Efficient Pd‐Catalyzed Direct Coupling of Aryl Chlorides with Alkyllithium Reagents

Abstract

Organolithium compounds are amongst the most important organometallic reagents and frequently used in difficult metallation reactions.H owever,t heir direct use in the formation of C À Cbonds is less established. Although remarkable advances in the coupling of aryllithium compounds have been achieved, Csp 2 ÀCsp 3 coupling reactions are very limited. Herein, we report the first general protocol for the coupling or aryl chlorides with alkyllithium reagents.P alladium catalysts based on ylide-substituted phosphines (YPhos) were found to be excellently suited for this transformation giving high selectivities at room temperature with avariety of aryl chlorides without the need for an additional transmetallation reagent. This is demonstrated in gram-scale synthesis including building blocks for materials chemistry and pharmaceutical industry.Furthermore,the direct coupling of aryllithiums as well as Grignard reagents with aryl chlorides was also easily accomplished at room temperature.

Phosphorus-ylides: powerful substituents for the stabilization of reactive main group compounds

“…10 ). 66 The donor strength and the steric properties of the YPhos ligands were found to be highly tunable depending on the nature of the Z substituent in the ylide-backbone. Thus, while offering steric protection through the large phosphonium moiety, donor strengths similar to those of NHCs, which are usually considered to be stronger donors, could be reached.…”

Phosphorus‐Containing Superbases: Recent Progress in the Chemistry of Electron‐Abundant Phosphines and Phosphazenes

“…[19,42] During research on ylide and yldiide compounds as ligands in transition metal complexes and the stabilization of reactive low-valent main group elements, Gessner and co-workers connected the strongly π-donating ylidyl groups as substituents to a phosphorus atom and obtained electron-abundant ylidylphosphines (YPhos). [108,109,110,111,112] Three simple reaction paths A-C in Scheme 14 were presented to synthesize ylidylphosphines starting from alkylphosphonium salts, which can be easily prepared via reaction of the respective phosphine with alkylhalides (Scheme 14). [113,115] Depending on the nature of Z, double deprotonation with metal bases and subsequent nucleophilic substitution at halophosphines deliver the desired YPhos ligands 34a-e in moderate to high yields of 69-92 % (route A).…”

“…[106] The latest findings in palladium catalysis gave rise to rather labile PÀ C bonds of triphenylphosphonium functionalities in common YPhos ligands, which results in inactive catalytic systems on course of the reaction, Gessner et al replaced the phenyl by cyclohexyl groups. [108,109,114] The resulting ligands in Cy Y Me PCy 2 (34k-m) show elevated stability and a remarkable performance in palladium-catalyzed amination reactions of aryl chlorides at room temperature (Scheme 14). [108,109] YPhos ligands in general represent valuable electron-rich phosphines, which was demonstrated by their readily formation of transition metal complexes, such as gold(I) [106,111,115] or palladium [112][113][114] complexes, which have been successfully employed as catalysts in amination and hydroamination reactions, as well as alpha arylation with arylchlorides among others.…”

“…[108,109,114] The resulting ligands in Cy Y Me PCy 2 (34k-m) show elevated stability and a remarkable performance in palladium-catalyzed amination reactions of aryl chlorides at room temperature (Scheme 14). [108,109] YPhos ligands in general represent valuable electron-rich phosphines, which was demonstrated by their readily formation of transition metal complexes, such as gold(I) [106,111,115] or palladium [112][113][114] complexes, which have been successfully employed as catalysts in amination and hydroamination reactions, as well as alpha arylation with arylchlorides among others. [116] Scheme 11.…”

Amino−Organolithium Compounds and their Aggregation for the Synthesis of Amino−Organoaluminium Compounds

“…[3b,14] Here, especially amines and ethers play a vital role. [14c] Currently, organolithium chemistry is evolving in several directions: First, experimental charge density studies revealed the nature of these unusual coordination bonds, [15] second, catalytic coupling reactions are still improved, [16] third, greener approaches try to avoid the usage of solvents and exploit solid organolithium compounds in mechanochemical reactions, [17] and fourth, they might be applied for syn-gas chemistry. [18] Besides the crystallographic studies, which give the exact structure, but only of (single-)crystalline compounds, NMR spectroscopic studies reveal the aggregation in solution, which sometimes differs, depending on, e. g., concentration and solvent.…”