Facile Aryl C–N Bond Formation via SNAr Using Photothermal Red Light Activation

Nucleophilic aromatic substitution (SNAr) is a valuable and widely used method for forming aromatic C–N bonds, which are of immense interest in both industry and academia. However, there remains a longstanding challenge in applying this approach to less activated electrophiles, due to negative charge buildup in the transition state, resulting in high activation energy barriers. Inspired by our previous work on the Newman Kwart Rearrangement (NKR), a high barrier (35-43 kcal/mol) C–S bond forming reaction, we sought to leverage photothermal conversion for challenging C–N bond forming SNAr reactions. In this work, we demonstrate that incorporation of an inexpensive photothermal agent, carbon black, and irradiation with red light affords several lightly activated, intermolecular substitution reactions. Attempts to apply this approach to electron neutral and electron rich aryl halides resulted in unproductive reactivity, leading us to examine the reaction barriers. Computations revealed elevated barriers which were within the range previously achieved during our photothermally mediated NKR. Electron neutral, intramolecular analogs were synthesized and found to undergo productive reactivity in short time frames (3-20 minutes), indicating that the inhomogeneous nature of the photothermal heating was a challenge in terms of colocalizing two reactants sufficiently close to the nanoparticle surface. This concept was further leveraged into a one pot, two step SNAr, where an initial intermolecular reaction occurs at a lower barrier, which then primes the substrate for a second, intramolecular substitution. This approach allowed for the formation of a diverse scope of fused heterocycles.