N-Arylation and N-Alkylation of Amides via the Merger of Base Metal Catalysis and Photocatalysis
Final Report Abstract
Methods to forge C–N bonds are of paramount importance to organic chemists and the pharmaceutical industry because of the abundance of molecules with biological activity bearing C–N bonds. During my postdoctoral stay at Princeton University under the mentorship of Professor Dr. David W. C. MacMillan, I focused on the development of a novel methodology to form C–N bonds between amides and aryl halides. The utilization of a nickel catalyst in combination with a photocatalyst led to the development of a mild protocol, using visible light as the energy source to drive chemical reactions. This approach can constitute distinct advantages over traditional approaches as it does not only proceed at milder conditions but also does not require the design and synthesis of specialized ligands. Indeed, the operational simplicity and broad aplicability of photocatalytic reactions has already led to their wide adoption in the chemical industry. Following mechanistic elucidations that lend support to an energy transfer mechanism, we found that the developed C–N coupling method was applicable to a broad spectrum of primary amides and (hetero)aryl halides with secondary amides still remaining a mostly unmet challenge. We also showcased the utility by the expansion of this methodology to the synthesis of two pharmacologically active compounds, further proving its possible significance to the pharmaceutical industry.
