Predictable Selectivity in Remote C−H Oxidation of Steroids: Analysis of Substrate Binding Mode. Issue 31 (20th May 2020)

• Record Type: Journal Article
• Authors: Olivo, Giorgio; Capocasa, Giorgio; Ticconi, Barbara; Lanzalunga, Osvaldo; Di Stefano, Stefano; Costas, Miquel
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 31(2020)
• Page Start: 12703
• Page End: 12708
• Publication Date: 2020-05-20
• Subjects: hydrogen bonds -- molecular recognition -- oxidation -- steroids -- supramolecular catalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202003078
• Languages: English
• ISSNs: 1433-7851

Abstract

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 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. Abstract : Analysis of the substrate binding mode of amino‐steroids to a supramolecular catalyst enables rational prediction of site selectivity in C(sp 3 )−H oxidation of amino‐steroids. This strategy was applied to late‐stage C(sp 3 )−H oxidation of amino‐steroids at C15 (or C16), with a selectivity tunable by modification of the catalyst chirality and metal.