Chlorination of (Phebox)Ir(mesityl)(OAc) by Thionyl Chloride

Pincer (Phebox)Ir(mesityl)(OAc) (2) (Phebox = 3,5-dimethylphenyl-2,6-bis(oxazolinyl)) complex, formed by benzylic C-H activation of mesitylene (1,3,5-trimethylbenzene) using (Phebox)Ir(OAc)2OH2 (1), was treated with thionyl chloride to rapidly form 1-(chloromethyl)-3,5-dimethylbenzene in 50% yield at 23 °C. A green species was obtained at the end of reaction, which decomposed during flash column chromatography to form (Phebox)IrCl2OH2 in 87% yield.

Besides Pd, Rh and Cu catalysts for carrying out arene C-H chlorination have been reported [2,13,14]. The Shilov Pt system is well-known for effecting the chlorination of methane, but studies on other substrates are rare [4,7]. An alternative method, using a Mn-porphyrin complex [15], can catalyze selective C-H chlorination without proceeding via formation of a metal-carbon bond [6].

OPEN ACCESS
Despite these recent advances, C-H bond chlorination is still far from being a robust and versatile synthetic method for constructing C-Cl bond [1]. The substrate scope is largely limited to aromatics and a directing group is needed to ensure regioselectivity. Development of new organometallic reactions relevant to C-H activation and C-Cl bond formation are required to overcome these challenges.

Scheme 2.
Chlorination of (Phebox)Ir(mesityl)(OAc) by thionyl chloride to form 1-(chloromethyl)-3,5-dimethylbenzene. Along with 1-(chloromethyl)-3,5-dimethylbenzene, a green species formed at the end of reaction (Scheme 2). We could not characterize this green species from the complex 1 H-NMR spectrum of the reaction mixture. The green species turned purple at −196 °C when frozen by liquid nitrogen, and reverted back to green when warming back to room temperature.
Currently we can only speculate on the mechanism of C-Cl bond formation, due to the complex 1 H-NMR spectrum of the chlorination reaction mixture.  [31][32][33][34] may form which could be responsible for C-Cl bond formation. Ison and coworkers recently reported the formation of methanol from methyl-ligated Cp*Ir IV (NHC) μ-oxo dimer (Cp* = C5Me5, NHC = N-heterocyclic carbene) by dioxygen [33,35], as an example of carbon-hetero bond formation via high-valent Ir-alkyl complex. Alternatively direct electrophilic attack on the M-C bond by thionyl chloride may occur without formation of a high oxidation state Ir complex.

General
Solvents and reagents were purchased from VWR or Sigma Aldrich, and used without further purification. A MBraun glove box was used to store complex 2 under argon (<0.1 ppm O2 and <0.1 ppm H2O). 1 H-and 13 C-NMR analyses were performed on a 300, 400 or 500 MHz Varian spectrometer, using benzene solvent chemical shifts as reference at 7.16 ppm in 1 H{ 13 C} NMR spectrum (C6D5H) or 128.6 ppm for 13 C{ 1 H} NMR spectrum (C6D6). Silica gel (230-400 mesh) for flash column chromatography was purchased from SiliCycle. J-Young NMR tubes (5 mm outer diameter) were purchased from Sigma Aldrich. Reusable culture tubes (50 mL), equipped with PTFE-faced phenolic caps, were manufactured by Kimax or Pyrex. To ensure high product yield, air was rigorously removed by three cycles of freeze-pump-thaw treatment for all reactions containing Ir. The reaction yield was measured using an internal standard (1,4-bis(trifluoromethyl)benzene in C6D6) added at the end of the reaction, followed by 1 H{ 13 C} NMR analysis.

Chlorination of Complex 2
Complex 2 (3.2 μmol, 10.6 mM, 2.1 mg) was dissolved in C6D6 (200 μL) in a regular 5-mm outer-diameter J-Young NMR tube in a glove box. The tube, with the J-Young valve closed, was then taken out of glove box. The valve was briefly opened under a vigorous flush of argon and an air-free (by 3 cycles of freeze-pump-thaw treatment) solution (100 μL) of thionyl chloride (63.6 mM, 6.4 μmol) in C6D6 was quickly added. The valve was quickly closed upon delivery of thionyl chloride. The red solution turned dark instantly upon addition of thionyl chloride.
After 10 min at 23 °C, the reaction mixture was analyzed directly by 1 H-NMR spectroscopy. After obtaining the initial spectrum, an internal standard, (1,4-bis(trifluoromethyl)benzene in C6D6 was added to the reaction mixture under air for quantitation. (Phebox)Ir(mesityl)(OCOCH3) (2) was made in one step from complex 1 using mesitylene under argon. Complex 1 (20 mg, 32 μmol, 106 mM), mesitylene (3 mL, 7.19 M) and K2CO3 (4 equivalents, 18 mg, 424 mM) were added to a reusable culture tube (50 mL), equipped with PTFE-faced black phenolic caps and a magnetic stir bar, in a glove box under argon. The tube was then taken out of the glove box and heated in an oil bath at 130 °C for 12 h. At the end of reaction, mesitylene solvent was removed under vacuum.

Syntheses and Characterizations
In a glove box, ether dissolved complex 2 and the solution obtained was filtered through glass wool plug packed in a glass pipette. Complex 2 was obtained in >90% yield by 1  X-ray crystal structure determination of complex 2 was reported previously [25].