Palladium-catalyzed Intramolecular Direct Arylation Research Articles

Palladium-Catalyzed intramolecular direct arylation of aromatic tertiary amide compounds revisited

We have investigated the palladium-catalyzed intramolecular direct arylation of three aromatic tertiary amide compounds. For the C–H activation of the benzene ring, heating over 120 °C in the presence of PCy3·HBF4 and PivOH was indispensable, and the formation of the regioisomer could not be suppressed. The introduction of a branched alkyl chain hampered the smooth reaction. In contrast, the C–H activation of the pyridine ring proceeded even at 100 °C, and the target compound was obtained quantitatively. These results were qualitatively supported by theoretical DFT calculations.

Palladium-Catalyzed Intramolecular Direct Arylation of Aromatic Tertiary Amide Compounds Revisited

Palladium-Catalyzed Intramolecular Direct Arylation of Aromatic Tertiary Amide Compounds Revisited

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkylation. Subsequent palladium-catalyzed intramolecular direct arylation efficiently builds the central seven-membered ring. The target was prepared in 12 linear steps with five isolations in an overall yield of 8%.

Synthesis of Benzopyran-Fused Flavone Derivatives via Microwave-Assisted Intramolecular C–H Activation

A microwave-assisted intramolecular direct arylation method for the synthesis of benzopyran-fused flavone derivatives containing natural flavone backbones is described. Different polyalkoxy flavones were synthesized and functionalized with 2-bromobenzyl bromide. The resulting compounds were subjected to palladium-catalyzed intramolecular direct arylation reactions supported by microwave irradiation to produce fused tetracyclic flavones. In the case of the 7-substituted chrysin derivative, the regioselectivity of the coupling was also examined.

Catalytic Synthesis of Chiral Phosphole Oxides via Desymmetric C–H Arylation of o-Bromoaryl Phosphine Oxides

A palladium-catalyzed intramolecular direct arylation reaction of o-bromoaryl phosphine oxides was developed to afford a variety of P-stereogenic phosphole oxides in good yields. The enantioselectivities were closely associated with the specific structures of substrates, which ranged from 4–94%. As a result of ready availability of starting materials and simple operation to improve the enantioselectivities of the products with low ee values, the method provides a simple and straightforward procedure for the synthesis of P-stereogenic phosphole oxides.

Synthesis of Phenanthrothiazoles and 1,2-Di(heteroaryl)benzenes through Successive Pd-Catalyzed Direct Arylations.

Palladium-catalyzed direct arylation of 4-(2-bromophenyl)-2-methylthiazole proceeds with high efficiency at the thiazolyl C5 position using aryl bromides as the aryl source. This transformation provides simple access to 4-(2-bromophenyl)-2-methyl-5-arylthiazoles, which can be further converted into phenanthrothiazoles via palladium-catalyzed intramolecular direct arylation. When the direct arylation of 4-(2-bromophenyl)-2-methyl-5-arylthiazoles is conducted in the presence of an external heteroarene such as thiazoles, thiophenes, or imidazo[1,2-a]pyridines, the intermolecular arylation of such external heteroarenes proceeds faster than the intramolecular reaction, allowing the formation of 1,2-di(heteroaryl)benzene derivatives.

One pot synthesis of diarylfurans from aryl esters and PhI(OAc)2 via palladium-associated iodonium ylides.

The example of palladium-catalyzed intermolecular cyclization for the synthesis of various diarylfurans in which one of the aromatic rings originates from the phenolic part of the starting ester and the other one from PhI(OAc)2 has been reported. The reaction is carried out through two steps: the rearrangement of palladium-associated iodonium ylides to form o-iodo diaryl ether and then palladium catalyzed intramolecular direct arylation. This reaction can tolerate a variety of functional groups and is alternative or complementary to the previous methods for the synthesis of diarylfurans.

Amide-bridged ladder poly(p-phenylene): synthesis by direct arylation and π-stacked assembly

Amide-bridged ladder poly(p-phenylene) was synthesized in two steps, through the polycondensation of aromatic diamines and dicarboxylic acid derivatives followed by palladium-catalyzed intramolecular direct arylation.

ChemInform Abstract: Palladium‐Catalyzed Intramolecular Direct Arylation for Phosphorus Heterocycle Synthesis.

A palladium-catalyzed intramolecular direct arylation of bromo-substituted phosphine oxides is reported for the synthesis of phosphorus-containing heterocycles with good to excellent yields (78–98%)

Synthesis of aza-fused isoquinolines through domino cross-aldol condensation and palladium-catalyzed intramolecular direct arylation.

A straightforward method has been developed for the synthesis of aroyl-substituted imidazo-/benzimidazo-fused isoquinolines. The cascade reaction proceeds via a cross-aldol condensation of 2-(1H-imidazol-1-yl/benzimidazolyl-1-yl)-1-arylethanones and 2-bromobenzaldehyde followed by palladium-catalyzed intramolecular C-H functionalization. This approach offers a simple and efficient alternative one-pot protocol for the assembly of imidazo/benzimidazo[2,1-a]isoquinolines in moderate to good yields.

Palladium-Catalyzed Intramolecular Direct Arylation for Phosphorus Heterocycle Synthesis

A palladium-catalyzed intramolecular direct arylation of bromo-substituted phosphine oxides is reported for the synthesis of phosphorus-containing heterocycles with good to excellent yields (78–98%)

ChemInform Abstract: Synthesis of Pyrrolo[1,2‐f]phenanthridine‐Annulated Polycyclic Heterocycles from Palladium‐Catalyzed Intramolecular Direct Arylation Reaction.

A concise synthesis of pyrrolo[1,2-f]phenanthridine-annulated polycyclic heterocycles has been achieved in good yields by palladium-catalyzed intramolecular direct arylation reaction.

Synthesis of pyrrolo[1,2-f]phenanthridine-annulated polycyclic heterocycles from palladium-catalyzed intramolecular direct arylation reaction

A concise synthesis of pyrrolo[1,2-f]phenanthridine-annulated polycyclic heterocycles has been achieved in good yields by palladium-catalyzed intramolecular direct arylation reaction.

Cascade Palladium‐Catalyzed Direct Intramolecular Arylation/Alkene Isomerization Sequences: Synthesis of Indoles and Benzofurans

One route, two cycles: A palladium-catalyzed intramolecular direct arylation reaction combined with an isomerization step provided a straightforward synthetic route to both indoles and benzofurans (see scheme). Isolation and functionalization of intermediate alkene isomers allowed the formation of variants having substituents remote from the core.

Palladium-Catalyzed Intramolecular Coupling of 2-[(2-Pyrrolyl)silyl]aryl Triflates through 1,2-Silicon Migration

Palladium-catalyzed intramolecular direct arylation of 2-[(2-pyrrolyl)silyl]aryl triflates gives 3,2'-silicon-bridged 2-arylindoles and -pyrroles in good to high yields. The reaction proceeds through cleavage of C-OTf, C-Si, and C-H bonds to result in the formation of C-C and C-Si bonds. Various kinds of functional groups such as OMe, CN, Cl, F, and SiMe(3) tolerated the conditions. The new reaction allows synthesis of functionalized Si-bridged 2-arylindoles that emit intense and efficient blue fluorescence in the solid state.

Palladium-Catalyzed Intramolecular Direct Arylation of Benzoic Acids by Tandem Decarboxylation/C−H Activation

A novel protocol for the palladium-catalyzed intramolecular direct arylation of benzoic acids is reported, which combines decarboxylation and C-H activation into one efficient process. With the optimized catalyst system of palladium trifluoroacetate, silver carbonate, and the proper solvent mixture (5% DMSO/dioxane), dibenzofuran derivatives are formed in excellent yield and selectivity.

Silicon-Bridged Biaryls

The authors present a modular approach to silicon-bridged biaryls. Their key step is the palladium-catalyzed intramolecular direct arylation of 2-(arylsilyl)aryl triflates 7, 9 and 11. The approach is applicable to symmetrical, asymmetrical as well as heteroaromatic substrates and usually proceeds in good to excellent yields. The 2-(arylsilyl)aryl triflates were obtained by sequential silylation, retro-Brook rearrangement and triflation.

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.

Microwave-Assisted, Palladium-Catalyzed Intramolecular Direct Arylation for the Synthesis of Novel Fused Heterocycles

An efficient synthesis of novel fused heterocycles has been established via microwave-assisted palladium-catalyzed intramolecular direct arylation. The acyclic aryl bromides are readily available from microwave-assisted one-pot annulation of N-(2-bromobenzyl)-2-aminophenols and ethyl 2-bromoalkanoates. The intramolecular direct arylation is then performed in the presence of palladium(II) acetate and dppf (10 mol% each) in toluene using potassium carbonate (2 equiv) as the base under microwave heating (150 °C, 1 h) to afford the products in 43-99% yields. Steric effect is observed for Ar-Ar bond formation, giving a substantial amount of the debromination byproduct.