(Eta3-phenylallyl)(phosphanyloxazoline)palladium complexes: X-ray crystallographic studies,NMR investigations,and Ab initio/DFT calculations

All possible (eta(3)-allyl)palladium complexes (1-4) of the ligand (4S)-[2-(2'-diphenylphosphanyl)phenyl]-4,5-dihydro-4-(2-propyl)-oxazole (L 1) and eta(3)-allyl ligands with one to three phenyl substituents at the terminal allylic centers were synthesized and characterized by X-ray crystal structure analysis and, with respect to allylic isomers, by NMR investigations. Equilibrium geometries, electronic structures, and relative energies of isomeric complexes were computed by restricted Hartree-Fock (RHF) and density functional theory (DFT) calculations; experimentally determined isomer ratios could be reproduced. The results allowed important conclusions to be drawn regarding the mechanism of Pd-catalyzed asymmetric allylic substitutions.     

Kinetics of lipid layer formation at interfaces

A formal kinetic model of lipid layer formation at an interface in contact with a liposomal suspension is developed and investigated. Neglecting diffusion (for sufficiently high bulk concentrations) the kinetic scheme consists of two consecutive processes: (I) irreversible transformation of ‘soluble’ intact vesicles from the ‘subsurface’ layer into ‘adsorbed’ ones (‘defected’ or ‘ruptured’ liposomes, ‘mesophases’); and (II) irreversible transformation of the ‘adsorbed’ vesicles into a lipid monolayer. The resulting set of two differential equations is analyzed making use of the ‘steady-state concentration’ approach (with ‘adsorbed’ vesicles as intermediate compound). Numerical results illustrate the predicted kinetic behavior which depends on the relative magnitude of the rates of the two consecutive processes. Approximate analytical solutions in the case of a much slower process I are obtained in some limiting cases. The model is used to estimate rate constants from previously established experimental kinetic data at the air/water interface.     

Origin of enantioselectivity with heterobidentate sulfide-tertiary amine (sp) ligands in palladium-catalyzed allylic substitution

A series of new chiral heterobidentate sulfide-tertiary amine (sp³) ligands 3a-c, 6 were readily prepared from cheap and easily available (R)-cysteine and l-(+)-methionine. A Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate was used as a model reaction to examine the catalytic efficiencies of these aziridine sulfide ligands, and ligand 3b afforded the enantioselectivity of up to 91% ee. The origin of enantioselectivity for heterobidentate sulfide-tertiary amine (sp³) ligands was first rationalized based on X-ray crystallographic data, and NMR spectroscopic data for relevant intermediate palladium allylic complexes. Our results demonstrated that the sulfur atom was a better π-allyl acceptor than the nitrogen atom for heterobidentate sulfide-tertiary amine (sp³) ligands, and the steric as well electronic properties of the palladium allylic complexes were crucial for the enantioselectivity.     

Simple palladium‐catalyzed C–N bond formation for poor nucleophilicity of aminonaphthalenes

Aromatic amines is not used commonly in allylic amination, presumably because of their less nucleophilic nature compared with the more extensively used benzylamine or relatively stable anionic nitrogen nucleophiles. An eco‐friendly method for C–O bond activation of allylic acetates using palladium associated with ligands in water leading to N‐allylation was described in this study. The palladium‐catalyzed allylic amination of allylic acetate with aminonaphthalenes gave 34–95% yields to the corresponding N‐allylic aminonaphthalenes. Copyright © 2011 John Wiley & Sons, Ltd.     

Syntheses a l'aide de sulfones : XXIII. Sur la selectivite de la synthese des sulfones Allyliques

The role of the palladium ligands on the yield and regioselectivity of the reaction of conjugated dienes with arenesulphinic acids (or of allylic acetates with sodium arenesulphinates) has been investigated. Arenesulphinic acids catalyse the isomerisation of allylic sulphones.     

Bulky monodentate phosphoramidites in palladium-catalyzed allylic alkylation reactions: aspects of regioselectivity and enantioselectivity

A series of bulky monodentate phosphoramidite ligands, based on biphenol, BINOL and TADDOL backbones, have been employed in the Pd-catalysed allylic alkylation reaction. Reaction of disodium diethyl 2-methyl malonate with monosubstituted allylic substrates in the presence of palladium complexes of the phosphoramidite ligands proceeds smoothly at room temperature. The regioselectivities observed depend strongly on the leaving group and the geometry of the allylic starting compounds. Mono-coordination occurs when these ligands are ligated in [Pd(allyl)(X)] complexes (allyl=C3H5, 1-CH3C3H4, 1-C6H5C3H4, 1,3-(C6H5)2C3H3; X=Cl, OAc). The solid-state structure determined by X-ray diffraction of [Pd(C3H5)(1)(Cl)] reveals a non-symmetric coordination of the allyl moiety, caused by the stronger trans influence of the phosphoramidite ligand relative to X-. In all of these complexes, the syn,trans isomer is the major species present in solution. Because of fast isomerisation and high reactivity of the syn,cis complex, the major product formed upon alkylation is the linear product, especially for monosubstituted phenylallyl substrates in the presence of halide counterions. In the case of biphenol- and BINOL-based phosphoramidites, however, a strong memory effect is observed when 1-phenyl-2-propenyl acetate is employed as the substrate. In this case, nucleophilic attack competes effectively with the isomerisation of the transient cinnamylpalladium complexes. The asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate afforded the chiral product in up to 93 % ee. Substrates with smaller substituents gave lower enantioselectivities. The observed stereoselectivity is explained in terms of a preferential rotation mechanism, in which the product is formed by attack on one of the isomers of the intermediate [Pd[1,3-(C6H5)2C3H3](L)(OAc)] complex.     

A rapid and precise assay for peroxide as 'active oxygen' in products, by flow injection analysis in a high pressure system with spectrophotometric detection

A simple, rapid and automated assay for ‘active oxygen’ originating from hydrogen peroxide, or other organic peroxides, in products is presented employing flow injection (FI) analysis. The product is dispersed and peroxide dissolved in a solvent of 5% (v/v) acetic acid, which constitutes the carrier stream. Ammonium molybdate can be added to this carrier stream to increase sensitivity as required. The sample solution is injected into the acid carrier stream, which is then merged with iodide ion in situ in a two-stream manifold. The ‘active oxygen’ in the product oxidises acidified iodide to iodine, which is detected spectrophotometrically at 350 nm. The closed conditions prevent interference from atmospheric oxygen and the short reaction time minimises the potential for interference from side reactions. Standard HPLC equipment is used throughout, employing a back-pressure to improve precision (high pressure flow injection). Conditions have been investigated using screening multivariate experimental design (two-level quarter fractional factorial design incorporating centre points) to identify and optimise the critical variables. The method has been fully validated (with sample solution R.S.D.s typically < 0.5%, LOQs of 0.04 or 0.006 μg ml⁻¹ as ‘active oxygen’ for acid or acid/molybdate carriers respectively) and is quicker and simpler than the currently employed manual titration approach. It should be applicable to a range of ‘active oxygen’ products.     

Palladium‐Catalyzed Cascade Double C—N Bond Activation: A New Strategy for Aminomethylation of 1,3‐Dienes with Aminals

A new palladium‐catalyzed selective aminomethylation of conjugated 1,3‐dienes with aminals via double C—N bond activation is described. This simple method provides an effective and rapid approach for the synthesis of linear α,β‐unsaturated allylic amines with perfect regioselectivity. Mechanistic studies disclosed that one palladium catalyst cleaved two distinct C—N bond to furnish a cascade double C—N bond activation, in which an allylic 1,3‐diamine and allylic 1,2‐diamine were initially formed as key intermediates through the palladium‐catalyzed C—N bond activation of aminal and the α,β‐unsaturated allylic amine was subsequently produced via palladium‐catalyzed C—N bond activation of the allylic diamines.     

Palladium-catalyzed asymmetric allylic alkylation with an enamine as the nucleophilic reagent

An enamine can serve as a good nucleophile for palladium-catalyzed asymmetric allylic alkylation, avoiding the use of an unstablilized ketone enolate formed by strong bases. In the presence of a palladium complex of chiral metallocene-based phosphino-oxazoline ligands, the reaction was carried out smoothly with high catalytic activity and excellent enantioselectivity. Different distances between the two Cp rings of ferrocene and ruthenocene affected the catalytic behavior in the reaction. Furthermore, high catalytic activity and good enantioselectivity were also afforded by the ferrocene-based diphosphine ligands with only planar chirality.     

A facile highly regio- and stereoselective preparation of N-tosyl allylic amines from allylic alcohols and tosyl isocyanate via Palladium(II)-catalyzed aminopalladation-beta-heteroatom elimination

The high regio- and stereoselectivity have been obtained from the allylic substitution reaction catalyzed by palladium(II) species. From allylic alcohols, one-pot reaction with tosyl isocyanate followed by palladium(II)-catalyzed allylic substitution gives N-tosyl (E)-allylic amines in high yield. The substitution occurs only at the gamma-position of the 1- or 3-substituted allylic alcohols.     

The mechanism of nucleophilic addition to η3-allylpalladium complexes: the influence of ligands on rates and regiochemistry

The influence of the ligands L in η³-(3-methylbutenyl)palladium(L₂) complexes on the rates and regiochemistry of nucleophilic addition has been studied. Acceptor ligands such as phosphines and 1,5-cyclooctadiene have been found to increase the rate of addition as well as the preference for reaction at the more substituted allyl terminus. There is a good correlation between the rates and the ¹³C NMR shifts of the more substituted η³-allyl terminus, indiating that the NMR shifts can be used to predict acceptor properties of the ligands. There is a fair agreement between the rates and the regiochemistry of the palladium catalyzed nucleophilic displacement of allylic acetate from these complexes and those for the stoichiometric reactions involving η³-allyl complexes.     

Palladium catalyzed oxidation of monoterpenes: NMR study of palladium(II)-monoterpene interactions

Reactions of the monoterpenes β-pinene, limonene and myrcene with Pd(II) complexes in acetic acid solutions were studied by ¹H NMR spectroscopy. Various π-allyl palladium complexes were detected in situ and their interaction with CuCl₂ has been investigated. The results clarify the mechanism of allylic oxidation of these substrates mediated by Pd(II)/Cu(II)-based catalytic systems. Originally introduced to regenerate reduced palladium species, CuCl₂ has been shown to play an important role in the formation and/or decomposition of key reaction intermediates - π-allyl palladium complexes. β-Pinene and myrcene readily react with Pd(OAc)₂ giving corresponding π-allyls, with two complexes acyclic and cyclic being formed from myrcene. On the other hand, the formation of π-allyl complexes from limonene occurs at a significant rate only in the presence of CuCl₂. NMR observations, including selective paramagnetic enhancement of spin-lattice relaxation, indicate that π-allyl palladium intermediates specifically interact with Cu(II) ions in the reaction solutions. Such interaction probably involves Cu(II) bonding to Pd(II) via bridging ligands, and seems to be responsible for the accelerative effect of CuCl₂ in the palladium catalyzed oxidation of the monoterpenes. Indeed, most of these reactions do not occur at all in the absence of CuCl₂.     

Role of planar chirality of S,N- and P,N-ferrocene ligands in palladium-catalyzed allylic substitutions

Palladium-catalyzed asymmetric allylic substitutions using thioether and phosphino derivatives of ferrocenyloxazoline as ligands have been investigated with a focus on studying the role of planar chirality. In allylic alkylation, up to 98% ee and 95% ee were achieved with S,N- and P,N-ligands, respectively. In allylic amination, 97% ee was realized with P,N-ligands in the presence of TBAF. Several palladium allylic complexes were characterized by X-ray diffraction and/or solution NMR. Thioether derivatives of ferrocenyloxazolines with only planar chirality showed lower enantioselectivity in the allylic alkylation except 5c because of the formation of a new chirality on sulfur atom during the coordination of sulfur with palladium. On the other hand, in the planar chiral P,N-ligands without central chirality, (Sp)-11a-c there was no such disturbance and comparatively higher enantioselectivity in both palladium-catalyzed allylic alkylation and amination was provided.     

Allenes as carbon nucleophiles in intramolecular attack on (pi-1,3-diene)palladium complexes: evidence for trans carbopalladation of the 1,3-diene

Reaction of allene-substituted cyclohexa- and cyclohepta-1,3-dienes with [PdCl(2)(PhCN)(2)] gave eta(3)-(1,2,3)-cyclohexenyl- and eta(3)-(1,2,3)-cycloheptenylpalladium complexes, respectively, in which C-C bond formation between the allene and the 1,3-diene has occurred. Analysis of the (pi-allyl)palladium complexes by NMR spectroscopy, using reporter ligands, shows that the C-C bond formation has occurred by a trans carbopalladation involving nucleophilic attack by the middle carbon atom of the allene on a (pi-diene)palladium(II) complex. The stereochemistry of the (pi-allyl)palladium complexes was confirmed by benzoquinone-induced stereoselective transformations to allylic acetates.     

Development of chiral (S)-prolinol-derived ligands for palladium-catalyzed asymmetric allylic alkylation: effect of a siloxymethyl group on the pyrrolidine backbone

A series of novel chiral aminophosphine ligands are designed and readily prepared from (S)-prolinol. The reactivity and selectivity in the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a dimethyl malonate-BSA-LiOAc system using these chiral ligands are evaluated, and the structural elucidation of ligands and palladium complex is also conducted. Moreover, a series of trialkylsilylated chiral aminophosphine ligands are prepared and applied to palladium-catalyzed asymmetric allylic alkylation (up to 98% ee).     

Synthesis of (+) or (-)-2-(8′-Diphenylphosphino-1′-naphthyl)oxazoline Ligands and Their Application in Pd-Catalyzed Allylic Alkylation Reaction

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Palladium catalyzed reaction of allylic geminal diacetates with nucleophiles

The influence of ligands on the palladium catalyzed reaction of allylic-1,1-diol diacetate (1) with sodium dimethyl malonate was studied. When PPh₃ was used as the ligand, the malonate anion was found to attack the carbonyl carbon atom, but it would attack the allylic carbon atom while dppe was used as the ligand. The properties of nucleophiles also influence the position of attack. By suitable choice of the nucleophiles and ligands, dialkylated products can be obtained from 1.     

The synthesis of new planar chiral heterobidentate chelate ligands for asymmetric catalysis

A series of new heterobidentate N,S; N,O and N,P chelate ligands have been synthesised where the sole source of chirality is derived from a planar chiral ferrocene unit and have been shown to give up to 79% ee (R) in the palladium catalysed allylic substitution reaction, suggesting that they may be suitable in other palladium catalysed processes.     

Reaction of vinyl epoxides with palladium-switchable bisnucleophiles: synthesis of carbocycles

The selective activation of substrates I, potential bisnucleophiles, was achieved by using different palladium catalysts. The synthetic potential of this strategy has been demonstrated in the regiodivergent synthesis of carbocycles from substrates of type I, bearing malonate-type pronucleophiles and an alkenyl stannane, with vinyl epoxides. A selective palladium-catalyzed reaction of I with the vinyl epoxide gives rise to an allylic alcohol, which, after activation as a carbonate, led to the cyclization product by a second palladium-catalyzed reaction. The transmetalation process is favored with palladium-catalysts without phosphines or arsines as the ligands. On the other hand, the use of palladium complexes with PPh3 as the ligand inhibits the transmetalation pathway and promotes the nucleophilic attack of the malonate-type anions on the intermediate (eta 3-allyl)-palladium complexes.     

Design and synthesis of enantiopure 1-[1(S)-(2-pyridyl)alkyl]-2(R)-isopropylaziridines, new ligands for asymmetric catalysis

Enantiopure 1-(2-pyridyl)alkyl aziridines were designed as bidentate ligands for asymmetric catalysis. Their synthesis involved the addition of organometallic reagents to the imine prepared from 2-pyridinealdehyde and an enantiopure β-aminoalcohol, followed by cyclisation of the β-aminoalcohol moiety to the aziridine ring. Two such ligands (N–N)* were prepared from (S)-valinol and converted to the complexes (η³-allyl)(N–N)*Pd⁺SbF₆⁻, one of which was characterised by X-ray crystallography. Modest enantioselectivities were achieved in a representative Pd-catalysed allylic substitution reaction.