Tunneling Controls the Reaction Pathway in the Deformylation of Aldehydes by a Nonheme Iron(III)–Hydroperoxo Complex: Hydrogen Atom Abstraction versus Nucleophilic Addition

Abstract

Mononuclear nonheme iron(III)-hydroperoxo intermediates play key roles in biological oxidation reactions. In the present study, we report the highly intriguing reactivity of a nonheme iron(III)−hydroperoxo complex, [(TMC)Fe III (OOH)] 2+ (1), in the deformylation of aldehydes, such as 2-phenylpropionaldehyde (2-PPA) and its derivatives; that is, the reaction pathway of the aldehyde deformylation by 1 varies depending on reaction conditions, such as temperature and substrate. At temperature above 248 K, the aldehyde deformylation occurs predominantly via a nucleophilic addition (NA) pathway. However, as the reaction temperature is lowered, the reaction pathway changes to a hydrogen atom transfer (HAT) pathway. Interestingly, the reaction rate becomes independent of temperature below 233 K with a huge kinetic isotope effect (KIE) value of 93 at 203 K, suggesting that the HAT reaction results from tunneling. In contrast, reactions with a deuterated 2-PPA at the αposition and 2-methyl-2-phenylpropionaldehyde proceed exclusively via a NA pathway irrespective of the reaction temperature. We conclude that the bifurcation pathways between NA and HAT result from the tunneling effect in the HAT reaction by 1. To the best of our knowledge, this study reports the first example showing that tunneling plays a significant role in the activation of substrate C−H bonds by a mononuclear nonheme iron(III)−hydroperoxo complex.

Diazaphosphinanes as hydride, hydrogen atom, proton or electron donors under transition-metal-free conditions: thermodynamics, kinetics, and synthetic applications

“…This intermediately points out an extremely large KIE( 1a ) of 31.3, implying a tunneling effect in this HAT process. Such a large KIE has been found in biochemical 30 and transition-metal systems, 31 but seldom observed in organic HAT processes. Similarly, the rate of the analogous HAT of 1b k HAT ( 1b ) was determined to be 0.74 M −1 s −1 (Table S5 † ).…”

Large Isotope Effects in Organometallic Chemistry

“…[10,[12][13][14][15][16][17][18][19][20][21][22][23][24][25] Since deuterium has a shorter deBroglie wavelength and a poor ability to tunnel compared to hydrogen, large isotope effects are often taken to indicate quantum tunneling of hydrogen nuclei through an energy barrier. [39][40][41][42][43][44][45][46][47][48][49][50][51][52] (b) Compound effects from multiple reaction steps. Experimentally observed isotope effects can be influenced by more than one elementary reaction step.…”

“…[10,[12][13][14][15][16][17]72] Experimental evidence for proton tunneling has been collected (and also debated) in an array of chemical fields, particularly enzymology and physical organic chemistry. [19,73,74] Within synthetic organometallic chemistry, the temperature dependence of rates and KIEs has been used both to support a tunneling pathway [39][40][41]50,49] and to rule out tunneling. [64,69] Kinetic analysis under different reaction conditions is used to support non-tunneling explanations (b) and (c) for large observed isotope effects, especially when an isotope effect is found to change under different measurement conditions.…”

Catalytic Selective Oxidation of Primary and Secondary Alcohols Using Nonheme [Iron(III)(Pyridine‐Containing Ligand)] Complexes

“…[ 15 ] In the case of nonheme iron enzymes and their models, key intermediates are high‐valent iron‐oxo intermediates, such as iron(III)‐super‐oxo, iron(III)‐peroxo, iron(III)‐hydroperoxo, and iron(IV)‐ or iron(V)‐oxo species. [ 14a,16 ] While iron(III)‐superoxo species have been recognized as active oxidants in the C–H bond activation and oxygen atom transfer (OAT) reactions although the intermediates are only able to activate weak C–H bonds in hydrocarbons, the reactivities of nonheme iron(III)–hydroperoxo species are still a matter of debate and subject of in‐depth experimental and theoretical investigations. [ 17 ] On the other hand, nonheme iron(IV)‐oxo species are competent oxidants capable of abstracting hydrogen atom in C–H bond activation reactions.…”