Mechanistic Investigation of the Nickel-Catalyzed Carbonylation of Alcohols

The carbonylation of alcohols represents
a straightforward and
atom-efficient methodology for the preparation of carboxylic acids.
It is desirable to perform these reactions under precious metal-free
and low-pressure conditions, with regioselectivity control. In this
work, we present a detailed mechanistic study of a catalytic system
based on NiI2, which can carbonylate benzylic alcohols
in a highly regioselective manner to the corresponding branched carboxylic
acids, core motifs for nonsteroidal drugs. The combination of catalytic
amounts of nickel and iodide is crucial for efficient catalytic and
regioselective conversion. Quantum-chemical computations were used
to evaluate the underlying mechanistic processes. They revealed that
a combination of two mechanisms is responsible for the observed reactivity
and that the oxidative addition of alkyl halides to the Ni(0) species
follows a radical oxidation pathway via two one-electron steps.