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Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols


The discovery of catalysts that can be used to synthesize complex organic compounds by enantioselective transformations is central to advances in the life sciences1; for this reason, many chemists aim to discover catalysts that allow for preparation of chiral molecules as predominantly one mirror-image isomer2. The ideal catalyst should not contain precious elements3 and should bring reactions to completion in a few hours through operationally simple procedures. Here we introduce a set of small organic molecules that can catalyse reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which might serve as intermediates in the preparation of biologically active molecules. A distinguishing feature of this catalyst class is the presence of a ‘key’ proton embedded within their structure. Catalysts are derived from the abundant amino acid valine and are prepared in large quantities in four steps with inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mole per cent catalyst in less than six hours at room temperature to generate products in more than 85 per cent yield and ≥97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents are expected to render this advance important for future progress in syntheses of amines and alcohols, which are useful in chemistry, biology and medicine.

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Figure 1: The significance of homoallylic amines and alcohols illustrated by three approaches to their catalytic enantioselective synthesis.
Figure 2: Chiral amino alcohols as candidates for catalyst precursors.
Figure 3: Efficient and enantioselective catalytic allyl additions to aldimines.
Figure 4: Practical, scalable and highly α-selective catalytic enantioselective allyl additions to imines.
Figure 5: Catalytic enantioselective additions to isatins and reactions with an allenylboron reagent.


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This research was supported by the US National Institutes of Health, Institute of General Medical Sciences (grant GM-57212). S.T. was a Swiss National Science Foundation Postdoctoral Fellow; E.M.V. was an AstraZeneca Graduate Fellow. We thank B. Li for assistance in securing X-ray structures, S. J. Meek, S. J. Malcolmson and K. L. Tan for discussions, Boston College for providing access to computational facilities and Frontier Scientific for gifts of various organoboron reagents.

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Authors and Affiliations



D.L.S. and T.P. were involved in the discovery, design and development of the catalysts; D.L.S., S.T. and T.P. worked on applications to enantioselective additions to imines; D.L.S. and E.M.V. developed the enantioselective allyl and allene additions to isatins, respectively; D.L.S., S.T., T.P. and F.H. carried out mechanistic and computational studies. A.H.H. conceived, designed and directed the investigations and wrote the manuscript with revisions provided by D.L.S. and E.M.V. This work is part of a collaborative programme between A.H.H. and M.L.S. involving the development of amino acid-derived chiral catalysts.

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Correspondence to Amir H. Hoveyda.

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Silverio, D., Torker, S., Pilyugina, T. et al. Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols. Nature 494, 216–221 (2013).

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