The Institute for Molecular Engineering, The University of Chicago , Chicago Illinois, 60637, United States.
J Org Chem. 2018 Mar 2;83(5):2912-2919. doi: 10.1021/acs.joc.8b00143. Epub 2018 Feb 9.
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.
研究了胺对自由基介导的硫醇-烯偶联（TEC）反应动力学和效率的影响。通过改变硫醇反应物和胺添加剂，可以表明当胺具有足够的碱性足以将硫醇去质子化生成硫醇盐阴离子时，胺会延迟硫自由基介导的反应，例如，当弱碱性胺四甲基乙二胺以 5mol%的比例掺入丁基 2-巯基乙酸酯和烯丙基醚之间的 TEC 反应中时，最终转化率从定量降低到<40%。或者，当使用酸性较弱的硫醇丁基 3-巯基丙酸酯时，则观察不到效果。通过将铵和硫醇盐添加剂引入 TEC 配方中，确定了硫醇盐阴离子是延迟的物种。通过硫自由基与硫醇盐阴离子的反应形成双硫自由基阴离子（DRA）物种，这是催化自由基和 TEC 速率减少的原因。通过密度泛函理论计算和将反应模拟为缔合电子转移过程，计算了 DRA 形成的热力学和动力学趋势。这些趋势与各种硫醇盐阴离子在 TEC 反应中的延迟趋势很好地相关。
