When Reactions Cross Back: Dynamical Effects in Manganese–Oxo Epoxidation
- 1Department of Chemistry
- 2Indian Institute of Technology Bombay
Abstract
The oxidation of alkenes into valuable functional products such as alcohols, carbonyls, and epoxides remains a cornerstone transformation in synthetic chemistry, yet achieving precise control over reaction pathways and selectivity continues to pose challenges. Although prior work has emphasized the influence of axial ligand identity—often comparing ligands with substantial electronic or steric divergence—this study delves into how subtle variations between structurally similar ligands, namely pyridine (Py) and 4-tert-butylpyridine (Ty), modulate the reactivity and stereoselectivity of manganese porphyrin-catalysed epoxidation. First-principles DFT calculations show that the activation of the manganese oxo species, a key step that initiates the catalytic cycle, proceeds with similar kinetic and thermodynamic profiles for both Py and Ty. The catalytic process involves initial olefin attack by the Mn-oxo to form a cis-oriented radical intermediate. This can either cyclize directly to give cis-epoxide, undergo internal rotation to yield a trans-radical species (eventually forming trans-epoxide), or proceed through a stepwise path that leads to carbonyl products via carbocation intermediates and hydride shifts. Notably, the substitution of Py with Ty selectively increases the barrier for transradical ring closure, attributed to differential stabilization of the radical and transition state, suggesting that small axial ligand changes primarily influence the later stages of the reaction coordinate. To uncover phenomena beyond static energy landscapes, quasi-classical trajectory (QCT) simulations were employed. These revealed that dynamic effects—such as momentum flow and intermediate lifetimes—govern the actual reaction outcomes. Despite DFT predicting comparable energetic profiles, QCT simulations captured ligand-dependent differences in mechanism: Ty-ligated systems predominantly followed rapid, ballistic pathways with minimal non-reactive trajectories, while Py-ligated analogs exhibited a greater variety of mechanisms, including more frequent non-reactive trajectories and unrelaxed intermediates. Reaction onset, as indicated by Mn–O bond elongation, occurred earlier with Ty, reflecting a sharper reaction impulse. These dynamic features correlate well with experimental observations of enhanced reactivity and diastereoselectivity for the Ty system. Collectively, these findings underscore that traditional static models may overlook critical aspects of reactivity. The presence of intermediates on potential energy surfaces does not inherently imply mechanistic relevance unless validated by real-time trajectory analysis. This study emphasizes the necessity of integrating dynamical simulations to gain a more accurate and mechanistically rich understanding of transition metal-catalysed oxidation reactions.
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BibTeX
@misc{nettem2026when,
title = {{When Reactions Cross Back: Dynamical Effects in Manganese–Oxo Epoxidation}},
author = {Chandrasekhar Nettem and Gopalan Rajaraman},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009683/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009683/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - When Reactions Cross Back: Dynamical Effects in Manganese–Oxo Epoxidation
AU - Chandrasekhar Nettem
AU - Gopalan Rajaraman
PY - 2026
DA - 2026/09/30
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009683/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009683/v1
AB - The oxidation of alkenes into valuable functional products such as alcohols, carbonyls, and epoxides remains a cornerstone transformation in synthetic chemistry, yet achieving precise control over reaction pathways and selectivity continues to pose challenges. Although prior work has emphasized the influence of axial ligand identity—often comparing ligands with substantial electronic or steric divergence—this study delves into how subtle variations between structurally similar ligands, namely pyridine (Py) and 4-tert-butylpyridine (Ty), modulate the reactivity and stereoselectivity of manganese porphyrin-catalysed epoxidation. First-principles DFT calculations show that the activation of the manganese oxo species, a key step that initiates the catalytic cycle, proceeds with similar kinetic and thermodynamic profiles for both Py and Ty. The catalytic process involves initial olefin attack by the Mn-oxo to form a cis-oriented radical intermediate. This can either cyclize directly to give cis-epoxide, undergo internal rotation to yield a trans-radical species (eventually forming trans-epoxide), or proceed through a stepwise path that leads to carbonyl products via carbocation intermediates and hydride shifts. Notably, the substitution of Py with Ty selectively increases the barrier for transradical ring closure, attributed to differential stabilization of the radical and transition state, suggesting that small axial ligand changes primarily influence the later stages of the reaction coordinate. To uncover phenomena beyond static energy landscapes, quasi-classical trajectory (QCT) simulations were employed. These revealed that dynamic effects—such as momentum flow and intermediate lifetimes—govern the actual reaction outcomes. Despite DFT predicting comparable energetic profiles, QCT simulations captured ligand-dependent differences in mechanism: Ty-ligated systems predominantly followed rapid, ballistic pathways with minimal non-reactive trajectories, while Py-ligated analogs exhibited a greater variety of mechanisms, including more frequent non-reactive trajectories and unrelaxed intermediates. Reaction onset, as indicated by Mn–O bond elongation, occurred earlier with Ty, reflecting a sharper reaction impulse. These dynamic features correlate well with experimental observations of enhanced reactivity and diastereoselectivity for the Ty system. Collectively, these findings underscore that traditional static models may overlook critical aspects of reactivity. The presence of intermediates on potential energy surfaces does not inherently imply mechanistic relevance unless validated by real-time trajectory analysis. This study emphasizes the necessity of integrating dynamical simulations to gain a more accurate and mechanistically rich understanding of transition metal-catalysed oxidation reactions.
ER -