In The Palladium Research Articles

Enantioselectivity in the synthesis of 3,5-disubstituted Δ 2-isoxazolines

The R-isomer of ISO-1, a 3,5-disubstituted Δ 2-isoxazoline, has been implicated as a potential therapeutic agent for the treatment of Type 1 Diabetes via the antagonism of macrophage migration inhibitory factor (MIF). Δ 2-Isoxazolines can be prepared by the palladium(II)-mediated cyclization of substituted β,γ-unsaturated oximes. While this reaction results in racemic mixtures, we have developed a stereoselective variant of this method based on the incorporation of an enantiomeric palladium complex in the reaction mixture. The use of chiral bisoxazoline ligands in the palladium(II)-mediated ring closure reaction has been shown to enhance the enantiomeric excess due to chirality at C5 of the Δ 2-isoxazoline.

The Use of Iminopyridines as Efficient Ligands in the Palladium(II)‐Catalyzed Cyclization of (Z)‐4′‐Acetoxy‐2′‐butenyl 2‐Alkynoates.

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The use of iminopyridines as efficient ligands in the palladium(II)-catalyzed cyclization of ( Z)-4′-acetoxy-2′-butenyl 2-alkynoates

Iminopyridines were found to be a sort of efficient bidentate ligands for the palladium(II)-catalyzed cyclization of ( Z)-4′-acetoxy-2′-butenyl 2-alkynoates in acetic acid to afford the α-( Z)-acetoxyalkylidene-β-vinyl-γ-butyrolactones. The iminopyridine ligands could not only inhibit β-hydride elimination but also stabilize the vinyl-palladium intermediate in acetic acid in the reaction.

Spectrophotometric determination of palladium(II) based on its catalytic effect on the reduction of azure I by sodium hypophosphite

A catalytic-spectrophotometric method for the determination of traces of palladium(II) is proposed. The reaction is based on the catalytic action of palladium(II) on the reduction of azure I (λmax = 647 nm) by sodium hypophosphite. The various variables affecting the sensitivity were studied, and a study of interfering ions was also carried out. The reaction gave a detection limit of 4.3 ng/mL palladium(II) and good reproducibility with a relative standard deviation of 1.53–1.98% in the palladium(II) concentration range 40–200 ng/mL. The method yielded another linear range (5–40 ng/mL) when using slightly different conditions. In this case, the detection limit was 0.78 ng/mL palladium(II), and the relative standard deviation for ten replicate analyses of 20 ng/mL palladium(II) was 2.05%. The method was applied to the determination of palladium in a sample of activated charcoal.

Chemoenzymatic synthesis of enantiomerically enriched 2-oxobicyclo[ m.1.0]alkan-3-yl acetate derivatives

Racemic α′-acetoxy α,β-unsaturated cyclopentanone and cyclohexanone have been resolved into the corresponding enantiomerically enriched α′-hydroxylated and acetoxylated compounds with 96–97% ee via PLE hydrolysis. Stereoselectivity in the palladium(II)-catalyzed reaction between the enantiomerically enriched α′-acetoxylated compounds and diazomethane has been investigated. In the α′-acetoxylated cyclopentenone, preferential cyclopropanation occurs in the anti-form, whereas α′-acetoxylated cyclohexenone affords both syn- and anti-products ( syn: anti, 61:36%). The relative configuration of the products was determined by NOE experiments.

Palladium Complexes Bearing Novel Strongly Bent Trans-Spanning Diphosphine Ligands: Synthesis, Characterization, and Catalytic Activity

The new air-stable chelating diphosphine ligands 1,8-bis(diisopropylphosphino)triptycene (2) and 1-(diisopropylphosphino)-8-(diphenylphosphino)triptycene (3) were synthesized in 51−73% yield from readily available starting materials. The examination of their coordination modes in the palladium(II) complexes [PdCl2(2)] (4) and [PdCl2(3)] (5) by means of 1H, 13C, and 31P NMR is consistent with the formation of trans-spanned complexes. X-ray analysis of 4 and 5 confirmed the structure but disclosed a strong distortion of the palladium centers from the expected square-planar geometry toward a butterfly-like environment. Further investigation revealed that 2 can also behave as a binucleating ligand, forming the quasi-closed halogen-bridged dipalladium complex 6, featuring an unusual nonplanar Pd2(μ-Cl)2Cl2 core. The catalytic activity of the new ligands and complexes was tested in palladium-catalyzed cross-coupling reactions of aryl chlorides with phenylboronic acid.

Metal complexes with pyridone-based radicals: Preparation and properties of a dinuclear paddle-wheel copper(II) complex and a mononuclear palladium(II) complex

Abstract We prepared and characterized dinuclear copper(II) and mononuclear palladium(II) complexes coordinated with a pyridine-based open-shell ligand, 5-(4′,4′,5′,5′-tetramethylimidazoline-3′-oxide-1′-oxyl)-2(1H)-pyridone (=HL). In the copper(II) dinuclear complex [Cu2(L)4(DMF)2] (1), four deprotonated ligands are coordinated as bridging ligands to form a paddle-wheel type unit. In the palladium(II) complex trans-[PdCl2(HL)2] (2), two HL ligands in the neutral hydroxypyridine form are coordinated to the trans positions of the metal ion via the nitrogen atoms. The hydroxyl groups of the ligands are hydrogen-bonded to the chlorine atoms of neighboring molecules, thereby creating a hydrogen-bonded double-chain molecular arrangement. Magnetic susceptibilities of these complexes were measured and analyzed. The small intramolecular antiferromagnetic interaction in the latter complex may originate from superexchange through the diamagnetic metal center.

Fast and mild palladium(ii)-catalyzed 1,4-oxidation of 1,3-dienes via activation of molecular oxygen with a designed cobalt(ii) porphyrin

The use of a Co(porphyrin)-amide ligand, , in the palladium(II)-catalyzed 1,4-diacetoxylation of conjugated dienes under O2 results in aerobic oxidation. The catalyst was highly active under O2, and the 1,4-diacetoxylation reaction could also be performed under air.

Regiocontrol in the palladium(II)-catalysed oxycarbonylation of unsaturated polyols

The regiocontrol of palladium(II)-catalysed oxycarbonylation of pentenetriols was studied for its potential exploitation in the carbonylation methodology for construction of tetrahydrofuran derivatives with defined stereochemistry. Synthesis of model substrates, the partially protected pentenetriols with diverse protecting groups was carried out starting from D-mannitol. The availability of the protecting group for carbonylation was tested, from the chemo-, regio-, and stereoselectivity point of view. It was found that course as well as stereochemistry of the process may be controlled by β-OH with silyl protected O-function in the α-position.

New Chiral Diamide Ligands Containing Redox‐Active Hydroquinone Groups. Synthesis and Results in the Palladium(II)‐Catalyzed 1,4‐Diacetoxylation of 1,3‐Dienes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Deuterium-labeling studies establishing stereochemistry at the oxypalladation step in Wacker-type oxidative cyclization of an o-allylphenol.

The stereochemical pathway (syn or anti) of the oxypalladation step was studied in the palladium(II)-catalyzed Wacker-type cyclization of stereospecifically deuterated 6-(2-hydroxyphenyl)-3-deuteriocyclohexenes, cis-3-d-1 and trans-3-d-1, giving dihydrobenzofuran derivatives. The stereochemistry was determined to be syn in the reaction catalyzed by a dicationic palladium(II) catalyst generated from Pd(MeCN)4(BF4)2 and (S,S)-ip-boxax in the presence of benzoquinone in methanol, while it is mainly anti in the reaction catalyzed by PdCl2(MeCN)2 in the presence of a chloride ion.

New chiral diamide ligands containing redox-active hydroquinone groups. Synthesis and results in the palladium(II)-catalyzed 1,4-diacetoxylation of 1,3-dienes

Chiral ligands 8– 11, 22 and 23 were synthesized from different chiral diamines as a new class of ligands for the Pd(II)-catalyzed 1,4-diacetoxylation of 1,3-dienes. The synthesis from the diamines and protected benzoic acids was performed in a few simple steps and gave the ligands in high overall yields. The hydroquinone groups present in the ligands are in situ oxidized to benzoquinone to give the active ligands. Application of these ligands in the 1,4-diacetoxylation reaction afforded the oxidation product with high regio- and diastereoselectivity and an enantiomeric excess up to 42% was obtained. Possible coordination modes of the metal to the ligand are discussed, and experiments were made to investigate the coordination by varying the reaction conditions or making changes to the ligands.

Tuning the Regioselectivity in the Palladium(II)‐Catalyzed Isomerization of Alkylidene Cyclopropyl Ketones: A Dramatic Salt Effect.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Double bonds in motion: bis(oxazolinylmethyl)pyrroles and their metal-induced planarization to a new class of rigid chiral C2-symmetric complexes.

The synthesis of a new class of chiral C(2)-symmetric tridentate N-donor ligands, a series of 2,5-bis(2-oxazolinylmethyl)pyrroles, was achieved in four steps starting from the known 2,5-bis(trimethylammoniomethyl)pyrrole diiodide (1). Reaction of 1 with NaCN in dimethyl sulfoxide gave 2,5-bis(cyanomethyl)pyrrole (2) cleanly, which was then cyclized with amino alcohols to give the 2,5-bis(2-oxazolinylmethyl)pyrroles 3 a-c (3 a: bis[2-(4,4'-dimethyl-5-hydrooxazolyl)methyl]pyrrole; 3 b: (S,S)-bis[2-(4-isopropyl-4,5-dihydrooxazolyl)methyl]pyrrole; 3 c: (S,S)-bis[2-(4-tertiobutyl-4,5-dihydrooxazolyl)methyl]pyrrole). Metallation of 3 a-c with one molar equivalent of tBuLi and their subsequent reaction with a stoichiometric amount of [PdCl(2)(cod)] (cod=cyclooctadiene) gave the palladium(II) complexes 4 a-c. Whereas the arrangement of the N-donor atoms in the crystallographically characterized complex 4 a is almost ideally square planar, all three heterocycles in the ligand are twisted out of the coordination plane, leading to a chiral conformation of the complex. Attempts to freeze out these two conformers in solution at 200 K (NMR) failed, and this suggests that the activation barrier for conformational racemization is significantly below 10 kcal mol(-1). The palladium-induced shift of two double bonds as well as the porphyrinogen/porphyrin-type oxidation of the complexes 4 a-c led to the planarization of the 2,5-bis(oxazolinylmethyl)pyrrolide ligands in the palladium(II) complexes 5 a-c, 6 b, and 6 c, and to the formation of rigid chiral C(2)-symmetric systems as shown by X-ray diffraction studies. The formation of the conjugated system of double bonds in this transformation is accompanied by the emergence of an intra-ligand chromophore. This is evident in the absorption spectrum of 6 c which displays an intense band with a maximum at 485 nm attributable to an intra-ligand pi*<--pi transition and a characteristic vibrational progression of nu approximately 1350 cm(-1). Complexes 4 b and 4 c were tested in the catalytic asymmetric Michael addition of ethyl 2-cyanopropionate to methyl vinylketone (catalyst loading: 1 mol %) and were found to give maximum ee values of 43 % (4 b) and 21 % (4 c) at low conversions.

Substituent effects in columnar β-diketonate metallomesogens

A systematic study of the mesomorphic properties of two homologous series of copper(II) and palladium(II) complexes 1a–b derived from unsymmetrical β-diketonate derivatives 2 containing a variety of functional substituents (X = H, CH3, C2H5, OCH3, Cl, Br, I, CN) on the phenyl ring is reported. These disc-like molecules all contain eight n-octyloxy chains, required for the formation of columnar phases appended to the central β-diketonate core. All complexes exhibited columnar phases studied by differential scanning calorimetry, polarized optical microscopy and powder X-ray diffraction. The mesomorphic results indicated that all compounds formed stable enantiotropic columnar mesophases, and the formation of columnar phases was strongly dependent on the electronic and/or the steric factors of the substituents. For compounds containing bulky substituents (i.e. X = Me, Et) a rectangular columnar phase (Colr) was observed, however, other compounds containing electron-withdrawing substituents (i.e. X = Cl, Br, I) exhibited a hexagonal columnar phase (Colh). Most of the palladium(II) complexes, except for X = CH3 and OCH3 derivatives, have lower clearing temperatures than those of the copper(II) analogues, and this is probably due to a weaker molecular interaction between the cores in the palladium(II) complexes. Lattice constants for these two types of compound obtained by powder X-ray diffraction were found to be insensitive to the metal center incorporated. These values were all relatively close in magnitude, which indicated that the two structures were quite similar. A satisfactory linear relationship with a correlation coefficient of 0.974 between the clearing temperatures and the Hammett σp constants of substituents was obtained only for the copper complexes.

Use of the Pauson-Khand reaction products as monomers in the palladium(II)-catalyzed homopolymerization and copolymerization of norbornene derivatives

New norbornene derivatives synthesized from Pauson-Khand reaction products were homopolymerized and copolymerized with norbornene with an allyl-palladium complex as a catalyst. The ketone group was tolerated by the polymerization reaction. Monomers bearing protected alcohols were easily homopolymerized. Most of the homopolymers were soluble in tetrahydrofuran, CH 2 Cl 2 , toluene, and cyclohexane. As the steric bulkiness of the substituent increased, the chain length of the homopolymer decreased. Copolymers with a molecular weight of up to 153,800 were formed and were soluble in tetrahydrofuran, CH 2 Cl 2 , toluene, and diethyl ether.

Structural characterization and complexation behavior of ferrocene bearing dipeptide chain (-L-Ala-L-Pro-NHPy)

Ferrocene 1 bearing dipeptide chain (-L-Ala-L-Pro-NHPy) was synthesized and characterized by spectroscopy and X-ray crystallography. The single-crystal X-ray structure determination of the ferrocene 1 revealed that a hydrogen-bonded network is formed in an antiparallel manner to give a highly organized assembly, wherein each molecule is connected to two neighboring molecules through N–H⋯N and N–H⋯O intermolecular hydrogen bonds, forming a seven-membered intermolecularly hydrogen-bonded ring. The ferrocene 1 served as a monodentate ligand to form the 2:1 trans-complex 2 with PdCl 2(MeCN) 2. The rotational barrier of the two pyridyl rings in the palladium(II) complex 2 was 10.1 kcal mol −1.

Unusually accelerated silylmethyl transfer from tin in stille coupling: implication of coordination-driven transmetalation.

The palladium-catalyzed cross-coupling reaction of 2-PyMe2SiCH2SnBu3 with aryl iodide (Ar-I) exclusively produced the 2-PyMe2SiCH2 transferred product 2-PyMe2SiCH2Ar. The relative transfer ability of organic group from tin was found to be 2-PyMe2SiCH2 >> Ph > Me > Bu >> PhMe2SiCH2, which implies the beneficial pyridyl-to-palladium coordination effect. Thus, the transfer of the silylmethyl group from tin to palladium was remarkably accelerated by simply appending the 2-pyridyl group on silicon. The pyridyl-to-palladium coordination was validated in the palladium(II) complex 2-PyMe2SiCH2PdClPPh3 by 1H NMR and X-ray crystal structure analysis. The cross-coupling product was used for further transformations. The C-Si oxidation of the cross-coupling product 2-PyMe2SiCH2Ar afforded ArCH2OH in high yield. The fluoride ion-catalyzed 1,2-addition of 2-PyMe2SiCH2Ar to carbonyl compound (RR'C=O) gave ArCH2C(OH)RR' in high yield.

1,2-Bis(2-pyridylethynyl)benzene, a novel trans-chelating bipyridyl ligand. structural characterization of the complexes with silver(I) triflate and palladium(II) chloride.

The design, synthesis, and complexation characteristics of the bipyridyl ligand 1,2-bis-(2-pyridylethynyl)benzene are described. The X-ray crystallographic characterization of the 1:1 complexes of 1,2-bis(2-pyridylethynyl)benzene with silver(I) triflate and palladium(II) chloride are described. In the X-ray crystal structure of the silver(I) triflate complex the ligand is essentially planar with negligible distortion compatible with a good fit of the cation in the "cavity" between the pyridine N atoms. Indeed the silver center is almost linear with the N(1)-Ag(1)-N(2) angle of 177.02(10) degrees. The ligand is also essentially planar in the palladium(II) chloride complex with square planar coordination about the palladium with the N(1)-Pd(1)-N(2), Cl(2)-Pd(1)-Cl(2), and N(1)-Pd(1)-Cl(2) angles at 179.53(7), 177.17(2), and 90.52(5) degrees, respectively.

Stereoselective synthesis of chiral polyfunctionalized cyclohexane derivatives. Palladium(II)-mediated reaction between cyclohexenones and diazomethane

Several chiral polyfunctionalyzed cyclohexanones and cyclohexenones have been synthesized through Diels–Alder cycloadditions, stereoselectivity being stated by X-ray structural analysis and NOE experiments. The chemoselectivity in the palladium(II)-catalyzed reaction between cyclohexenones and diazomethane has been investigated. Thus, in those enones bearing an amide function on the γ-carbon, the preferential addition occurs at the carbonyl giving epoxides which, under acid conditions, rearrange to tetrahydrobenzoxazoles. The other cyclohexenones afford cyclopropanes as a result of addition to the CC bond. A mechanistic approach to explain the whole process is proposed.