Pre-electrolysis of LiClO4 in Acetonitrile: Electrochemically Induced Protolytic Carbon–Carbon Bond Formation of Benzylic Ethers and Acetals with Allyl Trimethylsilane and Other Carbon Nucleophiles

The pre-electrolysis of LiClO4 in acetonitrile in an undivided cell applying only “catalytic” amounts of current (e.g., 0.05 F) led to the formation of a strong acidic medium for the activation of benzylic ethers and acetals. The activated primary and secondary benzylic ethers and acetals could be converted with a range of carbon nucleophiles, such as allyl trimethylsilane, silyl enol ethers, and enol acetates, for the formation of new carbon–carbon bonds. A chemoselective reaction was observed when electron-deficient benzylic acetals were converted with allyl trimethylsilane to the monoallylated products, whereas an electron-rich benzylic acetal led to the double allylated product under activation of both ether groups.


General Information
All chemicals or reagents purchased from commercial suppliers were used without further purification, if not otherwise stated, or were prepared according to known literature procedures.
If water or air sensitive compounds have been used, the experiments were carried out in heat gun dried glassware using conventional SCHLENK techniques under nitrogen atmosphere.
Electrochemical reactions were carried out using an AIM-TTI Instruments MX100T Triple Output Multi-Range DC Power Supply (35 V, 3 A) or a HMP4040 Programmable Power Supply 384 W ROHDE&SCHWARZ (32 V, 10 A) power supply.These reactions were performed in an undivided cell equipped with a stirring bar, and platinum electrodes.All known compounds were characterized by 1 H and 13 C NMR and 19 F NMR if applicable.Unknown compounds were identified by 1 H NMR, 13 C NMR, 19 F NMR if applicable, IR and HRMS.NMR spectroscopy: NMR spectra were recorded either on a Bruker Avance 300 (300 MHz), on a Bruker Avance III (500 MHz) or on a Bruker Avance DRX (500 MHz).Chemical shifts are reported in parts per million (ppm).The spectra are referenced to the residual solvent peak of CDCl3.In the 1 H NMR spectra this corresponds with the singlet of the solvent signal of CDCl3 at δ = 7.26 ppm.The 13 C NMR spectra were referenced to the central line of the triplet of CDCl3 at δ = 77.16ppm.The stated form of the signal describes the appearance of the signal and not the theoretically expected form.

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Infrared Spectroscopy: The IR spectra were obtained with a Shimadzu IRSpirit with a QATR-S cell.The wave numbers λ -1 are given in reciprocal centimeters (cm -1 ).
Chromatography: Flash chromatography was carried out using MACHERY-NAGEL silica gel 60 (0.040-0.063 mm).Thin layer chromatography was carried out on MERCK TLC plates coated with silica gel 60 F254 with fluorescence indicator.For the detection of the signals ultraviolet light (λ = 254 nm) was used or heating after the plate has been dipped into a potassium permanganate-solution.
MS/HRMS: MS and HRMS spectra of products were obtained with a WATERS Q-TOF Premier (ESI, pos.mode or APCI) or THERMO SCIENTIFIC DFS (EI) spectrometers.

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2 Synthesis of the starting materials

Synthesis of benzyl ethers
Most benzyl ethers were synthesized by combining an adapted literature procedure by FLEISCHER [1] for reducing carbonyl groups with another procedure by FAN [2] for ether synthesis.
The ketone (10 mmol, 1.0 equiv.) was dissolved in ethanol (20 mL).The mixture was stirred vigorously while sodium borohydride (454 mg, 12.0 mmol, 1.2 equiv.) was slowly added.The conversion of the ketone was determined by GC-MS analysis.Afterwards, a solution of NH4Cl (20 mL) was added carefully and the mixture was extracted with Et2O (3 x 30 mL).The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo.Sufficient purity of the alcohol was confirmed by 1 H NMR spectroscopy.The benzyl alcohol was then dissolved in THF (20 mL) and cooled to 0 °C, before sodium hydride (60% in mineral oil, 520 mg, 13.0 mmol, 1.3 equiv.) was added.After stirring for 20 minutes at this temperature, methyl iodide (0.8 mL, 13.0 mmol, 1.3 equiv.) was added.The conversion of the alcohol was confirmed by GC-MS analysis.Afterwards, water (20 mL) was added slowly.The aqueous layer was extracted with Et2O (3 x 30 mL) and the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo.The residue was purified by column chromatography to furnish the respective benzyl ether.

Synthesis of acetals
To a solution of the respective aldehyde (5.0 mmol) in the alcohol (ROH, 66 mL) trifluoroacetic acid (1 mol%) was added.This mixture was stirred for 30 minutes at room temperature and then a saturated aqueous NaHCO3 solution (6 mL) was added.The aqueous layer was extracted with Et2O (3 x 30 mL) and the combined organic layers were dried over MgSO4.After filtration and removal of the solvent in vacuo, the residue was purified by column chromatography to furnish the respective acetals.
After completion of the reaction, an aqueous saturated Na2CO3 solution (5 mL) was added and the mixture was extracted with Et2O (3 x 30 mL).The combined organic layers were dried over MgSO4, filtered and the solvent was removed under reduced pressure.The residue was purified by column chromatography to furnish the respective product.S7