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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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.
The authors declare no competing financial interests.
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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