Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals


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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Figure 1: Reagent-controlled enantioselective radical C–C bond-forming cyclizations.
Figure 2: Origin of enantioselectivity in the cyclizations.


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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).

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N.K. and D.J.P. conceived the study and co-wrote the manuscript. N.K. designed and performed experiments and M.P.P. performed experiments. J.J.W.M. performed the computational study.

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Correspondence to David J. Procter.

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The authors declare no competing financial interests.

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Crystallographic data for compound 2a (CIF 2576 kb)

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Crystallographic data for compound 4 (CIF 551 kb)

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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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