The Versatile Reactivity of Oximes with Vinyl Boronic Acids and Development of 4-Phosphono-β-Lactams

The tunable reactivity of oximes with alkenyl boronic acids towards C–O versus C–N bond formation has been explored. O-alkenyl oximes have been evaluated as precursors to α-imino aldehydes by a copper-mediated etherification of benzophenone oxime with alkenyl boronic acids and a subsequent [1,3] rearrangement. This transformation provides a unique alternative to traditional electrophilic amination routes and helps to address the challenges associated with the installation of these moieties in complex pharmaceutical and material targets. The copper-catalyzed C–N bond coupling of α,β-unsaturated oximes with alkenyl boronic acids for the formation of N-vinyl nitrones has also been investigated. This facile transformation is a significant advance from the only previously reported method for the preparation of N-vinyl nitrones from N-(alkylseleno)imine precursors. Furthermore, the synthetic utility of these unique N-vinyl nitrone products has been illustrated with their thermal rearrangement to highly substituted pyridines. Lastly, a new family of phosphono-β-lactams has been developed as potential antibiotic agents. Synthesis of the desired compounds was achieved by the intramolecular cyclization of α-halo amides which occurs rapidly at room temperature under basic conditions. The modular synthetic route employed can be easily adapted to provide access to 4,5- and 4,6-fused phosphonate-containing β-lactams.