Pd-catalyzed reduction of aryl halides using dimethylformamide as the hydride source

The Pd-catalyzed homocoupling of aryl halides in a basic DMF solution is often accompanied by the dehalogenation of the substrate as side reaction. When an inorganic base such as sodium bicarbonate is used, the reducing role of the solvent has been demonstrated using DMF-d₇ and GC/MS analysis.     

Palladium-catalyzed cross-coupling of trimethoxysilylbenzene with aryl bromides and chlorides using phosphite ligands

Phosphites were employed as ligands in palladium-catalyzed Hiyama coupling reactions. The optimized reaction conditions were equimolar amounts (5 mol % each) of Pd(acac)₂ and phosphite 1 in p-xylene at 80 °C with TBAF as an additive. This catalyst system exhibited high activities in the reactions with trimethoxysilylbenzene and aryl bromides that have electron-donating or electron-withdrawing groups. In the case of aryl chlorides, substrates possessing electron-withdrawing groups gave the coupled products in high yields.     

Suzuki-Miyaura cross-coupling of aryl and alkyl halides using palladium/imidazolium salt protocols

A simple new protocol for the high yielding Suzuki-Miyaura cross-couplings of aryl chlorides with aryl boronic acids using a palladium/imidazolium salt catalytic system is presented. The first examples of a palladium/imidazolium salt protocol for sp³-sp³ Suzuki-Miyaura couplings of alkyl halides are also disclosed.     

Direct arylation of oxazole and benzoxazole with aryl or heteroaryl halides using a palladium-diphosphine catalyst

Through the use of PdCl(dppb)(C₃H₅) as a catalyst, a range of aryl bromides and chlorides undergoes coupling via C-H bond activation/functionalization reaction with oxazole or benzoxazole in good yields. This air-stable catalyst can be used at low loadings with several substrates. Surprisingly, better results in terms of substrate/catalyst ratio were obtained in several cases using electron-excessive aryl bromides than with the electron-deficient ones. This seems to be mainly due to the relatively low thermal stability of some of the 2-arylbenzoxazoles formed with electron-deficient aryl halides. With these substrates, in order to obtain higher yields of product, the reactions had to be performed at a lower temperature (100-120 °C) using a larger amount of catalyst. On the other hand, in the presence of the most stable products, the reactions were performed at 150 °C using as little as 0.2 mol% catalyst. Arylation of benzoxazole with heteroaryl bromides also gave the coupling products in moderate to high yields using 0.2-5 mol% catalyst. With this catalyst, electron-deficient aryl chloride such as 4-chlorobenzonitrile, 4-chloroacetophenone or 2-chloronitrobenzene have also been used successfully.     

Palladium-catalyzed carbonylative synthesis of N-cyanobenzamides from aryl iodides/bromides and cyanamide

A novel and convenient protocol for the synthesis of N-cyanobenzamides starting from readily available aryl halides and cyanamide via palladium-catalyzed aminocarbonylation has been developed. The protocol utilizes Mo(CO)₆ as the CO source or CO(gas) and affords the desired N-cyanobenzamides in moderate to good yields.     

Sonogashira reaction of aryl halides with propiolaldehyde diethyl acetal catalyzed by a tetraphosphine/palladium complex

All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyzes the Sonogashira reaction of propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.     

Direct synthesis of 3-arylpropionic acids by tetraphosphine/palladium catalysed Heck reactions of aryl halides with acrolein ethylene acetal

Through the use of [PdCl(C₃H₅)]₂/Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters was observed. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides.     

Microwave-promoted aminocarbonylation of aryl triflates using Mo(CO)6 as a solid CO source

Palladium-catalyzed carbonylations of aryl triflates with a range of nucleophiles using Mo(CO)₆ as a solid CO source were explored. The reactions proceeded smoothly providing moderate to good yields of the corresponding aryl amides, esters, or acylsulfonamides after only 20 min of microwave irradiation. The acyl transfer reagent 4-dimethylaminopyridine was found to promote some of the more difficult transformations.     

Improving palladium-catalyzed cyanation of aryl halides: development of a state-of-the-art methodology using potassium hexacyanoferrate(II) as cyanating agent

Benzonitriles are easily accessible via palladium-catalyzed cyanation of aryl halides using potassium hexacyanoferrate(II) as cyanide source. This method is applicable on both activated and deactivated aryl and heteroaryl bromides and activated chlorides giving the corresponding benzonitriles in good to excellent yield. Advantageously, the used cyanating agent is non-toxic and cheap. The presented catalyst system is rather simple and it is not necessary to add expensive phosphines, making the novel method also attractive for industrial applications.     

Microwave-assisted, Mo(CO)6-mediated, palladium-catalyzed amino-carbonylation of aryl halides using allylamine: from exploration to scale-up

Palladium-catalyzed aminocarbonylations of various (hetero)aryl halides with allylamine using Mo(CO)₆ as a solid, in situ CO source, were explored. Microwave-enhanced conditions proved to be highly useful in promoting the conversions in a mere 10-20 min with various (hetero)aryl iodides, bromides and chlorides. The scale-up of a microwave-enhanced aminocarbonylation to 25 mmol scale was performed successfully.     

Identification of new catalysts for the asymmetric reduction of imines into chiral amines with polymethylhydrosiloxane using high-throughput screening

The use of high-throughput techniques allowed the rapid identification of new catalysts for the enantioselective reduction of imines using polymethylhydrosiloxane (PMHS) as a reducing agent. By a simple modification of the chiral ligand structure that came out of the screening, the enantioselectivity of the reduction was increased from 40% ee to 60% ee.     

Efficient palladium catalysts for the amination of aryl chlorides: a comparative study on the use of phosphium salts as precursors to bulky, electron-rich phosphines

Alkyl-di-(1-adamantyl)phosphonium salts are practical ligand precursors for the palladium-catalyzed amination of aryl chlorides. In the presence of typically 0.5 mol% Pd(OAc)₂ and 1 mol% of ligand precursor a variety of activated and deactivated aryl chlorides can be aminated in good to excellent yield (73-99%). Applying optimized conditions catalyst turnover numbers up to 10,000 have been achieved.     

Palladium-catalyzed carbonylation of aryl bromides using microwave heating and bis[CP-Fe(II)-(CO)2] as a carbon monoxide source

A palladium-catalyzed, microwave assisted carbonylative reaction is described for the synthesis of benzamides from aryl bromides and primary or secondary amines. The developed method uses bis(cyclopentadienyldicarbonyliron) as a solid source of carbon monoxide to produce a diverse set of secondary and tertiary amides in 42–82% yield.     

Co2(CO)8 as a convenient in situ CO source for the direct synthesis of benzamides from aryl halides (Br/I) via aminocarbonylation

A fast, mild, and functional group tolerant method for the direct synthesis of benzamides from aryl halides (Br, I) via aminocarbonylation, using solid Co₂(CO)₈ as a convenient CO source, has been demonstrated. The developed method is applicable to a wide variety of 1° and cyclic and acyclic 2° amines. Nitro substituted (o, m and p) aryl halides have easily been converted to the corresponding benzamides, without the reduction of the nitro group, in high yields using this in situ carbonylation methodology under microwave irradiation.     

Chemoselective reduction of azides catalyzed by molybdenum xanthate by using phenylsilane as the hydride source

A chemoselective, neutral, and efficient strategy for the reduction of azides to corresponding amines catalyzed by dioxobis(N,N,-diethyldithiocarbamato) molybdenum complex (1, MoO₂[S₂CNEt₂]₂) in the presence of phenylsilane is discovered. This chemoselective reduction strategy tolerates a variety of reducible functional groups.     

Palladium-catalyzed oxyarylation of olefins using silver carbonate as the base. Probing the mechanism by electrospray ionization mass spectrometry

The Pd(OAc)₂-catalyzed oxyarylation of electron-rich (8 and 12) and electron-poor (10) olefins by ortho-iodophenols (3a-d) was studied using Ag₂CO₃ as the base, in acetone, and in the presence and absence of PPh₃. The corresponding adducts of oxyarylation were obtained in moderate yields. The reaction mechanism was examined by electrospray ionization mass spectrometry (ESI-MS). Cationic arylpalladium intermediate (14), formed by the oxidative insertion of Pd(0) into 3a, and the cationic palladacycles (15), obtained by reaction of 14 with olefins 8 and 12, were intercepted by ESI-MS and characterized by ESI-MS/MS.     

Convenient method for the synthesis of phthalazinones via carbonylation of 2-bromobenzaldehyde using Co2(CO)8 as a CO source

A simple one-pot synthesis of phthalazinones by the condensation and intra-molecular carbonylative cyclization of 2-bromobenzaldehydes with hydrazines is reported. This method utilizes solid Co₂(CO)₈ as carbonyl source making it readily accessible in small-scale laboratory applications.     

A simple and facile stereoselective synthesis of (Z)- and (E)-allyl halides catalyzed by silica supported sodium hydrogen sulfate: factors influencing the yields and stereochemistry of allyl halides

A simple, mild and efficient stereoselective synthesis of (Z)- and (E)-allyl bromides and iodides has been developed by treatment of the Baylis-Hillman adducts with lithium bromide and iodide, respectively, in methylene chloride catalyzed by silica supported sodium hydrogen sulfate at room temperature. The role of various solvents, different reacting metallic halides, nature of the adducts and activity of several heterogeneous catalysts on the yields and stereochemistry of the products have been thoroughly studied.