Density Functional Theory Study of the Mechanisms of Iron‐Catalyzed Regioselective Anti‐Markovnikov Addition of C‐H Bonds in Aromatic Ketones to Alkenes

Abstract

The mechanisms of iron-catalyzed regioselective anti-Markovnikov addition of C-H bonds in the aromatic ketones to alkenes are studied using Density Functional Theory (DFT) calculations with the B3LYP-D3 method. Our results show that the overall catalytic cycle includes the initial generation of aromatic ketone C-H activation, the coordination and insertion of a styrene, and finally C-C reductive elimination. Two different alkylation products are obtained through the linear or branched formation via several different paths. The formation of the linear product is energetically favorable over that of the branched product, which is in agreement with the experimental observation. The rate-limiting step for the whole catalytic cycle to obtain the main linear product is the reductive elimination step where the Gibbs free energy in solvent THF ΔG sol is 13.5 kcal/mol computed using the SMD method.

Allenes for Versatile Iron-Catalyzed C–H Activation by Weak O-Coordination: Mechanistic Insights by Kinetics, Intermediate Isolation, and Computation

“…The latter is in good agreement with our deuterium labeling and kinetic studies where an approximately first order in iron and zero order in both substrates were observed, as well as with the experimental Gibbs energy of activation of 23.1 kcal·mol –1 (determined from the Eyring equation, Figure ) and the detrimental effect exerted by PMe 3 on catalysis (Figure bottom). This contrasts with previously reported suggestions of the reductive elimination being rate determining for the related alkene system. , Subsequently, insertion of 2a in Fe–IV , and concurrent hydride insertion, generates pentacoordinated intermediate Fe–V . Lastly, coordination of PMe 3 results in the hexacoordinated intermediate Fe–VI , which undergoes reductive elimination ( TS VI‑VII ).…”

“…This contrasts with previously reported suggestions of the reductive elimination being rate determining for the related alkene system. 86,87 Subsequently, insertion of 2a in On the basis of our experimental, kinetic, and computational studies, we propose the catalytic cycle to be initiated by the formation of the coordinatively unsaturated intermediate B through the decoordination of one PMe 3 ligand (Scheme 5). The equilibrium between precatalyst A and the unsaturated species B leads to the experimentally observed induction period.…”

“…In this context it is noteworthy that [Fe­(PMe 3 ) 4 ] was very recently employed by Kakiuchi and co-workers for the catalytic C–H alkylation of phenones with substituted alkenes (Scheme ). − Inspired by this recent contribution, the present transformation with allenes sets the stage for value-adding postmodifications. [Fe­(PMe 3 ) 4 ] has also previously been utilized for the catalytic borylation of vinyl arenes .…”

DFT Study on the Mechanisms of Iron-Catalyzed Ortho C–H Homoallylation of Aromatic Ketones with Methylenecyclopropanes

“…Meanwhile, it can be seen that the distances between C(6) and Fe become longer from 2.10 Å in 6 to 2.26 Å in 7 , respectively. The reductive elimination step is often included in the mechanism studies Ligands exchange and the catalyst regeneration: the ligand exchange reaction between the intermediate 7 and R 1 yields the intermediate 8a and the product P .…”

Iron‐Catalyzed Chemoselective C−N Coupling Reaction: A Protecting‐Group‐Free Amination of Aryl Halides Bearing Amino or Hydroxy Groups

“…Scheme 4a shows a plausible catalytic cycle of the amination. Although we once proposed the reaction mechanism based on a monomeric Fe II -amide species, [18] we have herein revised it with the Fe-dimer active species according to the present DFT study where dimeric complex Fe 2 (NPh 2 ) 4 [22] is > 30 kcal/mol lower in energy than monomeric complex Fe (NPh 2 ) 2 (See Figure S49 in Supporting Information for details). The dimeric-Fe II -amide complex A undergoes the oxidative addition with an aryl halide to form iron(II)-iron(IV) complex B.…”