Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides, and Iodides: Scope and Structure-Activity Relationships

Reaction Scheme

Abstract

Boronic acids which quickly deboronate under basic conditions, such as polyfluorophenylboronic acid and five- membered 2-heteroaromatic boronic acids, are especially chal- lenging coupling partners for Suzuki-Miyaura reactions. Never- theless, being able to use these substrates is highly desirable for a number of applications. Having found that monodentate biarylphosphine ligands can promote these coupling processes, we developed a precatalyst that forms the catalytically active species under conditions where boronic acid decomposition is slow. With this precatalyst, Suzuki-Miyaura reactions of a wide range of (hetero)aryl chlorides, bromides, and triflates with polyfluorophenyl, 2-furan, 2-thiophene, and 2-pyrroleboronic acids and their analogues proceed at room temperature or 40 ?C in short reaction times to give the desired products in excellent yields.

Substrates

Procedure

A vial was equipped with a magnetic stir bar and charged with XPhos-Pd-G2 (2-3 mol%) and the boronic acid (1.5 mmol). The vessel was sealed with a screw-cap septum, and then evacuated and backfilled with argon (this process was repeated a total of 3 times). Then, the aryl halide or pseudo halide (1.0 mmol) and degassed THF (2 mL) were added via syringe (aryl halides that were solids at room temperature were added with the precatalyst and the boronic acid). Then, degassed 0.5 M aqueous K3PO4 solution (4 mL) was added via syringe and the reaction was stirred at room temperature or 40 �C for 30 min or 2 h. At this point, diethyl ether (10 mL) and water (10 mL) were added to the mixture, and the aqueous phase was extracted with diethyl ether (3 x 10 mL). The organic phase was dried over MgSO4, concentrated in vacuo, and purified via the Biotage SP4

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