Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
J Org Chem. 2023 Mar 17;88(6):3359-3371. doi: 10.1021/acs.joc.2c02777. Epub 2023 Feb 16.
Two types of electrophilic trifluoromethylthiolating reagents were developed in the past 10 years in our laboratory. The development of the first type of reagent, trifluoromethanesulfenate , which is highly reactive toward a variety of nucleophiles, was based on an unexpected discovery in the initial design for the development of an electrophilic trifluoromethylthiolating reagent with a hypervalent iodine skeleton. A structure-activity study disclosed that α-cumyl trifluoromethanesulfenate (reagent without the iodo substituent is equally effective. Subsequent derivatization let us develop an α-cumyl bromodifluoromethanesulfenate that could be used for the preparation of [F]ArSCF. To remediate the low reactivity of the type I electrophilic trifluoromethylthiolating reagent for Friedel-Crafts trifluoromethylthiolation of electron-rich (hetero)arenes, we designed and prepared -trifluoromethylthiosaccharin , which exhibits broad reactivity toward various nucleophiles, including electron-rich arenes. A comparison of the structure of -trifluoromethylthiosaccharin with that of -trifluoromethylthiophthalimide showed that the replacement of one carbonyl group in -trifluoromethylthiophthalimide with a sulfonyl group made -trifluoromethylthiosaccharin much more electrophilic. Thus, the replacement of both carbonyls with two sulfonyl groups would further increase the electrophilicity. Such a rationale prompted us to design and develop the current most electrophilic trifluoromethylthiolating reagent, -trifluoromethylthiodibenzenesulfonimide , and its reactivity was much higher than that of -trifluoromethylthiosaccharin . We further developed an optically pure electrophilic trifluoromethylthiolating reagent, (1)-(-)--trifluoromethylthio-2,10-camphorsultam , for the preparation of optically active trifluoromethylthio-substituted carbon stereogenic centers. Reagents - now constitute a powerful toolbox for the introduction of the trifluoromethylthio group into the target molecules.
在过去的 10 年中，我们实验室开发了两种亲电性三氟甲基硫代试剂。第一种试剂三氟甲磺酸酯的开发，是基于对开发具有高价碘骨架的亲电性三氟甲基硫代试剂的初步设计中的一个意外发现。结构活性研究表明，α-枯基三氟甲磺酸酯（没有碘取代基的试剂）同样有效。随后的衍生化使我们开发了一种α-枯基溴二氟甲磺酸酯，可用于制备[F]ArSCF。为了改善 I 型亲电性三氟甲基硫代试剂对富电子（杂）芳环的弗里德尔-克拉夫茨三氟甲基硫代反应的低反应性，我们设计并制备了 -三氟甲基硫代蔗糖，它对各种亲核试剂表现出广泛的反应性，包括富电子芳环。-三氟甲基硫代蔗糖的结构与 -三氟甲基硫代邻苯二甲酰亚胺的结构比较表明，在 -三氟甲基硫代邻苯二甲酰亚胺中用磺酰基取代一个羰基使 -三氟甲基硫代蔗糖更具亲电性。因此，用两个磺酰基取代两个羰基会进一步增加亲电性。基于这一原理，我们设计并开发了目前最具亲电性的三氟甲基硫代试剂 -三氟甲基硫代二苯并磺酰亚胺，其反应性比 -三氟甲基硫代蔗糖高得多。我们进一步开发了一种光学纯亲电性三氟甲基硫代试剂，(1)-(-)--三氟甲基硫代-2,10-樟脑磺酰胺，用于制备光学活性的三氟甲基硫代取代碳立体中心。试剂 - 现在构成了将三氟甲基硫代基团引入目标分子的强大工具包。
