Palladium-catalyzed direct and regioselective C-H bond functionalization/oxidative acetoxylation of indoles

The first general examples of palladium-catalyzed direct and selective oxidative C3-acetoxylation of indoles are presented. The mild reaction conditions (70 °C and with weak base, KOAc) in this indole C-H-acetoxylation are notable.     

Palladium-catalyzed Heck-type reaction of 2-chloro acetamides with olefins

Conditions have been developed for the palladium-catalyzed Heck-type reaction of 2-chloro acetamides with several olefins. The regiochemistry of the products obtained speaks in favor of an involvement of palladium enolates in this reaction.     

Palladium-catalyzed acetoxylation of arenes by 1,2,3-triazole-directed CH activation

A facile and efficient method for the regioselective acetoxylation of 1,4-disubstituted 1,2,3-triazoles via Pd-catalyzed C$\text{<mglyph src="https://sdfestaticassets-eu-west-1.sciencedirectassets.com/shared-assets/16/entities/sbnd"></mglyph>}$H bond activation was developed. The cheap acetic acid was applied as the acetoxyl source to convert aromatic sp² C$\text{<mglyph src="https://sdfestaticassets-eu-west-1.sciencedirectassets.com/shared-assets/16/entities/sbnd"></mglyph>}$H bonds into C$\text{<mglyph src="https://sdfestaticassets-eu-west-1.sciencedirectassets.com/shared-assets/16/entities/sbnd"></mglyph>}$O bonds in high regioselectivity, employing 1,2,3-triazole as an elegant directing group and K₂S₂O₈ as the oxidant. A range of 1,2,3-triazoles bearing acetoxyl group can be synthesized with the reaction facilely.     

Palladium-catalyzed C-H perfluoroalkylation of arenes

A new Pd-catalyzed reaction for the coupling between perfluoroalkyl iodides (R(F)I) and simple aromatic substrates is described. The perfluoroalkylated arene products are obtained in good to excellent yields in the presence of a phosphine-ligated Pd catalyst and Cs(2)CO(3) as a base. The development, optimization, scope, and preliminary mechanistic studies of these transformations are reported.     

Palladium-catalyzed benzylic C-H insertion of 2-substituted N-iminopyridinium ylides

Palladium-catalyzed direct benzylic C-H arylation of 2-alkyl substituted N-iminopyridinium ylides is described. The insertion can be conducted with several electron-poor and electron-rich aryl chlorides in good yields. This work adds to the few examples of sp3 C-H insertions that have been reported so far.     

Palladium-catalyzed oxidative sp2 C-H bond acylation with alcohols

An efficient method was developed for the direct acylation of arene sp(2) C-H bonds with alcohols using palladium chloride as a catalyst and peroxide as the oxidant. The alcohols were oxidized to their corresponding aldehydes in situ and efficiently coupled with 2-arylpyridines to give aryl ketones in chlorobenzene.     

Palladium-catalyzed oxidative allylic C-H silylation

Palladium-catalyzed allylic C-H silylation was performed with use of hexamethyldisilane as the silyl source. These C-H functionalization reactions occur only in the presence of hypervalent iodine reagents or other strong oxidants and proceed with excellent regioselectivity, providing the linear allylic isomer of the allylsilane products. In demonstrating the first oxidative allylic C-H silylation of alkenes, this study marks an important advance for the catalytic C-H functionalization method.     

Palladium-catalyzed C-H arylation of 2,5-substituted pyrroles

The palladium-catalyzed direct arylation of 2,5-substituted pyrrole derivatives with diaryliodonium salts to generate tri-, tetra-, and penta-substituted pyrrole products is described. The scope and limitations of these transformations are also reported.     

Palladium-catalyzed C-H aminations of anilides with N-fluorobenzenesulfonimide

The first amide-directed, palladium-catalyzed, intermolecular, highly selective C-H aminations with the non-nitrene-based nitrogen source N-fluorobenzenesulfonimide have been developed. This methodology might provide a new pathway for directed metal-catalyzed aromatic C-H amination.     

Palladium-catalyzed direct ortho C-H arylation of 2-arylpyridine derivatives with aryltrimethoxysilane

A Pd(OAc)(2)-catalyzed cross-coupling reaction between 2-arylpyridine and aryltrimethoxysilane in the presence of AgF and BQ in 1,4-dioxane was studied. After various reaction parameters (catalyst, oxidant, additive, solvent and reaction temperature) were examined, the optimal conditions for the reaction were identified. The synthesis is compatible to aryltrimethoxysilane with both electron-withdrawing and electron-donating groups on the aryl moiety with moderate yields. The kinetic isotope effect (k(H)/k(D)) for the C-H bond activation was provided.     

Palladium-catalyzed direct ortho-alkynylation of aryl acetamides with low catalyst loading

The palladium-catalyzed alkynylation of phenylacetic acid derivatives using 4-CF₃C₆F₄NH₂ as the auxiliary is described. The reaction efficiency can be greatly promoted by pyridine ligand, which enables the reaction to proceed at a catalyst loading as low as 1 mol%. Various functional groups are tolerated under the reaction conditions. The kinetic studies show that the rate of the reaction is first order in phenylacetamide and the Pd(OAc)₂ in combination of the pyridine ligand provides a highly robust and effective catalyst.     

Highly stereoselective synthesis of tetrasubstituted alkenes via hydroamination of alkynes and C-H acetoxylation

A novel reaction including the sequence of hydroamination of alkynes and subsequent oxidative C-H bond functionalization has been developed in the presence of diacetoxyiodobenzene (DIB). The method allows us to synthesize a wide range of tetrasubstituted (E)-alkenes and provides a potential method to construct densely functionalized carbonyl compounds.     

Palladium-catalyzed C-H bond functionalization of C6-arylpurines

A highly regioselective Pd-catalyzed C(Ar)-H bond activation method was developed for the modification of purines (nucleosides) with different functional groups by using purine as a directing group. This approach provides a new access to a variety of functionalized purines (nucleosides) which are potentially of great importance in medicinal chemistry.     

Palladium-catalyzed direct 2-alkylation of indoles by norbornene-mediated regioselective cascade C-H activation

A palladium-catalyzed direct 2-alkylation reaction of free N-H indoles has been developed. This reaction relies on a norbornene-mediated cascade C-H activation process at the indole ring, which features high regioselectivity and excellent functional group tolerance. The reaction represents the first example for a generally applicable, direct C-H alkylation of indole at the 2-position.     

Palladium-catalyzed intermolecular directed C-H amidation of aromatic ketones

Pd-catalyzed directed ortho C-H amidation of aromatic ketones with both sulfonamides and amides has been accomplished. The use of an electron-deficient Pd complex, Pd(OTf)(2), is crucial for the success of this transformation. Some key intermediates of the reaction, that is, the cyclopalladation complexes of ketones, have been characterized by X-ray crystallography. Experimental analysis of these palladacycles and also the experimental results with N-methyl sulfonamides indicate that the new reaction does not seem to proceed through a nitrene intermediate. The utility of the newly developed reaction was demonstrated for the synthesis of useful organic intermediates such as 2- and 3-alkyl indoles and 2-aminophenyl ketones.     

Palladium-catalyzed ortho-selective C–H bond chlorination of aromatic ketones

A palladium-catalyzed ortho-selective C–H bond chlorination reaction for the preparation of 2-chloro aromatic ketones was described. Both electron-withdrawing and electron-donating groups on the aromatic rings are well tolerated under the optimized conditions. The 2-chloro aromatic ketones obtained by our method could be applied to synthesize the derivatives of 1H-indazole or benzo[d]isoxazole.     

Palladium-catalyzed alkylation of 1,4-dienes by C-H activation

Activated: the title reaction proceeds with a broad range of nucleophiles and variously substituted 1,4-dienes under mild conditions, and provides direct access to the corresponding 1,3-diene-containing products with high regio- and stereocontrol (see scheme; 2,6-DMBQ=2,6-dimethylbenzoquinone, EWG=electron-withdrawing group). This is the first catalytic allylic C-H alkylation that proceeds in the absence of sulfoxide ligands.     

Palladium-catalyzed oxygenation of unactivated sp3 C-H bonds

This communication describes a new palladium-catalyzed method for the oxygenation of unactivated sp3 C-H bonds. A wide variety of alkane substrates containing readily available oxime and/or pyridine directing groups are oxidized with extremely high levels of chemo-, regio-, and in some cases diastereoselectivity. The substrate scope of these reactions is discussed, and the high selectivities are rationalized on the basis of the requirements of putative palladium alkyl intermediates.