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Issaian, Adena; Faizi, Darius J.; Bailey, Johnathan O.; Mayer, Peter; Berionni, Guillaume; Singleton, Daniel A.; Blum, Suzanne A. (2017): Mechanistic Studies of Formal Thioboration Reactions of Alkynes. In: Journal of Organic Chemistry, Vol. 82, No. 15: pp. 8165-8178
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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 Delta G(double dagger) = 27.1 +/- 0.1 kcal mol(-1) at 90 degrees C, Delta H-double dagger = 13.8 +/- 1.0 kcal mol(-1), and Delta S-double dagger = -37 +/- 3 cal mol(-1) K-1, measured over the range 70-90 degrees C. Carbon kinetic isotope effects supported a rate-determining Ad(E)3 mechanism wherein alkyne activation by neutral ClBcat is concerted with cyclative attack by nucleophilic sulfur. A Hammett study found a rho(+) 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.