An In-Depth Computational Study of Alkene Cyclopropanation Catalyzed by Fe(porphyrin)(OCH₃) Complexes. The Environmental Effects on the Energy Barriers

Abstract

Iron porphyrin methoxy complexes, of the general formula [Fe(porphyrin)(OCH 3 )], are able to catalyze the reaction of diazo compounds with alkenes to give cyclopropane products with very high efficiency and selectivity. The overall mechanism of these reactions was thoroughly investigated with the aid of a computational approach based on density functional theory calculations. The energy profile for the processes catalyzed by the oxidized [Fe III (Por)(OCH 3 )] (Por = porphine) as well as the reduced [Fe II (Por)(OCH 3 )] − forms of the iron porphyrin was determined. The main reaction step is the same in both of the cases, that is, the one leading to the terminal -carbene intermediate [Fe(Por)(OCH 3 )(CHCO 2 Et)] with simultaneous dinitrogen loss; however, the reduced species performs much better than the oxidized one. Contrarily to the iron(III) profile in which the carbene intermediate is directly obtained from the starting reactant complex, the favored iron(II) process is more intricate. The initially formed reactant adduct between [Fe II (Por)(OCH 3 )] − and ethyl diazoacetate ( EDA ) is converted into a closer reactant adduct, which is in turn converted into the terminal iron porphyrin carbene [Fe(Por)(OCH 3 )(CHCO 2 Et)] − . The two corresponding transition states are almost isoenergetic, thus raising the question of whether the rate-determining step corresponds to dinitrogen loss or to the previous structural and electronic rearrangement. The ethylene addition to the terminal carbene is a downhill process, which, on the open-shell singlet surface, presents a defined but probably short-living diradicaloid intermediate, though other spin-state surfaces do not show this intermediate allowing a direct access to the cyclopropane product. For the crucial stationary points, the more complex catalyst [Fe( 2 )(OCH 3 )], in which a sterically hindered chiral bulk is mounted onto the porphyrin, was investigated. The corresponding computational data disclose the very significant effect of the porphyrin skeleton on the reaction energy profile. Though the geometrical features around the reactive core of the system remain unchanged, the energy barriers become much lower, thus revealing the profound effects that can be exerted by the three-dimensional organic scaffold surrounding the reaction site.

Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions

“…The outer-sphere mechanism, on the other hand, involves intermolecular reaction with the olefin either in a single step or via radical intermediates . More recent computational work has focused on catalysts that promote the outer-sphere mechanism, employing bulky ligands or dimeric metal species. , Mechanistic studies on simpler catalysts of the Ru-Pheox type are, however, still rather scarce . While previously studied copper and rhodium catalysts have only one or two coordination sites available, the situation is greatly complicated in the case of Ru-Pheox ( 2 ) due to its octahedral C 1 -symmetric environment with four inequivalent positions that could lead to different intermediates (see Scheme A).…”

YfeX – A New Platform for Carbene Transferase Development with High Intrinsic Reactivity

“…The electrostatic embedding scheme was used to describe the interactions between the two regions, while hydrogen link atoms were used to treat the boundary between the QM and the MM region. The QM region was represented using the UB3LYP functional with the 6‐31G(d) basis set for all atoms except Fe where the LANL2DZ basis set with an effective core potential (ECP; labeled BS1) was used, as in previous, similar studies on carbene transfer reactions [56,57,66,87] . The MM region was described with the Amber force field.…”

Biocatalytic Intramolecular C−H aminations via Engineered Heme Proteins: Full Reaction Pathways and Axial Ligand Effects

“…[ 5j , 11a , 11c , 11d ] The connections among the transition states with the species before and after them in the reaction pathway were confirmed via intrinsic reaction coordinate calculations in Gaussian 09. To evaluate if the actual heme substituents in the real proteins could affect the conclusions from the results using non‐substituted porphyrins as found in certain substituted porphyrins, [23] additional calculations using the full heme substituents were done using the same approach as in our recent computational work which reproduced heme protein catalyzed reaction stereoselectivities within 1 % error. [24] …”