Halosulfonamidation of camphene: chemo and stereoselectivity, rearrangement, solvent interception, heterocyclization†

Abstract

The first study on oxidative sulfonamidation of camphene is presented. By varying the reaction conditions, the nature of the sulfonamide, the oxidizing agent, the ratio of the reagents, and the solvent, it is possible to control not only the direction of amidation of the double bond of camphene, leading to the formation of the corresponding amides or amidines, but also the rearrangement or retention of the camphene structure. In the NIS-induced reaction, no rearrangement occurs, leading to N-sulfonylamidine derivatives of isocamphane. The NBS-induced reaction takes place with solvent (acetonitrile) intersection and with or without rearrangement, resulting in N-sulfonylamine with isocamphane or camphane motif, depending, strikingly, on the ratio of the reactants. A mechanism that explains the diversity of products has been proposed and confirmed by theoretical calculations. It includes various intermediates formed via electrophilic addition of a halogen, such as an open carbocation for Br⁺, or the anchimerically assisted iodonium cation for I⁺. Additionally, the basicity of the reaction medium can change depending on the ratio of the reagents. For example, in CH₂Cl₂, which is incapable of being trapped by the intermediate cations, the formation of bromosulfonamide occurs only with triflamide due to the highest halogening activity of the intermediate CF₃SO₂NHBr. The structure of the products formed in up to 96% yield was proved by NMR, HRMS and, for the key products, by X-ray analysis. When performing the NBS-induced bromosulfonation of camphene using triflamide with subsequent addition of potassium carbonate (K₂CO₃), no dehydrobromination occurred. However, when using cesium fluoride (CsF) as a base, an unexpected quinazoline product was obtained. This opens up the possibility for further transformations.