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 coworkers 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: Firstly, 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. Secondly, 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 a too 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.

Computational and Experimental Insights into Asymmetric Rh‐Catalyzed Hydrocarboxylation with CO2

“…Computational analysis of Rh‐( S )‐SEGPHOS : The Rh‐SEGPHOS‐catalyzed hydrocarboxylation was here investigated computationally with the styrene‐type α,β‐unsaturated carbonyl substrates sub1 and sub2 (Figure 1), which previously have been studied experimentally by Mikami and co‐workers [2c] . The overall hydrocarboxylation mechanism for substrates of this type has been reported with [Rh(cod)Cl] 2 (SI, Figure S1) [5] . We have here studied the full mechanism with Rh‐( S )‐SEGPHOS as the catalyst and methyl 2‐phenylacrylate ( sub1 ) as the substrate, with the energy profile shown in Figure S2 (Supporting Information).…”

“…At TS3 , both the phenyl group and the carbonyl oxygen of the substrate interact with the Rh‐center. It is important to highlight that for the comparative analysis of the four ligands, only outer sphere CO 2 insertion was considered, [5] because the TS conformations, where interactions between Rh and CO 2 take place (referred to as inner sphere CO 2 insertion), show very high barriers (TS4_S and TS4_R, Supporting Information, Table S1). The four studied chiral ligands are given in Figure 3.…”

“…A computational analysis of the related non‐enantioselective Rh‐COD‐catalyzed hydrocarboxylation reaction showed that during C−CO 2 bond formation, the CO 2 molecule does not interact with rhodium [5] . Moreover, it was shown that benzylic substrates display an unusual η 6 ‐coordination mode, with the nucleophilic carbon positioned up to 3.6 Å away from rhodium [5] . The same substrate binding mode and preference for an outer sphere CO 2 insertion were found computationally for the chiral Rh‐( S )‐SEGPHOS catalyst [6] .…”

Reductive Carbon–Carbon Bond Forming Reactions with Carbonyls Mediated by Rh–H Complexes

“…[ 39 ] Very recently, Hopmann et al disclosed the detailed mechanism of Rh‐catalyzed α‐carboxylation of α,β‐unsaturated esters with CO 2 by using DFT theory, and they detected a Rh–H complex derived from [RhCl(cod)] 2 and Et 2 Zn using 1 H NMR. [ 40 ]…”

Exploration of New Biomass‐Derived Solvents: Application to Carboxylation Reactions

“…Unfortunately,i nformation on overall environmental impacts and full life-cyclea ssessments (LCAs) of the solvents introduced here remainlimited. [7,10] In the frame of our ongoing research program on CÀC bond-forming reactions involving CO 2 , [11] we became particularly interested to examine the use of biomass-derived solvents in av ariety of carboxylative transformations (Scheme 1B). Utilization of CO 2 , [12] and particularlyd evelopment of CÀCb ondforming reactions involving CO 2 , [13] is ah ighly promising field of research that potentially can solve many globali ssues,s uch as replacement of depleting natural resources.…”