Enantioselective 1,3-Dipolar Cycloadditions of α-Methylene Lactams to Construct Spirocycles
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1.
California Institute of Technology
Abstract
Spirocyclic scaffolds are important motifs due to their potential to bestow favorable effects on pharmaceutical compounds. However, there is a need for efficient methods for their enantioselective construction. We report a method for the asymmetric 1,3-dipolar cycloaddition of diazoacetates or nitrile oxides with α-methylene lactams to prepare chiral spirocyclic heterocycles. The methodology is high yielding (up to 91% yield) and enantioselective (up to 89% ee) for a wide range of N-substituents and 6- and 7-membered ring lactam substrates.
Copyright and License
© 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0.
Acknowledgement
The NIH-NIGMS (R01GM080269), NIH-NIGMS (R35GM145239), and Heritage Medical Research Investigators Program are thanked for the support of our research program. Y.N. thanks Shionogi & Co., Ltd. for a postdoctoral research fellowship. K.J.G. thanks the NSF GRFP for funding.
Contributions
Y.N. and K.J.G. contributed equally.
Conflict of Interest
The authors declare no competing financial interest.
Attached Files
acs.orglett.3c01978.pdf - published article
ol3c01978_si_001.pdf - supporting information
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Additional details
- ISSN
- 1523-7052
- PMCID
- PMC10496134
- National Institutes of Health
- R01GM080269
- National Institutes of Health
- R35GM145239
- California Institute of Technology
- National Science Foundation
- Available
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2023-08-29Published online
- Caltech groups
- Heritage Medical Research Institute