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Predictable Selectivity in Remote C−H Oxidation of Steroids: Analysis of Substrate Binding Mode
Author(s) -
Olivo Giorgio,
Capocasa Giorgio,
Ticconi Barbara,
Lanzalunga Osvaldo,
Di Stefano Stefano,
Costas Miquel
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202003078
Subject(s) - selectivity , substrate (aquarium) , supramolecular chemistry , catalysis , chemistry , reactivity (psychology) , combinatorial chemistry , molecule , organic chemistry , medicine , oceanography , alternative medicine , pathology , geology
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 3 )−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 3 )−H oxidation of amino‐steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.