Seggio Anne, Lannou Marie-Isabelle, Chevallier Floris, Nobuto Daisuke, Uchiyama Masanobu, Golhen Stéphane, Roisnel Thierry, Mongin Florence
Synthèse et ElectroSynthèse Organiques, UMR 6510 CNRS, Université de Rennes 1, Bâtiment 10A Case 1003, Campus Scientifique de Beaulieu, Rennes Cedex, France.
Chemistry. 2007;13(35):9982-9. doi: 10.1002/chem.200700608.
Metalation of N-phenylpyrrole by using an in situ mixture of ZnCl(2)TMEDA (0.5 equiv; TMEDA=N,N,N',N'-tetramethylethylenediamine) and LiTMP (1.5 equiv; TMP=2,2,6,6-tetramethylpiperidino) was optimized. The reaction carried out at room temperature in THF resulted in incomplete metalation (56 % conversion) and selectivity (mixture of 2-iodo and 2,2'-diiodo derivatives in an 86:14 ratio after trapping with iodine). By using diethyl ether (DEE), toluene, or hexane instead of THF, low conversions of 17, 38, or 23 % were observed, respectively, but the formation of the diiodide was avoided. When hexane was used as solvent, strong lithium-complexing ligands such as [12]crown-4 and N,N'-dimethylpropylideneurea (DMPU) inhibited the reaction whereas more (hemi)labile ligands (TMEDA>THF approximately DME) favored it. This result shows that a temporary accessibility of lithium to interact with the rest of the base and/or the substrate is a prerequisite for an efficient metalation. A 75 % yield of 2-iodo-N-phenylpyrrole was obtained after reaction with the base in the presence of five equivalents of TMEDA for two hours at room temperature, and subsequent trapping with iodine. We were able to successfully replace the spare TMP with a less expensive butyl group.
通过使用氯化锌 - N,N,N',N'-四甲基乙二胺（0.5当量；TMEDA = N,N,N',N'-四甲基乙二胺）和双(三甲基硅基)氨基锂（1.5当量；TMP = 2,2,6,6 - 四甲基哌啶基）的原位混合物对N - 苯基吡咯进行金属化反应得到了优化。在室温下于四氢呋喃中进行的反应导致金属化不完全（转化率为56%）且选择性不佳（用碘捕获后得到2 - 碘代和2,2'-二碘代衍生物的混合物，比例为86:14）。用乙醚（DEE）、甲苯或己烷代替四氢呋喃时，分别观察到低转化率，即17%、38%或23%，但避免了二碘化物的形成。当使用己烷作为溶剂时，强锂络合配体如[12]冠 - 4和N,N'-二甲基亚丙基脲（DMPU）会抑制反应，而更多（半）不稳定配体（TMEDA > 四氢呋喃 ≈ 二甲醚）则有利于反应。该结果表明，锂与碱的其余部分和/或底物相互作用的临时可及性是有效金属化的先决条件。在室温下，在五当量的TMEDA存在下与碱反应两小时，随后用碘捕获，得到了75%产率的2 - 碘代 - N - 苯基吡咯。我们能够成功地用较便宜的丁基取代多余的TMP。
