Silver-mediated palladium-catalyzed direct C-H arylation of 3-bromoisothiazole-4-carbonitrile

Silver(I) fluoride-mediated Pd-catalyzed C-H direct arylation/heteroarylation of 3-bromoisothiazole-4-carbonitrile (1a) gives twenty-four 5-aryl/heteroaryl-3-bromoisothiazole-4-carbonitriles. The reaction was partially optimized with respect to catalyst, ligand, and base. During this study 3,3'-dibromo-5,5'-biisothiazole-4,4'-dicarbonitrile (3a) was isolated as a byproduct and subsequently prepared via the silver-mediated Pd-catalyzed oxidative dimerization of 3-bromoisothiazole-4-carbonitrile in 67% yield. The analogous phenylation and oxidative dimerization of 3-chloroisothiazole-4-carbonitrile (1b) gave 3-chloro-5-phenylisothiazole-4-carbonitrile (4) and 3,3'-dichloro-5,5'-biisothiazole-4,4'-dicarbonitrile (3b) in 96% and 69% yields, respectively.     

Mild and efficient palladium-catalyzed intramolecular direct arylation reactions

The influence of ligand, stoichiometric base, and additive has been evaluated in the context of intramolecular direct arylation reactions. Under the optimal conditions, arylation of simple arenes can be performed under very mild conditions, with heating to 50 °C. The role of the pivalic acid additive is rationalized by invoking a concerted palladation-deprotonation pathway where the pivalate is behaving as either an intramolecular base from the palladium metal or through an intermolecular deprotonation in a similar manner as that previously described by Echavarren and Maseras.     

Intramolecular palladium-catalyzed direct arylation of alkenyl triflates

A catalyst generated from Pd(OAc)2 and dppp is effective for the direct intramolecular arylation of alkenyl triflates. Conjugated alkene-arene-containing carbocycles are produced in good yield. The process tolerates a variety of aryl substituents as well a simple heteroaryl groups. Electron-deficient aryl rings deliver faster reactions.     

Palladium-catalyzed benzylic direct arylation of benzyl sulfones with aryl halides

An effective palladium catalyst system for the direct arylation of benzyl sulfones with aryl halides has been developed. The catalytic reaction provides a facile route to diarylmethyl sulfones. The products can be transformed further via desulfonylative functionalization mediated by aluminum compounds.     

Palladium-catalyzed benzylic arylation of 2-methyl azaarenes

A palladium-catalyzed benzylic sp(3) direct arylation of electron-deficient heterocycles is reported. The method described enables the introduction of electron-rich and -poor aromatics at the benzylic position of heterocycles without the need for preactivation or the use of directing groups.     

Regioselective palladium-catalyzed arylation of 2-furaldehyde

An efficient regioselective method for the direct arylation of 2-furaldehyde to provide a range of pi-diverse 5-aryl-2-formylfuran derivatives is described. The method employs functionalized aryl halides and a catalytic amount of palladium(II) chloride under relatively mild conditions.     

A new strategy for the synthesis of benzylic sulfonamides: palladium-catalyzed arylation and sulfonamide metathesis

An efficient two-step strategy has been developed to access diversely functionalized benzylic sulfonamides. Execution of this strategy required the development of two reaction methods: the palladium-catalyzed cross-coupling of aryl halides with CH-acidic methanesulfonamides and a metathesis reaction between the resulting alpha-arylated sulfonamides and diverse amines. The broad scope of the cross-coupling process combined with a versatile sulfonamide metathesis constitutes an efficient strategy for the synthesis of various benzylic sulfonamides.     

Efficient palladium-catalyzed direct arylation of azines and diazines using ligand-free conditions

The use of the palladium-catalyzed direct arylation was successfully tested on different electron-deficient heterocycles. The results demonstrate the effectiveness of the method based on the intramolecular coupling reaction providing polyazacyclic systems. This new application was obtained by using ligand-free conditions with the mixture of Pd(OAc)₂ and TBAC as catalytic system. With suitable substrates different products arising from regioselective coupling were observed.     

Synthesis of benzodiquinanes via tandem palladium-catalyzed semipinacol rearrangement and direct arylation

A palladium-catalyzed tandem semipinacol rearrangement/direct arylation reaction using α-aryl isopropenyl-tert-cyclobutanols has been developed. This reaction gives access to benzodiquinanes in moderate to good yields and tolerates alkyl-, alkoxy-, and halogen-substituted aryl groups.     

Ruthenium(0)-catalyzed sp3 C-H bond arylation of benzylic amines using arylboronates

A Ru-catalyzed direct arylation of benzylic sp(3) carbons of acyclic amines with arylboronates is reported. This highly regioselective and efficient transformation can be performed with various combinations of N-(2-pyridyl) substituted benzylamines and arylboronates. Substitution of the pyridine directing group in the 3-position proved to be crucial in order to achieve high arylation yields. Furthermore, the pyridine directing group can be removed in high yields via a two-step protocol.     

Direct palladium-catalyzed C-3 arylation of indoles

An efficient protocol for palladium-catalyzed direct C-3 arylation of indoles containing unprotected heterocyclic nitrogen atom has been developed.     

A novel three-step synthesis of Celecoxib via palladium-catalyzed direct arylation

A novel three linear step synthesis of Celecoxib was achieved in 33% overall yield via a key regioselective direct C-H arylation reaction between a 1,3-disubstituted pyrazole and an aryl bromide.     

A palladium-catalyzed alkylation/direct arylation synthesis of nitrogen-containing heterocycles

A norbornene-mediated palladium-catalyzed sequence is described in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one reaction vessel. The aryl-heteroaryl bond-forming step occurs via a direct arylation reaction. A number of six-, seven-, and eight-membered ring-annulated indoles, pyrroles, pyrazoles, and azaindoles were synthesized from the corresponding bromoalkyl azole and an aryl iodide.     

Functionalization of a simple dithienylethene via palladium-catalyzed regioselective direct arylation

The direct arylation on the thienyl groups of a diarylethene with various aryl iodides efficiently provided arylated dithienylethenes under palladium catalysis. Unsymmetrically substituted dithienylethenes were also synthesized by this protocol. This procedure allows a rapid access to a variety of aryl-substituted dithienylethenes from a single substrate of a simple dithienylethene.     

Regioselective palladium-catalyzed arylation of 3-carboalkoxy furan and thiophene

[reaction: see text] The regioselective palladium(0)-catalyzed arylation of 3-furoate and 3-thiophenecarboxylate esters with aryl bromides is described. Conditions were developed that allow for the selective synthesis of either 2-aryl or 5-aryl products.     

Site-selective amination and/or nitrilation via metal-free C(sp2)–C(sp3) cleavage of benzylic and allylic alcohols

Benzylic/allylic alcohols are converted via site-selective C(sp²)–C(sp³) cleavage to value-added nitrogenous motifs, viz., anilines and/or nitriles as well as N-heterocycles, utilizing commercial hydroxylamine-O-sulfonic acid (HOSA) and Et₃N in an operationally simple, one-pot process. Notably, cyclic benzylic/allylic alcohols undergo bis-functionalization with attendant increases in architectural complexity and step-economy.

Benzylic/allylic alcohols are converted via site-selective C(sp²)–C(sp³) cleavage to value-added nitrogenous motifs, viz., anilines and/or nitriles as well as N-heterocycles, utilizing commercial hydroxylamine-O-sulfonic acid (HOSA) and Et₃N in an operationally simple, one-pot process.     

Organocatalyzed Friedel-Crafts arylation of benzylic alcohols

Electron-rich aromatic and heteroaromatic rings are functionalized directly with a variety of benzylic alcohols under mild conditions. The reaction is catalyzed by commercially available pentafluorophenylboronic acid, which is stable under ambient conditions and recoverable. The reaction itself is highly atom economical and produces water as the only byproduct. A Friedel-Crafts mechanism is proposed.     

Palladium-catalyzed benzylic arylation of N-benzylxanthone imine

The direct benzylic arylation of N-benzylxanthone imine with aryl chloride proceeds under palladium catalysis, yielding the corresponding coupling product. The product is readily transformed to benzhydrylamine. Taking into consideration that the imine is readily available from benzylic amine, the overall transformation represents a formal cross-coupling reaction of aryl halide with alpha-aminobenzyl metal.     

Direct palladium-catalyzed arylation of cyclopropenes

The first examples of direct palladium-catalyzed arylation and heteroarylation of cyclopropenes have been demonstrated. This method allows for efficient synthesis of various tetrasubstituted cyclopropenes, incuding nonracemic cyclopropenes, which are not available via known asymmetric cyclopropenation methods. Mechanistic studies strongly suggest an electrophilic path for this Heck-type transformation.     

Fluoradenes via palladium-catalyzed intramolecular arylation

A novel approach towards 7b-aryl-indeno[1,2,3-jk]fluorene based on a nitrogen-containing core is reported. The acid-promoted Friedel-Crafts reaction of 9-(2-bromophenyl)-9-fluorenol with carbazole, triphenylamine or triindole afforded 9-(2-bromophenyl)fluorenyl-carbazole, -triphenylamine and -triindole derivatives, which were subsequently converted to 7b-aryl-fluoradenes via palladium-catalyzed intramolecular C-H direct arylation as a key step.