Hyperpositive nonlinear effects in asymmetric catalysis

Abstract

Asymmetric amplification is a curious phenomenon that is believed to play a key role in the emergence of biological homochirality, and thus of life itself. In asymmetric catalysis, it is achieved via positive nonlinear effects, which allow high product enantiomeric excesses with a non-enantiopure catalyst. However, it has also been proposed that non-enantiopure catalysts may be even more enantioselective than their enantiopure counterparts, although such a case has never been experimentally observed so far. Here, we present an example of such a hyperpositive nonlinear effect in asymmetric catalysis. We found that addition of dialkylzinc reagents to benzaldehyde gave higher product enantiomeric excesses with only partially resolved chiral N-benzyl-ephedrine ligands. A mechanistic study was carried out and our results point towards a two-component catalysis, where mononuclear as well as aggregated catalysts are in equilibrium and in competition. These results introduce an unprecedented class of asymmetric amplification in enantioselective catalysis.

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Fig. 1: Hyperpositive NLE.
Fig. 2: Impact of catalyst loading on the e.e. of the product.
Fig. 3: Temperature dependence study.
Fig. 4: Catalyst order as a function of catalyst loading.
Fig. 5: Evolution of product e.e. as a function of time and at different catalyst loadings.
Fig. 6: Proposed enantiodivergent model for the (−)-NBE-catalysed addition of dialkylzincs to benzaldehyde.

Data availability

Complete experimental procedures, compound characterization data and kinetic rate profiles are available in the Supplementary Information.

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Acknowledgements

We acknowledge the CNRS and the Ministère de l’Enseignement Supérieur et de la Recherche (MESR) for a PhD grant to Y.G. This work is part of the Strasbourg IDEX programme and we thank NIE Labex for support (ANR-11-LABX-0058_NIE). We thank L. H. Gade (University of Heidelberg) and J. Moran (University of Strasbourg) for helpful comments on this work.

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Y.G. performed the synthetic experiments and data analyses. A.M.-F. and T.A. participated in data analyses. S.B.-L. conceptualized and supervised the study and wrote the manuscript with Y.G.

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Correspondence to Stéphane Bellemin-Laponnaz.

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Supplementary information

Supplementary Information

Supplementary methods, Figs. 1–7, Tables 1–5 and references.

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Geiger, Y., Achard, T., Maisse-François, A. et al. Hyperpositive nonlinear effects in asymmetric catalysis. Nat Catal 3, 422–426 (2020). https://doi.org/10.1038/s41929-020-0441-1

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