Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α-Fluorination of Ketenes: Synthetic and Mechanistic Studies
Name
Lee-2014-Enantioselective nucleophile.pdf
Size
728.87 KB
Format
Adobe PDF
Checksum (MD5)
b26f3fab124a873d35836b6a5fcc4a12
Author(s)
Lee, Sarah Yunmi
Neufeind, Stefan
Fu, Gregory C.
Date Issued
June 2014
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Lee, Sarah Yunmi, Stefan Neufeind, and Gregory C. Fu. “Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α-Fluorination of Ketenes: Synthetic and Mechanistic Studies.” Journal of the American Chemical Society 136, no. 25 (June 25, 2014): 8899–8902. © 2014 American Chemical Society
Version
Final published version
Abstract
The catalytic asymmetric synthesis of alkyl fluorides, particularly α-fluorocarbonyl compounds, has been the focus of substantial effort in recent years. While significant progress has been described in the formation of enantioenriched secondary alkyl fluorides, advances in the generation of tertiary alkyl fluorides have been more limited. Here, we describe a method for the catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C[subscript 6]F[subscript 5]ONa to furnish tertiary α-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C[subscript 6]F[subscript 5]ONa) is critical for turnover, releasing the catalyst (PPY*) from an N-acylated intermediate. The available data can be explained by a reaction pathway wherein the enantioselectivity is determined in the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived from the addition of PPY* to the ketene. The structure and the reactivity of the product of this proposed elementary step, an α-fluoro-N-acylpyridinium salt, have been examined.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/ja5044209
