Generation of an aromatic amide-derived phosphane (Aphos) library by self-assisted molecular editing and applications of Aphos in room-temperature Suzuki-Miyaura reactions

Aromatic amide-derived phosphanes (Aphos) are hemilabile P,O-coordinating ligands, which, when combined with a Pd precursor, yield a promising precatalyst system for Suzuki-Miyaura cross-coupling reactions. A focused library of Aphos ligands has been constructed for structural optimization, with the target of improving catalytic efficacy. By using microwave irradiation at accurately regulated temperature, an expeditious and reproducible one-pot synthesis and screening protocol was designed and experimentally validated. The success is based on a unique self-assisted molecular editing (SAME) process in which both the substrate and the product molecules catalyze formation of the product. Thus, starting from a 4-chlorobenzamide-derived Aphos as the substrate, parallel reactions with a selected set of arylboronic acids, in the absence of an added external phosphane ligand to Pd, produced a family of structurally edited Aphos ligands. The resultant reaction mixture containing the new Aphos, the Pd species, and the base could be used for in situ screening of the Aphos efficacy in a reference Suzuki-Miyaura coupling reaction. The structures of all Aphos ligands were characterized by 31P NMR spectroscopy and their catalytic profiles in the reference reaction were evaluated by HPLC analysis. These data allowed the identification of an efficient Aphos ligand, capable of promoting room-temperature Suzuki-Miyaura coupling of unactivated and sterically hindered aryl chlorides with arylboronic acids under mildly basic conditions.     

Phospha-palladacycles and N-heterocyclic carbene palladium complexes: efficient catalysts for CC-coupling reactions

Due to the great importance of palladium-catalyzed Heck-type reactions in scientific and industrial chemistry, a lot of publications and reviews have been published during the last years describing this matter under different aspects. This article presents a summary of catalytic applications of palladium complexes with phosphorus ligands containing a metallated sp³-carbon centre (“palladacycles”) or with N-heterocyclic carbene ligands in C-C and C-N coupling reactions of aryl halides including recent results of mechanistic discussions about their role in the catalytic cycle.     

Palladium-catalyzed coupling reaction of amino acids (esters) with aryl bromides and chlorides

The bulky and electron-rich MOP type ligands and Pd(dba)₂ combinations showed high efficiency for the coupling reactions of amino acids and inactive aryl halides to give N-aryl amino acids. Under the catalytic conditions, not only α-amino acids, but also β-, γ-, and δ-amino acids have been coupled with aryl chlorides in moderate to high yields; in the case of optically pure β-amino acids as substrates, the optical purities of the coupling products retained.     

Mizoroki-Heck reaction, catalysis by nitrogen ligand Pd complexes and activation of aryl bromides

Nitrogen ligands are an excellent alternative for the traditional P-ligands in the Pd catalyzed Mizoroki-Heck reaction. Pd complexes of dimethyl glyoxime, 8-hydroxyquinoline, salen, picolinic acid, DAB ligands gave high yields of the E-cinnamates and E-stilbenes. Acetophenone oxime N,N-dimethybenzyl amine and ferrocenyl oxime palladacycle were better catalysts and comparable yields, TON (95,000) and TOF's (2500 h⁻¹) to P-ligand catalysts, were obtained. Aryl iodides, aryl bromides and in a few cases, aryl chlorides could be also be activated by these complexes by the use of Lewis acid and (C₄H₉)₄NI as additive. DAB ligands gave good yields with electron rich aryl bromides and the use of ionic liquid improved the yield. These metal complexes can be readily synthesized and the N-ligands possess the advantage of easy functional group modifications and convenient synthetic methods compared to P-ligands. The degradation reactions associated with P-ligands is not observed in the N-ligands, with comparable high thermal, moisture and air stability and insensitivity.     

Polynuclear isocyanide complexes of rhenium

The arylation of carbonylgold chloride with diarylzinc compounds yields either triarylgoldzinc or diarylgoldzinc chlorides, depending on the reactant ratio and the nature of the aryl group. The same reactions with diphenylcadmium and diphenylmercury yield exclusively diphenylgoldcadmium chloride and diphenylgoldmercury chloride, respectively. The reactions of the products with N,N,N′,N′-tetramethylethylenediamine and triphenylphosphine were studied.Phenylgold has been obtained as a very unstable solid from diphenylgoldzinc chloride and diphenylgoldmercury chloride.     

Stereoselective synthesis of N-protected pyrrolidines via Pd-catalyzed reactions of γ-(N-acylamino) alkenes and γ-(N-Boc-amino) alkenes with aryl bromides

The stereoselective synthesis of N-acyl- and N-Boc-protected pyrrolidines via Pd-catalyzed reactions of γ-(N-acylamino) alkenes and γ-(N-Boc-amino) alkenes with aryl bromides is described. These reactions effect formation of two bonds in a single operation and proceed with generally high levels of diastereoselectivity. In contrast to previously described reactions of γ-(N-arylamino) alkenes, these transformations proceed in high yield and high regioselectivity with both electron-rich and electron-deficient aryl bromides as well as vinyl bromide substrates.     

Palladium complex containing two sterically hindered ligands as highly efficient catalyst for Suzuki–Miyaura reaction

A new palladium(II) complex containing two sterically hindered ligands, a P,P‐bonded diphosphine and N,N‐bonded Schiff base, within the same coordination sphere has been synthesized and investigated as a catalyst for the Suzuki–Miyaura cross‐coupling reactions of aryl halides with arylboronic acids. The reaction was highly efficient with aryl bromides in water at room temperature and aryl chlorides in dimethylformamide under relatively mild conditions. Excellent yields of coupling products were obtained for a wide range of aryl halides including heteroaryl halides with a low loading of catalyst. Copyright © 2015 John Wiley & Sons, Ltd.     

Palladium complexes with picolyl functionalized N-heterocyclic carbene ligands and their application in the Mizoroki–Heck reaction

A series of Pd complexes of picoline-functionalized N-heterocyclic carbenes with different substituents were synthesized. The molecular structures of selected complexes were determined by X-ray diffraction studies, showing a pseudo-square-planar structure with a Pd center surrounded by carbene, pyridine, and two chloride ligands. The influence of the different substituents on the structure and reactivity of the complexes has been studied. The catalytic properties of the complexes were investigated in the Mizoroki–Heck reaction for cross-coupling of bromobenzene with a variety of aryl halides. Their performances varied in these reactions but showed good product regioselectivities.     

An efficient, mild, and selective Ullmann-type N-arylation of indoles catalyzed by copper(I) complex

A wide range of N-arylated indoles are selectively synthesized through intermolecular C(aryl)-N bond formation from the corresponding aryl iodides and indoles through Ullmann-type coupling reactions in the presence of a catalytic amount of easily available N,N,N′,N′-tetramethyl-BINAM-CuI complex under very mild reaction conditions.     

N,N′-Mono substituted acyclic thioureas: efficient ligands for the palladium catalyzed Heck reaction of deactivated aryl bromides

A series of N,N′-mono substituted acyclic thiourea ligands are found to be highly active phosphine-free catalysts for palladium catalyzed Heck reaction of aryl iodides and bromides with olefins. We have achieved high turnover numbers for aryl iodides with olefins (TONs up to 970,000 for the reaction of iodobenzene with styrene).     

Asymmetric hydroarylation of norbornene derivatives catalyzed by palladium complexes of chiral quinolinyl-oxazolines

Chiral quinolinyl-oxazolines were found to be efficient ligands in the enantioselective palladium-catalyzed Heck-type hydroarylation of norbornene and its derivatives. The ligands with a medium sized alkyl group on the oxazoline ring provided higher enantioselectivities. The presence of electron-donating substituents on the aryl iodide increased the selectivity and the yield of the reactions. The configuration of (−)-exo-2-phenylbicyclo[2.2.1]heptane has been assigned as (1R,2R).     

Copper powder-catalyzed N-arylation of imidazoles in water using 2-(hydrazinecarbonyl)pyridine N-oxides as the new ligands

2-(2-Hydrazinecarbonyl)pyridine N-oxides, which were derived from pyrrole-2-carbohydrazides and pyridine N-oxides, were synthesized and utilized as the ligands for copper powder-catalyzed N-arylation of imidazoles with aryl halides in water. Imidazoles could be arylated smoothly with various aryl halides to provide the title products in preferable yields without the need of an inert atmosphere.     

Cu(I) mediated one-pot synthesis of azobenzenes from bis-Boc aryl hydrazines and aryl halides

N,N^′-bis-Boc aryl hydrazines underwent Cu(I) catalyzed couplings with aryl halides to provide N,N^′-bis-Boc diaryl hydrazines. The resulting N,N^′-bis-Boc diaryl hydrazines are readily oxidized to the azobenzenes in the presence of Cu(I) and a base. A prolonged heating of the initial coupling reactions directly provides the corresponding azobenzenes in one pot.     

Pd2dba3/P(i-BuNCH2CH2)3N: a highly efficient catalyst for the one-pot synthesis of trans-4-N,N-diarylaminostilbenes and N,N-diarylaminostyrenes

A Pd₂dba₃/P(i-BuNCH₂CH₂)₃N catalyzed one-pot synthesis of unsymmetrically substituted trans-4-N,N-diarylaminostilbenes and both symmetrically and unsymmetrically substituted N,N-diarylaminostyrene derivatives is reported. The procedure involves two or more palladium catalyzed sequential coupling reactions (an amination and an inter-molecular Heck reaction) in one-pot using the same catalyst system with two different aryl halides, including aryl chlorides and hetero aryl halides as the coupling partners.     

Effects of solvent and base on the palladium-catalyzed amination: PdCl2(Ph3P)2/Ph3P-catalyzed selective arylation of primary anilines with aryl bromides

A readily accessible catalytic system, PdCl₂(Ph₃P)₂/Ph₃P, was developed for the selective arylation of primary anilines with aryl bromides. The strong influence of solvents and bases on the catalytic activity was observed. In refluxing o-xylene, triphenylphosphine shows high efficiency for Pd-catalyzed intermolecular amination reactions. By changing the bases, mono- and diarylation of primary amines could be selectively achieved in high yields. Moreover, the catalytic system showed good toleration for the steric hindrance of anilines. A series of N,N,N′,N′-tetraaryl-1,1′-biphenyl-4,4′-diamines, important intermediates of OLED hole transport materials, were synthesized facilely via coupling reactions between 4,4′-diaminobiphenyls and aryl bromides.     

A convenient synthesis of quinolines by reactions of o-isocyano-β-methoxystyrenes with nucleophiles

2,4-Disubstituted quinolines have been synthesized by reactions of o-isocyano-β-methoxystyrenes, which can be easily prepared from commercially available o-aminophenyl ketones in three steps, with alkyl(or aryl)lithiums in generally good yields. Subsequently, o-isocyano-β-methoxystyrenes have also proved to react efficiently with lithium dialkylamides to afford the corresponding 4-substituted N,N-dialkylquinolin-2-amines in satisfactory yields.     

A novel ditopic ring-expanded N-heterocyclic carbene ligand-assisted Suzuki-Miyaura coupling reaction in aqueous media

A series of seven-membered ditopic ring-expanded N-heterocyclic carbene (dre-NHC) precursors, bearing sterically demanding and electron-rich aryl groups, were synthesised in moderate yields via the reaction of 1,2,4,5-tetrakis(bromomethyl)benzene with the corresponding N,N′-diarylformamidines in the presence of K₂CO₃ in acetonitrile under an air atmosphere. All new compounds were characterised by HRMS, NMR spectroscopy, and microanalysis, as well as X-ray crystallography for compound 1c. The development of an efficient catalytic system for the Suzuki-Miyaura coupling reaction of aryl chlorides with various boronic acids was also investigated using the in situ generated dre-NHC ligands.     

Ugi amine-derived P,N- and P,P-ligands with N-alkyltriethoxysilyl tethers: synthesis and evaluation of mesoporous silica-supported Pd complexes in asymmetric allylic substitution reactions

A facile approach to the synthesis of several types of chiral P,N- and P,P-ligands bearing triethoxysilyl groups starting from N,N-diemthyl-1-ferrocenylethylamine (Ugi amine) has been developed. Allyl palladium complexes of these ligands have been prepared, characterized, and grafted on mesoporous silica. The resulting silica-supported complexes have been shown to catalyze asymmetric allylic alkylation and aminations reactions with moderate enantioselectivities.     

Diversity-oriented synthesis of 1,2,3,5-tetrahydrobenzo[e][1,2,4]oxadiazepines and 2,3-dihydro-1H-benzo[e][1,2,4]triazepines by base-induced [4 + 3] annulation reactions

The base-induced formal [4 + 3] annulation reactions of N-(ortho-chloromethyl)aryl amides with nitrones or hydrazonoyl chlorides have been reported. When nitrones are used as the 1,3-dipole, the corresponding reaction afforded a series of 1,2,3,5-tetrahydrobenzo[e][1,2,4]oxadiazepine derivatives. Highly functionalized 2,3-dihydro-1H-benzo[e][1,2,4]triazepine derivatives were also synthesized via an unprecedented tandem aza-Michael addition/rearrangement aromatization between N-(ortho-chloromethyl)aryl amides and hydrazonoyl chlorides.     

Variation of xanthene-based bidentate ligands in the palladium-catalyzed arylation of ureas

A series of xanthene-based bidentate ligands containing various substituents on diphenylphosphino groups were synthesized and tested in the palladium-catalyzed arylation reaction of urea with unactivated aryl bromides. It was found that both steric and electronic properties of the ligands have a pronounced effect on the yields and ratios of the products. Arylation of urea and phenylurea with unactivated aryl bromides in the presence of Pd₂dba₃·CHCl₃/3,5-(CF₃)₂Xantphos and Cs₂CO₃ as base in dioxane at 100°C gave the corresponding N,N′-diarylureas in 62-98% yields.