Palladium-Catalyzed Chemoselective Activation of sp3 vs sp2 C-H Bonds: Oxidative Coupling To Form Quaternary Centers

The oxidative activation of alkyl C-H bonds vs arene C-H bonds with Pd(OAc)(2) has been found to be generalizable to a number of nucleophilic substrates, allowing the formation of a range of hindered quaternary centers. The substrates share a common mechanistic path wherein Pd(II) initiates an oxidative dimerization. The resultant dimer modifies the palladium catalyst to favor activation of alkyl C-H bonds, in contrast to the trends typically observed via a concerted metalation-deprotonation mechanism. Notably, insertion occurs at the terminus of the alkyl arene for hindered substrates. Two different oxidant systems were discovered that turn over the process. Parameters have been identified that predict which substrates are productive in this reaction.