Rhodium-Catalyzed Hydrocarboxylation: Mechanistic Analysis Reveals Unusual Transition State for Carbon–Carbon Bond Formation

The mechanism of rhodium-COD-catalyzed
hydrocarboxylation of styrene
derivatives and α,β-unsaturated carbonyl compounds with
CO2 has been investigated using density functional theory
(PBE-D2/IEFPCM). The calculations support a catalytic cycle as originally
proposed by Mikami and co-workers including β-hydride elimination,
insertion of the unsaturated substrate into a rhodium–hydride
bond, and subsequent carboxylation with CO2. The CO2 insertion step is found to be rate limiting. The calculations
reveal two interesting aspects. First, during C–CO2 bond formation, the CO2 molecule interacts with neither
the rhodium complex nor the organozinc additive. This appears to be
in contrast to other CO2 insertion reactions, where CO2–metal interactions have been predicted. Second, the
substrates show an unusual coordination mode during CO2 insertion, with the nucleophilic carbon positioned up to 3.6 Å
away from rhodium. In order to understand the experimentally observed
substrate preferences, we have analyzed a set of five alkenes: an
α,β-unsaturated ester, an α,β-unsaturated
amide, styrene, and two styrene derivatives. The computational results
and additional experiments reported here indicate that the lack of
activity with amides is caused by an overly high barrier for CO2 insertion and is not due to catalyst inactivation. Our experimental
studies also reveal two putative side reactions, involving oxidative
cleavage or dimerization of the alkene substrate. In the presence
of CO2, these alternative reaction pathways are suppressed.
The overall insights may be relevant for the design of future hydrocarboxylation
catalysts.