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N-silyl oxyketene imines are underused yet highly versatile reagents for catalytic asymmetric synthesis

Nature Chemistry volume 2, pages 937–943 (2010)Cite this article

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Abstract

The reactions of acyl anion equivalents (d1 synthons) with carbonyl electrophiles allow for the construction of a wide range of molecules useful for the synthesis of biologically active compounds, natural products and chiral ligands. Despite their utility, significant challenges still exist for developing catalytic, enantioselective variants of these reactions. For example, the asymmetric benzoin process, arguably the most characteristic reaction of d1 synthetic equivalents, finds no general solution for reactions involving aliphatic acyl anions. In this Article, we introduce a new class of stable, isolable silyl ketene imines derived from protected cyanohydrins. These nucleophiles serve as acyl anion equivalents in Lewis base catalysed aldol addition reactions and allow for the preparation of cross-benzoin and glycolate-aldol products in high yield and with exceptional diastereo- and enantioselectivities.

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Figure 1: Reaction pathways available to N-silyl oxyketene imines.
Figure 2
Figure 3: Transformations of nitriles 6ba and 11.
Figure 4: Proposed catalytic cycle for N-silyl oxyketene imine additions to aromatic aldehydes via Lewis base activation of Lewis acids.

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Acknowledgements

The authors are grateful to the National Science Foundation (NSF CHE-0414440 and 0717989) for financial support. T.W.W. thanks Abbott Laboratories for a Graduate Fellowship in Synthetic Organic Chemistry.

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  1. Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, 61801, Illinois, USA

    Scott E. Denmark & Tyler W. Wilson

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  1. Scott E. Denmark
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T.W.W. planned and carried out the experimental work. S.E.D. initiated and directed the project. The manuscript was written jointly by the authors.

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Correspondence to Scott E. Denmark.

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Denmark, S., Wilson, T. N-silyl oxyketene imines are underused yet highly versatile reagents for catalytic asymmetric synthesis. Nature Chem 2, 937–943 (2010). https://doi.org/10.1038/nchem.857

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