Amine Induced Retardation of the Radical-Mediated Thiol–Ene Reaction via the Formation of Metastable Disulfide Radical Anions

5 years ago

Amine Induced Retardation of the Radical-Mediated Thiol–Ene Reaction via the Formation of Metastable Disulfide Radical Anions

Kangmin Kim, John T. Goodrich, Dillon M. Love, Charles B. Musgrave, Brady T. Worrell, Benjamin D. Fairbanks, Mark P. Stoykovich, Christopher N. Bowman

The effect of amines on the kinetics and efficacy of radical-mediated thiol–ene coupling (TEC) reactions was investigated. By varying the thiol reactant and amine additive, it was shown that amines retard thiyl radical-mediated reactions when the amine is adequately basic enough to deprotonate the thiol affording the thiolate anion, e.g., when the weakly basic amine tetramethylethylenediamine was incorporated in the TEC reaction between butyl 2-mercaptoacetate and an allyl ether at 5 mol %, the final conversion was reduced from quantitative to <40%. Alternatively, no effect is observed when the less acidic thiol butyl 3-mercaptopropionate is employed. The thiolate anion was established as the retarding species through the introduction of ammonium and thiolate salt additives into TEC formulations. The formation of a two-sulfur three-electron bonded disulfide radical anion (DRA) species by the reaction of a thiyl radical with a thiolate anion was determined as the cause for the reduction in catalytic radicals and the TEC rate. Thermodynamic and kinetic trends in DRA formations were computed using density functional theory and by modeling the reaction as an associative electron transfer process. These trends correlate well with the experimental retardation trends of various thiolate anions in TEC reactions.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.8b00143

DOI: 10.1021/acs.joc.8b00143