Phospholidines incorporating an N,N′-dimethyl oxamide moiety: reactivity towards amines and alcohols revisited

Abstract

This study has established that the products of the reaction of the phenoxy derivative 4a with p-anisidine are not phosphoramides 7a and 4b, but the salts 11a and 12, confirming that only ammoniolysis takes place. These results are discussed in terms of mechanism (addition-elimination with the critical deprotonation of the primary zwitterionic intermediate 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°, appears therefore to be of little significance for the presumed reduced rate of the first step. In the second stage of the methanolysis the regioselectivity (carbonyl versus phosphoryl) of attack on various monoesters 8 depends both on catalysis and substitution (R¹) of the starting phospholidines 4. Particularly relevant is the attack 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 reactivity of monomethyl esters of type 8 in the second step are discussed.