| We have established a new rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes with a wide range of nucleophiles including alcohols, phenols, aromatic amines, aliphatic amines, carboxylates, and malonates. The products of these reactions are generated in high yield and excellent enantioselectivity (typically greater than 90%). This methodology represents one of the most rapid and resource-efficient routes to this class of compound. During the development of this new process, an intriguing halide effect on catalyst activity and enantioselectivity was observed. Our observations regarding the influence of halide ligands on the outcome of the rhodium-catalyzed ARO reaction will likely find application in other transition metal-catalyzed processes.; A highly regio- and diastereoselective rhodium-catalyzed ring opening reaction of vinyl epoxides has also been developed. These reactions occur with a wide range of alcohol and aromatic amine nucleophiles to give the trans-1,2-addition products, which is a complementary outcome compared to the commonly used palladium catalyst systems.; The newly rhodium-catalyzed ARO reaction was subsequently applied to the ring opening of azabicyclic alkenes. Despite the challenges associated with changing from an oxygen leaving group to a nitrogen leaving group, these reactions occur in high yield. This methodology was used in the total synthesis of a diamine kappa-opioid analgesic agent.; Two new reactions using rhodium catalysts and aryl boronic acid nucleophiles were developed. The first reaction involves the arylative asymmetric ring opening of oxabicyclic alkenes. This is the first time that boronic acids have been used with rhodium catalysis to perform allylic functionalizations. The second is an aqueous rhodium-catalyzed addition of boronic acids to styrenes. This is the first time that catalytic additions to unactivated olefins has been possible with rhodium. In these reactions, the products retain the alkene functionality that is typically lost in rhodium-catalyzed addition reactions. |
