Palladium-Catalyzed Oxidative Functionalization of C-H Bonds. Palladium-Catalyzed Oxidative Functionalization of C-H Bonds.

The ability to selectively functionalize complex molecules is an ongoing challenge to chemists; the use of transition-metal catalysts can allow for the direct transformation of C–H bonds into a variety of different functional groups. Two significant challenges to this approach are regioselectivity and diversity of functionalization. The approach discussed herein towards achieving regioselectivity has been to use substrates with pendant ligands, which coordinate to a palladium catalyst and direct electrophilic C–H activation to a specific C–H bond. In order to incorporate a variety of functional groups into the substrate, both oxidative functionalization reactions, to form C–OR and C–F bonds, and oxidative coupling reactions, for the formation of a new C–C bond from two C–H bonds have been developed. We have pioneered a method for the Pd-catalyzed acetoxylation of activated and unactivated, primary and secondary sp3 C–H bonds using pyridine and quinoline directing groups. Additionally, we have demonstrated one of the first metal-catalyzed C–F bond-forming reactions, using commercially available electrophilic fluorine sources as oxidants. This methodology was applied to the formation of a both sp2 and sp3 C–F bonds. The formation of C–C bonds is an ongoing challenge to organometallic chemists. We felt that in order to maximize atom economy and the overall efficiency, the coupling of two C–H bonds to form a C–C bond would be an ideal process. Using heterocycles as directing groups, select C–H bonds can be coupled under mild reaction conditions. With Oxone as the terminal oxidant, Pd(OAc)2 catalyzes oxidative homodimerization of these heterocyclic substrates to afford homocoupled products in high yield and very high regioselectivity. The selective formation of unsymmetrical aryl-aryl’ bonds would be a more general process. We have found that palladium, in the presence of benzoquinone and Ag2CO3, can catalyze the cross-coupling of C–H bonds. The first C–H activation is ligand directed followed by a second, undirected C–H activation. The coupled products are formed in high regioselectivity, where the undirected C–H bond activation typically occurs at the least sterically hindered C–H bond.PhDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/62370/1/kamihull_1.pd