Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals

• Published in: Nature (London) 2016-04, Vol.532 (7598), p.218-222
• Main Authors: Murphy, John J., Bastida, David, Paria, Suva, Fagnoni, Maurizio, Melchiorre, Paolo
• Format: Article
• Language: English
• Subjects: 639/638/403; 639/638/439/890; 639/638/77/889; Analysis; Atmospheric chemistry; Carbon; Catalysis; Catalysts; Chemical bonds; Chemical properties; Chemistry, Organic; Humanities and Social Sciences; letter; multidisciplinary; Organic chemistry; Radicals (Chemistry); Science; Trapping
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature17438

A combination of photoredox and asymmetric organic catalysis enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to construct quaternary carbon stereocentres with high fidelity. Radical solution to quaternary stereogenic centre synthesis Quaternary stereogenic centres — carbon atoms with four distinct carbon substituents attached — are found in many biologically active natural products. A central goal of modern organic chemistry is to develop new catalytic enantioselective carbon–carbon bond-forming strategies that can be used to generate such centres. These authors demonstrate how a combination of photoredox and asymmetric organic catalysis enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to set quaternary carbon stereocentres with high fidelity. This method appears to be the first application of iminium ion activation, a successful catalytic strategy for enantioselective polar chemistry, in the realm of radical reactivity. An important goal of modern organic chemistry is to develop new catalytic strategies for enantioselective carbon–carbon bond formation that can be used to generate quaternary stereogenic centres. Whereas considerable advances have been achieved by exploiting polar reactivity 1 , radical transformations have been far less successful 2 . This is despite the fact that open-shell intermediates are intrinsically primed for connecting structurally congested carbons, as their reactivity is only marginally affected by steric factors 3 . Here we show how the combination of photoredox 4 and asymmetric organic catalysis 5 enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to obtain quaternary carbon stereocentres with high fidelity. Critical to our success was the design of a chiral organic catalyst, containing a redox-active carbazole moiety, that drives the formation of iminium ions and the stereoselective trapping of photochemically generated carbon-centred radicals by means of an electron-relay mechanism. We demonstrate the generality of this organocatalytic radical-trapping strategy with two sets of open-shell intermediates, formed through unrelated light-triggered pathways from readily available substrates and photoredox catalysts—this method represents the application of iminium ion activation 6 (a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.