Abstract
Olefin metathesis catalysts provide access to molecules that are indispensable to physicians and researchers in the life sciences1,2. A persisting problem, however, is the dearth of chemical transformations that directly generate acyclic Z allylic alcohols, including products that contain a hindered neighbouring substituent or reactive functional units such as a phenol, an aldehyde, or a carboxylic acid. Here we present an electronically modified ruthenium–disulfide catalyst that is effective in generating such high-value compounds by cross-metathesis. The ruthenium complex is prepared from a commercially available precursor and an easily generated air-stable zinc catechothiolate. Transformations typically proceed with 5.0 mole per cent of the complex and an inexpensive reaction partner in 4–8 hours under ambient conditions; products are obtained in up to 80 per cent yield and 98:2 Z:E diastereoselectivity. The use of this catalyst is demonstrated in the synthesis of the naturally occurring anti-tumour agent neopeltolide and in a single-step stereoselective gram-scale conversion of a renewable feedstock (oleic acid) to an anti-fungal agent. In this conversion, the new catalyst promotes cross-metathesis more efficiently than the commonly used dichloro–ruthenium complexes, indicating that its utility may extend beyond Z-selective processes.
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Acknowledgements
This research was supported by a grant from the National Science Foundation (CHE-1362763). R.K.M.K. and M.Y. were partially supported as AstraZeneca Graduate Fellows. We thank Boston College for access to computational facilities.
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M.J.K. and R.K.M.K. carried out the catalyst synthesis, method development studies and applications related to renewable feedstock, S.T. performed the computational investigations, M.Y. carried out the experiments in connection with neopeltolide, and M.S.M. studied modes of catalyst decomposition. A.H.H. conceived and directed the investigations and composed the manuscript with revisions provided by the other authors.
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Koh, M., Khan, R., Torker, S. et al. High-value alcohols and higher-oxidation-state compounds by catalytic Z-selective cross-metathesis. Nature 517, 181–186 (2015). https://doi.org/10.1038/nature14061
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DOI: https://doi.org/10.1038/nature14061
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