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Enantioconvergent Alkylations of Amines by Alkyl Electrophiles: Copper-Catalyzed Nucleophilic Substitutions of Racemic α-Halolactams by Indoles

Bartoszewicz, Agnieszka and Matier, Carson D. and Fu, Gregory C. (2019) Enantioconvergent Alkylations of Amines by Alkyl Electrophiles: Copper-Catalyzed Nucleophilic Substitutions of Racemic α-Halolactams by Indoles. Journal of the American Chemical Society, 141 (37). pp. 14864-14869. ISSN 0002-7863. PMCID PMC7055584 . https://resolver.caltech.edu/CaltechAUTHORS:20190909-093503148

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Abstract

Transition-metal catalysis has the potential to address shortcomings in the classic S_N2 reaction of an amine with an alkyl electrophile, both with respect to reactivity and to enantioselectivity. In this study, we describe the development of a user-friendly method (reaction at room temperature, with commercially available catalyst components) for the enantioconvergent nucleophilic substitution of racemic secondary alkyl halides (α-iodolactams) by indoles. Mechanistic studies are consistent with the formation of a copper(I)–indolyl complex that reacts at different rates with the two enantiomers of the electrophile, which interconvert under the reaction conditions (dynamic kinetic resolution). This investigation complements earlier work on photoinduced enantioconvergent N-alkylation, supporting the premise that this important challenge can be addressed by a range of strategies.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/jacs.9b07875DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7055584/PubMed CentralArticle
https://doi.org/10.1021/jacs.0c00943DOICorrection
ORCID:
AuthorORCID
Bartoszewicz, Agnieszka0000-0002-1534-2690
Matier, Carson D.0000-0002-1618-7944
Fu, Gregory C.0000-0002-0927-680X
Additional Information:© 2019 American Chemical Society. Received 23 July 2019. Published online 9 September 2019. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences; Grant No. R01-GM109194), the Bengt Lundqvist Memorial Foundation of the Swedish Chemical Society (fellowship for A.B.), Boehringer–Ingelheim Pharmaceuticals (Scientific Advancement Grant to G.C.F.), and the Dow Next Generation Educator Fund (grant to Caltech). We thank Prof. Jonas C. Peters, Dr. Quirin M. Kainz, Dr. J. M. Ahn, Lawrence M. Henling, Dr. Nathan D. Schley, Dr. Mona Shahgholi, Dr. Michael K. Takase, Dr. Scott C. Virgil, and Dr. Susan L. Zultanski for assistance and helpful discussions. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHR01-GM109194
Bengt Lundqvists MinnesfondUNSPECIFIED
Swedish Chemical SocietyUNSPECIFIED
Boehringer IngelheimUNSPECIFIED
Dow Next Generation Educator FundUNSPECIFIED
Issue or Number:37
PubMed Central ID:PMC7055584
Record Number:CaltechAUTHORS:20190909-093503148
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190909-093503148
Official Citation:Enantioconvergent Alkylations of Amines by Alkyl Electrophiles: Copper-Catalyzed Nucleophilic Substitutions of Racemic α-Halolactams by Indoles. Agnieszka Bartoszewicz, Carson D. Matier, and Gregory C. Fu. Journal of the American Chemical Society 2019 141 (37), 14864-14869. DOI: 10.1021/jacs.9b07875
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98510
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Sep 2019 17:07
Last Modified:14 Apr 2020 18:45

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