Ytterbium-mediated synthesis of 2 , 4-diarylpyrroles from α-halo oxime ethers

A novel and efficient ytterbium promoted reductive cyclisation dimerization of α-bromo-oxime ethers affording 2,4-diarylpyrroles with high regioselectivity has been developed. Compared with the reported synthesis methods, the method has the following advantages: readily available and safe starting material, one-pot single step operation and mild and neutral reaction conditions.


General details
THF was distilled from sodium benzophenone under nitrogen.All reactions were conducted under a nitrogen atmosphere.Metallic ytterbium and and all other chemicals were purchased from a commercial source without further purification before use.Petroleum ether (PE) used refers to the 60-90 o C boiling point fraction of petroleum.The flash column chromatography was carried out on silica gel (200-300 mesh). 1 H and 13 C NMR spectra were recorded in CDCl 3 on a 400 MHz spectrometer.
Chemical shifts in 1 H NMR spectra are reported in parts per million (ppm, δ) downfield from the internal standard Me 4 Si (TMS, δ = 0.00 ppm).Chemical shifts in 13 C NMR spectra are reported relative to the central line of the chloroform signal (δ = 77.0ppm) or DMSO signal (δ = 40.0ppm).HRMS were obtained with a TOF-Q III instrument.
General procedure for Synthesis of of α-halo oxime ethers [16] The appropriate α-haloketone (10.0 mmol) and O-methyl (or Benzyl) hydroxylamine hydrochloride (15.0 mmol) were dissolved in ethanol (30 mL) containing one drop of concentrated sulphuric acid.The mixture was stirred at room temperature (heating, if necessary) for 2-12 h.The reaction progress was monitored by TLC.When the starting material disappeared, the solvent was evaporated in vacuum to near dryness.
Ether (50 mL) was added and the solution was washed with 1 M aqueous KHSO 4 (2 × 20 ml), saturated aqueous NaHCO 3 (20 ml) and water (20 ml).The organic phase was dried over Na 2 SO 4 , filtered and the solvent evaporated in vacuum.The residue was purified by column chromatography (PE/dichloromethane) through deactivated silica gel.Finally, solvents were removed in vacuum affording the corresponding α-halo oxime ethers.

General procedure for Synthesis of 2, 4-diarylpyrroles
α-halo oxime ethers (0.5 mmol) and ytterbium powder (0.75 mmol, 130 mg) were suspended in dry THF (5 mL) under a N 2 atmosphere, catalytic amount I 2 was added, the mixture was stirred (the color turned to brown) under a N 2 atmosphere at room S3 temperature for 12h, then was quenched with 10 mL H 2 O, The resulting mixture was extracted with ethyl acetate (3×20 mL) The organic phase was dried over Na 2 SO 4 , filtered and the solvent evaporated in vacuum.The residue was purified by column chromatography (PE/EA) through silica gel.Finally, solvents were removed in vacuum affording the corresponding pyrroles.