A lingering problem in the area of Pd(II)-catalyzed C�H functionalization is the dearth of suitable ligands to lower the activation energy for C�H cleavage. In our studies of aerobic Pd(II)-catalyzed C�H olefination reactions of phenylacetic acids, we have discovered dramatic rate increases when mono-N-protected amino acids are used as ligands. In light of these findings, systematic ligand tuning was undertaken, which has resulted in major improvements in substrate scope, reaction rate, and catalyst turnover. We present evidence from intermolecular competition studies and kinetic isotope effect experiments that implies that the observed rate increases are a result of acceleration in the C�H cleavage step. Furthermore, these studies suggest that the origin of this phenomenon is a change in the mechanism of C�H cleavage from electrophilic palladation to concerted metallation/deprotonation. Recent work has also demonstrated that amino acids ligands can enable efficient C�H functionalization with other substrates, including phenethyl alcohols and can accelerate other categorically distinct C�H functionalization reactions, including C�H/R�BX2 cross-coupling.

Ligand-accelerated catalysis in Pd(II)-mediated C–H functionalization

243rd National Meeting (2012)

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