<Emphasis Type="Italic">N</Emphasis>-Propylphthalimide-substituted bis-(NHC)PdX<Subscript>2</Subscript> complexes: synthesis,characterization and catalytic activity in direct arylation reactions

Palladium-catalyzed direct arylation of heteroaromatics has become a popular method for producing carbon–carbon bonds via C–H bond activation. A wide diversity of heteroaromatics such as furan, thiophenes and thiazoles can be used for this reaction. This paper reports the synthesis of N-propylphthalimide-substituted bis-(NHC)PdX₂ complexes (NHC = N-heterocyclic carbene), and their catalytic activity in direct arylation reactions. The complexes have been prepared from Ag(I)NHC precursors by transmetallation and characterized by spectroscopy and elemental analysis. The bis-(NHC)PdX₂ complexes show excellent activity as catalysts in the direct arylation reactions of 2-n-butylfuran, 2-n-butylthiophene and 2-isopropylthiazole.     

Palladium-catalysed direct 3- or 4-arylation of thiophene derivatives using aryl bromides

The palladium-catalysed direct 3- or 4-arylation of 2,5-disubstituted thiophenes using aryl bromides gives a simple access to a variety of 3- or 4-arylthiophene derivatives. Moderate to good yields of 3-arylated thiophenes were obtained using 2,5-dimethylthiophene. In the presence of unsymmetrically disubstituted, 2-acetyl-5-methylthiophene, a regioselective arylation on carbon 4 of thiophene was observed. This reaction provides only HX associated to the base as by-product and reduces the number of steps to prepare these compounds.     

Palladium-catalyzed direct 5-arylation of formyl- or acetyl-halothiophene derivatives

Pd(OAc)₂ was found to catalyze the direct arylation of some functionalized halothiophene derivatives allowing the synthesis in only one step of polyfunctionalized arylated thiophenes. In the presence of 2-acetyl-3-chlorothiophene, 2-acetyl-4-chlorothiophene, 2-acetyl-3-bromothiophene diethylacetal or 2-(4-bromothiophen-2-yl)-[1,3]dioxolane, and a variety of aryl bromides, the 5-arylation products were obtained in moderate to high yields employing only 0.5 mol% catalyst. On the other hand, the use of 2-formyl-3-chlorothiophene, 2-acetyl-3-bromothiophene or 2-formyl-3-bromothiophene gave disappointing results.     

Direct arylation of oxazoles at C2. A concise approach to consecutively linked oxazoles

The synthesis of bis- and trisoxazoles via direct arylation is discussed. A variety of aryl groups can be installed at the 2-position of 5-aryl and 5-carboxy-substituted oxazoles under mild conditions using palladium catalysis on water. The direct arylation method can be extended to the synthesis of bis- and trisoxazoles if 2-triisopropylsilyl-4-iodooxazole is used as the electrophile in the arylation.     

Arylation of unactivated arenes

Transition metal-catalyzed and metal-free direct arylation of unactivated arenes is described. The transition metal-catalyzed direct arylation of unactivated arenes as a state-of-the-art method towards biaryl synthesis is highlighted in this Perspective.     

Catalytic direct arylation with aryl chlorides, bromides, and iodides: intramolecular studies leading to new intermolecular reactions

A catalyst for the intramolecular direct arylation of a broad range of simple and heterocyclic arenes with aryl iodides, bromides, and chlorides has been developed. These reactions occur in excellent yield and are highly selective. Studies with aryl iodides substrates revealed that catalyst poisoning occurs due to the accumulation of iodide in the reaction media. This can be overcome by the addition of silver salts which also permits these reactions to occur at lower temperature. The utility of the methodology is illustrated by a rapid synthesis of a carbazole natural product and by the synthesis of sterically encumbered tetra-ortho-substituted biaryls via ring-opening reactions of the direct arylation products. Mechanistic investigations have provided insight into the catalyst's mode of action and show the presence of a kinetically significant C-H bond cleavage in palladium-catalyzed direct arylation of simple arenes. Knowledge garnered from these studies has led to the development of new intermolecular arylation reactions with previously inaccessible arenes, opening the door for the development of other new direct arylation processes.     

Synthesis of [1]benzothieno[3,2-b][1]benzothiophene (BTBT) and its higher homologs through palladium-catalyzed intramolecular decarboxylative arylation

We report herein an effective method for the construction of 4- and 7-ring benzo-fused thieno[3,2-b]thiophenes, involving palladium-catalyzed intramolecular decarboxylative arylation as the key step.     

Palladium-catalyzed direct arylation of 5-chloropyrazoles: a selective access to 4-aryl pyrazoles

The use of a temporary protection by a chloro group at C5 of pyrazoles allows the synthesis of the 4-arylated pyrazoles, which were previously inaccessible by palladium-catalyzed direct arylation, with complete regioselectivity and in high yields using in most cases as little as 0.5-0.1 mol % Pd(OAc)(2) as the catalyst with electron-deficient aryl bromides. Moreover, from 5-chloro-1,3-dimethylpyrazole, sequential catalytic C4 arylation, dechlorination, catalytic C5 arylation reactions allowed the synthesis of a 4,5-diarylated pyrazole derivative.     

Palladium‐Catalyzed Direct C?H Arylation of Isoxazoles at the 5‐Position

A palladium‐catalyzed direct arylation of isoxazoles with aryl iodides has been achieved. The C H bond at the 5‐position is activated selectively to give coupling products in moderate to good yields. This direct arylation was applied to the synthesis of a spiro‐type chiral ligand, which proved to be most effective to the palladium‐catalyzed tandem cyclization of a dialkenyl alcohol.     

Palladium‐Catalyzed Direct C?H Arylation of Isoxazoles at the 5‐Position

A palladium‐catalyzed direct arylation of isoxazoles with aryl iodides has been achieved. The C H bond at the 5‐position is activated selectively to give coupling products in moderate to good yields. This direct arylation was applied to the synthesis of a spiro‐type chiral ligand, which proved to be most effective to the palladium‐catalyzed tandem cyclization of a dialkenyl alcohol.     

A direct synthesis of substituted thiophenes via α-oxoketene dithioacetals. II.

The regioselective deprotonation of S,S-dimethyl-α-oxoketene dithioacetal at the (Z)-S-methyl group leads to a direct synthesis of 2-S-methyl-3,4-disubstituted thiophenes.     

Pd-catalyzed direct arylation of tautomerizable heterocycles with aryl boronic acids via C-OH bond activation using phosphonium salts

The first direct arylation via C-OH bond activation of tautomerizable heterocycles has been achieved using phosphonium salts, on the basis of a combination of the phosphonium coupling and Suzuki-Miyaura cross-coupling conditions. Optimal reaction condition is obtained through screening of phosphonium salts, Pd catalysts, and bases. The direct arylation via C-OH bond activation tolerates a variety of tautomerizable heterocycles and aryl boronic acids. The mechanism of the Pd-catalyzed phosphonium coupling is proposed to proceed via a domino seven-step process including the unprecedented heterocycle-Pd(II)-phosphonium species. Application of the Pd-catalyzed direct arylation via C-OH bond activation using PyBroP leads to the most efficient synthesis of the biologically important 6-arylpurine ribonucleoside in a single step from unactivated and unprotected inosine.     

Developments in Direct C?H Arylation of (Hetero)Arenes under Microwave Irradiation

This minireview describes the progress made in the development of direct C? H arylation approaches through the application of focused microwave irradiation. The synergistic combination of microwave‐assisted techniques with the rapidly evolving domain of C? H arylation has opened new vistas in the efficient synthesis of a diverse array of biologically important (hetero)arenes.     

Rapid access to diverse α-carbolines through sequential transition metal catalyzed amination and direct C–H arylation

An efficient sequence of Pd catalyzed amination and direct C–H arylation for a synthesis of pharmacologically important α-carbolines is described. The outstanding feature in the synthetic sequence is that a combination of DBU and 2-(dicyclohexylphosphino)biphenyl (DCHPB) plays a critical role to not only enhance the reactivity but also suppress hydrodehalogenation in the direct C–H arylation step. The reaction protocol provides α-carbolines with various substituents including base-sensitive ester and ketone moieties in moderate to excellent yields. Moreover, combination with Cu catalyzed amination further enhanced the versatility of the α-carboline synthesis.     

Direct Pd-catalyzed arylation of 1,2,3-triazoles

A highly efficient method for the synthesis of multisubstituted 1,2,3-triazoles via a direct Pd-catalyzed C-5 arylation has been developed.     

Pd/C as a Catalyst for Completely Regioselective CH Functionalization of Thiophenes under Mild Conditions

The completely C3‐selective arylation of thiophenes and benzo[b]thiophenes was achieved by using Pd/C as a heterogeneous catalyst without ligands or additives under mild reaction conditions. The practicability of this transformation is demonstrated by notable functional group tolerance and the insensitivity of the reaction to H₂O and air. This method is also applicable to nitrogen‐ and oxygen‐containing heterocycles, yielding the corresponding C2‐arylated products. Three‐phase tests along with Hg‐poisoning and hot‐filtration tests suggest that the catalytically active species is heterogeneous in nature.     

Perylene bisimide‐based semiconducting polymers: Synthesis via palladium‐catalyzed direct arylation,characterization, optoelectrical properties,and nanomorphology

Perylene bisimide (PBI)‐based acceptor polymers have been synthesized by the facile and environmental‐friendly palladium‐catalyzed direct arylation. The direct arylation using a bromothiophene‐extended PBI monomer, which was designed for the direct arylaion, proceeded to yield PBI‐based acceptor polymers (PPBI3T). As a result of screening the direct arylation conditions, PPBI3T with the number average molecular weight of 14,000 was successfully synthesized, and the spectroscopic and optoelectronic analysis demonstrated the synthesis of PPBI3T with the desired structure. The random compolymerization among naphthalene bisimide (NBI)‐based monomer, PBI‐based monomer, and 3,4‐dimethylthiophene afforded the random copolymers composed of NBI‐ and PBI‐based components (P(NBI3T‐PBI3T)). The composition of each component was controlled by changing the monomer feed ratio, and furthermore, the optical and electrochemical properties of P(NBI3T‐PBI3T) were also tunable by controlling the composition of each component. To the best of our knowledge, these results were the first accomplishment for the direct arylation synthesis of PBI‐based acceptor polymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3151–3158     

A new class of pyrazolopyridine nucleus with fluorescent properties, obtained through either a radical or a Pd arylation pathway from N-azinylpyridinium N-aminides

The synthesis of dipyridopyrazole and pyridopyrazolopyrazine derivatives--both of which incorporate a 3-aryl moiety--can be achieved in moderate yields by intramolecular radical arylation of pyridinium N-aminides using tris(trimethylsilyl)silane and azobisisobutyronitrile. Improved results were obtained on using Pd direct arylation in conjunction with microwave irradiation. A preliminary study into the fluorescent properties of the target compounds is also reported.     

Allocolchicinoid synthesis via direct arylation

[reaction: see text] A formal enantioselective synthesis of allocolchicine and a synthesis of a C-ring analogue have been achieved by employing an intramolecular direct arylation of an aryl chloride to form the biaryl carbon-carbon bond and the seven-membered ring.     

Visible-light-mediated Gomberg-Bachmann reaction: An efficient photocatalytic approach to 2-aminobiphenyls

An efficient, metal-free and highly selective protocol for the synthesis of 2-aminobiphenyls via visible-light-mediated arylation of anilines using aryl diazonium salts (Gomberg-Bachmann reaction) has been reported. The reaction is an example of photoredox catalysed direct C(sp²)–H arylation of anilines using eosin Y as an organophotoredox catalyst. The presented visible-light-mediated environmentally sustainable approach has the potential to earn a decent position among the classical and contemporary methods for the synthesis of aminobiaryls.