Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes via a decarboxylative aldol cyclization
Abstract
The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-ketoesters via an interrupted asymmetric allylic alkylation is disclosed. Substrates possessing pendant aldehydes undergo decarboxylative enolate formation in the presence of a chiral Pd catalyst and subsequently participate in an enantio- and diastereoselective, intramolecular aldol reaction to furnish spirocyclic β-hydroxy ketones which may be oxidized to the corresponding enantioenriched diketospiranes. Additionally, this chemistry has been extended to α-allylcarboxy lactam substrates leading to a formal synthesis of the natural product (−)-isonitramine.
Additional Information
© 2020 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. All publication charges for this article have been paid for by the Royal Society of Chemistry. Received 26th April 2020; Accepted 20th June 2020; First published 23 Jun 2020. This manuscript is dedicated to the memory of Prof. Teruaki Mukaiyama. The authors wish to thank NIH-NIGMS (R01GM080269), Astellas Pharma, Inc. (postdoctoral fellowship to K. I.), the Alfried Krupp von Bohlen and Halbach Foundation (fellowship to M. W.) and Amgen, Inc. (graduate fellowship to S. B.). We also thank Dr Scott C. Virgil for his support with chromatographic analysis, high-resolution mass analysis, and assistance during the crystallization process. The authors declare no conflicts of interest.Attached Files
Published - d0sc02366c.pdf
Supplemental Material - d0sc02366c1.pdf
Supplemental Material - d0sc02366c2.cif
Files
Additional details
- PMCID
- PMC7574022
- Eprint ID
- 104205
- Resolver ID
- CaltechAUTHORS:20200702-103837298
- NIH
- R01GM080269
- Astellas Pharma, Inc.
- Alfried Krupp von Bohlen and Halbach Foundation
- Amgen
- Royal Society of Chemistry
- Created
-
2020-07-02Created from EPrint's datestamp field
- Updated
-
2021-11-16Created from EPrint's last_modified field