PHOSPHOLIDINES INCORPORATING AN N,N'-DIMETHYL OXAMIDE MOIETY - REACTIVITY TOWARDS AMINES AND ALCOHOLS REVISITED

This study has established that the product of the reaction of the phe noxy derivative 4a with p-anisidine are not phosphoramides 7a and 4b, but the salts 11a and 12, confirming that only ammoniolysis takes plac e. These results are discussed in terms of mechanism (addition-elimina tion with the critical deprotonation of the primary zwitterionic inter mediate A formed) and the influence of steric hindrance. Methanolysis of the methylamino derivative 4d, as with all phospholidines of type 4 studied so far, proceeds in two distinct stages. The monoester 8d can be characterized, as can the analogous 8f resulting in the opening of the amino derivative 4f. The effect of reducing the NPN angle to ca. 90 degrees, appears therefore to be of little significance for the pre sumed reduced rate of the first step. In the second stage of the metha nolysis the regioselectivity (carbonyl versus phosphoryl) of attack on various monoesters 8 depends both on catalysis and substitution (R(1) ) of the starting phospholidines 4. Particularly relevant is the attac k on PO with a consistent reaction rate on the methylamino derivative 8d in basic media, while the sterically equivalent methoxy derivative 8g then undergoes attack on the carbonyl. Factors controlling the reac tivity of monomethyl esters of type 8 in the second step are discussed .