Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published September 8, 2023 | v1
Journal Article Open

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

  • 1. ROR icon California Institute of Technology


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.


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


Files (15.1 MB)
Name Size Download all
3.9 MB Preview Download
11.2 MB Preview Download

Additional details

October 25, 2023
October 26, 2023