A Robust and Efficient Catalyst Possessing an Electron‐Deficient Ligand for the Palladium‐Catalyzed Direct Arylation of Heteroarenes

Abstract

The exploration of the direct arylation capacity of a unique, thermally stable, and air‐stable Pd0–phosphine catalyst is reported. Besides decisively contributing to catalyst robustness, the electron‐deficient trifluoromethyl‐substituted triphenylphosphine ligands make the palladium center more electron‐deficient and accelerate the direct arylation step. The combination of only 0.5–2 mol‐% of the catalyst and a substoichiometric quantity of pivalic acid generates an efficient system to promote biaryl‐forming reactions of a broad range of electronically varied hetarenes and aryl bromides. The observed regioselective arylations suggest that a concerted metalation–deprotonation pathway is involved in the C–H activation step.

Regioselectivity in palladium-catalysed direct arylation of 5-membered ring heteroaromatics

“…116 In 2015, using Fagnou's conditions but in the presence of an electron-deficient phosphine ligand instead of electron-rich PCy 3 , Soos et al also regioselectively obtained C5-arylated thiazoles. 170 In 2009, the use of ligand-free PdIJOAc) 2 with KOAc as the base in DMA at 150 °C was also found to promote the direct C5-arylation of thiazole derivatives very regioselectively under very low catalyst concentration. By using electron-deficient aryl bromides, the reaction can be performed employing as little as 0.4-0.1 mol% catalyst (Scheme 72, bottom).…”

C−H Activation Based Functionalization of Furfural Derivatives

“…In 2012, X. Li and co-workers explored the use of azomethine ylides as nitrogen-delivering directing group in CÀ H activation reaction under Rh(III) catalysis. [126] Prepared from 5,5-dimethylpyrazolidin-3-one and the corresponding furfurals, these azomethine ylides (56) hydrazone. In the specific case of furfurals, the reaction proceeds through a 6-endo-trig cyclization (as opposed to a 6exo-trig Michael-type addition observed with benzaldehyde derived ylides).…”

“…Under similar conditions, Soos and coworkers also performed the arylation reaction with a preformed Pd(0) catalyst having (3,5‐bis(trifluoromethyl))triphenyl phosphine as ligand (Scheme 7a), [56] while Liu and Ke reported an analogous arylation using a PdCl 2 ‐α‐hydroxyimine as pre‐catalyst (Scheme 7b) [57] . The C5 direct arylation of 1 has been employed as a key step in the preparation of several pharmaceutically active compounds, such as the already mentioned neuropeptide analogs, [46] and drugs for the treatment of breast cancer such as Lapatinib [58] and some chalcone derivatives [59] …”

Facile Synthesis of Thienopyrroledione-Based π-Conjugated Polymers via Direct Arylation Polycondensation under Aerobic Conditions

“…To avoid catalytic deactivation, the polycondensation reaction must be carried out in an oxygen- and moisture-free environment and thus requires the extra steps of solvent distillation and storage in an inert atmosphere. Alternatively, direct arylation polycondensation using biphasic water/toluene conditions has recently been reported, and some reports of the molecular design and development of robust Pd catalysts for direct arylation in air and water have been published. − These observations prompted our interest in the facile synthesis of π-conjugated polymers via direct arylation under aerobic conditions, which would allow easy handling in air and the use of commercially available reagent-grade solvents, thus avoiding the tedious purification and storage of solvents under an inert atmosphere. As part of an ongoing study of direct sp 2 C–H functionalization strategies toward the synthesis of π-conjugated polymers, this work focuses on exploring the tolerance of Pd-catalyzed direct arylation polycondensation to aerobic reaction conditions.…”