Mechanistic Insights into Rh-Catalyzed Regio- and Enantioselective Hydroformylation of Cyclopropyl-Functionalized...

Asymmetric hydroformylation (AHF) is a valuable method to convert cheaper feedstock alkenes into value-added products. In view of the contemporary importance of these reactions, we have examined the mechanism of AHF of cyclopropyl-functionalized trisubstituted alkenes by using syngas (CO and H₂) catalyzed by [Rh(R,S)-Yanphos], offering high regio- and enantioselectivities by deploying a combination of computational, kinetic, and spectroscopic tools. Our comprehensive density functional calculations suggest that the regio- and enantioselectivities originate from the irreversible alkene insertion step, where the branched pathway exhibits a notable energetic advantage of 4.7 kcal/mol in the key migratory insertion to the re face of the alkene. The alkene insertion transition state (TS) is the turnover-determining TS, and the active catalyst [RhH(CO)((R,S)-Yanphos)] is the turnover-determining intermediate, with an energetic span of 19.9 kcal/mol for the pathway leading to the R enantiomer of the product. Our kinetic studies revealed a first-order dependence on the alkene and a quasi-first-order dependence on the Rh catalyst at high conversions. Slow catalyst activation is found to be more likely than catalyst deactivation or product inhibition. The molecular and energetic details may help in the design of new experiments leveraging trisubstituted alkenes in AHF reactions.