Oh Young-Ho, Yun Wonhyuck, Kim Chul-Hee, Jang Sung-Woo, Lee Sung-Sik, Lee Sungyul, Kim Dong-Wook
Department of Applied Chemistry, Kyung Hee University, Duckyoung-daero 1732, Yongin City 446-701, Korea.
Department of Chemistry, Inha University, 100 Inha-ro, Nam-gu, Incheon 402-751, Korea.
Molecules. 2021 May 15;26(10):2947. doi: 10.3390/molecules26102947.
We present the intra- and inter-molecular organocatalysis of S2 fluorination using CsF by crown ether to estimate the efficacy of the promoter and to elucidate the reaction mechanism. The yields of intramolecular S2 fluorination of the veratrole substrates are measured to be very small (<1% in 12 h) in the absence of crown ether promoters, whereas the S2 fluorination of the substrate possessing a crown ether unit proceeds to near completion (~99%) in 12 h. We also studied the efficacy of intermolecular rate acceleration by an independent promoter 18-crown-6 for comparison. We find that the fluorinating yield of a veratrole substrate (leaving group = -OMs) in the presence of 18-crown-6 follows the almost identical kinetic course as that of intramolecular S2 fluorination, indicating the mechanistic similarity of intra- and inter-molecular organocatalysis of the crown ether for S2 fluorination. The calculated relative Gibbs free energies of activation for these reactions, in which the crown ether units act as Lewis base promoters for S2 fluorination, are in excellent agreement with the experimentally measured yields of fluorination. The role of the metal salt CsF is briefly discussed in terms of whether it reacts as a contact ion pair or as a "free" nucleophile F.
我们展示了通过冠醚使用CsF对S2氟化进行的分子内和分子间有机催化，以评估促进剂的效果并阐明反应机理。在没有冠醚促进剂的情况下，藜芦醚底物的分子内S2氟化产率被测定为非常低（12小时内<1%），而具有冠醚单元的底物的S2氟化在12小时内进行至接近完全（~99%）。为了进行比较，我们还研究了独立促进剂18-冠-6对分子间速率加速的效果。我们发现，在18-冠-6存在下，藜芦醚底物（离去基团 = -OMs）的氟化产率遵循与分子内S2氟化几乎相同的动力学过程，表明冠醚对S2氟化的分子内和分子间有机催化在机理上具有相似性。对于这些反应，其中冠醚单元作为S2氟化的路易斯碱促进剂，计算得到的相对吉布斯自由能活化能与实验测量的氟化产率非常吻合。我们根据金属盐CsF是作为接触离子对还是作为“游离”亲核试剂F发生反应，简要讨论了其作用。
