Ligand-Activated Lithium-Mediated Zincation of N-Phenylpyrrole

International audienceMetalation of N-phenylpyrrole using an in situ mixture of ZnCl2*TMEDA (0.5 equiv) and LiTMP (1.5 equiv) was optimized. The reaction carried out at rt in THF resulted in incomplete metalation (56% conversion) and selectivity (mixture of 2-iodo and 2,2'-diiodo derivatives in a 86/14 ratio after trapping with iodine). Using 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 DMPU inhibited the reaction whereas more (hemi)labile ligands (TMEDA > THF ~ 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 5 equiv of TMEDA for 2 h at rt, and subsequent trapping with iodine. Replacement of the spare TMP by a less expensive butyl group was attempted with success