A Highly Efficient Synthesis of Z-Macrocycles using Stereoretentive, Ruthenium-Based Metathesis Catalysts
A highly efficient, Z-selective ring-closing metathesis system for the formation of macrocycles using a stereoretentive, ruthenium-based catalyst supported by a dithiolate ligand is reported. The catalyst is remarkably active as observed in initiation experiments showing complete catalyst initiation at −20 °C within 10 minutes. Macrocyclization reactions generated Z-products from easily accessible diene starting materials bearing a Z-olefin moiety. This approach provides a more efficient and selective route to Z-macrocycles relative to previously reported systems. Reactions were completed within shorter reaction times, and turnover numbers of up to 100 could be achieved. Macrocyclic lactones ranging in size from twelve- to seventeen-membered rings were synthesized in moderate to high yields (67–79 %) with excellent Z-selectivity (95–99 %).
© 2017 Wiley. Manuscript received: May 5, 2017; Accepted manuscript online: June 23, 2017; Version of record online: July 12, 2017. Funding from the Office of Naval Research (N00014-14-1-0650), NIH (GM031332), and NSF (CHE-1502616) is acknowledged. T.S.A. recognizes NSF for support through a Graduate Research Fellowship. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. The authors would like to thank M. A. Pribisko, W. J. Wolf, C. W. Lee, T. P. Montgomery, and N. F. Nathel for helpful suggestions. D. Vandervelde and W. J. Wolf are acknowledged for their help with initiation experiments. N. Torian and M. Shahgholi are thanked for their assistance with high-resolution mass spectrometry. Materia, Inc. is acknowledged for generous donations of 4. The authors declare no conflict of interest.
Accepted Version - 90da9015fc87851a2f6b6605598cb3034540abdead56f03bd5c7fc5ed09db1ca.pdf
Supplemental Material - anie201704670-sup-0001-SI1.pdf
Accepted Version - nihms915248.pdf
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