C–H Functionalization

The conversion of carbon-hydrogen (C–H) bonds into new functional groups represent a powerful strategy for the construction of organic molecules. The C–H functionalization field has transformed the way that chemists approach the synthesis of natural products and bioactive molecules, enabling fast and efficient derivatization. However, despite tremendous recent progress, selective C–H functionalization can still only be achieved in the context of a limited set of organic substrates and types of C–H sites. Our group is focused on the development of new transition metal-catalyzed C–H functionalization methods to enable the selective C–H functionalization of a variety of different substrates, ranging from simple, commodity chemicals such as benzene and methane to complex natural products and pharmaceuticals. Our work in this area includes:

  • The development of novel organic reactions and methods
  • The application of these methods in the context of complex molecules
  • The rational design of new catalysts informed by detailed mechanistic analysis

Key references:

  1. Bour, J. R.; Camasso, N. M.; Sanford, M. S. “Oxidation of NiII to NiIV with Aryl Electrophiles Enables Ni-Mediated Aryl–CF3 Coupling,” J. Am. Chem. Soc. 2015, 137, 8034-8037.
  2. Camasso, N. M.; Sanford, M. S. “Design, Synthesis, and Carbon-Heteroatom Coupling Reactions of Organometallic Nickel(IV) Complexes,” Science2015, 347, 1218-1220.
  3. Pérez-Temprano, M. H.; Racowski, J. M.; Kampf, J. W.; Sanford, M. S. “Competition Between sp3-C–N vs sp3-C–F Reductive Elimination from PdIV Complexes,” J. Am. Chem. Soc. 2014, 136, 4097-4100.
  4. Maleckis, A.; Kampf, J. W.; Sanford, M. S. “A Detailed Study of Acetate-Assisted C–H Activation at Palladium(IV) Centers,” J. Am. Chem. Soc. 2013, 135, 6618-6625.Mbofana, C. T.; Chong, E.; Lawniczak, J.; Sanford, M. S. “Iron-Catalyzed Oxyfunctionalization of Aliphatic Amines at Remote Benzylic C–H Sites,” Org. Lett. 2016, 18, 4258-4261.
  5. Cook, A. K.; Schimler, S. D.; Matzger, A. J.; Sanford, M. S. “Catalyst-Controlled Selectivity in the C–H Borylation of Methane and Ethane,” Science 2016,351, 1421-1424.
  6. Topczewski, J. T.; Cabrera, P. J.; Saper, N. I.; Sanford, M. S. “Palladium-Catalysed Transannular C–H Functionalization of Alicyclic Amines,”Nature 2016, 531, 220-224.
  7. Lee, M.; Sanford, M. S. “Platinum-Catalyzed, Terminal-Selective C(sp3)–H Oxidation of Aliphatic Amines,” J. Am. Chem. Soc. 2015, 137, 12796-12799.