A New Chiral P,N‐Ligand Derived from 1‐Phenylphospholane‐2‐carboxylic Acid (Phenyl‐P‐proline) for Palladium‐Catalyzed Asymmetric Allylic Substitution Reactions

New types of P,N‐ligands, cis‐ and trans‐ 3 , containing a tetrahydroisoquinoline skeleton as an N‐donor were synthesized from (1R,2S)‐1‐phenylphospholane‐2‐carboxylic acid (phenyl‐P‐proline, 1 ). The cis isomer, cis‐ 3 , was found to act as an excellent ligand in palladium‐catalyzed asymmetric allylic substitution reactions. The reactions of 1,3‐diphenyl‐2‐propenyl acetate ( 5 ) with several nucleophiles in the presence of [Pd(π‐allyl)Cl]₂, cis‐ 3 (Pd : ligand=1 : 2), and a base afforded the desired products in high yields with high enantioselectivity. It was suggested that these ligands did not serve as P,N‐bidentate ligands but as P‐monodentate ligands in these reactions.     

Palladium‐Catalyzed Heck‐Type Reactions of Allylic Esters with Arylboronic Acids or Potassium Aryltrifluoroborates

A selective and general route to (E)‐1,3‐diaryl‐prop‐1‐enes and (E)‐3‐arylallyl acetates has been developed by palladium‐catalyzed Heck‐type reactions of allylic esters with arylboronic acids or potassium aryltrifluoroborates. The present method selectively proceeds including β‐OAc elimination or β‐H elimination on the basis of the boronic acids. Whereas a variety of allylic esters were reacted with arylboronic acids, palladium(II) acetate [Pd(OAc)₂], tetra(n‐butyl)ammonium chloride [(n‐Bu)₄NCl] and postassium dihydrogen phosphate (KH₂PO₄) to afford the corresponding diarylation products in moderate to good yields, treatment of allylic esters with potassium aryltrifluoroborates furnished the corresponding monoarylation products.     

Palladium‐Catalyzed,Highly Efficient,Regiocontrolled Arylation of Electron‐Rich Allylamines with Aryl Halides

The highly efficient and regioselective palladium‐catalyzed Heck coupling of aryl bromides with electron‐rich allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regioselectivity and reactivity of the reaction. The combination of palladium acetate [Pd(OAc)₂] and 1,3‐bis(diphenylphosphino)propane (dppp) in ethylene glycol (EG) constitutes a highly effective catalyst system for internal arylation of N‐Boc‐allylamine (tert‐butyl methyl allyliminodicarbonate) with aryl bromides to give good to excellent regioselectivities, while the catalyst system consisting of Pd(OAc)₂, tetrabutylammonium bromide (TBAB) and 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) additive allows for a variety of aryl bromides to react efficiently with N,N‐(Boc)₂‐allylamine (di‐tert‐butyl allyliminodicarbonate) in water to exclusively afford the linear (E)‐allylamine products in high yields.     

Application of SDP Ligands for Pd‐Catalyzed Allylic Alkylation

Chiral spiro diphosphines (SDP) are efficient ligands for the Pd‐catalyzed asymmetric allylic alkylation of 1,3‐diphenyl‐2‐propenyl acetate with dimethyl malonate and related nucleophiles. The newly synthesized ligand DMM‐SDP ( 1e ) with 3,5‐dimethyl‐4‐methoxy groups on the P‐phenyl rings of the phosphine shows the highest enantioselectivity (up to 99.1% ee). Diethylzinc as a base is critical for obtaining high enantioselectivity in the allylic alkylation using β‐dicarbonyl nucleophiles. The structure of catalyst [PdCl₂((S)‐SDP)] was determined by single crystal X‐ray diffraction. The SDP ligands create an effective asymmetric environment around the palladium, resulting in high enantioselectivities for the asymmetric allylic alkylation reaction     

Palladium‐Catalyzed Highly Regioselective Arylation of Allylamines with Thiophenes and Furans

A palladium‐catalyzed highly regioselective and stereoselective direct arylation of allylamine derivatives with a wide range of thiophenes and furans has been developed. In the presence of palladium(II) acetate [Pd(OAc)₂] catalyst and appropriate oxidants, the coupling reaction proceeded with excellent group compatibility and high efficiency, leading exclusively to γ‐arylated linear (E)‐allylamines. It was found that the choice of solvent, olefin substrate and oxidant had an important influence on reaction efficiency, and the use of sterically demanding N,N‐diprotected allylamines bearing a carbamate moiety is crucial for securing high regioselectivity and stereoslectivity. This method provides a straightforward approach for the efficient synthesis of various γ‐heteroarylated, linear (E)‐allylamines.     

Palladium‐Catalyzed Carbonylation of Diols to Cyclic Carbonates

The catalytic alkoxycarbonylation of 1,2‐diols by (neocuproine)palladium(II) acetate (neocuproine=2,9‐dimethyl‐1,10‐phenanthroline) or palladium(II) acetate/(−)‐sparteine using N‐chlorosuccinimide as the oxidant affords cyclic carbonates. The oxidative carbonylation of diols proceeds under mild conditions, requiring only 1 atm of carbon monoxide, and produces cyclic carbonates in moderate to good yields. Both 1,2‐ and 1,3‐diols can be carbonylated using (neocuproine)Pd(OAc)₂ and sodium dichloroisocyanuric acid, which serves as a competent oxidant and base for this system, to yield 5‐ and 6‐membered cyclic carbonates.     

Regioselective Heck Reaction of N‐Vinylphthalimide: A General Strategy for the Synthesis of (E)‐N‐Styrylphthalimides and Phenethylamines

The arylation of N‐vinylphthalimide takes place at the β‐position with aryl iodides, bromides and chlorides using palladium acetate [Pd(OAc)₂] or phenone oxime‐derived palladacycles as catalysts under phosphine‐free conditions. The reaction is succesfully carried out in organic solvents, such as DMF, in the presence of an organic base, such as dicyclohexylmethylamine, and with TBAB as additive at 120 °C under conventional or microwave heating. (E)‐N‐Styrylphthalimides are mainly obtained using a rather low palladium loading (0.05–1 mol%). Similar catalytic efficiency is observed using a Kaiser oxime resin‐derived palladacycle, which allows reuse of the polymeric complex for three cycles. The high regioselectivity observed supports that these palladacycles work as a source of Pd(0) species operating mainly through a neutral mechanism. The syntheses of 2‐thienylphenethylamine and mescaline have been performed by subsequent hydrogenation with Wilkinson’s catalyst and hydrazinolysis.     

Palladium Catalytic Species Containing Chiral Phosphites: Towards a Discrimination between Molecular and Colloidal Catalysts

Palladium nanoparticles ( Pd1 – Pd3 ) stabilized by chiral diphosphite ligands ( 1 – 3 ), were synthesized and tested as catalysts for the allylic alkylation reaction, using different substrates (rac‐ I , rac‐ III and rac‐ V ). Carbohydrate ligands ( 1 and 2 ), only differing in the C‐3 configuration, led to a remarkable difference in stability of the corresponding nanoparticles: while Pd1 is a robust catalyst, Pd2 decomposes into molecular species. In addition, the high enantioselective systems, Pd1 and Pd3 , are only active for a substrate containing phenyl groups. Concerning the catalytic behaviour of the corresponding molecular systems, palladium complexes coordinated to ligands 1 or 3 , gave excellent asymmetric inductions, but an analogous catalyst accommodating ligand 2 , was not found selective.     

MOP‐Type Binaphthyl Phosphite and Diamidophosphite Ligands and Their Application in Catalytic Asymmetric Transformations

Monodentate phosphite and diamidophosphite ligands have been developed based on O‐methyl‐BINOL. These chiral ligands are easy to prepare from readily accessible phosphorylating reagents – (S_a or R_a)‐2‐chlorodinaphtho[2,1‐d:1′,2′‐f][1,3,2]dioxaphosphepine and (2R,5S)‐2‐chloro‐3‐phenyl‐1,3‐diaza‐2‐phosphabicyclo[3.3.0]octane. The new ligands have demonstrated excellent enantioselectivity in the palladium‐catalysed allylic substitution reactions of (E)‐1,3‐diphenylallyl acetate with sodium p‐toluenesulfinate (up to 99 % ee), pyrrolidine (up to 97 % ee), dipropylamine (up to 95 % ee) and dimethyl malonate (up to 99 % ee). In the palladium‐catalysed deracemization of ethyl (E)‐1,3‐diphenylallyl carbonate, up to 96 % enantioselectivity has been achieved. The diamidophosphite ligands have exhibited very good enantioselectivity in the Rh‐catalysed asymmetric hydrogenation of dimethyl itaconate (up to 90 % ee).     

Stable Synthetic Bacteriochlorins for Photodynamic Therapy: Role of Dicyano Peripheral Groups,Central Metal Substitution (2H,Zn, Pd), and Cremophor EL Delivery

A series of four stable synthetic bacteriochlorins was tested in vitro in HeLa cells for their potential in photodynamic therapy (PDT). The parent bacteriochlorin (BC), dicyano derivative (NC)₂BC and corresponding zinc chelate (NC)₂BC–Zn and palladium chelate (NC)₂BC–Pd were studied. Direct dilution of a solution of bacteriochlorin in an organic solvent (N,N‐dimethylacetamide) into serum‐containing medium was compared with the dilution of bacteriochlorin in Cremophor EL (CrEL; polyoxyethylene glycerol triricinoleate) micelles into the same medium. CrEL generally reduced aggregation (as indicated by absorption and fluorescence) and increased activity up to tenfold (depending on bacteriochlorin), although it decreased cellular uptake. The order of PDT activity against HeLa human cancer cells after 24 h incubation and illumination with 10 J cm^?2 of near‐infrared (NIR) light is (NC)₂BC–Pd (LD₅₀=25 nM ) > (NC)₂BC > (NC)₂BC–Zn ≈ BC. Subcellular localization was determined to be in the endoplasmic reticulum, mitochondria and lysosomes, depending on the bacteriochlorin. (NC)₂BC–Pd showed PDT‐mediated damage to mitochondria and lysosomes, and the greatest production of hydroxyl radicals as determined using a hydroxyphenylfluorescein probe. The incorporation of cyano substituents provides an excellent motif for the enhancement of the photoactivity and photostability of bacteriochlorins as PDT photosensitizers.     

Fabrication of Palladium Membranes Supported on a Silicalite‐1 Zeolite‐Modified Alumina Tube for Hydrogen Separation

Thin palladium membranes were fabricated on macroporous α‐Al₂O₃ tubes by electroless plating. The silicalite‐1 (Sil‐1) zeolite serving as intermediate and diffusion barrier layer was introduced to modify the surface roughness and pore size of the porous substrate and prevent the atomic interdiffusions of the metal elements between Pd layer and the support. The Pd composite membranes were studied by scanning electron microscopy (SEM), X‐ray diffraction (XRD), and electron probe microanalysis (EPMA), revealing that morphology and structure of the Sil‐1 layer significantly influence the Pd membrane preparation. Single‐gas permeation tests were carried out with gas H₂ and N₂ to determine the permeation performance of the membranes. The resulting membrane exhibited long‐term stability under hydrogen permeation.     

Synthesis of Methylene‐Bridge Polyarenes through Palladium‐Catalyzed Activation of Benzylic Carbon‐Hydrogen Bond

In the presence of palladium(II) acetate [Pd(OAc)₂] and an N‐heterocyclic carbene (NHC) ligand, fluorene derivatives can be generated in good to excellent yields from 2‐halo‐2′‐methylbiaryls through the benzylic C H bond activation (14 examples; 81–97% yields). The scope and limitations of this protocol have been examined. A wide range of functional groups, such as alkyl, alkoxy, ester, nitrile, and others, is able to tolerate the reaction conditions herein. The cyclization of an isotope‐labelled biphenyl gave the corresponding product with a primary kinetic isotope effect (k_H/k_D=4.8:1), which indicates that the rate‐determining step of this reaction is the activation of the benzylic C H bond. Moreover, indenofluorenes were also accessed in excellent results from terphenyls (3 examples; 91–92% yields). The cascade reaction of 2,6‐dichloro‐2′‐methylbiphenyl with diphenylacetylene produced 8,9‐diphenyl‐4H‐cyclopenta[def]phenanthrene in 60% yield through the activation of an aryl and a benzylic C H bond.     

A Highly Efficient Tandem Reaction of 2‐(gem‐Dibromovinyl)phenols(thiophenols) with Organosilanes to 2‐Arylbenzofurans (thiophenes)

2‐Arylbenzofurans(thiophenes) were prepared through an efficient tandem elimination–intramolecular addition–Hiyama cross‐coupling reaction. In the presence of tetra‐(n‐butyl)ammonium fluoride (TBAF), palladium(II) acetate [Pd(OAc)₂] and triphenylphosphine (PPh₃), the reaction of 2‐(gem‐dibromovinyl)phenols(thiophenols) with phenyl(trialkoxy)silanes proceeded smoothly and generated the corresponding products with good yields in one‐pot. It should be noted that TBAF plays an important role in the tandem reaction.     

Mizoroki–Heck Reactions Catalyzed by Dichloro{bis[1‐(dicyclohexylphosphanyl)piperidine]}palladium: Palladium Nanoparticle Formation Promoted by (Water‐Induced) Ligand Degradation

The palladium‐based dichlorobis[1‐(dicyclohexylphosphanyl)piperidine] complex – [(P{(NC₅H₁₀)(C₆H₁₁)₂})₂Pd(Cl)₂] is readily prepared in quantitative yield from the reaction of [Pd(cod)(Cl)₂] (cod=cycloocta‐1,5‐diene) with two equivalents of 1‐(dicyclohexylphosphanyl)piperidine in toluene under N₂ within only a few minutes at room temperature. This complex is a highly active Heck catalyst with excellent functional group tolerance, which reliably operates at low catalyst loadings. Various activated, non‐activated, deactivated, functionalized, sterically hindered, and heterocyclic aryl bromides, which may contain nitro, chloro or trifluoromethane groups, nitriles, acetales, ketones, aldehydes, ethers, esters, lactones, amides, anilines, phenols, alcohols, carboxylic acids, and heterocyclic aryl bromides, such as pyridines and derivatives, as well as thiophenes and aryl bromides containing methylsulfanyl groups have been successfully coupled with various (also functionalized) alkenes in excellent yields and selectivities (the E‐isomers are typically exclusively formed) at 140 °C in the presence of 0.05 mol % of the catalyst in DMF. Even though lower catalyst loadings could be used for many electronically activated, non‐activated and some electronically deactivated aryl bromides without noticeable loss of activity, the great advantage of the reaction protocol presented here lies in its reliability and general applicability, which allows its direct adoption to other aryl bromides without the neccessity of its modification. Experimental observations indicated that palladium nanoparticles are the catalytically active form. Consequently, whereas comparable levels of activity were observed for dichloro‐bis(aminophosphine) complexes of palladium, a dramatic drop in activity was found for their phosphine‐based analogue [(P(C₆H₁₁)₃)₂Pd(Cl)₂].     

Simple Methodology for Heck Arylation at C‐8 of Adenine Nucleosides

A simple method for the arylation of 8‐vinyladenine nucleoside derivatives is reported. With a broad set of aryl iodides and bromides, the reaction is catalyzed by the simple combination palladium acetate/tris(o‐tolyl)phosphine/triethylamine [Pd(OAc)₂/(o‐tol)₃P/Et₃N]. As expected, aryl chlorides are more difficult coupling partners but some undergo reactions with more exotic catalysts. Although trans‐olefins are the major products, minor amounts of cis‐isomers are detected in some cases, and a post‐arylation mechanism for their formation is proposed. Finally, by subtle catalyst modulation chemoselective N‐arylation of the nucleoside can be achieved in the presence of the vinyl moiety.     

Palladium on Carbon‐Catalyzed Cross‐Coupling using Triarylbismuths

Simple and efficient protocols for the 10% palladium on carbon (Pd/C)‐catalyzed cross‐coupling reactions between triarylbismuths and aryl halides have been developed. A variety of iodo‐ and bromobenzenes possessing an electron‐withdrawing group on the aromatic nucleus were smoothly cross‐coupled in the presence of 10% Pd/C, sodium phosphate dodecahydrate (Na₃PO₄⋅12 H₂O) and 1,4‐diazabicyclo[2.2.2]octane (DABCO) in heated N‐methyl‐2‐pyrrolidone (NMP) as the solvent. For the arylations of iodobenzenes, the reactions effectively proceeded under the combined use of caesium fluoride (CsF) and 2,2′‐biquinoline. Furthermore, a ligand‐free 10% Pd/C‐catalyzed cross‐coupling reaction between the aryl iodides and triarylbismuths was also established by the addition of tetra‐n‐buthylammonium fluoride trihydrate (TBAF⋅3 H₂O) in which the palladium metals were hardly leached from the catalyst into the reaction media.     

Functionalized cellulose‐supported triphenylphosphine and its application in Suzuki cross‐coupling reactions

A new heterogeneous cellulose tagged triphenylphosphine (Cell‐OPPh₃) was synthesized and subsequently coordinated with Pd(OAc)₂ to form a cellulose‐supported triphenylphosphine palladium complex (Cell‐OPPh₃‐Pd). Cell‐OPPh₃ and the corresponding palladium complex were fully characterized by TGA, SEM, TEM, and NMR analysis. Results of catalytic activity experiments indicate that the Cell‐OPPh₃‐Pd complex can efficiently catalyze Suzuki–Miyaura cross‐coupling reactions of aryl halides with arylboronic acids at mild reaction conditions. The coupling products can be obtained in good to excellent yields (up to 98%). The work‐up procedure is simple and the catalyst could be easily recovered by filtration, and then reused in next run. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41427.     

Recoverable Palladium Catalysts for Suzuki–Miyaura Cross‐ Coupling Reactions Based on Organic‐Inorganic Hybrid Silica Materials Containing Imidazolium and Dihydroimidazolium Salts

The systems formed by palladium acetate [Pd(OAc)₂] and hybrid silica materials prepared by sol‐gel from monosilylated imidazolium and disilylated dihydroimidazolium salts show catalytic activity in Suzuki–Miyaura cross‐couplings with challenging aryl bromides and chlorides. They are very efficient as recoverable catalysts with aryl bromides. Recycling is also possible with aryl chlorides, although with lower conversions. In situ formation of palladium nanoparticles has been observed in recycling experiments.     

Extremely Efficient Cross‐Coupling of Benzylic Halides with Aryltitanium Tris(isopropoxide) Catalyzed by Low Loadings of a Simple Palladium(II) Acetate/Tris(p‐tolyl)phosphine System

Highly efficient coupling reactions of benzylic bromides or chlorides with aryltitanium tris(isopropoxide) [ArTi(O‐i‐Pr)₃] catalyzed by a simple palladium(II) acetate/tris(p‐tolyl)phosphine [Pd(OAc)₂/ P(p‐tolyl)₃] system are reported. The coupling reactions proceed in general at room temperature employing low catalyst loadings of 0.02 to 0.2 mol%, affording coupling products in excellent yields of up to 99%. For benzylic bromides bearing strong electron‐withdrawing cyano (CN) or trifluoromethyl (CF₃) substituents, the reactions require a higher catalyst loading of 1 mol%, or the reactions are carried out at 60 °C. The catalytic system also tolerates (1‐bromoethyl)benzene bearing β‐hydrogen atoms while using a catalyst loading of 1 mol% to afford the coupling product in a 70% yield.     

Gold(I)‐Catalyzed Intramolecular Hydroamination of N‐Allylic N′‐Arylureas to form Imidazolidin‐2‐ones

Treatment of N‐allylic N′‐arylureas with a catalytic 1:1 mixture of di‐tert‐butyl‐o‐biphenylphoshphine gold(I) chloride and silver hexafluorophosphate (1 mol%) in chloroform at room temperature led to 5‐exo‐hydroamination to form the corresponding imidazolidin‐2‐ones in excellent yield. In the case of N‐allylic ureas that possessed an allylic alkyl, benzyloxymethyl, or acetoxymethyl substituent, gold(I)‐catalyzed 5‐exo‐hydroamination leads to formation of the corresponding trans‐3,4‐disubstituted imidazolidin‐2‐ones in excellent yield with ≥50:1 diastereoselectivity.