Origins of Enhanced Enantioselectivity in the Pd-Catalyzed Decarboxylative Allylic Alkylation of N-Benzoyl Lactams
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1.
California Institute of Technology
Abstract
We explore the origins of the marked improvement in enantioselectivity in the inner-sphere (PHOX)Pd-catalyzed allylic alkylation of N-benzoyl lactam nucleophiles over their carbocyclic counterparts. We employ density functional theory calculations to aid in the interpretation of experimental results. Ultimately, we propose that the enhancement in enantioselectivity arises primarily from noncovalent interactions between the substrate and ligand rather than secondary substrate chelation, as previously hypothesized.
Copyright and License
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Acknowledgement
We further thank Zachary P. Sercel for insightful discussion and assistance.
Funding
The NIH-NIGMS (R35GM145239), Heritage Medical Research Investigators Program, and Caltech are thanked for their support of our research program. We thank the Caltech High Performance Computing Center for support. W.A.G. thanks the NSF (CBET-2005250) for support.
Contributions
Conceptualization, computations, manuscript preparation, A.Q.C.; Conceptualization, computations, editing, T.Z.; conceptualization, supervision, editing, B.M.S. and W.A.G.III. All authors have read and agreed to the published version of the manuscript.
Data Availability
The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials.
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Additional details
- PMCID
- PMC10662798
- National Institutes of Health
- R35GM145239
- Caltech High Performance Computing Center
- National Science Foundation
- CBET-2005250
- California Institute of Technology
- Heritage Medical Research Institute
- Caltech groups
- Heritage Medical Research Institute