I.General Considerations Unless stated otherwise, reactions were conducted in oven-dried glassware under an atmosphere of nitrogen. Diethylether and tetrahydrofuran were dried using a DriSolv system using CuO and molecular sives under argon, all other reaction solvents were purified and dried according to literature. 1 All commercially obtained reagents were used as received unless otherwise specified. Organomagnesium reagents synthesized were titrated before use using either diphenylacetic acid 2 or no-d NMR 3 to determine molarity and stored under an atmosphere of argon gas at room temperature. Thin-layer chromatography (TLC) was visualized using low wavelength ultraviolet light (UV) for all aryl species or phosphomolybdic acid otherwise. Gas chromatography (GC) was performed on an Agilent Technologies 6850 Series II. 1 H NMR spectra were recorded on a Varian spectrometer (at 300.09 MHz or 500.02 MHz) and are reported relative to the residual solvent signals or the internal standard. Data for 1 H NMR spectra are reported as follows: chemical shift (δ ppm), multiplicity, coupling constant (Hz) and integration. 31 P{ 1 H} NMR spectra were recorded on a Varian spectrometer (at 121.48 MHz or 202.13 MHz) and are reported relative to an external standard of 0.1% H3PO4 in D2O at 0 ppm. Infrared spectra were taken using Nicolet Magna-550 Fourier Transform Infrared Spectrophotometer in ATR mode.

Palladium(II)-catalyzed C–H oxidation reactions could streamline the synthesis of pharmaceuticals, agrochemicals, and other complex organic molecules. Existing methods, however, commonly exhibit poor catalyst performance with high Pd loading (e.g., 10 mol %) and a need for (super)stoichiometric quantities of undesirable oxidants, such as benzoquinone and silver(I) salts. The present study probes the mechanism of a representative Pd-catalyzed oxidative C–H arylation reaction and elucidates mechanistic features that undermine catalyst performance, including substrate-consuming side reactions and sequestration of the catalyst as inactive species. Systematic tuning of the quinone co-catalyst overcomes these deleterious features. Use of 2,5-di-tert-butyl-p-benzoquinone enables efficient use of molecular oxygen as the oxidant, high reaction yields, and >1900 turnovers by the palladium catalyst.

An electrochemical method has been developed for a mediated oxidation of primary alcohols to carboxylic acids. The method is compatible with a variety of alcohols bearing nitrogen-containing heterocycles in undivided batch and flow modes. The use of a heterogeneous NiOOH electron−proton transfer mediator avoids the need for homogeneous catalysts that contribute to more unit operations during downstream purging and increased process mass intensity. To demonstrate the applicability of this method for continuous processing, a single-pass flow electrochemical oxidation of nicotinyl alcohol to nicotinic acid is demonstrated with a 77% isolated yield. The NiOOH-coated anodes show no reduction in catalysis efficiency over 12 h, and minimal Ni metal leaching (22.3 μg per liter) is observed.

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Highly efficient biphasic ozonolysis of alkenes using a high-throughput film-shear flow reactor