C–O Bond Activation as a Strategy in Palladium-Catalyzed Cross-Coupling

The activation of strong C–O bonds in cross-coupling catalysis can open up new oxygenate-based feedstocks and building blocks for complex-molecule synthesis. Although Ni catalysis has been the major focus for cross-coupling of carboxylate-based electrophiles, we recently demonstrated that palladium catalyzes not only difficult C–O oxidative additions but also Suzuki-type cross-couplings of alkenyl carboxylates under mild conditions. We propose that, depending on the reaction conditions, either a typical Pd(0)/(II) mechanism or a redox-neutral Pd(II)-only mechanism can operate. In the latter pathway, C–C bond formation occurs through carbopalladation of the alkene, and C–O cleavage by β-carboxyl elimination.

1 Introduction

2 A Mechanistic Challenge: Activating Strong C–O Bonds

3 Exploiting Vinylogy for C–Cl and C–O Oxidative Additions

4 An Alternative Mechanism for Efficient Cross-Coupling Catalysis

5 Conclusions and Outlook