To Bind or Not to Bind: Mechanistic Insights into C–CO2 Bond Formation with Late Transition Metals

In transition metal-mediated carboxylation reactions, CO2 inserts into a metal–nucleophile bond. At the carboxylation transition state (TS), CO2 may interact with the metal (inner-sphere path) or may insert without being activated by the metal (outer-sphere path). Currently, there is no consensus as to which path prevails. In order to establish general predictions for the insertion of CO2 into metal–carbon bonds, we computationally analyze a series of experimentally reported Cu, Rh, and Pd complexes. Our focus is on carboxylation of aromatic substrates, including Csp3 benzyl and Csp2 aryl and alkenyl nucleophiles. We observe clear trends, where the nature of the nucleophile determines the preferred path: benzylic Csp3 nucleophiles favor outer-sphere and Csp2 systems favor inner-sphere CO2 insertion into the metal–carbon bond. An exception are Cu–benzyl bonds, where inner- and outer-sphere CO2 insertions are found to be competitive, highlighting the need to include both paths in mechanistic studies and in the rationalization of experimental results. For insertion into Pd–Csp2 bonds, we find that the metal–CO2 interactions at the TS are weak and may be beyond 3 Å for sterically congested ligands. Nonetheless, on the basis of a comparison to other TSs, we argue that the CO2 insertion into Pd–Csp2 bonds should be classified as inner-sphere.