Mechanistic Studies of Formal Thioboration Reactions of Alkynes

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.