Rational Design of Supramolecular Fe and Mn Oxidation Catalysts
Abstract
Modern organic synthesis aims to prepare the target molecule in a minimal number of steps. Hence, the efficiency, selectivity, and predictability of each of these steps need to be carefully optimized, even at a late stage of a synthetic route. This is particularly true in the case of aliphatic C-H functionalization, since differentiating one C-H bond among many others with similar properties in organic molecules often stands as an open challenge. Remote, inactivated C-H sites are especially difficult to target. Supramolecular catalysis represents one of the tools to overcome such problems. As occurs in enzymes, substrate binding to a supramolecular catalyst constrains their relative orientation, and the resulting preorganization can increase reactivity and unlock unusual selectivity in a rational and predictable manner, meeting late-stage functionalization requirements. In fact, supramolecular catalysis, which was initially oriented to the comprehension of the mechanisms of the involved reactions, is currently and rapidly evolving into a synthetically useful tool. One decade ago, in 2017, we described Fe- and Mn-based supramolecular catalysts equipped with crown ether recognition sites able to efficiently catalyze the oxidation of inactivated C-H bonds in protonated primary amines. Substrate preorganization induced by recognition enables elusive oxidation at remote C8 and C9 sites in linear alkyl chains. Since then, a number of follow-up investigations allowed us to rationally elicit unnatural reactivity and selectivity in different bioinspired oxidation reactions, including predictable, late-stage C-H oxidation of steroids. In addition, an in-depth analysis of such oxidation processes provides a deep comprehension of the action mechanism of these supramolecular catalysts. In this Account, we discuss the above investigations aiming to show (i) the rational approach to the design of a supramolecular oxidation catalyst, (ii) the experimental and theoretical tools that help understand and assess its mechanism of action, and (iii) its potential to address synthetic challenges. Eventually, a section that compares our approach to the one of other research groups illustrates the state of the art in supramolecular oxidation catalysis.
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BibTeX
@article{olivo2026rational,
title = {{Rational Design of Supramolecular Fe and Mn Oxidation Catalysts}},
author = {Giorgio Olivo and Miquel Costas and Stefano Di Stefano},
journal = {Accounts of Chemical Research},
year = {2026},
month = jul,
doi = {10.1021/acs.accounts.6c00368},
url = {https://hal.science/hal-05786768v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rational Design of Supramolecular Fe and Mn Oxidation Catalysts
AU - Giorgio Olivo
AU - Miquel Costas
AU - Stefano Di Stefano
PY - 2026
DA - 2026/07/21
JO - Accounts of Chemical Research
DO - 10.1021/acs.accounts.6c00368
UR - https://hal.science/hal-05786768v1
AB - Modern organic synthesis aims to prepare the target molecule in a minimal number of steps. Hence, the efficiency, selectivity, and predictability of each of these steps need to be carefully optimized, even at a late stage of a synthetic route. This is particularly true in the case of aliphatic C-H functionalization, since differentiating one C-H bond among many others with similar properties in organic molecules often stands as an open challenge. Remote, inactivated C-H sites are especially difficult to target. Supramolecular catalysis represents one of the tools to overcome such problems. As occurs in enzymes, substrate binding to a supramolecular catalyst constrains their relative orientation, and the resulting preorganization can increase reactivity and unlock unusual selectivity in a rational and predictable manner, meeting late-stage functionalization requirements. In fact, supramolecular catalysis, which was initially oriented to the comprehension of the mechanisms of the involved reactions, is currently and rapidly evolving into a synthetically useful tool. One decade ago, in 2017, we described Fe- and Mn-based supramolecular catalysts equipped with crown ether recognition sites able to efficiently catalyze the oxidation of inactivated C-H bonds in protonated primary amines. Substrate preorganization induced by recognition enables elusive oxidation at remote C8 and C9 sites in linear alkyl chains. Since then, a number of follow-up investigations allowed us to rationally elicit unnatural reactivity and selectivity in different bioinspired oxidation reactions, including predictable, late-stage C-H oxidation of steroids. In addition, an in-depth analysis of such oxidation processes provides a deep comprehension of the action mechanism of these supramolecular catalysts. In this Account, we discuss the above investigations aiming to show (i) the rational approach to the design of a supramolecular oxidation catalyst, (ii) the experimental and theoretical tools that help understand and assess its mechanism of action, and (iii) its potential to address synthetic challenges. Eventually, a section that compares our approach to the one of other research groups illustrates the state of the art in supramolecular oxidation catalysis.
SN - 0001-4842
SN - 1520-4898
ER -