Reports: AC1
48660-AC1 Synthesis of Hydroxamic Acids through -NOH Insertion of Ketones
Treatment of cyclobutanone or cyclopentanone with N-hydroxybenzenesulfonamide under basic conditions yields the ring expanded cyclic hydroxamic acid in 18-69% yield. The yield of the cyclic hydroxamic acid increases with increasing amounts of N-hydroxybenzenesulfonamide and is highest using sodium hydroxide as the base and protic solvents. Reactions of substituted cyclobutanones give ring expanded products where the –NOH group regio and stereoselectively inserts to the more substituted position. These results appear similar to the Baeyer-Villiger reaction. A series of experiements illuminates the mechanism of this transformation. 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. Overall, this transformation appears similar to the Angeli-Rimini conversion of aldehydes to hydroxamic acids and may find use in the preparation of cyclic hydroxamic acid containing natural products, such as siderophores. These results also inform the design of new donors of nitroxyl (HNO), a newly explored pharmaceutical agent for the treatment of heart disease.
