Development of an Improved System for the Carboxylation of Aryl Halides through Mechanistic Studies

The nickel-catalyzed carboxylation
of organic halides or pseudohalides using carbon dioxide is an emerging
method to prepare synthetically valuable carboxylic acids. Here, we
report a detailed mechanistic investigation of these reactions using
the carboxylation of aryl halides with (PPh3)2NiIICl2 as a model reaction. Our studies allow
us to understand several general features of nickel-catalyzed carboxylation
reactions. For example, we demonstrate that both a Lewis acid and
halide source are beneficial for catalysis. To this end, we establish
that heterogeneous Mn(0) and Zn(0) reductants are multifaceted reagents
that generate noninnocent Mn­(II) or Zn­(II) Lewis acids upon oxidation.
In a key result, a rare example of a well-defined nickel­(I) aryl complex
is isolated, and it is demonstrated that its reaction with carbon
dioxide results in the formation of a carboxylic acid in high yield
(after workup). The carbon dioxide insertion product undergoes rapid
decomposition, which can be circumvented by a ligand metathesis reaction
with a halide source. Our studies have led to both a revised mechanism
and the development of a broadly applicable strategy to improve reductive
carboxylation reactions. A critical component of this strategy is
that we have replaced the heterogeneous Mn(0) reductant typically
used in catalysis with a well-defined homogeneous organic reductant.
Through its use, we have increased the range of ancillary ligands,
additives, and substrates that are compatible with the reaction. This
has enabled us to perform reductive carboxylations at low catalyst
loadings. Additionally, we demonstrate that reductive carboxylations
of organic (pseudo)­halides can be achieved in high yields in more
practically useful, non-amide solvents. Our results describe a mechanistically
guided strategy to improve reductive carboxylations through the use
of a homogeneous organic reductant, which may be broadly translatable
to a wide range of cross-electrophile coupling reactions.