Rhodium(ii)-catalyzed C-H aminations using N-mesyloxycarbamates: reaction pathway and by-product formation.

N-Mesyloxycarbamates are practical nitrene precursors that undergo C-H amination reactions in the presence of rhodium dimer catalysts. Under these conditions, both oxazolidinones and chiral amines have been prepared in a highly efficient manner. Given the elevated reactivity of the intermediates involved in the catalytic cycle, mechanistic details have remained hypothetical, relying on indirect experiments. Herein a density functional theory (DFT) study is presented to validate the catalytic cycle of the rhodium-catalyzed C-H amination with N-mesyloxycarbamates. A concerted pathway involving Rh-nitrene species that undergoes C-H insertion is found to be favored over a stepwise C-N bond formation manifold. Density functional calculations and kinetic studies suggest that the rate-limiting step is the C-H insertion process rather than the formation of Rh-nitrene species. In addition, these studies provide mechanistic details about competitive by-product formation, resulting from an intermolecular reaction between the Rh-nitrene species and the N-mesyloxycarbamate anion.

Synthesis of oxazolidinones: rhodium-catalyzed C-H amination of N-mesyloxycarbamates.

N-Mesyloxycarbamates undergo intramolecular C-H amination reactions to afford oxazolidinones in good to excellent yields in the presence of rhodium(ii) carboxylate catalysts. The reaction is performed under green conditions and potassium carbonate is used, forming biodegradable potassium mesylate as a reaction by-product. This method enables the production of electron-rich, electron-deficient, aromatic and heteroaromatic oxazolidinones in good to excellent yields. Conformationally restricted cyclic secondary N-mesyloxycarbamates furnish cis-oxazolidinones in high yields and selectivity; DFT calculations are provided to account for the observed selectivity. trans-Oxazolidinones were prepared from acyclic secondary N-mesyloxycarbamates using Rh2(oct)4. The selectivity was reverted with a cytoxazone N-mesyloxycarbamate precursor using large chiral rhodium(ii) carboxylate complexes, affording the corresponding cis-oxazolidinone. This orthogonal selectivity was used to achieve the formal synthesis of (-)-cytoxazone.