Trojan Michal, Hroch Adam, Gruden Evelin, Cvačka Josef, Čejka Jan, Tavčar Gašper, Rybáčková Markéta, Kvíčala Jaroslav
Department of Organic Chemistry, University of Chemistry and Technology, Prague Technická 5 166 28 Prague 6 Czech Republic
Department of Inorganic Chemistry and Technology, "Jožef Stefan" Institute Jamova Cesta 39 Ljubljana Slovenia.
RSC Adv. 2024 Jul 15;14(31):22326-22334. doi: 10.1039/d4ra04332d. eCollection 2024 Jul 12.
Nucleophilic fluorination of secondary aliphatic substrates, especially of halides, still remains a challenge. Among the available reagents, TBAT belongs to one of the best choices due to its stability, affordable price and low toxicity. With the aim to improve its selectivity, we synthesized three analogues modified in the aryl part of the TBAT reagent with one or two electron donating methoxy groups or with one electron withdrawing trifluoromethyl group. All three reagents are air-stable compounds and their structure was confirmed by a single crystal X-ray analysis. In testing the reactivity and selectivity of the reagents with a library of secondary bromides, as well as of other selected primary and secondary substrates, we found that substitution with methoxy groups mostly improves both reactivity and selectivity compared to TBAT, while the substitution with trifluoromethyl group leads to inferior results. Difluorosilicates modified by more than two electron donating methoxy groups proved to be unstable and decomposed spontaneously to the HF anion. DFT calculations of tetramethylammonium analogues of the studied reagents disclosed that the substitution of the phenyl group with the methoxy substituent lowers the transitions state energy of the decomposition to a fluorosilane-fluoride complex, while the substitution with the trifluoromethyl group has an opposite effect.
仲脂肪族底物的亲核氟化反应，尤其是卤化物的亲核氟化反应，仍然是一个挑战。在现有的试剂中，TBAT因其稳定性、价格合理和低毒性而属于最佳选择之一。为了提高其选择性，我们合成了三种在TBAT试剂的芳基部分进行修饰的类似物，分别带有一个或两个供电子甲氧基或一个吸电子三氟甲基。这三种试剂都是空气稳定的化合物，其结构通过单晶X射线分析得以确证。在测试这些试剂与一系列仲溴化物以及其他选定的伯底物和仲底物的反应活性和选择性时，我们发现与TBAT相比，用甲氧基取代大多能提高反应活性和选择性，而用三氟甲基取代则导致较差的结果。被两个以上供电子甲氧基修饰的二氟硅酸盐被证明是不稳定的，会自发分解为HF阴离子。对所研究试剂的四甲基铵类似物进行的DFT计算表明，用甲氧基取代苯基会降低分解为氟硅烷 - 氟化物络合物的过渡态能量，而用三氟甲基取代则有相反的效果。
