A new approach to cyclic hydroxamic acids: intramolecular cyclization of N-benzyloxy carbamates with carbon nucleophiles

N-Alkyl-N-benzyloxy carbamates, 2, undergo facile intramolecular cyclization with a variety of carbon nucleophiles to give functionalized five- and six-membered protected cyclic hydroxamic acids, 3, in good to excellent yields. This method can be extended to prepare seven-membered cyclic hydroxamic acids in moderate yields. The sulfone intermediates 3 from this study can be alkylated while the corresponding phosphonates have been shown to undergo HWE reaction. The α,β-unsaturated synthon, 8, prepared by thermal elimination of sulfoxide 3m, undergoes Michael addition with secondary amines. The usefulness of this approach to prepare polydentate chelators has been demonstrated by the synthesis of bis cyclic hydroxamic acids 12, 14, and 15.

Graphical abstractN-Alkyl-N-benzyloxy carbamates, 2, undergo facile intramolecular cyclization with a variety of carbon nucleophiles to give functionalized five- and six-membered benzyl protected cyclic hydroxamic acids, 3, in good to excellent yields. The products of the cyclization are useful intermediates as demonstrated by the preparation of bis cyclic hydroxamic acids 12, 14, and 15.Figure optionsDownload full-size imageDownload as PowerPoint slide