration at phosphorus furthermore, chlorination of 139 with BuLi-CCl4... 

Phosphoras(ni), phosphothio-, and phosphoseleno-compounds are oxidized by Oxone in THF/MeOH to produce phosphono-, phosphonothio-, and phosphonoseleno- compounds, respectively, with predominant retention of configuration at phosphorus (eq 75). Thioalkyl or amino groups attached to phosphorus are unaffected. 

In contradistinction to nucleoside H-phosphouate mouoesters, the corresponding H-phosphonothioates are chiral at the phosphorus center. Since the stereochemistry at the phosphorus center can be controlled [200,201] during oxidation of nucleoside H-phosphonothioates, one may obtain phosphate analogues with the same or with iuverted configuration. 

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