Nucleophilic substitution reactions of benzyl- and diphenylmethyl-phosphonamidic chlorides with amines: competition between the usual SN2(P) mechanism and elimination–addition with an alkylideneoxophosphorane (phosphene) intermediate

Abstract

The substitution reaction of PhCH₂P(O)(NMe₂)Cl with Me₂NH or Et₂NH in CHCl₃ is very sensitive to the bulk of the nucleophile (200 times slower with Et₂NH), affords only the product derived from Me₂NH in competition experiments, and gives largely undeuterated product with Et₂ND; these features are in accord with an S_N2(P) mechanism. The corresponding reaction of Ph₂CHP(O)(NMe₂)Cl is relatively insensitive to the bulk of the nucleophile (5 times slower with Et₂NH), gives some of the product derived from Et₂NH in competition experiments, and gives extensively deuterated product with Et₂ND; these features point to an elimination–addition (EA) mechanism with an alkylideneoxophosphorane intermediate [Ph₂CP(O)NMe₂]. There is only a modest (13–19 fold) increase in the rate of substitution on going to ArPhCHP(O)(NMe₂)Cl (Ar = 4-NO₂C₆H₄) but with R₂ND there is now very rapid H/D exchange at the α carbon atom. This suggests that the elimination stage of the EA mechanism comprises rapid reversible formation of the conjugate base followed by rate-limiting expulsion of chloride ion.