Mild and General Palladium-Catalyzed Synthesis of Methyl Aryl Ethers Enabled by the Use of a Palladacycle Precatalyst

Abstract

A general method for the Pd-catalyzed coupling of methanol with (hetero)aryl halides is described. The reactions proceed under mild conditions with a wide range of aryl and heteroaryl halides to give methyl aryl ethers in high yield.

Well-defined nickel and palladium precatalysts for cross-coupling

“…In conjunction with the dialkylbiarylphosphine ligands also developed by the Buchwald group, palladacycle-based precatalysts have now been used for nearly every type of cross-coupling. Recent notable applications of this system include facilitating state-of-the-art Suzuki–Miyaura 29 , Negishi 30–33 and aryl amination 34–38 reactions, as well as the cyanation 39,40 and hydroxylation 41 of aryl halides, the synthesis of methyl aryl ethers 42 and the aminocarbonylation of aryl bromides 43 . Buchwald precatalysts are now available commercially in preloaded capsules, which contain varying amounts and types of palladacycle, and are conveniently used in synthetic chemistry.…”

Palladium-Catalyzed Hydroxylation of Aryl and Heteroaryl Halides Enabled by the Use of a Palladacycle Precatalyst

“…18 We reasoned that the same catalyst would also promote the cross-coupling of hydroxide salts with (hetero)aryl halides. In addition, the use of L5 as a sole ligand would be operationally more simple and practical for hydroxylation, compared with the previous use of the dual biarylphosphine ligands L1 and L2 .…”

Transition‐Metal‐Catalyzed Utilization of Methanol as a C1 Source in Organic Synthesis

“…[38] Notably,m ethanol serves as ac onvenient methoxy group precursor for the synthesis of such methyl ethers.R egarding their preparation, the Williamson ether synthesis represents apowerful method that converts alcohols (ROH) into ethers (ROR'). [40] Next, Buchwald and co-workers [41] also described apalladium-catalyzed arylation of methanol and CD 3 OD that proceeds under mild reaction conditions.V arious aryl and heteroaryl halides were found to be suitable substrates and gave the corresponding products in excellent yields (Scheme 16). However,t he applicability of this method is limited because of the drastic reaction conditions, low functional group tolerance,and the necessity to use toxic reagents.A lternatively,i n2 012, Beller and co-workers [39] reported the first synthetic method for the palladiumcatalyzed coupling of aryl halides with methanol to synthesize substituted anisoles in moderate to good yields (Scheme 15).…”