A long-range intramolecular functionalization by alkoxyl radicals: a long-range intramolecular oxygenation of C(15) of the androstane skeleton

Orito, Kazuhiko; Ohto, M.; Suginome, Hiroshi

doi:10.1039/c39900001074

“…C 15 oxidation is very attractive, since C 15 ‐oxygenated steroids are known to inhibit natural sterol biosynthesis, and some of these derivatives have found application as anti‐hypertensive and anti‐cholesterol drugs . However, D‐ring oxidation is elusive, and the only reported methodology requires several steps, the key one being Breslow's templated, stoichiometric remote functionalization …”

Section: Figurementioning

confidence: 99%

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

Olivo

¹

,

Capocasa

²

,

Ticconi

³

et al. 2020

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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(sp3)−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(sp3)−H oxidation of amino‐steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.

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“…C 15 oxidation is very attractive, since C 15 ‐oxygenated steroids are known to inhibit natural sterol biosynthesis, and some of these derivatives have found application as anti‐hypertensive and anti‐cholesterol drugs . However, D‐ring oxidation is elusive, and the only reported methodology requires several steps, the key one being Breslow's templated, stoichiometric remote functionalization …”

Section: Figurementioning

confidence: 99%

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

Olivo

¹

,

Capocasa

²

,

Ticconi

³

et al. 2020

View full text Add to dashboard Cite

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(sp3)−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(sp3)−H oxidation of amino‐steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.

show abstract

Mercury(II) Oxide-Iodine

Iwasa

¹

,

Rawal

²

2001

Encyclopedia of Reagents for Organic Synthesis

0

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A long-range intramolecular functionalization by alkoxyl radicals: a long-range intramolecular oxygenation of C(15) of the androstane skeleton

Cited by 9 publications

References 6 publications

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

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

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

Mercury(II) Oxide-Iodine

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