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

Abstract

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.

Elusive Reaction Intermediates in Solution Explored by ESI‐MS: Reverse Periscope for Mechanistic Investigations

“…Remarkably this catalytic step,w hich formally is an isomerization, is revealed by the presence of product ions, specific to the two isomers,i nt he tandem mass spectra. [46] Similarly in ar ecent study of the Heck arylation of allylated malonates,t he C À Cb ond-forming reaction during aryl insertion into the terminal carbon atom of ap alladiumcoordinated allylated malonate was observed by ESI-MS. [48] Interestingly,inthis investigation, which is based on detection of palladium(II) intermediates by ESI-MS,apossible chelation of palladium by both carbonyl groups of the reactant was also suggested. Scheme 1shows some of the more significant palladium intermediates,a sd iscussed above,w hich were detected and characterized by ESI-MS.…”

“…[13a] Ther elatively easy sampling by ESI-MS of palladium complexes has also been exploited for the investigation of the palladium-mediated desulfitative synthesis of aryl ketones. [46] In this recent contribution, the reaction was investigated by using acetonitrile and as odium arylsulfinate as starting materials.T he analysis of the reaction mixture resulted in the observation and characterization of the cationic portion of five palladium-containing intermediates.T his finding confirmed the formation of the Pd-aryl [47] bond by loss of SO 2 , which was replaced by CH 3 CN,inthe palladium coordination sphere.T he next step was the crucial carbopalladation of acetonitrile.…”

Diastereoconvergent Synthesis of Chiral Diarylmethyl Sulfones by Direct Sulfonylation of Diarylmethanols Diastereomixtures with Sodium Sulfinates Catalyzed by SnBr2

“…To further explore the scope and limitations of the developed method, a variety of sodium sulfinates were applied for the sulfonylation of 3a as nucleophiles under the established conditions (Scheme ). When the reactions using sodium sulfinates 10a – 10c with substituents at the para ‐position on the aromatic rings were examined, the reactions proceeded smoothly, affording good results regardless of the electric nature of the substituents.…”

Three-component oxysulfenylation reaction: two simple and convenient approaches to β-alkoxy sulfides

“…19 The rest of the chemicals were purchased from Sinopharm Chemical Reagent Co., Adamas, Aladdin and TCI and were used as received. NMR multiplicities are abbreviated as follows: s = singlet, d = doublet, m = multiplet, br = broad signal.…”