Acid-catalysed methanolysis of methylphenylphosphinic amides: dependence of the stereochemistry on the nucleophilicity of the departing amine and the acidity of the reaction medium

Abstract

(+)-(S)-Methylphenylphosphinic amide (4) has been prepared and converted, by the reaction of its potassium salt with p-fluoronitrobenzene, into (+)-(S)-(N-p-nitrophenyl) methyl phenylphosphinic amide (7). In methanolic 0.15M-hydrogen chloride these amides, as well as (–)-(S)-(N-phenyl)methylphenylphosphinic amide (6), give methyl methylphenylphosphinate (3) stereospecifically with inversion of configuration. At higher concentrations of hydrogen chloride, retention of configuration becomes increasingly important, and for (6) and (7) eventually exceeds inversion. At a given acidity the proportion of reaction proceeding with retention depends on the nucleo-philicity of the leaving group in the amide, increasing in the order (4) < (7) < (6). These results are difficult to rationalise in terms of competing SN 2(P)(inversion) and SN1 (P)(racemisation) mechanisms. Possible alternative explanations involve nucleophilic catalysis by chloride ion and/or the formation of five-co-ordinate intermediates.