A robust palladium-catalyzed cyanation procedure: beneficial effect of zinc acetate

Conditions that ensure a more reproducible Pd(0)-mediated procedure to convert aryl bromides to aryl cyanides have been developed that entail the use of zinc dust to keep the Pd in the zero oxidation state and zinc acetate to ensure high catalytic activity. This procedure is applicable to a wide range of substrates and obviates the need for stringent removal of oxygen from the reaction medium.     

A facile microwave-assisted palladium-catalyzed cyanation of aryl chlorides

We report an efficient method for the preparation of aryl nitriles from aryl chlorides under either microwave assisted or thermal conditions. A catalyst system comprising tris(dibenzylidene acetone)dipalladium (Pd₂(dba)₃) and 2-(2′,6′-dimethoxybiphenyl)dicyclohexylphosphine (S-Phos) is shown to effectively promote cyanation of various aryl chlorides with Zn(CN)₂ as the cyanide source.     

Ligand-free palladium-catalyzed cyanation of aryl halides

[reaction: see text] A practical, ligand-free cyanation of aryl bromides that utilizes as little as 0.1 mol % Pd(OAc)(2) in combination with a nontoxic cyanide source, M(4)[Fe(CN)(6)] (M = K, Na), is described. The reactions are performed in DMAC at 120 degrees C and provide the corresponding aryl nitrile in 83-96% yield, typically in less than 5 h. TON values of up to 7100 were attained.     

Hydroamination/Heck reaction sequence for a highly regioselective one-pot synthesis of indoles using 2-chloroaniline

A one-pot indole synthesis consisting of a highly regioselective TiCl(4)-catalyzed hydroamination and a 5-endo Heck cyclization starting from 2-chloroaniline is described, using an in-situ generated, sterically hindered imidazol-2-ylidene palladium complex.     

A denitrogenative palladium-catalyzed cascade for regioselective synthesis of fluorenes

We herein report a denitrogenative palladium-catalyzed cascade for the modular and regioselective synthesis of polysubstituted fluorenes. Hydrazone facilitates the Pd(ii) to Pd(iv) oxidative addition in a Catellani pathway and is also the methylene synthon in the proposed reaction. Aryl iodides and 2-bromoarylaldehyde hydrazones undergo a norbornene-controlled tandem reaction sequence to give a broad scope of fluorenes in the presence of a palladium catalyst. The method described is scalable and adaptable to a three-component reaction with in situ generation of the hydrazone group. Preliminary mechanistic investigations have been conducted.

Hydrazone assists Pd(ii)/(iv) oxidative addition and is the methylene synthon in a palladium-catalyzed, norbornene-mediated regioselective synthesis of fluorenes.     

Synthesis of activated 3-substituted indoles: an optimised one-pot procedure

3-Substituted-4,6-dimethoxyindoles can be synthesised in a one-pot procedure from 3,5-dimethoxyaniline and 2-haloketones in the presence of lithium bromide and sodium bicarbonate.     

Progress in the palladium-catalyzed cyanation of aryl chlorides

The development of new palladium catalysts for the cyanation of various aryl and heteroaryl chlorides is described. The combination of amine co-catalysts with chelating phosphine ligands, for example, 1,4-bis(diphenylphosphino)butane (dppb) or 1,5-bis(diphenylphosphino)pentane (dpppe), allows an efficient cyanation of chloroarenes with simple potassium cyanide. General palladium-catalyzed cyanation of nonactivated and deactivated chloroarenes is possible for the first time. Studies of the oxidative addition of aryl halides to palladium triphenylphosphine complexes in the presence and absence of amines suggest that the co-catalyst is capable of preventing catalyst deactivation caused by the presence of excess cyanide ions in solution.     

Controllable access to trifluoromethyl-containing indoles and indolines: palladium-catalyzed regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides

The synthesis of diverse products from the same starting materials is always attractive in organic chemistry. Here, a palladium-catalyzed substrate-controlled regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides has been developed, which provides a direct but controllable access to a variety of structurally diverse trifluoromethyl-containing indoles and indolines. In more detail, with respect to γ,δ-alkenes, 1,1-geminal difunctionalization of unactivated alkenes with trifluoroacetimidoyl chloride enables the [4 + 1] annulation to produce indoles; as for β,γ-alkenes, a [3 + 2] heteroannulation with the hydrolysis product of trifluoroacetimidoyl chloride through 1,2-vicinal difunctionalization of alkenes occurs to deliver indoline products. The structure of alkene substrates differentiates the regioselectivity of the reaction.

A palladium-catalyzed dual functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides toward the synthesis of structurally diverse trifluoromethyl-containing indoles and indolines has been developed.     

A new and efficient one-pot synthesis of indoles

The synthesis of indoles is accomplished in high yields from phenylhydrazines and pyruvic acid using microwave irradiation.     

Efficient palladium-catalyzed N-arylation of indoles

[equation--see text] The N-arylation of indoles, including a variety of substituted ones, has been carried out using bulky, electron-rich phosphines as the supporting ligand in combination with Pd(2)(dba)(3). Using this catalyst system, the efficient coupling of indole and a variety of substituted indoles with aryl iodides, bromides, chlorides, and triflates can be achieved.     

Mild and general methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides

[reaction: see text] New methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides have been developed, featuring sterically demanding, electron-rich phosphines. Highly challenging electron-rich aryl chlorides, in addition to electron-neutral and electron-deficient substrates, as well as nitrogen- and sulfur-containing heteroaryl chlorides can all undergo efficient cyanation under relatively mild conditions using readily available materials. In terms of substrate scope and temperature, these methods compare very favorably with the state-of-the-art cyanations of aryl chlorides.     

TEMPO-catalyzed oxidative dimerization and cyanation of indoles for the synthesis of 2-(1H-indol-3-yl)-3-oxoindoline-2-carbonitriles

A method for the combinative oxidative homo dimerization and cyanation of free indole derivatives catalysed by TEMPO along with silver carbonate was demonstrated for the first time This new methodology is both atom and step efficient and is applicable to a broad scope of substrates, allowing the synthesis of a range of synthetically valuable 2-(1H-indol-3-yl)-3-oxoindoline- 2-carbonitriles in moderate to excellent yields. Furthermore, selected compounds 6b and 6g exhibit moderate to good anti-schistosomicidal activities.     

The palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates

A palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates has been developed, providing aryl nitriles in moderate to excellent yields. It represents a facile procedure to access aryl nitriles.     

Novel 2,2-bipyridine ligand for palladium-catalyzed regioselective carbonylation

[reaction: see text] A palladium-catalyzed highly regioselective one-step carbonylation of 2,5-dibromo-3-methylpyridine is reported. A range of alkyl esters and amides can be prepared in good yield with better than 95:5 regioselectivity via this method. Key to the high regioselectivity for the formation aromatic amides is the introduction of a novel nonphosphine-based 2,2-bipyridine ligand. This novel reaction was scaled up smoothly in the plant to a 130-kg batch size and facilitated the delivery of bulk material for the clinical trials of Sch 66336, a candidate for oncologic treatments.     

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.     

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.