CaltechAUTHORS
  A Caltech Library Service

Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α‑Fluorination of Ketenes: Synthetic and Mechanistic Studies

Lee, Sarah Yunmi and Neufeind, Stefan and Fu, Gregory C. (2014) Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α‑Fluorination of Ketenes: Synthetic and Mechanistic Studies. Journal of the American Chemical Society . ISSN 0002-7863. PMCID PMC4091276. http://resolver.caltech.edu/CaltechAUTHORS:20140616-085001666

[img]
Preview
PDF (ACS AuthorChoice) - Published Version
See Usage Policy.

689Kb
[img] Crystallographic Info File (CIF) - Supplemental Material
See Usage Policy.

135Kb
[img] Crystallographic Info File (CIF) - Supplemental Material
See Usage Policy.

170Kb
[img] Crystallographic Info File (CIF) - Supplemental Material
See Usage Policy.

2134Kb
[img]
Preview
PDF (Experimental procedures and compound characterization data) - Supplemental Material
See Usage Policy.

3571Kb

Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:20140616-085001666

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_6F_5ONa to furnish tertiary α-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C_6F_5ONa) 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja5044209DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja5044209PublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja5044209PublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091276/PubMed CentralArticle
ORCID:
AuthorORCID
Fu, Gregory C.0000-0002-0927-680X
Additional Information:© 2014 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Received: May 2, 2014. Publication Date (Web): June 12, 2014. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences R01-GM57034) and the Deutsche Forschungsgemeinschaft (fellowship to S.N.). We thank Trixia M. Buscagan, Dr. Nathan D. Schley, Dr. Michael K. Takase (X-ray Crystallography Facility; a Bruker KAPPA APEX II X-ray diffractometer was purchased via NSF CRIF:MU award CHE-0639094 to the California Institute of Technology), Dr. David VanderVelde (NMR Facility), and Dr. Scott C. Virgil (Caltech Center for Catalysis and Chemical Synthesis, supported by the Gordon and Betty Moore Foundation) for assistance.
Funders:
Funding AgencyGrant Number
NIH National Institute of General Medical SciencesR01-GM57034
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
NSF CRIF:MU AwardCHE-0639094
Gordon and Betty Moore FoundationUNSPECIFIED
PubMed Central ID:PMC4091276
Record Number:CaltechAUTHORS:20140616-085001666
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140616-085001666
Official Citation:Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α-Fluorination of Ketenes: Synthetic and Mechanistic Studies Sarah Yunmi Lee, Stefan Neufeind, and Gregory C. Fu Journal of the American Chemical Society 2014 136 (25), 8899-8902 DOI: 10.1021/ja5044209
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:46273
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 Jun 2014 19:55
Last Modified:21 Jul 2017 14:33

Repository Staff Only: item control page