Functionalization of enamides via visible-light photoredox catalysis

The direct use of light from the sun in chemical transformations by plant in nature has long since influenced scientists to harness this elegant strategy. The unique photochemistry of molecules has been studied for decades and generation of the reactive states of catalysts by visible light can be done simply through the use of household lightbulbs. In recent years, the use of these visible light activated catalysts in the synthesis of organic compounds has gained widespread recognition and application to a plethora of different synthetic strategies.

We desired to apply visible-light photoredox catalysis in novel strategies for the synthesis of chiral amines, a structural feature present in a multitude of medicinally important structures. We successfully achieved a tandem reaction with enamides as starting materials using photoredox catalysis, although our first attempt did not synthesize chiral amines, but in a serendipitous finding we found a way to make chiral amines very efficiently from petroleum feedstocks. This was through the discovery of a highly efficient, atom economical strategy for the direct synthesis of benzylic amines via photoredox hydroarylation of enamides. To demonstrate the utility of this transformation we applied this photoredox hydroarylation methodology to the gram-scale synthesis of the benzylic amine moiety of cinacalcet, a pharmaceutical used to treat hyperparathyroidism. Future studies will be aimed toward the detailed study of the mechanism of this photoredox hydroarylation of enamides.