Institut für Chemie und Biochemie, Freie Universität Berlin , Takustrasse 3, D-14195 Berlin, Germany.
J Org Chem. 2014 May 16;79(10):4492-502. doi: 10.1021/jo500534t. Epub 2014 Apr 30.
A methyl 2-trifluoromethyl-2-siloxycyclopropanecarboxylate was smoothly deprotonated by lithium diisopropylamide and reacted with carbon disulfide and methyl iodide to afford a dihydrothiophene derivative. The crucial step in this transformation is a ring-expansion of the anionic intermediate by [1,3] sigmatropic rearrangement. The dihydrothiophene was converted into the corresponding 5-trifluoromethylthiophene derivative by phosphoryl chloride in refluxing pyridine. A one-pot version of the reaction sequence efficiently provided the thiophene in good yield. Analogously, aryl- and alkyl-substituted isothiocyanates instead of carbon disulfide afforded the corresponding trifluoromethyl-substituted pyrroles in moderate to very good overall yields. Explorative reactivity studies with the methylthio-substituted thiophene and pyrrole derivatives demonstrate that they are precursors of a range of interesting trifluoromethyl-substituted products, including new members from the thienothiophene and thienopyrrole class.
一种 2-三氟甲基-2-硅氧基环丙羧酸甲酯的简便脱质子化及与二硫化碳和碘甲烷的反应，得到二氢噻吩衍生物
通过锂二异丙基酰胺对 2-三氟甲基-2-硅氧基环丙羧酸甲酯进行脱质子化反应，与二硫化碳和碘甲烷反应，得到二氢噻吩衍生物。此转化的关键步骤是通过[1,3]西格玛重排使阴离子中间体环扩张。在回流吡啶中，用氯化磷将二氢噻吩转化为相应的 5-三氟甲基噻吩衍生物。该反应序列的一锅法版本可有效地以良好的产率提供噻吩。类似地，用芳基和烷基取代的异硫氰酸酯代替二硫化碳，以中等至非常好的总收率得到相应的三氟甲基取代的吡咯。对甲基硫取代的噻吩和吡咯衍生物的探索性反应性研究表明，它们是一系列有趣的三氟甲基取代产物的前体，包括噻吩并噻吩和噻吩并吡咯类的新成员。
