A general strategy for the perfluoroalkylation of arenes and arylbromides by using arylboronate esters and [(phen)CuR(F)

A versatile method for the synthesis of aryl perfluoroalkanes from arenes and aryl bromides is described. Substituted arenes or aryl bromides are converted in situ to an aryl boronate ester that readily undergoes perfluoroalkylation in air with [(phen)CuR(F)]. A broad range of aryl bromide substrates were perfluoroalkylated in good yield for the first time. [(phen)CuCF(3)] is now commercially available and has been prepared on 20?g scale.     

A novel and convenient synthesis of benzonitriles: electrophilic cyanation of aryl and heteroaryl bromides

N-Cyano-N-phenyl-p-methylbenzenesulfonamide has been used as a more benign electrophilic cyanation reagent for the synthesis of various benzonitriles from (hetero)aryl bromides via formation of Grignard reagents. Electronically different and sterically demanding aryl bromides including functionalized substrates and heteroaryl bromides are successfully cyanated in good to excellent yields. The efficiency of the present methodology is shown by the expeditious syntheses of interesting pharmaceutical intermediates. Notably, chemoselective monocyanation of dibromoarenes is also achieved.     

An improved protocol for the Pd-catalyzed alpha-arylation of aldehydes with aryl halides

An improved protocol for the Pd-catalyzed alpha-arylation of aldehydes with aryl halides has been developed. The new catalytic system allows for the coupling of an array of substrates including challenging electron-rich aryl bromides and less reactive aryl chlorides. The utility of this method has been demonstrated in a new total synthesis of (+/-)-sporochnol.     

First palladium-catalyzed Heck reactions with efficient colloidal catalyst systems

For the first time it has been shown that palladium colloids are effective and active catalysts for the olefination of aryl bromides (Heck reaction). Worthy of note are the high activities of the catalyst system for activated aryl bromides under optimized reaction conditions, which are better than or comparable with “classical” palladium phosphine complexes. Addition of phosphines strongly retards the reaction rate of the colloid catalyst. Nevertheless, this type of catalyst is not suitable for the activation of non-activated substrates, especially technically interesting aryl chlorides.     

Palladium‐Catalyzed Direct Cross‐Coupling of Carboranyllithium with (Hetero)Aryl Halides

A palladium‐catalyzed direct C‐arylation reaction of readily available cage carboranyllithium reagents with aryl halides has been developed for the first time. This method is applicable to a wide range of aryl halide substrates including aryl iodides, aryl bromides, and heteroaromatic halides.     

Simple kinetic method for distinguishing between homogeneous and heterogeneous mechanisms of catalysis,illustrated by the example of “ligand-free” Suzuki and Heck reactions of aryl iodides and aryl bromides

Using a simple method based on an analysis of the phase trajectories of competing reactions of several substrates, it has been established that the selectivity of catalytically active species in the Suzuki reaction of aryl bromides depends on the nature of the catalyst precursor. This indicates that there is a considerable contribution from heterogeneous catalysis. At the same time, in the reaction involving aryl iodides, when the catalyst concentration in the solution is much higher, the selectivity of the catalyst is precursor-independent, suggesting that homogeneous catalysis is dominant. In the Heck reaction of both aryl bromides and aryl iodides, pure homogeneous catalysis takes place.     

1,2,3-Triazol-5-ylidene-palladium complex catalyzed Mizoroki-Heck and Sonogashira coupling reactions

The bis-1,4-dimesityl-1,2,3-triazol-5-ylidene-palladium complex (1a) successfully catalyzes the Mizoroki-Heck and Sonogashira coupling reactions with aryl bromides to give the corresponding alkenes and alkynes, respectively, in good to excellent yields. In the Mizoroki-Heck reaction, electron-rich, electron-poor, and functionalized aryl bromides and alkenes are tolerated, while the substrates are limited to electron-poor aryl halides in the Sonogashira coupling reaction. The palladium complex also catalyzes cross-coupling reactions with aryl chlorides to give higher yields of products than does the bis-IMes-Pd complex analogue (2), under specific conditions.     

Aminomethylations via cross-coupling of potassium organotrifluoroborates with aryl bromides

[reaction: see text] The Suzuki-Miyaura cross-coupling reaction of N,N-dialkylaminomethyltrifluoroborates with aryl halides allows the construction of an aminomethyl aryl linkage through a disconnection based on dissonant reactivity patterns. A variety of these aminomethyltrifluoroborate substrates were prepared in good to excellent yields and then shown to cross-couple with equal facility to both electron-rich and electron-poor aryl halides as well as to a variety of heteroaromatic bromides.     

Visible‐Light‐Promoted Nickel‐ and Organic‐Dye‐Cocatalyzed Formylation Reaction of Aryl Halides and Triflates and Vinyl Bromides with Diethoxyacetic Acid as a Formyl Equivalent

A simple formylation reaction of aryl halides, aryl triflates, and vinyl bromides under synergistic nickel‐ and organic‐dye‐mediated photoredox catalysis is reported. Distinct from widely used palladium‐catalyzed formylation processes, this reaction proceeds by a two‐step mechanistic sequence involving initial in situ generation of the diethoxymethyl radical from diethoxyacetic acid by a 4CzIPN‐mediated photoredox reaction. The formyl‐radical equivalent then undergoes nickel‐catalyzed substitution reactions with aryl halides and triflates and vinyl bromides to form the corresponding aldehyde products. Significantly, besides aryl bromides, less reactive aryl chlorides and triflates and vinyl halides serve as effective substrates for this process. Since the mild conditions involved in this reaction tolerate a plethora of functional groups, the process can be applied to the efficient preparation of diverse aromatic aldehydes.     

Desulfinative palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides with aryl bromides under air

A highly efficient and mild palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides and aryl bromides for the selective synthesis of unsymmetrical biaryls has been developed. This methodology has the advantages of easily accessible starting materials, functional group tolerance and a wide range of substrates, which provide rapid access to biaryls derivatives. In this protocol, abundant and stable aryl bromides serve as the aryl sources by coupling reaction of the aryl group generated from arylsulfonyl hydrazides via in situ release of nitrogen and sulfur dioxide. No external oxidants or acids are needed for this kind of transformation.     

A simple catalyst for aqueous phase Suzuki reactions based on palladium nanoparticles immobilized on an ionic polymer

Palladium nanoparticles immobilized on a cross-linked imidazolium-containing polymer were evaluated as a catalyst for Suzuki carbon-carbon cross-coupling reactions using water as the solvent. The nanocatalysts show good catalytic activities for aryl iodides and aryl bromides and moderate activity with aryl chloride substrates. Coupling of sterically hindered substrates could also be achieved in reasonable yields. The heterogeneous catalyst is stable, can be stored without precautions to exclude air or moisture, and can be easily recycled and reused.     

Cross‐Electrophile Coupling of Vinyl Halides with Alkyl Halides

An improved method for the reductive coupling of aryl and vinyl bromides with alkyl halides that gave high yields for a variety of substrates at room temperature with a low (2.5 to 0.5 mol %) catalyst loading is presented. Under the optimized conditions, difficult substrates, such as unhindered alkenyl bromides, can be coupled to give the desired olefins with minimal diene formation and good stereoretention. These improved conditions also worked well for aryl bromides. For example, a gram‐scale reaction was demonstrated with 0.5 mol % catalyst loading, whereas reactions at 10 mol % catalyst loading completed in as little as 20 minutes. Finally, a low‐cost single‐component pre‐catalyst, (bpy)NiI₂ (bpy=2,2′‐bipyridine) that is both air‐ and moisture‐stable over a period of months was introduced.     

Rapid homogeneous-phase Sonogashira coupling reactions using controlled microwave heating

A microwave-enhanced, rapid and efficient homogeneous-phase version of the Sonogashira reaction is presented. It has been applied to the coupling of aryl iodides, bromides, triflates, and aryl chloride, as well as pyridine and thiophene derivatives with trimethylsilylacetylene. Excellent yields (80-95%) for substrates containing a large variety of substituents in different positions are obtained in 5-25 min.     

Pd-catalyzed cross-coupling of α-(acyloxy)-tri-n-butylstannanes with alkenyl, aryl, and heteroaryl electrophiles

Racemic and scalemic α-(acyloxy)-tri-n-butylstannanes undergo Pd-catalyzed cross-couplings with alkenyl/aryl/heteroaryl iodides, bromides, and triflates in moderate to good yields in THF at 45 °C. Simple aryl iodides and unprotected aza-arenes, two classes of electrophiles that typically react sluggishly, are also good substrates. Cross-couplings proceed with retention of configuration at the alkenyl and stannyl-substituted stereocenters.     

Synthesis of Phenols: Organophotoredox/Nickel Dual Catalytic Hydroxylation of Aryl Halides with Water

A highly effective hydroxylation reaction of aryl halides with water under synergistic organophotoredox and nickel catalysis is reported. The OH group of the resulting phenols originates from water, following deprotonation facilitated by an intramolecular base group on the ligand. Significantly, aryl bromides as well as less reactive aryl chlorides served as effective substrates to afford phenols with a wide range of functional groups. Without the need for a strong inorganic base or an expensive noble‐metal catalyst, this process can be applied to the efficient preparation of diverse phenols and enables the hydroxylation of multifunctional pharmaceutically relevant aryl halides.     

N,N-dimethyl glycine-promoted Ullmann coupling reaction of phenols and aryl halides

[reaction: see text] Ullmann-type diaryl ether synthesis can be performed at 90 degrees C using either aryl iodides or aryl bromides as the substrates under the assistance of N,N-dimethylglycine.     

Copper-catalyzed N-arylation of sulfonamides with aryl bromides under mild conditions

This Letter describes a copper catalyzed sulfonamide coupling reaction with aryl bromides to form N-aryl sulfonamides under mild conditions, including the first examples of Cu-catalyzed sulfonamide coupling at room temperature. The reaction protocol tolerates a broad range of substrates including a variety of primary and secondary sulfonamides and challenging heteroaryl bromides such as 2-bromothiazole.     

Barbier–Negishi Coupling of Secondary Alkyl Bromides with Aryl and Alkenyl Triflates and Nonaflates

A mild and practical Barbier–Negishi coupling of secondary alkyl bromides with aryl and alkenyl triflates and nonaflates has been developed. This challenging reaction was enabled by the use of a very bulky imidazole‐based phosphine ligand, which resulted in good yields as well as good chemo‐ and site selectivities for a broad range of substrates at room temperature and under non‐aqueous conditions. This reaction was extended to primary alkyl bromides by using an analogous pyrazole‐based ligand.     

Copper‐Catalyzed Reductive Cross‐Coupling of Nonactivated Alkyl Tosylates and Mesylates with Alkyl and Aryl Bromides

A copper‐catalyzed reductive cross‐coupling reaction of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides was developed. It provides a practical method for efficient and cost‐effective construction of aryl–alkyl and alkyl–alkyl C?C bonds with stereocontrol from readily available substrates. When used in an intramolecular fashion, the reaction enables convenient access to various substituted carbo‐ or heterocycles, such as 2,3‐dihydrobenzofuran and benzochromene derivatives.     

Cross‐Coupling of Sodium Sulfinates with Aryl,Heteroaryl, and Vinyl Halides by Nickel/Photoredox Dual Catalysis

An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.