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Enantioselective silyl protection of alcohols catalysed by an amino-acid-based small molecule


Reliable, selective and environmentally friendly chemical transformations are crucial to the development of new therapeutics and the design of novel materials. Chiral catalysts that can be easily prepared and used to obtain organic molecules of high enantiomeric purity are critical to modern chemical synthesis1. The development of protecting groups that shield reactive functionalities has also proved indispensable in the preparation of complex biologically active molecules2. Here we present a chiral catalyst that promotes the enantioselective protection of a secondary alcohol as one of the most commonly used protected forms of an alcohol: a silyl ether. The catalyst is a small, simple molecule that can be prepared in three steps from commercial materials without the need for rigorously controlled conditions. Enantioselective silylations are performed with commercial silyl chlorides and produce yields of up to 96 per cent at an enantiomeric ratio of up to 98:2. Chiral catalysts for selective formation of commonly used protecting groups such as silyl ethers should significantly enhance the ability of chemical synthesis to deliver, in a more practical and efficient manner, important organic molecules.

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Figure 1
Figure 2: Enantioselective silylations of achiral diols with different silyl chloride reagents catalysed by 9.
Figure 3


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We are grateful to our colleague S. J. Miller for discussions and a critical reading of the manuscript. This work was supported by the United States National Institutes of Health, Institute of General Medical Sciences (grant to A.H.H. and M.L.S.). We are grateful to J. F. Traverse for experimental assistance.

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Correspondence to Amir H. Hoveyda or Marc L. Snapper.

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Zhao, Y., Rodrigo, J., Hoveyda, A. et al. Enantioselective silyl protection of alcohols catalysed by an amino-acid-based small molecule. Nature 443, 67–70 (2006).

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