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

Abstract

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.