Predictability is a key requirement to encompass late-stage C-H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp)-H oxidation, as it requires distinguishing a specific C-H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C-H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host-guest adduct by NMR analysis. These analyses indicate which remote C-H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late-stage C(sp)-H oxidation of amino-steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.

Predictable Selectivity in Remote C-H Oxidation of Steroids: Analysis of Substrate Binding Mode

Olivo G;Lanzalunga O;Di Stefano S;
2020

Abstract

Predictability is a key requirement to encompass late-stage C-H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp)-H oxidation, as it requires distinguishing a specific C-H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C-H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host-guest adduct by NMR analysis. These analyses indicate which remote C-H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late-stage C(sp)-H oxidation of amino-steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.
2020
Istituto per i Sistemi Biologici - ISB (ex IMC)
C-H activation
steroid
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/456235
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