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Catalytic asymmetric carbon–carbon bond formation via allylic alkylations with organolithium compounds

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Abstract

Carbon–carbon bond formation is the basis for the biogenesis of nature's essential molecules. Consequently, it lies at the heart of the chemical sciences. Chiral catalysts have been developed for asymmetric C–C bond formation to yield single enantiomers from several organometallic reagents. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general catalytic methodology for enantioselective C–C formation has proven elusive, until now. Here, we report a copper-based chiral catalytic system that allows carbon–carbon bond formation via allylic alkylation with alkyllithium reagents, with extremely high enantioselectivities and able to tolerate several functional groups. We have found that both the solvent used and the structure of the active chiral catalyst are the most critical factors in achieving successful asymmetric catalysis with alkyllithium reagents. The active form of the chiral catalyst has been identified through spectroscopic studies as a diphosphine copper monoalkyl species.

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Figure 1
Figure 2: Mechanistic study of chiral catalyst formation and the effect of copper salt and co-solvents present in the alkyllithium reagent.

Change history

  • 15 March 2011

    In the version of this Article originally published, the Acknowledgements section was incorrect. This error has now been corrected in all versions of the Article.

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Acknowledgements

The authors acknowledge the Netherlands Organization for Scientific Research (NWO-CW) and the National Research School Catalysis (NRSC-C) for financial support. M.P. thanks the Xunta de Galicia for an Angeles Alvariño contract and Fondo Social Europeo. M.F.-M. thanks the Spanish Ministry of Science and Innovation (MICINN) for a postdoctoral fellowship.

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M.P. and M.F.-M. studied solvent effects and optimized the reaction conditions. P.H.B. performed ligand screening. A.R. performed copper salt screening. S.R.H. carried out NMR studies. M.P., M.F.-M, P.H.B. and A.R. evaluated the scope of the organolithium addition reaction. All authors contributed to designing the experiments, analysing the data and editing the manuscript. S.R.H. and B.L.F. guided the research and wrote the manuscript.

Corresponding authors

Correspondence to Syuzanna R. Harutyunyan or Ben L. Feringa.

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The authors declare no competing financial interests.

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Pérez, M., Fañanás-Mastral, M., Bos, P. et al. Catalytic asymmetric carbon–carbon bond formation via allylic alkylations with organolithium compounds. Nature Chem 3, 377–381 (2011). https://doi.org/10.1038/nchem.1009

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