DFT and AFIR Study on the Mechanism and the Origin of Enantioselectivity in Iron-Catalyzed Cross-Coupling Reactions

Abstract

The mechanism of the full catalytic cycle for Fe-chiral-bisphosphine-catalyzed cross-coupling reaction between alkyl halides and Grignard reagents (Nakamura and co-workers, J. Am. Chem. Soc. 2015, 137, 7128) was rationalized by using density functional theory (DFT) and multicomponent artificial force-induced reaction (MC-AFIR) methods. The computed mechanism consists of (a) C-Cl activation, (b) transmetalation, (c) C-Fe bond formation, and (d) C-C bond formation through reductive elimination. Our survey on the prereactant complexes suggested that formation of Fe(BenzP*)Ph and Fe(BenzP*)Ph complexes are thermodynamically feasible. Fe(BenzP*)Cl complex is the active intermediate for C-Cl activation. Fe(BenzP*)Ph complex can be formed if the concentration of Grignard reagent is high. However, it leads to biphenyl (byproduct) instead of the cross-coupling product. This explains why slow addition of Grignard reagent is critical for the cross-coupling reaction. The MC-AFIR method was used for systematic determination of transition states for C-Fe bond formation and C-C bond formation starting from the key intermediate Fe(BenzP*)PhCl. According to our detailed analysis, C-C bond formation is the selectivity-determining step. The computed enantiomeric ratio of 95:5 is in good agreement with the experimental ratio (90:10). Energy decomposition analysis suggested that the origin of the enantioselectivity is the deformation of Ph-ligand in Fe-complex, which is induced by the bulky tert-butyl group of BenzP* ligand. Our study provides important mechanistic insights for the cross-coupling reaction between alkyl halides and Grignard reagents and guides the design of efficient Fe-based catalysts for cross-coupling reactions.

A DFT Study on FeI/FeII/FeIII Mechanism of the Cross-Coupling between Haloalkane and Aryl Grignard Reagent Catalyzed by Iron-SciOPP Complexes

“…The reaction mechanism from Fe II BrPh(SciOPP) is studied as it is predicted to be the starting species in cross-coupling reactions. The TSs with lowest energy spin states as found in our previous study were only considered, due to large system size [38]. The first step is the C-Br activation of bromocycloheptane by quintet Fe II BrPh(SciOPP) ( 5 2 PhBr ), through an atom transfer mechanism ( Figure 2).…”

Intra- and intermolecular Fe-catalyzed dicarbofunctionalization of vinyl cyclopropanes

“…14 Pioneering mechanistic studies by Kochi 15 in the 1970s and more recent reports by Bedford, 16 Nakamura, 17 Norrby, 18 Fürstner, 19 Tonzetich, 20 Koszinowski, 21 and Neidig 22 have led to a greater understanding of these transformations. In 2017, parallel quantum mechanical studies in our lab 23 and by Morokuma 24 were reported on the mechanism of chiral bisphosphine cross-coupling reactions between a-chloro esters and aryl Grignard reagents. These studies revealed a mechanism involving halogen abstraction by an aryl Fe(I) complex, leading to an alkyl radical and halo aryl Fe(II) species (Scheme 2; circled).…”

The CuFe2O4@SiO2@ZrO2/SO42−/Cu nanoparticles: an efficient magnetically recyclable multifunctional Lewis/Brønsted acid nanocatalyst for the ligand- and Pd-free Sonogashira cross-coupling reaction in water

“…Palladium is a toxic, rare and expensive transition metal that is mainly used along with toxic and air-sensitive phosphine ligands. 4 More importantly, the presence of copper as a co-catalyst promotes the Glaser-type homo-coupling of terminal acetylenes to generate a by-product (Scheme 1); thus, various attempts have been developed to perform the reaction under copper-free and Pdfree conditions in a mild, safe, ecofriendly, and cost-effective manner; in this regard, one strategy is the use of cheaper and safer alternative transition metals including Ni, 5 Cu, 6 Fe, 7 and Co. 8 Among these, the potential of Cu for application in the C-N as well as C-C cross coupling reactions is well-known; 9 moreover, several achievements have been reported for the Cu-catalyzed Sonogashira reaction; the recent examples include the use of Cu 2 O/RGO, 10 Cu/ Mn bimetallic, 9 CuI/PPh 3 /K 2 CO 3 , 11 CuI/K 3 PO 4 /1,4-dioxane, 12 and Au$CuFe 2 O 4 @silica as catalysts for this reaction. 2 Recently, Sun and coworkers 13 have reported the application of a Cu-MOF derived from two-phase Cu/Cu 2 O-rGO as an efficient catalyst for the Sonogashira reaction.…”