Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols
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Author(s)
Buchwald, Stephen Leffler
Shi, Shiliang
Wong, Zackary Leland
Date Issued
March 2016
Journal
Nature
Publisher
Nature Publishing Group
Citation
Shi, Shi-Liang, Zackary L. Wong, and Stephen L. Buchwald. “Copper-Catalysed Enantioselective Stereodivergent Synthesis of Amino Alcohols.” Nature 532, no. 7599 (March 28, 2016): 353–356.
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Author's final manuscript
Abstract
The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge3. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1038/nature17191
