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.
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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. | ||||||||||||
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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: | 17 Feb 2022 18:54 |
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