Expanding the Scope of Enantioselective Rhodium-Catalyzed Allylic Substitution with a Nitrile Anion

Abstract

In chemistry, a pair of molecules that have the same connectivity, but are non-superimposable mirror images, much like the human hand, are called enantiomers. In nature, enzymes are able to catalyze the selective synthesis of one of these forms. However, in the laboratory, we currently rely on metal-catalysts to fulfill this role. The efficiency and side effects of a drug can be drastically changed depending on which enantiomer is present. As a result, the pharmaceutical industry is interested in the selective synthesis of one enantiomer of a drug over the other. Furthermore, crucial drugs in the pharmaceutical industry contain a nitrile functional group (-C≡N), which are largely found on aromatic or fully-substituted carbons to prevent the release of toxic cyanide. This research involves the use of a chiral rhodium catalyst to direct the formation of one enantiomer over another in the synthesis of fully-substituted nitriles. Hence, the synthetic utility of this reaction is especially beneficial to the pharmaceutical industry. For example, one of the top 200 drugs in 2015, verapamil, is a nitrile containing compound. Verapamil is a calcium channel blocker prescribed to treat high blood pressure by relaxing the blood vessels to allow for easier blood flow. The presentation will describe the development and evaluation of the scope of this novel reaction and our efforts to develop a synthesis of (S)-verapamil.