Ligand-activated lithium-mediated zincation of N-phenylpyrrole.
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.
Seggio
Anne
A
Synthèse et ElectroSynthèse Organiques, UMR 6510 CNRS, Université de Rennes 1, Bâtiment 10A Case 1003, Campus Scientifique de Beaulieu, Rennes Cedex, France.
Lannou
Marie-Isabelle
MI
Chevallier
Floris
F
Nobuto
Daisuke
D
Uchiyama
Masanobu
M
Golhen
Stéphane
S
Roisnel
Thierry
T
Mongin
Florence
F
D008024:Ligands; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*; D017967:Zinc Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D008024:Ligands; D011758:Pyrroles; D017967:Zinc Compounds; C517402:N-phenylpyrrole; D008094:Lithium; D015032:Zinc