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 direct arylation of simple arenes in synthesis of biaryl molecules

Significant progress has been made in the direct arylation of simple arenes. A number of catalyst systems have been developed which enable the intramolecular direct arylation of aryl chlorides, bromides and iodides in high yield as well as conditions capable of achieving intermolecular direct arylation with simple arenes. This account describes recent progress by our group and others in the development of these reactions.     

Palladium-catalyzed cross-coupling of polyfluoroarenes with simple arenes

The most efficient method to construct biaryls is the direct dehydrogenative cross-coupling of two different aromatic rings. Such an ideal cross arylation starting from distinct polyfluoroarenes and simple arenes was presented. The selectivity of the cross-coupling was controlled by both of the electronic property of fluoroarenes and steric hindrance of simple arenes. Diisopropyl sulfide was essential to promote the efficacy.     

Palladium-catalyzed meta-CH bond iodination of arenes with I2

Palladium-catalyzed highly meta-selective CH iodination of phenylacetic acid, benzylphosphonate and benzylsulfonate scaffolds with molecular I₂ is developed using a pyridine-type template. The practical ester linkages enable the directing template easily installed and readily removed. The substrate scope is broad, and alkyl, methoxyl, trifluomethyl, and halo substituents are compatible with this reaction. Further transformations of ibuprofen iodide intermediates by Pd-catalyzed CC and C–heteroatom bond formation illustrate the broad utility of this method.     

Palladium-catalyzed oxime ether directed regioselective C-H alkoxylation of arenes

A palladium-catalyzed highly regioselective ortho-C(sp²)-H alkoxylation of oxime ethers with PhI(OAc)₂ as the oxidant and alcohols as the alkoxylation reagents has been developed. Mono-alkoxylated and acetoxylated products could be selectively obtained via tuning the reaction conditions. A series of oxime ethers were tolerated, affording the corresponding products in moderate to good yields. Both primary and secondary alcohols survived the reaction conditions. Moreover, the directing group can be easily removed, thereby providing a straightforward access to substituted aryl ketones.     

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 direct arylation of benzoxazoles with unactivated simple arenes

Using CuBr(2) as an additive, the Pd-catalyzed intermolecular C-H-C-H cross-coupling between benzoxazoles and unactivated simple arenes has been developed. This protocol provides a straightforward approach for the biological activity of 2-arylbenzoxazole derivatives.     

Palladium-catalyzed C-H alkenylation of arenes using thioethers as directing groups

Thioethers have been proven to be reliable directing groups for palladium catalyzed alkenylation of arenes via C-H activation. Mechanistic investigation reveals that the C-H cleavage of arenes is the turnover-limiting step, and an acetate-bridged dinuclear cyclopalladation intermediate is involved. The alkenylated thioethers can be easily removed and transformed into a variety of useful groups.     

Palladium-catalyzed direct C-H arylation of unactivated arenes with aryl Halides

An efficient palladium-catalyzed direct C-H arylation of unactivated arenes has been discovered. This method employs aryl halides as the direct coupling partners with arenes without using any external ligands. This catalysis opens a new methodology for the preparation of symmetrical as well as unsymmetrical biaryls in a user-friendly approach.     

Palladium-catalyzed synthesis of pyrroles

Pyrrole derivatives are prepared in high yields by the catalytic action of a Pd(II) salt on 1-amino-3-alkyn-2-ols which are obtained from conjugate ynones.     

Palladium-catalyzed synthesis of coumarin

A palladium-catalyzed synthesis of coumarin, involving ring formation from o-iodophenol, norbornadiene, and carbon monoxide, followed by elimination of cyclopentadiene, is described, and contrasted with a new synthesis of aurone, based on the reaction of iodophenol, carbon monoxide, and phenylacetylene.     

Palladium-catalyzed synthesis of 2-allylindole and 2-allylbenzofuran derivatives from 2-((trimethylsilyl)ethynyl)arenes

A new protocol for the synthesis of 2-allylindole and 2-allylbenzofuran derivatives has been developed from readily accessible starting material, 2-((trimethylsilyl)ethynyl)arenes via Pd-catalysis. The presence of trimethylsilyl group in the alkyne is vital for this reaction. Stereoselectivity of 2-allylindole derivatives is controlled by the use of different nitrogen-protecting groups for 2-((trimethylsilyl)ethynyl)aniline. The CO₂Me protection gives Z-isomers, whereas acetyl protection gives E-isomers.     

Palladium-catalyzed reduction of olefins with triethylsilane

The versatility of the palladium(II) chloride and triethylsilane system has been tested in the hydrogenation of 1-alkenes. The reduction of 1-alkenes was carried out in the presence of triethylsilane, ethanol and a catalytic amount of palladium(II) chloride, at room temperature. This facile and efficient method affords high yields for hydrogenation of unsaturated alkenes to the corresponding alkanes.     

Palladium-catalyzed synthesis of quinoxaline derivatives

A palladium-catalyzed reductive N-heteroannulation of enamines derived from 2-nitrobenzenamines forming mixtures of 1,2-dihydroquinoxalines and 3,4-dihydroquinoxalin-2-ones is described. The reactions are performed using bis(dibenzylideneacetone)palladium(0), 1,3-bis(diphenylphosphino)propane, and 1,10-phenanthroline in DMF under 6 atm of carbon monoxide at 70 °C.     

Palladium-catalyzed synthesis of allenes.

Substituted allenes are selectively obtained in good yields from the reaction of Grignard reagents with propargylic or allenic halides in the presence of catalytic amounts of palladium chloride, triphenylphosphine and diisobutyl aluminum hydride, in tetrahydrofuran at room temperature.     

Palladium-catalyzed enantioselective domino heck-cyanation sequence: development and application to the total synthesis of esermethole and physostigmine

An efficient synthesis of functionalized 3-alkyl-3-cyanomethyl-2-oxindole 1 by a palladium-catalyzed domino Heck-cyanation reaction has been developed. Reaction of ortho-iodoanilide 5 with potassium ferro(II)cyanide, K(4)[Fe(CN)(6)], dissolved in DMF in the presence of palladium acetate and sodium carbonate afforded oxindole 1 in good to excellent yields. An enantioselective domino Heck-cyanation process has been developed for the first time using (S)-DIFLUORPHOS as a chiral supporting ligand, and an enantioselectivity of up to 79 % ee in the enantiomerically enriched oxindole was obtained under optimized conditions. A concise total synthesis of esermethole and physostigmine, powerful inhibitors of acetyl- and butyryl-cholinesterase, is documented.     

Palladium-catalyzed synthesis of tryptamines and tryptamine homologues: synthesis of psilocin

A new Pd-catalyzed method for the synthesis of tryptamines is developed, and its applications to the synthesis of Corey's aspidophytine tryptamine 15 and psilocin 20 are also described.     

Palladium-catalyzed synthesis of silyl-substituted enynes

Treatment of 1-ethynyl-1-phenyltetramethyldisilane, ethynyldimethylphenylsilane and ethynylmethyldiphenhlsilane with tetrakis(triphenylphosphine)palladium(0) at 100°C gave the corresponding enyne by head-to-head coupling, as the single regioisomer in high yield. Ethynyl-substituted mono- and di-silanes that have no phenyl group on the ethynylsilicon atom, however, afforded the enynes only in low yields.