Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: application of halide effects in the development of a general process

We have demonstrated halide effects in the rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes. By employing halide and protic additives, the catalyst poisoning effect of aliphatic amines is reversed allowing the amount nucleophile to react in high yield and ee. Second, by simply changing the halide ligand on the rhodium catalyst from chloride to iodide, the reactivity and enantioselectivity of reactions employing an aromatic amine, malonate or carboxylate nucleophile are dramatically improved. Third, through the application of halide effects and more forcing reaction conditions, less reactive oxabicycle 2.2.1] substrates react to generate synthetically useful enantioenriched cyclohexenol products. Application of these new conditions to the more reactive oxabenzonorbornadiene permits the reaction to be run with very low catalyst loadings (0.01 mol %).