Chemistry and Biochemistry Program, Schmid College of Science and Technology, Chapman University, One University Drive, Orange, California 92866, United States.
Department of Chemistry, Pomona College, 645 North College Avenue, Claremont, California 91711, United States.
Inorg Chem. 2022 Jun 27;61(25):9746-9755. doi: 10.1021/acs.inorgchem.2c01230. Epub 2022 Jun 14.
We report a mechanistic investigation of calcium bistriflimide-mediated sulfur(VI)-fluoride exchange (SuFEx) between sulfonyl fluorides and amines. We determine the likely pre-activation resting state─a calcium bistriflimide complex with ligated amines─thus allowing for corroborated calculation of the SuFEx activation barrier at ∼21 kcal/mol, compared to 21.5 ± 0.14 kcal/mol derived via kinetics experiments. Transition state analysis revealed: (1) a two-point calcium-substrate contact that activates the sulfur(VI) center and stabilizes the leaving fluoride and (2) a 1,4-diazabicyclo[2.2.2]octane additive that provides Brønsted-base activation of the nucleophilic amine. Stable Ca-F complexes upon sulfonamide formation are likely contributors to inhibited catalytic turnover, and a proof-of-principle redesign provided evidence that sulfonamide formation is feasible with 10 mol % calcium bistriflimide.
我们报告了钙三氟甲脒介导的磺酰氟与胺之间的硫（VI）-氟交换（SuFEx）的机理研究。我们确定了可能的预激活静止状态——与连接的胺配位的钙三氟甲脒配合物，从而允许通过动力学实验验证计算的 SuFEx 活化能垒约为 21 kcal/mol，而通过动力学实验验证计算的活化能垒为 21.5 ± 0.14 kcal/mol。过渡态分析显示：（1）两点钙-底物接触，激活硫（VI）中心并稳定离去氟；（2）1,4-二氮杂二环[2.2.2]辛烷添加剂提供亲核胺的 Brønsted 碱活化。磺酰胺形成时稳定的 Ca-F 配合物可能是催化循环抑制的原因，并且原理验证设计提供了证据，表明使用 10 mol%钙三氟甲脒可以实现磺酰胺的形成。
