Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent

Kumar Dilip Ashtekar, Mathew Vetticatt, Roozbeh Yousefi, James E. Jackson, Babak Borhan

    Research output: Research - peer-reviewArticle

    • 9 Citations

    Abstract

    Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the AdE3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted AdE3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile-alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized "sophomore textbook" image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions.

    LanguageEnglish (US)
    Pages8114-8119
    Number of pages6
    JournalJournal of the American Chemical Society
    Volume138
    Issue number26
    DOIs
    StatePublished - Jul 6 2016

    Profile

    Nucleophiles
    Alkenes
    Chemical activation
    Olefins
    Textbooks
    Alkalinity
    Isotopes
    Modulation
    Spectroscopy
    Electrons
    Substrates
    Spectrum Analysis

    ASJC Scopus subject areas

    • Chemistry(all)
    • Catalysis
    • Biochemistry
    • Colloid and Surface Chemistry

    Cite this

    Nucleophile-Assisted Alkene Activation : Olefins Alone Are Often Incompetent. / Ashtekar, Kumar Dilip; Vetticatt, Mathew; Yousefi, Roozbeh; Jackson, James E.; Borhan, Babak.

    In: Journal of the American Chemical Society, Vol. 138, No. 26, 06.07.2016, p. 8114-8119.

    Research output: Research - peer-reviewArticle

    Ashtekar, Kumar Dilip ; Vetticatt, Mathew ; Yousefi, Roozbeh ; Jackson, James E. ; Borhan, Babak. / Nucleophile-Assisted Alkene Activation : Olefins Alone Are Often Incompetent. In: Journal of the American Chemical Society. 2016 ; Vol. 138, No. 26. pp. 8114-8119
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