Mechanism of Rhodium-Catalyzed Intramolecular Hydroacylation: A Computational Study

Abstract

All-electron numerical density functional theory calculations with scalar relativistic corrections have been utilized to examine the mechanism of the intramolecular rhodium-catalyzed hydroacylation reaction. The gas-phase results reveal a key branch point early in the reaction at the oxidative addition step wherein the two important pathways evolve through five-coordinate Rh(III) intermediates characterized by an apical acyl group and an equatorial hydride, orientations seemingly counter to trans influence arguments. These pathways account for the gross features of the experimental product distribution as well as the isotope labeling outcomes observed by previous investigators in this area. A greatly simplified approximation to modeling the reaction environment was applied that focused on redressing the coordinative unsaturation prevalent during certain steps of the catalytic process by including an explicit molecule of solvent or an additional molecule of substrate. Such an approach allowed us to explain the catalytic deactivation, substrate inhibition and dependence of the reaction rate on this coordinated ligand. Importantly, the application of a popular QM/MM method was unable to locate some of the key stationary points along the reaction path.

Theoretical investigation of Ni(PMe3)4-catalyzed intermolecular hydroacylation of alkynes with benzaldehydes

“…The hydrogen migration in the five-coordinated Ni(PMe 3 ) 2 (H)(benzoyl)(alkyne) complex M4a is the rate-determining step for this channel. This is different from the studies of Morehead et al [27] and Wu et al [28].…”

“…Morehead and Sargent [27] studied theoretically the mechanism of rhodium-catalyzed intramolecular hydroacylation of alkenes using the two-layer ONIOM approach and found that reductive elimination was the rate-limiting step. Wu et al [28] studied rhodium-catalyzed intramolecular hydroacylation of 4-alkynals using MP2 calculations and concluded that oxidative addition of aldehydes was the rate-determining step.…”

Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights

“…In a closely related study, Morehead and Sargent investigated the mechanism of the intramolecular hydroacylation of olefins and reported a substrate-assisted reductive elimination that is critical to suppress both decarbonylation and catalyst deactivation pathways. 384 In 2009, Woo and Dong studied the intramolecular hydroacylation of ketones to afford seven-membered lactones. 385 Due to the lack of any spectroscopic evidence of reaction intermediates in these kind of transformations, the mechanistic investigations were complemented by computations at the B3LYP/LACV3P** level of theory.…”

Theoretical studies of nickel-catalyzed ring-opening hydroacylation of methylenecyclopropanes and benzaldehydes

“…Morehead et al [22] reported the reaction mechanisms of rhodium(I)-catalyzed hydroacylation of alkenes, and speculated that the reductive elimination was the rate-determining step. Wu et al [23] studied rhodium(I)-catalyzed hydroacylation of 4-alkynals, and thought that the oxidative addition of aldehydes was the rate-limiting step.…”