Synthesis of Cyclic Hydroxamic Acids through −NOH Insertion of Ketones

Abstract

Treatment of cyclobutanone or cyclopentanone with N-hydroxybenzenesulfonamide under basic conditions yields the ring-expanded cyclic hydroxamic acid in 18-69% yield. Reactions of substituted cyclobutanones give ring expanded products where the -NOH group regio- and stereoselectively inserts to the more substituted position. This expansion likely proceeds through a mechanism that includes addition of the N-anion of N-hydroxybenzenesulfonamide to the ketone and a C-nitroso intermediate that rearranges to the final product.

Recent advances in the chemical biology of nitroxyl (HNO) detection and generation

“…97 Interestingly, smaller ring-derived acyloxy nitroso compounds (cyclopentane or cyclobutane) do not hydrolyze to produce HNO but rearrange to cyclic hydroxamic acids. 98,99 Acyloxy nitroso compounds can be easily obtained from direct oxidation of the corresponding oxime with lead tetra-acetate and the addition of an excess amount of the appropriate acid generates various esters. 100,101 This approach allows structural modification to control HNO release as a function of the ease of hydrolysis of the ester group of the acyloxy nitroso compound.…”

Cyclic Hydroxamic Acid Analogues of Bacterial Siderophores as Iron‐Complexing Agents prepared through the Castagnoli–Cushman Reaction of Unprotected Oximes

“…Among the existings ynthetic methods for hydroxamic acid, intramolecular nucleophilic cyclizationontoO-protected acyclic hydroxamic acids, [14] nitroso moietyi nsertion in cyclic ketones, [15] ring-closing methathesis of bis-olefinic hydroxamic acids [16] are noteworthy.The only multicomponent approacht o hydroxamic acidsi ng eneral involvest he use of free [17] or Oprotected [18] hydroxylamine as an amine components urrogate in the Ugi reaction. However,n os trategies to accessc yclic hydroxamica cids, whichw ould involve multicomponent chemistry,h ave been described in the literature.…”

Ring expansions of acyloxy nitroso compounds

“…21 This methodology provides a direct and rapid method to generate structurally diverse cyclic hydroxamic acids from four and five membered ring ketones that are not easily accessible other methods (including the reaction of N-hydroxybenzenesulfonamide with the ketone under basic conditions). 22 …”