Mechanistic Studies of Formal Thioboration Reactions of Alkynes

Adena Issaian, Darius J. Faizi, Johnathan O. Bailey, Peter Mayer, Guillaume Berionni, Daniel A. Singleton, Suzanne A. Blum

Research output: Contribution to journalArticle

Abstract

Several formal heteroborylative cyclization reactions have been recently reported, but little physical-organic and mechanistic data are known. We now investigate the catalyst-free formal thioboration reaction of alkynes to gain mechanistic insight into B-chlorocatecholborane (ClBcat) in its new role as an alkynophilic Lewis acid in electrophilic cyclization/dealkylation reactions. In kinetic studies, the reaction is second-order globally and first-order with respect to both the 2-alkynylthioanisole substrate and the ClBcat electrophile, with activation parameters of ΔG = 27.1 ± 0.1 kcal mol-1 at 90 °C, ΔH = 13.8 ± 1.0 kcal mol-1, and ΔS = -37 ± 3 cal mol-1 K-1, measured over the range 70-90 °C. Carbon kinetic isotope effects supported a rate-determining AdE3 mechanism wherein alkyne activation by neutral ClBcat is concerted with cyclative attack by nucleophilic sulfur. A Hammett study found a ρ+ of -1.7, suggesting cationic charge buildup during the cyclization and supporting rate-determining concerted cyclization. Studies of the reaction with tris(pentafluorophenyl)borane (B(C6F5)3), an activating agent capable of cyclization but not dealkylation, resulted in the isolation of a postcyclization zwitterionic intermediate. Kinetic studies via UV-vis spectroscopy with this boron reagent found second-order kinetics, supporting the likely relevancy of intermediates in this system to the ClBcat system. Computational studies comparing ClBcat with BCl3 as an activating agent showed why BCl3, in contrast to ClBcat, failed to mediate the complete the cyclization/demethylation reaction sequence by itself. Overall, the results support a mechanism in which the ClBcat reagent serves a bifunctional role by sequentially activating the alkyne, despite being less electrophilic than other known alkyne-activating reagents and then providing chloride for post-rate-determining demethylation/neutralization of the resulting zwitterionic intermediate.

Original languageEnglish
Pages (from-to)8165-8178
Number of pages14
JournalJournal of Organic Chemistry
Volume82
Issue number15
DOIs
Publication statusPublished - 4 Aug 2017

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  • Datasets

    CCDC 1549063: Experimental Crystal Structure Determination

    Bailey, J. O. (Contributor), Berionni, G. (Contributor), Blum, S. A. (Contributor), Faizi, D. J. (Contributor), Issaian, A. (Contributor), Mayer, P. (Contributor) & Singleton, D. A. (Contributor), Cambridge Crystallographic Data Centre, 1 Jan 2017

    Dataset

    CCDC 1549064: Experimental Crystal Structure Determination

    Bailey, J. O. (Contributor), Berionni, G. (Contributor), Blum, S. A. (Contributor), Faizi, D. J. (Contributor), Issaian, A. (Contributor), Mayer, P. (Contributor) & Singleton, D. A. (Contributor), Cambridge Crystallographic Data Centre, 1 Jan 2017

    Dataset

    Cite this

    Issaian, A., Faizi, D. J., Bailey, J. O., Mayer, P., Berionni, G., Singleton, D. A., & Blum, S. A. (2017). Mechanistic Studies of Formal Thioboration Reactions of Alkynes. Journal of Organic Chemistry, 82(15), 8165-8178. https://doi.org/10.1021/acs.joc.7b01500