The rapid generation of molecular complexity from simple starting materials is a key challenge in synthesis. Enantioselective radical cyclization cascades have the potential to deliver complex, densely packed, polycyclic architectures, with control of three-dimensional shape, in one step. Unfortunately, carrying out reactions with radicals in an enantiocontrolled fashion remains challenging due to their high reactivity. This is particularly the case for reactions of radicals generated using the classical reagent, SmI2. Here, we demonstrate that enantioselective SmI2-mediated radical cyclizations and cascades that exploit a simple, recyclable chiral ligand can convert symmetrical ketoesters to complex carbocyclic products bearing multiple stereocentres with high enantio- and diastereocontrol. A computational study has been used to probe the origin of the enantioselectivity. Our studies suggest that many processes that rely on SmI2 can be rendered enantioselective by the design of suitable ligands.
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Samarium(II) folding cascades involving hydrogen atom transfer for the synthesis of complex polycycles
Nature Communications Open Access 15 November 2018
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This work was partially supported by The Leverhulme Trust (Postdoctoral Fellowship to N.K.; RPG-2012-761) and the EPSRC (DTA Studentship to M.P.) (Established Career Fellowship to D.J.P.; EP/M005062/1).
The authors declare no competing financial interests.
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Kern, N., Plesniak, M., McDouall, J. et al. Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals. Nature Chem 9, 1198–1204 (2017). https://doi.org/10.1038/nchem.2841
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