Mechanistic Insights into the Ni-Catalyzed Reductive Carboxylation of C-O Bonds in Aromatic Esters with CO : Understanding Remarkable Ligand and Traceless-Directing-Group Effects.

The mechanism of the Ni -catalyzed reductive carboxylation reaction of C(sp )-O and C(sp )-O bonds in aromatic esters with CO to access valuable carboxylic acids was comprehensively studied by using DFT calculations. Computational results revealed that this transformation was composed of several key steps: C-O bond cleavage, reductive elimination, and/or CO insertion. Of these steps, C-O bond cleavage was found to be rate-determining, and it occurred through either oxidative addition to form a Ni intermediate, or a radical pathway that involved a bimetallic species to generate two Ni species through homolytic dissociation of the C-O bond. DFT calculations revealed that the oxidative addition step was preferred in the reductive carboxylation reactions of C(sp )-O and C(sp )-O bonds in substrates with extended π systems. In contrast, oxidative addition was highly disfavored when traceless directing groups were involved in the reductive coupling of substrates without extended π systems. In such cases, the presence of traceless directing groups allowed for docking of a second Ni catalyst, and the reactions proceed through a bimetallic radical pathway, rather than through concerted oxidative addition, to afford two Ni species both kinetically and thermodynamically. These theoretical mechanistic insights into the reductive carboxylation reactions of C-O bonds were also employed to investigate several experimentally observed phenomena, including ligand-dependent reactivity and site-selectivity.