John Hartwig

Selective Functionalization of Alkyl and Aryl C-H Bonds – Installation of Temporary Functional Groups

Our group has developed practical methods for the catalytic functionalization of C-H bonds with main group reagents. These studies have led us to a general strategy of installing a single temporary functional group to form a range of products from one C-H bond functionalization reaction. This lecture will present a combination of methodology and mechanistic studies that connect these functionalizations with the properties of transition metal complexes and demonstration of the capabilities of these reactions for applications to medicine. The development of reactions that regioselectively convert aromatic and aliphatic C-H bonds to aryl and alkyl borane and silane derivatives will be presented, along with reactions of these main group species to form a series of functionalized products and additional examples of C-H bond functionalization by installing a versatile synthetic intermediate. The relationships between C-B, C-Si, and C-X bond-forming processes (X=N, O, F, CF₃) will be discussed.

• References:

-Chen, H.; Schlecht, S.; Semple, T.C.; Hartwig, J.F. “Thermal, Regiospecific, Catalytic Functionalization of Alkanes” Science 2000, 287, 1995-1998.

-Mkhalid, I.A.I.; Barnard, J.H.; Marder, T.B.; Murphy, J.M.; Hartwig, J.F. “C-H Activation for the Construction of C-B Bonds” Chem. Rev. 2010, 110, 890-931.

-Simmons, E.M.; Hartwig, J.F. “Catalytic functionalization of unactivated primary C–H bonds directed by an alcohol” Nature 2012,483, 70–73.

-Cheng, C.; Hartwig, J.F. “Rhodium-Catalyzed Intermolecular C–H Silylation of Arenes with High Steric Regiocontrol” Science, 2014, 343, 853-857.