Microwave Heated Continuous Flow Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones

A protocol for Pd­(II)-catalyzed desulfitative synthesis of aryl ketones from sodium aryl sulfinates and nitriles in continuous flow has been developed. The reactions proceed with microwave heating using microwave transparent tube reactors, affording the desired aryl ketones in fair to good yields. Microwave transparent aluminum oxide reactors were identified as a safe and thermostable alternative to borosilicate glass reactors

Continuous Flow Synthesis under High-Temperature/High-Pressure Conditions Using a Resistively Heated Flow Reactor

A cheap, easy-to-build, and effective resistively heated reactor for continuous flow synthesis at high temperature and pressure is herein presented. The reactor is rapidly heated directly using an electric current and is capable of rapidly delivering temperatures and pressures up to 400 °C and 200 bar, respectively. High-temperature and high-pressure applications of this reactor were safely performed and demonstrated by selected transformations such as esterifications, transesterifications, and direct carboxylic acid to nitrile reactions using supercritical ethanol, methanol, and acetonitrile. Reaction temperatures were between 300 and 400 °C with excellent conversions and good to excellent isolated product yields. Examples of Diels–Alder reactions were also carried out at temperatures up to 300 °C in high yield. No additives or catalysts were used in the reactions

Direct Palladium(II)-Catalyzed Synthesis of Arylamidines from Aryltrifluoroborates

A fast and convenient synthesis of arylamidines starting from readily available potassium aryltrifluoroborates and cyanamides is reported. The coupling was achieved by Pd(II)-catalysis in a one step 20 min microwave protocol using Pd(O₂CCF₃), 6-methyl-2,2′-bipyridyl, TFA, and MeOH, providing the corresponding arylamidines in moderate to excellent yields

Microwave Promoted Transcarbamylation Reaction of Sulfonylcarbamates under Continuous-Flow Conditions

Successful conditions for the transcarbamylation/transesterification reaction of sulfonylcarbamates with alcohols by microwave heating under continuous-flow conditions were developed. After optimization of the processes, two series of <i>O</i>-alkylsulfonylcarbamates were obtained in high yields and purities using microwave transparent borosilicate tube reactors. In order to also illustrate the usefulness of the protocol in a medicinal chemistry context, the methodology was used for the synthesis of three angiotensin II type 2 receptor ligands

Selective Synthesis of Spirooxindoles by an Intramolecular Heck–Mizoroki Reaction

We report a highly diastereoselective synthesis of cyclopentene–spirooxindole derivatives via an intramolecular Heck–Mizoroki reaction using aryl bromides as precursors. The reactions were performed under dry conditions or in a DMF–water system. This protocol can be useful to introduce several functionalities to the aromatic nucleus of the spirooxindoles. DFT calculations were performed to rationalize the high antiselectivity. A functionalized spiroproduct was transformed into a cyclic amino acid derivative

Theoretical and Experimental Investigation of Palladium(II)-Catalyzed Decarboxylative Addition of Arenecarboxylic Acid to Nitrile

The reaction mechanism of palladium­(II)-catalyzed decarboxylative addition of 2,6-dimethoxybenzoic acid to acetonitrile was investigated by means of density functional theory (DFT) calculations. Calculations of the free energy profile for decarboxylation and carbopalladation indicated carbopalladation as the rate-determining step of the reaction. Investigation of the free energy profile for a series of experimentally evaluated nitrogen-based bidentate palladium ligands revealed that higher energy is required for decarboxylation and carbopalladation employing the experimentally least efficient ligand. The DFT investigation also showed that the relative free energies of the transition states were lowered in polar solvent, and preparative experiments confirmed that a nonoptimal ligand could be greatly improved by addition of water to the reaction system

Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones from Sodium Arylsulfinates and Nitriles: Scope, Limitations, and Mechanistic Studies

A fast and efficient protocol for the palladium­(II)-catalyzed production of aryl ketones from sodium arylsulfinates and various organic nitriles under controlled microwave irradiation has been developed. The wide scope of the reaction has been demonstrated by combining 14 sodium arylsulfinates and 21 nitriles to give 55 examples of aryl ketones. One additional example illustrated that, through the choice of the nitrile reactant, benzofurans are also accessible. The reaction mechanism was investigated by electrospray ionization mass spectrometry and DFT calculations. The desulfitative synthesis of aryl ketones from nitriles was also compared to the corresponding transformation starting from benzoic acids. Comparison of the energy profiles indicates that the free energy requirement for decarboxylation of 2,6-dimethoxybenzoic acid and especially benzoic acid is higher than the corresponding desulfitative process for generating the key aryl palladium intermediate. The palladium­(II) intermediates detected by ESI-MS and the DFT calculations provide a detailed understanding of the catalytic cycle