Reactions of N-phenyl α-halogenophosphonamidates with alkoxide: migration of the anilino group from phosphorus to the α carbon atom

Abstract

When Me₂CClP(O)(NHPh)OMe is treated with 0.5M NaOMe–MeOH the anilino group migrates from phosphorus to the α carbon atom. Reaction is complete within 2 min at 60 °C and Me₂C(NHPh)P(O)(OMe)₂ is formed quantitatively. Similar behaviour is observed with MeCHClP(O)(NHPh)OMe but the reaction is ca. 50-times slower and in the later stages some of the resulting MeCH(NHPh)P(O)(OMe)₂ becomes demethylated. For the still less reactive compounds XCH₂P(O)(NHPh)OMe (X = Cl or I) demethylation of the substrate and/or product is extensive, but with ICH₂P(O)(NHPh)OEt in 0.15M NaOEt–EtOH at 60 °C the product PhNHCH₂P(O)(OEt)₂ can be obtained within 1 h in high yield. The relative rates of rearrangement of the various substrates are consistent with a mechanism involving a three-membered cyclic intermediate, the phosphorus analogue of an α-lactam.