Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Lactams: Enantioselective Construction of All-Carbon Quaternary Stereocenters in Saturated Nitrogen-Containing Heterocycles
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1.
California Institute of Technology
Abstract
Stereogenic nitrogen-containing heterocycles are ubiquitous in natural products and pharmaceutical compounds, but methods for their enantioselective construction have remained elusive. We report a general method for the asymmetric conjugate addition of arylboronic acids to β-alkyl/aryl α,β-unsaturated lactams that affords chiral β,β-disubstituted lactams. The transformation is operationally simple and air- and moisture-tolerant and uses a commercially available (S)-t-Bu-PyOx ligand. The method is high-yielding (up to 95% yield) and enantioselective (up to 97% ee) for a wide range of arylboronic acids and α,β-unsaturated lactams, including those with different ring sizes.
Copyright and License
© 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0.
Acknowledgement
The authors thank NIH-NIGMS (R35GM145239) and the Heritage Medical Research Institute Investigator Program for the support of our research program. The authors thank Mr. Christian Strong for NMR assistance, Dr. David VanderVelde for NMR assistance and maintenance of the Caltech NMR facility, and Dr. Scott Virgil for assistance with instrumentation and maintenance of the Caltech Center for Catalysis and Chemical Synthesis. T.Z. thanks the John Stauffer Charitable Trust for financial support. Y.N. thanks Shionogi & Co., Ltd. for a postdoctoral research fellowship.
Data Availability
The data underlying this study are available in the published article and its Supporting Information.
Conflict of Interest
The authors declare no competing financial interest.
Attached Files
acs.orglett.3c02064.pdf - published article
ol3c02064_si_001.pdf - supplementary information
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Additional details
Identifiers
- ISSN
- 1523-7052
- PMCID
- PMC10496148
Related works
- Is supplemented by
- https://pubs.acs.org/doi/suppl/10.1021/acs.orglett.3c02064/suppl_file/ol3c02064_si_001.pdf (URL)
Funding
- National Institutes of Health
- R35GM145239
- California Institute of Technology
Dates
- Available
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2023-08-28Published online