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Catalytic asymmetric carbon–carbon bond formation using alkenes as alkylmetal equivalents

Nature Chemistry volume 4, pages 649–654 (2012)Cite this article

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Abstract

Catalytic asymmetric conjugate addition reactions with organometallic reagents are powerful reactions in synthetic chemistry. Procedures that use non-stabilized carbanions have been developed extensively, but these suffer from a number of limitations that prevent their use in many situations. Here, we report that alkylmetal species generated in situ from alkenes can be used in highly enantioselective 1,4-addition initiated by a copper catalyst. Using alkenes as starting materials is desirable because they are readily available and have favourable properties when compared to pre-made organometallics. High levels of enantioselectivity are observed at room temperature in a range of solvents, and the reaction tolerates functional groups that are not compatible with comparable methods—a necessary prerequisite for efficient and protecting-group-free strategies for synthesis.

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Figure 1: Comparing alkenes and the organometallics typically used in catalytic asymmetric addition reactions.

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Acknowledgements

The authors acknowledge financial support from the EPSRC (EP/H003711/1, a Career Acceleration Fellowship to S.P.F.) and the Oxford University Press John Fell Fund. D. Daniels and B. Odell are thanked for their generous technical assistance with HPLC and NMR, respectively.

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Authors and Affiliations

  1. Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK

    Rebecca M. Maksymowicz, Philippe M. C. Roth & Stephen P. Fletcher

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  1. Rebecca M. Maksymowicz
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  2. Philippe M. C. Roth
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  3. Stephen P. Fletcher
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Contributions

R.M.M. and P.M.C.R. performed the experiments. All authors contributed to designing the experiments, analysing the data and editing the manuscript. S.P.F. guided the research and wrote the manuscript.

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Correspondence to Stephen P. Fletcher.

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Maksymowicz, R., Roth, P. & Fletcher, S. Catalytic asymmetric carbon–carbon bond formation using alkenes as alkylmetal equivalents. Nature Chem 4, 649–654 (2012). https://doi.org/10.1038/nchem.1394

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