Regiospecific Vinyl Phosphate/beta-Keto Phosphonate Rearrangements Initiated by Halogen-Metal Exchange

A new strategy has been developed for preparation of beta-keto phosphonates via a halogen-metal exchange induced 1,3-phosphorus migration of 2-bromovinyl phosphates. These intermediates can be prepared through conversion of an alpha-bromo ketone to the appropriate enolate by reaction with strong base, or through conjugate addition to an alpha-bromo alpha,beta-unsaturated ketone. In either case, trapping the resulting enolate by reaction with a dialkyl phosphorochloridate gives the 2-bromovinyl phosphate. Metalation can be accomplished upon treatment with n-BuLi, and rearrangement is facile once metalation has been achieved. Studies with isotopically labeled substrates have shown that this rearrangement is regiospecific, in contrast to vinyl phosphate/beta-keto phosphonate rearrangements induced by strong base where regioisomeric products are sometimes obtained.