Stereochemistry of the methoxide induced rearrangement of an α-bromophosphonamidate: cleavage of the P–N and P–C bonds in the azaphosphiridine oxide intermediate1

Abstract

Menthyl P-(bromomethyl)-N-tert-butylphosphonamidate 5 has been prepared from (1R,2S,5R)-(-)-menthol and the S _P diastereoisomer has been isolated. This rearranges with methoxide [Me ₃ (PhCH ₂ )N ⁺ MeO ^- in THF–MeOH] to give only the S _P diastereoisomer of menthyl methyl (tert-butylamino)methylphosphonate 6 and very largely (95%) the S _P diastereoisomer of menthyl methyl N-tert-butyl-N-methylphosphoramidate 7. The configurations of these products show that when the (postulated) azaphosphiridine oxide intermediate 16 suffers ring opening by methoxide, the P–N bond is cleaved (to give 6) with inversion of configuration but the P–C bond is cleaved (to give 7) with predominant retention. These contrasting stereochemistries suggest that nucleophilic attack on the PO group of the azaphosphiridine oxide generates a five-coordinate intermediate (not merely a transition state) that exists long enough to undergo pseudorotation.