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.     

Direct palladium-catalyzed C-3 alkynylation of indoles

The direct palladium-catalyzed coupling reaction of indoles with alkynyl bromides was described in this paper. In the presence of catalytic amount of PdCl₂(PPh₃)₂ and 2.0 equiv. NaOAc, the coupling reaction of indoles with alkynyl bromides proceeded smoothly at 50 °C to give the corresponding 3-alkynylindoles with high regioselectivity in good to excellent yields.     

Direct C-H bond arylation: selective palladium-catalyzed C2-arylation of N-substituted indoles

We present a new, practical method by which N-substituted indoles may be selectively arylated in the C2-position with good yields, low catalyst loadings, and a high degree of functional group tolerance. Our investigation found that two competitive processes, namely, the desired cross-coupling and biphenyl formation, were operative in this reaction. A simple kinetic model was formulated that proved to be instructive and provided useful guidelines for reaction optimization; the approach described within may prove to be useful in other catalytic cross-coupling processes.     

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.     

Direct palladium-catalyzed C-3 arylation of free (NH)-indoles with aryl bromides under ligandless conditions

A new method for the efficient, practical, and highly regioselective direct palladium-catalyzed C-3 arylation of free (NH)-indole and its electron-rich 1-unsubstituted derivatives under ligandless conditions is described. The reactions, which are run outside a glovebox without purification of solvent and reagents, involve treatment of free (NH)-indoles with activated, unactivated, and deactivated aryl bromides in refluxing toluene in the presence of K2CO3 as the base and a catalyst system consisting of a combination of Pd(OAc)2 and benzyl(tributyl)ammonium chloride. The experimental results are consistent with a catalytic cycle based on an electrophilic palladation pathway at the 3-position of 1-indolyl potassium salts.     

Palladium-catalyzed direct C-2 arylation of indoles with potassium aryltrifluoroborate salts

Mild conditions have been developed to achieve Pd(OAc)2-catalyzed regioselective cross-coupling between indoles and potassium aryltrifluoroarylborates in the presence of Cu(OAc)2 in acetic acid at room temperature. A variety of potassium aryltrifluoroborates selectively undergo the direct arylation across indoles and afford 2-aryl indoles in moderate to good yields.     

High-yielding palladium-catalyzed intramolecular alkane arylation: reaction development and mechanistic studies

Palladium-catalyzed alkane arylation reactions with aryl halides are described for the preparation of 2,2-dialkyl-dihydrobenzofuran substrates. These reactions occur in excellent yield and very high selectivity for the formation of one sole product arising from a reaction at nearby methyl groups. Mechanistic and computational studies point to the involvement of a concerted, inner-sphere palladation-deprotonation pathway that is enabled by the presence of three-center agostic interactions at the transition state. This mechanism accurately predicts the experimentally observed kinetic isotope effect as well as the site selectivity and should be useful in the design of new reactions and catalysts.     

Fluorous silica gel-supported perfluoro-tagged palladium nanoparticles: an efficient and reusable catalyst for direct C-2 arylation of indoles

The preparation of FSG-supported palladium nanoparticles and their application in direct C-2 arylation of indoles are presented. Moderate to good yields were obtained with ultra-low catalyst loading. The catalyst could be easily recovered by simple workup and reused up to seven runs with only a slight decrease in its activity.     

A route to annulated indoles via a palladium-catalyzed tandem alkylation/direct arylation reaction

A norbornene-mediated palladium-catalyzed tandem alkylation/C-H functionalization sequence is described, in which an alkyl-aryl bond and a heteroaryl-aryl bond are formed in one pot. A variety of highly substituted six- and seven-membered ring annulated indoles were synthesized in good yields from bromoalkyl indoles and aryl iodides.     

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.     

Direct C-4 arylation of crotonaldehyde with arenediazonium tetrafluoroborates

Arenediazonium tetrafluoroborates react with crotonaldehyde (2-butenal) in methanol in the presence of catalytic amounts of Pd(OAc)₂ to yield mainly 4,4-dimethoxy-1-butenylarenes. In most of the examples studied, small amounts of an isomeric byproduct were formed, presumably 3,3-dimethoxy-1-methylenepropylarenes. Because crotonaldehyde and arenediazonium salts are cheap and readily available, this reaction is a convenient access to protected 4-arylbutenals.     

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.     

Direct carboxamidation of indoles by palladium-catalyzed C-H activation and isocyanide insertion

A selective C3 carboxamidation of indoles including free (N-H) ones by palladium-catalyzed sequential C-H activation-isocyanide insertion has been developed.     

C-2/c-3 annulation and C-2 alkylation of indoles with 2-alkoxycyclopropanoate esters

The annulation reaction between various indoles and 2-alkoxycyclopropanoate esters is reported. Both high efficiency and complete stereochemical control were observed in some cases with this annulation process. A single stereocenter on the cyclopropane controls the diastereoselective formation of up to four new stereocenters. A different reaction course was observed with 3-substituted indole substrates, and an intervening C-3 to C-2-migration process arose that gives synthetically useful C-2 alkylation indole products.     

Room temperature palladium-catalyzed 2-arylation of indoles

This communication describes the rational development of a PdII-catalyzed method for the direct 2-arylation of indoles using [Ar-IIII-Ar]BF4. These reactions proceed under remarkably mild conditions (often at room temperature and in the presence of ambient air and moisture), and these features are believed to be the result of a PdII/IV mechanism operating in these systems. These transformations can be used to prepare functionally diverse 2-arylated indoles and pyrroles, and their potential utility has been expanded by the development of an in situ procedure for generating the iodine(III) arylating reagents.