Biaryl Synthesis via Pd-Catalyzed Decarboxylative Coupling of Aromatic Carboxylates with Aryl Halides

Abstract

A new strategy for the regiospecific construction of unsymmetrical biaryls is presented, in which easily available salts of carboxylic acids are decarboxylated in situ to give arylmetal species that serve as the nucleophilic component in a catalytic cross-coupling reaction with aryl halides. The catalyst system consists of a copper phenanthroline complex that mediates the extrusion of CO2 from aromatic carboxylates to generate arylcopper species, and a palladium complex that catalyzes the cross-coupling of these intermediates with aryl halides. This bimetallic system allows the direct coupling of various aryl, heteroaryl, or vinyl carboxylic acids with aryl or heteroaryl iodides, bromides, or chlorides at 160 degrees C in the presence of a mild base such as potassium carbonate. The present scope and potential economic impact of the reaction are demonstrated by the synthesis of 42 biaryls, some of which are of substantial industrial relevance. Remaining challenges and future perspectives of the new transformation are discussed.

Synthesis of Biaryls and Aryl Ketones via Microwave‐Assisted Decarboxylative Cross‐Couplings

“…This approach has successfully been employed in the synthesis of biaryls from aromatic carboxylates and aryl bromides, [3] chlorides, [4] and triflates, [5] as well as of aryl ketones from potassium a-oxocarboxylates. [6] Optimized reaction protocols have been developed for both small-and large-scale applications, [7] and the preparative value of this reaction type has been demonstrated in the synthesis of pharmaceutically relevant substances.…”

Copper‐Catalyzed Protodecarboxylation of Aromatic Carboxylic Acids

“…[8,9] We became interested in catalytic decarboxylations in the context of our work on copper/palladium-mediated decarboxylative cross-couplings of carboxylic acid salts with aryl halides. [10] This transformation represents an attractive new strategy for the synthesis of biaryls using aromatic carboxylates as sources of aryl nucleophiles instead of organometallic compounds. Unfortunately, it is still limited by the insufficent activity of the decarboxylation catalyst.…”

Recent Progress in Pd-Catalyzed Decarboxylative Coupling Reactions of (Hetero)aromatic Carboxylic Acids

“…将 Eq. 10 的反应温度升至 160 ℃, 以极少量 的 Pd/Cu 双金属催化反应(0.5 mol% Pd(acac) 2 , 1 mol% CuI, 3 mol% 1,10-phen), 反 应 同 样 高 产 (98%) [13,45] .…”