Iron-catalyzed isopropylation of electron-deficient aryl and heteroaryl chlorides

Sanderson, James N. and Dominey, Andrew P. and Percy, Jonathan M. (2017) Iron-catalyzed isopropylation of electron-deficient aryl and heteroaryl chlorides. Advanced Synthesis and Catalysis. ISSN 1615-4150 (https://doi.org/10.1002/adsc.201601097)

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Abstract

Traditional methods for the preparation of secondary alkyl-substituted aryl and heteroaryl chlorides challenge both selectivity and functional group tolerance. This contribution describes the use of statistical design of experiments to develop an effective procedure for the preparation of isopropyl-substituted (hetero)arenes with minimal isopropyl to n-propyl isomerization. The reaction tolerates electronically diverse aryl chloride coupling partners, with excellent conversion observed for strongly electron-deficient aromatic rings, such as esters and amides. Electron-rich systems, including methyl- and methoxy-substituted aryl chlorides, were found to be less reactive. Furthermore, the reaction was found to be most successful when heteroaryl chlorides were submitted to the cross-coupling protocol. By mapping substituent effects on reaction selectivity, we were able to show that electron-deficient aryl chlorides are essential for efficient coupling, and use electronic structure calculations to predict the likelihood of successful coupling through the estimation of the electron affinity of each aryl chloride. Moderate isolated yields were achieved with selected aryl chlorides, and moderate to good isolated yields were obtained for all the heteroaryl chlorides coupled. Excellent selectivity was observed when a 2,6-dichloroquinoline was used, allowing mono-substitution on a challenging substrate.

ORCID iDs

Sanderson, James N. ORCID logoORCID: https://orcid.org/0000-0003-1000-2897, Dominey, Andrew P. and Percy, Jonathan M. ORCID logoORCID: https://orcid.org/0000-0001-8636-2704;
  • Item type:Article
    ID code:59969
    Dates:
    Date
    Event
    24 January 2017
    Published
    24 January 2017
    Published Online
    14 December 2016
    Accepted
    Notes:This is the peer reviewed version of the following article: Sanderson, J. N., Dominey, A. P., & Percy, J. M. (2017). Iron-catalyzed isopropylation of electron-deficient aryl and heteroaryl chlorides. Advanced Synthesis and Catalysis, which has been published in final form at https://dx.doi.org/10.1002/adsc.201601097. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:27 Feb 2017 09:30
    Last modified:11 Nov 2024 11:38
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/59969
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