Mechanistic Aspects of Rhodium-Catalyzed Isoprene Hydroformylation: A Computational Study

The hydroformylation of conjugated dienes is a highly interesting reaction, giving access to bifunctional aldehyde products. However, due to low activity, caused by the formation of stable eta(3)-allylic intermediates, it has received much less academic attention, both experimentally and theoretically, than classical monoalkene hydroformylation. We herein present a comprehensive computational mechanistic study of the hydroformylation of isoprene as the simplest example of an asymmetrically substituted conjugated diene, via a Rh/dppe catalyst. A benchmarking study assessing the accuracy of Rh complex structures and energies with various methods was carried out, from which a protocol combining dispersion-corrected density functional theory (DFT) for geometries and vibrational corrections and DLPNO-CCSD(T) for reaction energies was derived. The predicted reaction mechanism of isoprene hydroformylation leading to the formation of 3-methyl-3-pentenal is derived from the classic Wilkinson cycle for monoene hydroformylation with a few deviations. Among them is the prediction of a eta(3)/eta(3)-allylic rearrangement following a Berry pseudorotation mechanism that has rarely been discussed in the literature. The prediction of the relevant intermediates and transition states is highly sensitive to the computational protocol, with the implicit solvation model introducing the greatest uncertainty. A TOF of 47 h(-1) was predicted to be in good agreement with experimental results. An investigation of subsequent product isomerization revealed a high hydrogen transfer barrier, making the isomerization via beta-hydride elimination unfavorable.