Electron-deficient Arylboronic Acids Research Articles

Identification of a Surprising Boronic Acid Homocoupling Process in Suzuki–Miyaura Cross-Coupling Reactions Utilizing a Hindered Fluorinated Arene

AbstractThe Suzuki–Miyaura cross-coupling reaction of 2-bromo-1,3-bis(trifluoromethyl)benzene with arylboronic acids was evaluated and determined to suffer from the formation of large amounts of boronic acid homocoupling products in conjunction with dehalogenation. Homocoupling product formation in this process likely occurs through a rare protonolysis/second transmetalation event rather than by the well-established mechanism requiring the involvement of O2. The scope of this boronic acid homocoupling reaction was investigated and shown to predominate with electron-deficient arylboronic acids. Finally, a good yield of cross-coupling products could be obtained by employing dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (SPhos) as the ligand.

Carbopalladation/Suzuki Coupling Cascade for the Generation of Quaternary Centers: Access to Pyrrolo[1,2-b]isoquinolines

A convergent route to pyrrolo[1,2-b]isoquinolines with a quaternary center at C-10 has been developed, which implies a sequential Pd(0)-catalyzed carbopalladation followed by cross-coupling reaction with boronic acids. The adequate catalytic system and experimental conditions, with and without the use of phosphane ligands, have been selected to control the chemoselectivity of the process, allowing a 6-exo-carbopalladation to generate a quaternary center and avoiding a direct Suzuki coupling. A variety of electron-rich and electron-deficient arylboronic acids can be used providing an efficient route to substituted pyrrolo[1,2-b]isoquinolines in moderate to good yields (up to 94%, 22 examples).

ChemInform Abstract: Visible‐Light‐Mediated Chan—Lam Coupling Reactions of Aryl Boronic Acids and Aniline Derivatives.

The copper(II)-catalyzed aerobic oxidative coupling reaction between aryl boronic acids and aniline derivatives was found to be improved significantly under visible-light-mediated photoredox catalysis. The substrate scope of this oxidative Chan–Lam reaction was thus expanded to include electron-deficient aryl boronic acids as viable starting materials.

Visible‐Light‐Mediated Chan–Lam Coupling Reactions of Aryl Boronic Acids and Aniline Derivatives

The copper(II)-catalyzed aerobic oxidative coupling reaction between aryl boronic acids and aniline derivatives was found to be improved significantly under visible-light-mediated photoredox catalysis. The substrate scope of this oxidative Chan-Lam reaction was thus expanded to include electron-deficient aryl boronic acids as viable starting materials.

Copper(I) 3-Methylsalicylate Mediates the Chan–Lam N-Arylation of Heterocycles

Copper(I) 3-methylsalicylate (CuMeSal) mediates N-arylation reactions between aryl boronic acids and aromatic heterocycles (Chan–Lam coupling) under moderate reaction conditions (K2CO3, methanol, 65 °C, in air, 3–5 h). Both electron-rich and electron-deficient aryl boronic acids and a diverse set of N-heterocycles were allowed to react and gave N-arylation products in reasonable yields, which demonstrate the utility of this catalyst.

Unusual (Z)-selective palladium(II)-catalysed addition of aryl boronic acids to vinylaziridines.

The palladium(II)-catalysed addition of arylboronic acids to vinylaziridines has been developed. This reaction proceeds via an insertion/ring-opening process to provide (Z)-allylsulfonamides preferentially. This stereoselectivity is complimentary to existing methods that typically proceed via a SN2' mechanism to yield (E)-allylsulfonamides. Electron-deficient arylboronic acids were the optimum substrates for this reaction, while electron-donating groups on the aromatic ring of the boronic acids resulted in moderate yields.

Chelation-Mediated Palladium(II)-Catalyzed Domino Heck−Mizoroki/Suzuki−Miyaura Reactions Using Arylboronic Acids: Increasing Scope and Mechanistic Understanding

A palladium(II)-catalyzed Heck-Mizoroki/Suzuki-Miyaura domino reaction involving metal coordinating dimethylaminoethyl vinyl ethers and a number of electron-rich and electron-deficient arylboronic acids has been developed. Through variation of the temperature and the concentration of the p-benzoquinone (p-Bq) ligand/reoxidant, conditions for the robust and convenient one-pot generation of diarylated-saturated ethers were identified. With the aid of coordination of the dimethylamino group to the arylpalladium intermediate, the otherwise predominant formation of the β-arylated olefin could be reversed. A reaction route involving a chelation-controlled carbopalladation, providing a p-Bq stabilized six-membered palladacycle, followed by transmetalation and reductive elimination is suggested to explain the selective formation of saturated diarylated ether products.

Copper-Catalyzed Chlorination of Functionalized Arylboronic Acids

A mild, efficient, Cu(I)-catalyzed method for the conversion of arylboronic acids to aryl chlorides is reported. This method is particularly useful for the conversion of electron-deficient arylboronic acids to aryl chlorides, a transformation that is inefficient in the absence of Cu catalysis.

Pd-Catalyzed Synthesis of C4-Aryl Pyrimidinone Nucleoside Analogues

A two-step synthesis of C4-aryl pyri­midinone nucleoside analogues from readily available thymidine is described, which involves O4-arylsulfonylation and then Suzuki cross-coupling reaction of arylboronic acids with the derived O4-mesylates. Most of the coupling reactions proceed efficiently at room temperature in toluene, and electron-deficient arylboronic acids may also be cross-coupled at elevated temperature in THP.

Pd-Catalyzed C−C Bond-Forming Reactions of Thymidine Mesitylene Sulfonate

Facile synthesis of C-4 aryl pyrimidinone nucleoside analogues from an easily prepared O4-arylsulfonate derivative of thymidine is reported. Two O4-arylsulfonylthymidine precursors, (4-methylphenyl)sulfonyl and (2,4,6-trimethylphenyl)sulfonyl, were prepared and analyzed for their stabilities. Of the two, the latter possessed suitable stability as well as reactivity for Pd-catalyzed C-C bond-forming reactions with a variety of arylboronic acids. These reactions at the C-4 position are nontrivial in comparison with similar reactions at the C-5 position of pyrimidine nucleosides, with hydrolysis of the arylsulfonate precursor being a competing reaction in some cases. There are pronounced solvent influences in these reactions, but successful reactions can be attained by careful control of conditions. Many reactions proceeded efficiently at room temperature, and electron-deficient arylboronic acids can also be cross-coupled under suitable conditions. Desilylation of these products was also nontrivial, and various conditions were tested. Finally, antiviral screening was performed with the C-4 aryl pyrimidinone nucleoside analogues, but none possessed any interesting activity. The study represents the first successful synthesis of C-4 aryl pyrimidinone nucleoside analogues by cross-coupling of arylboronic acids with an arylsulfonate derived from a pyrimidine nucleoside, as well as antiviral testing of this new class of compounds.

Highly Efficient 1,4-Additions of Electron-Deficient Aryl Boronic Acids with a Novel Rhodium(I) Quinonoid Catalyst

Rhodium(I) quinonoid catalysts are a remarkably efficient new class of reagents for the conjugate addition of aryl boronic acids. Herein, we describe the use of these reagents in catalyzing the highly efficient addition of a broad range of boronic acids, including heteroaromatic and the first example of trihalogenated aryl boronic acids.