Showing papers on "Heck reaction published in 2008"

Well-defined N-heterocyclic carbenes-palladium(II) precatalysts for cross-coupling reactions.

Abstract: Metal-catalyzed cross-coupling reactions, notably those permitting C−C bond formation, have witnessed a meteoritic development and are now routinely employed as a powerful synthetic tool both in academia and in industry. In this context, palladium is arguably the most studied transition metal, and tertiary phosphines occupy a preponderant place as ancillary ligands. Seriously challenging this situation, the use of N-heterocyclic carbenes (NHCs) as alternative ligands in palladium-catalyzed cross-coupling reactions is rapidly gaining in popularity. These two-electron donor ligands combine strong σ-donating properties with a shielding steric pattern that allows for both stabilization of the metal center and enhancement of its catalytic activity. As a result, the number of well-defined NHC-containing palladium(II) complexes is growing, and their use in coupling reactions is witnessing increasing interest. In this Account, we highlight the advantages of this family of palladium complexes and review their synt...

Microwave-assisted organic synthesis and transformations using benign reaction media.

Abstract: A nonclassical heating technique using microwaves, termed "Bunsen burner of the 21st century", is rapidly becoming popular and is dramatically reducing reaction times. The significant outcomes of microwave (MW)-assisted green chemistry endeavors, which have resulted in the development of synthetic protocols for drugs and fine chemicals synthesis that are relatively more sustainable, are summarized. The use of emerging microwave-assisted chemistry techniques in conjunction with greener reaction media is dramatically reducing chemical waste and reaction times in several organic syntheses and chemical transformations. A brief historic account of our own experiences in developing MW-assisted organic transformations, which involve various benign alternatives, such as solid-supported reagents, and greener reaction media, namely, aqueous, ionic liquid, and solvent-free, for the synthesis of various heterocycles, coupling reactions, oxidation-reduction reactions, and some name reactions are described. Synthesis of Heterocycles. The synthetic chemistry community has been under increased pressure to produce, in an environmentally benign fashion, the myriad of heterocyclic systems required by society in a short span of time, and one of the best options to accelerate these synthetic processes is to use MW technology. The efficient use of the MW heating approach for the synthesis of various heterocyclic compounds in aqueous and solvent-free medium is discussed. Organic Named Reactions. The application of MW chemistry for various named reaction such as the Prins reaction, the Suzuki reaction, the Heck reaction, the Aza-Michael reaction, Trost's gamma-addition, and the Cannizzaro reaction are summarized. Synthesis and Application of Ionic Liquids. Ionic liquids (ILs), being polar and ionic, in character couple with MW irradiation very efficiently and are, therefore, ideal MW-absorbing candidates for expediting chemical reactions. MW-assisted solvent-free synthesis and application of ILs are discussed. Oxidation-Reduction Reactions. MW protocols using mineral oxides such as alumina, silica, and clay to immobilize reagents on such solid supports have been extensively explored under "dry" media conditions. Various solvent-free examples of oxidation reactions are discussed that involve mixing of neat substrates with clay-supported iron(III) nitrate (clayfen) or iodobenzene diacetate (IBD) as an oxidant; some interesting MW reduction protocols using borohydrides are also discussed. Protection-Deprotection Reactions. The protection and deprotection of alcohols and amines are common events in multistep organic syntheses. Various protection and deprotection protocols under MW irradiation are discussed, including tetrahydropyranylation and (benzyloxycarbonyl) (Cbz)-protection, which are the most frequently employed methods.

A General and Highly Selective Chelate-Controlled Intermolecular Oxidative Heck Reaction

Abstract: A novel chelate-controlled intermolecular oxidative Heck reaction is reported that proceeds with a wide range of nonresonance stabilized α-olefin substrates and organoboron reagents to afford internal olefin products in good yields and outstanding regio- and E:Z stereoselectivities. Pd−H isomerization, common in many Heck reactions, is not observed under these mild, oxidative conditions. This is evidenced by outstanding E:Z selectivities (>20:1 in all cases examined), no erosion in optical purity for proximal stereogenic centers, and a tolerance for unprotected alcohols. Remarkably, a single metal/ligand combination, Pd/bis-sulfoxide complex 1, catalyzes this reaction over a broad range of coupling partners. Given the high selectivities and broad scope, we anticipate this intermolecular Heck reaction will find heightened use in complex molecule synthesis.

Oxygen and base-free oxidative heck reactions of arylboronic acids with olefins.

Abstract: A mild and efficient protocol for palladium-catalyzed oxidative Heck reactions of arylboronic acids with both electron-rich and -deficient olefins is described. In contrast to the normal oxidative Heck coupling, this new method works in the absence of a base, oxygen, or other external oxidants. With a wide variety of substrates tolerated, the method broadens the scope of palladium-catalyzed coupling reactions.

Palladium‐Catalyzed Tandem Heck Reaction/C ? H Functionalization—Preparation of Spiro‐Indane‐Oxindoles

Abstract: The oxindole framework is a motif common to natural products and pharmaceutically active compounds. In particular, 3,3-disubstituted oxindoles have shown promising biological activity. Considerable efforts have been dedicated to developing new methods for the preparation of these pharmacaphores, especially spiro-oxindoles: functionalization of heterocycles, variations of the Stolle reaction, epoxide rearrangement, Lewis acid promoted cyclization, Pummerer rearrangement, and various palladium-catalyzed methodologies. Within that last category, the intramolecular Heck reaction is of particular relevance here. Although tremendous efforts have been invested in the discovery of new palladium-catalyzed processes, there remains limited overlap between two key transformations, namely the Heck reaction and the direct arylation reaction, which appear to be orthogonal methodologies. Most relevant examples of reaction commonality entail carbopalladation to form a vinylpalladium intermediate and subsequent C H functionalization. The two examples that proceed by olefin insertion to form an alkylpalladium intermediate undergo C H insertion to form a cyclobutane product after reductive elimination. Of particular relevance to this work is the report from Grigg et al. on a Heck reaction that forms an alkylpalladium complex and then undergoes a heteroatom-directed arylation reaction to make a fivemembered ring. Herein we report an efficient preparation of spiro-fused indane-oxindoles by carbopalladation to form an alkylpalladium intermediate and subsequent functionalization of an unactivated aryl C H bond. (Scheme 1). To investigate the viability of a tandem Heck/arylation reaction sequence, we prepared N-(2-bromophenyl)acrylamides (5a–h) in a five-step sequence from 2-bromoaniline (1) (Scheme 2). Reductive amination between p-anisaldehyde and 2-bromoaniline afforded PMB-protected aniline 2 (PMB= p-methoxybenzyl). Amide bond formation between compound 2 and potassium mono-methyl malonate provided malonamic acid methyl ester 3, which was alkylated with the requisite substituted benzyl bromide to afford alkylation products 4a–h. Hydrolysis of the methyl ester, and treatment of the liberated carboxylic acid with diethylamine and paraformaldehyde, furnished acrylamides 5a–h in good yields. Initial efforts to effect the desired transformation from compound 5a to 6a employed the catalytic system reported by Fagnou and co-workers: Pd(OAc)2 (10 mol%), PtBu3HBF4 (20 mol%), and K2CO3 in DMA at 130 8C. [15,17] Gratifyingly, spiro-fused indane-oxindole 6a was observed under these conditions. A second product (7; see Scheme 4), assigned as the product formed by a reductive Heck reaction, was also observed in the complex reaction mixture. A series of palladium sources and ligands was screened in an effort to develop a cleaner reaction. Decreasing the catalyst loading in Scheme 1. Heck/C H functionalization tandem reaction. PMB=pmethoxybenzyl.

Supported Palladium Catalysts for Suzuki Reactions: Structure‐Property Relationships, Optimized Reaction Protocol and Control of Palladium Leaching

Abstract: Palladium on metal oxides and on activated carbon with particular properties (high palladium dispersion, low degree of reduction, water content) are shown to be highly active (tunrover number, TON =20,000; turnover frequency, TOF= 16,600), selective and robust catalysts for Suzuki cross-couplings of aryl bromides and activated aryl chlorides. Catalysts and reaction protocol offer combined advantages of high catalytic efficiency under ambient conditions (air and moisture), easy separation and reuse and quantitative recovery of palladium. The palladium concentration in solution during the reaction correlates clearly with the progress of the reaction and indicates that dissolved molecular palladium is in fact the catalytically active species. Dissolved palladium is redeposited onto the support at the end of the reaction. Additional minimization of the palladium content in solution (down to 0.1 ppm) could be achieved by simple procedures which meet the requirements of pharmaceutical industry.

Pincer Click Ligands

Abstract: Tridentate pincer-type ligands of the general form DCD (where D and D are groups containing coordinating atoms) have been used to spectacular effect in coordination, mechanistic, synthetic, and supramolecular chemistry, as well as in nanoscience and in the development of sensors and molecular switches. Most significantly, the realization that pincer ligands offer both a unique, highly protective environment for the coordinated metal center and opportunities to finetune the steric and electronic properties of the metal atom has generated extensive research into the use of these complexes as catalysts. As a result, many important and challenging catalytic processes based on such systems have been developed. It is generally accepted that the reactivity, selectivity, and catalytic performance of pincer-based systems rely to a great extent on the characteristics of the donor groups D in the carefully selected ligand. The optimization of tailor-made catalysts involves extensive experimental investigation, in which the laborious synthesis of the ligands is often a serious bottleneck. In particular, the synthesis of nonsymmetrically substituted DCD ligands (D and D are different groups) represents a considerable challenge, as their preparation usually includes a series of steps and separations that commonly result in low yields. Consequently, the development of efficient and powerful methods for the rapid synthesis of a wide variety of tailormade ligands is of high importance. Although several methods for the preparation of bidentate ligand libraries have been reported, a strategy for the building of a tridentate ligand library is, to the best of our knowledge, still unknown. Here, we report a conceptually new general approach for the efficient and facile preparation of a novel family of tridentate pincer ligands of the DCD type. The tridentate mode of coordination was shown by the preparation and structural characterization of transition-metal complexes of these new ligands. Palladium complexes of this readily prepared set of representative ligands proved to be highly efficient catalysts in the Heck reaction. Traditionally, pincer ligands are prepared by attaching donor atoms to a ligand backbone. We developed an entirely different synthetic route that allowed access to a broad range of tailor-made pincer ligands. In designing our approach, we considered a methodology which would allow the selective and facile incorporation of two complementary monomeric donor groups D and D by covalent assembly to afford a pincer-type system DCD. The resulting molecule must also have a potential carbanion between the donor groups so as to bind the metal center in a pincer-type mode (Scheme 1a).

Rapid and efficient Pd-catalyzed sonogashira coupling of aryl chlorides

Abstract: An efficient and effective microwave-assisted cross-coupling of terminal alkynes with various aryl chlorides including sterically hindered, electron-rich, electron-neutral, and electron-deficient aryl chloride is developed. It proceeds faster and generally gives good to excellent yields and also can be extended successfully to the Suzuki coupling and Buchwald−Hartwig amination, as well as the Heck coupling with inert aryl chlorides. The short reaction times and simple reaction conditions coupling with a broad substrate scope render this method particularly attractive for the efficient preparation of biologically and medicinally interesting molecules.

A general synthetic route to mixed NHC-phosphane palladium(0) complexes (NHC=N-heterocyclic carbene).

Abstract: Mixed NHC-phosphane palladium(0) complexes [(NHC)Pd(PR(3))] (NHC: N-heterocyclic carbene) are synthesized directly from commercially available reagents, with the possibility to tune the nature of both the NHC and the phosphane. Reaction of [NHC)Pd(allyl)Cl] (palladium source) and PR(3), in the presence of a base afforded, in isopropanaol, [(NHC)Pd-(PR(3))] in good yields. We found that the nature of the solvent played a key role in the efficient reduction of the Pd(II) precursor to Pd(0). Supported by experimental evidence we propose that the reduction step is driven by the isopropoxide anion formed in situ from isopropanol and a base. Detection of acetone in the reaction mixture confirms that the isopropoxide anion acts as the reducing agent. Moreover, different bases proved efficient for the reaction. The structures of the complexes were unambiguously confirmed by X-ray analysis. Exposure of these complexes to air does not lead to decomposition, but to the oxo-complex [(NHC)Pd(PR(3))(O(2))], which is stable both in the solid state and in solution.

A dramatic switch of enantioselectivity in asymmetric Heck reaction by benzylic substituents of ligands

Abstract: A series of benzylic substituted P,N-ligands 1 and 2 have been synthesized. The Pd-complexes of these ligands show high catalytic activity and enantioselectivity in catalyzing the asymmetric Heck reaction. A dramatic switch in enantioselectivity is realiz

Pd PEPPSI‐IPr‐Mediated Reactions in Metal‐Coated Capillaries Under MACOS: The Synthesis of Indoles by Sequential Aryl Amination/ Heck Coupling

Abstract: A method has been devised for the microwave-assisted, continuous-flow preparation of indole alkaloids by a two-step aryl amination/cross-coupling sequence of bromoalkenes and 2-bromoanilines. This process requires both the presence of a metal-lined flow tube (a 1180 micron capillary) and the Pd PEPPSI-IPr catalyst; without either, the catalyst or the film, there is zero turnover of this catalytic process. A silver film has been shown to provide some conversion (48-62 %), but optimal results (quantitative) across a variety of bromoalkenes and bromoanilines were achieved by using a highly porous palladium film. Possible roles for the Pd film are considered, as is the interplay of the catalyst and the film.

Combined Experimental and Theoretical Study of the Mechanism and Enantioselectivity of Palladium- Catalyzed Intermolecular Heck Coupling

Abstract: The asymmetric Heck reaction using P,N-ligands has been studied by a combination of theoretical and experimental methods The reaction follows Halpern-style selectivity; that is, the major isomer is produced from the least favored form of the pre-insertion intermediate The initially formed Ph-Pd(P,N) species prefers a geometry with the phenyl trans to N However, the alternative form, with Ph trans to P, is much less stable but much more reactive In the preferred transition state, the phenyl moiety is trans to P, but significant electron density has been transferred to the alkene carbon trans to N The steric interactions in this transition state fully account for the enantioselectivity observed with the ligands studied The calculations also predict relative reactivity and nonlinear mixing effects for the investigated ligands; these predictions are fully validated by experimental testing Finally, the low conversion observed with some catalysts was found to be caused by inactivation due to weak binding of the ligand to Pd(0) Adding monodentate PPh3 alleviated the precipitation problem without deteriorating the enantioselectivity and led to one of the most effective catalytic systems to date

Highly Efficient Nanocatalysts Supported on Hollow Polymer Nanospheres: Synthesis, Characterization, and Applications

Abstract: Hollow polymer nanospheres were employed in the fabrication of noble metal-supported catalysts via a supercritical route In this method, the metal precursors were first adsorbed on the polymer support in a supercritical CO2-ethanol solution, followed by H2 reduction, generating metal (Pd, Rh, Pt)/polymer composites The resultant Pd/polymer nanospheres were characterized by means of X-ray diffraction, scanning electron microscopy, transmission electron microscopy equipped with energy dispersive spectroscopy, and X-ray photoelectron spectroscopy analysis It was indicated that the Pd nanoparticles with a size of about 5 nm were uniformly attached to the surface of the polymer spheres The activities of the Pd/polymer composites for the allyl alcohol hydrogenation and Heck reaction were also investigated The catalyst exhibited a high activity and stability in these two reactions

Rationally Designed Pincer‐Type Heck Catalysts Bearing Aminophosphine Substituents: PdIV Intermediates and Palladium Nanoparticles

Abstract: The aminophosphine-based pincer complexes [C6H3-2,6-(XP(piperidinyl)2)2Pd(Cl)] (X=NH 1; X=O 2) are readily prepared from cheap starting materials by sequential addition of 1,1',1''-phosphinetriyltripiperidine and 1,3-diaminobenzene or resorcinol to solutions of [Pd(cod)(Cl)2] (cod=cyclooctadiene) in toluene under N2 in "one pot". Compounds 1 and 2 proved to be excellent Heck catalysts and allow the quantitative coupling of several electronically deactivated and sterically hindered aryl bromides with various olefins as coupling partners at 140 degrees C within very short reaction times and low catalyst loadings. Increased reaction temperatures also enable the efficient coupling of olefins with electronically deactivated and sterically hindered aryl chlorides in the presence of only 0.01 mol % of catalyst. The mechanistic studies performed rule out that homogeneous Pd 0 complexes are the catalytically active forms of 1 and 2. On the other hand, the involvement of palladium nanoparticles in the catalytic cycle received strong experimental support. Even though pincer-type Pd IV intermediates derived from 1 (and 2) are not involved in the catalytic cycle of the Heck reaction, their general existence as reactive intermediates (for example, in other reactions) cannot be excluded. On the contrary, they were shown to be thermally accessible. Compounds 1 and 2 show a smooth halide exchange with bromobenzene to yield their bromo derivatives in DMF at 100 degrees C. Experimental observations revealed that the halide exchange most probably proceeded via pincer-type Pd IV intermediates. DFT calculations support this hypothesis and indicated that aminophosphine-based pincer-type Pd IV intermediates are generally to be considered as reactive intermediates in reactions with aryl halides performed at elevated temperatures.

Electrophilic ipso-cyclization of N-(p-methoxyaryl)propiolamides involving an electrophile-exchange process.

Abstract: A novel electrophilic ipso-cyclization involving an electrophile-exchange process has been developed. In the presence of CuX (X = I, Br, SCN) and electrophilic fluoride reagents, a variety of N-(p-methoxyaryl)propiolamides and 4-methoxyphenyl 3-phenylpropiolate were cyclized to selectively afford the corresponding spiro[4.5]decenones in moderate to good yields. It is noteworthy that two azaquaternary tricyclic products were synthesized through a two-step pathway involving an electrophilic ipso-cyclization and then an intramolecular Heck reaction.

Suzuki- and Heck-Type Cross-Coupling with Palladium Nanoparticles Immobilized on Spherical Polyelectrolyte Brushes

Abstract: Received: August 28, 2007; Revised: December 4, 2007; Published online: February 8, 2008Abstract:We report on a systematic study of the useof palladium nanoparticlesimmobilized on sphericalpolyelectrolyte brushes – Pd@SPB – for Heck- andSuzuki-type coupling reactions. The spherical poly-electrolyte brush particles serving as carriers for thepalladium nanoparticles consist of a solid polystyrenecore with a radiusof 46nm onto which long chainsof cationic polyelectrolytesare grafted. The palladi-um nanoparticleshave directly been generatedwithin this brush layer and the stabilization of thenanoparticlesiseffected by the colloidal carriers, nofurther surface stabilization is necessary. We demon-strate that these composite particles present robustcatalysts for the Heck- and Suzuki-type coupling re-actions. This was shown by carrying out the Suzuki-and Heck-type coupling reactionsat relatively lowtemperatures(Suzuki reaction: 508C, Heck reaction:708C). We demonstrate that the catalytic compositeparticlesare not changed by these reaction condi-tionsand retain their full activity for at least fourruns. The yields obtained for both reactions are goodto excellent. The mild operation conditionsof thepalladium nanoparticlesare traced back to the ab-sence of surface stabilization. Further mechanisticimplications are discussed.Keywords:catalysis; Heck-type cross-coupling; palla-dium nanoparticles; spherical polyelectrolyte brush;Suzuki-type cross-coupling

Palladium(0) nanoparticles stabilized by phosphorus dendrimers containing coordinating 15-membered triolefinic macrocycles in periphery.

Abstract: A new family of phosphorus dendrimers containing on their surfaces 3, 6, 12, and 96 15-membered azamacrocycles has been synthesized. The coordinating ability of these macrocycles to palladium(0) atoms allowed the preparation of new dendrimers of several generations containing the corresponding metal complexes and several new nanoparticulated materials, where nanoparticles are stabilized mainly by the complexed dendrimers of the zero, first, and fourth generations. No reduction process of palladium(II) salts was needed to prepare nanoparticles of 2.5-7.9 nm diameter. All the new compounds and materials have been characterized by NMR, IR, elemental analysis and/or matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) spectrometry, high-resolution transmission electron microscopy, and electron diffraction. Also UV-vis spectra were obtained. The Mizoroki-Heck reaction has been catalyzed in a homogeneous and heterogeneous manner by using four different materials; in all cases, the catalyst could be recovered and reused several times.

A Simple and Efficient Route to Active and Dispersed Silica Supported Palladium Nanoparticles

Abstract: Various mesoporous silica supported Pd materials were prepared by different methodologies in order to control and optimize the metal nanoparticle sizes for catalytic applications. The catalytic activities (conversion, mol% and selectivity to methyl-cinnamate) of the supported palladium catalysts were investigated in the Heck reaction under microwave irradiation using various haloarenes. Pd materials prepared by co-precipitation exhibited a very poor activity in the Heck reaction compared to that of Pd impregnated samples. Impregnated materials prepared without the use of a specific reducing agent had comparable activities to those of APTS-NaBH4 reduced Pd materials, validating the simplicity of the methodology. High selectivities to methylcinnamate were obtained for all materials.

Density functional studies on palladium-catalyzed Suzuki-Miyaura cross-coupling reactions assisted by N- or P-chelating ligands

Abstract: DFT studies with the B3LYP functional have been carried out on the Suzuki-Miyaura cross-coupling reactions of phenyl chloride and phenylboronic acid catalyzed by palladium complexes with N- or P-chelating ligands. The full catalytic cycle, from the addition of reactants to the catalyst to the release of the cross-coupled product from the complexed intermediate, has been examined. The stages within the cycle, such as oxidative addition, transmetalation, and reductive elimination, were validated by linking the mechanistically relevant intermediates and transition states. Various derivatives of diimine, diphosphine, and diamine were considered as potential model ligands. The catalytic reaction employing diimine as the chelating ligand has been verified as the one with the most energetically feasible route.

First Pd@Organo−Si(HIPE) Open-Cell Hybrid Monoliths Generation Offering Cycling Heck Catalysis Reactions

Abstract: The syntheses and characterization of a new class of grafted organo−Si(HIPE) “high internal phase emulsion” open-cell matrixes is first proposed. Second, internal palladium particles heterogeneous nucleation is briefly discussed, leading finally to the generation of the new Pd@organo−Si(HIPE) series. The matrixes synthesized offer good turnovers and cycling performances For instance, the Pd@mercapto−Si(HIPE) matrix allows reaching at least 96% of Heck coupling catalysis yield during seven cycling tests. The Pd/iodobenzene molar ratio was settled at 0.004 and 0.002. The turnover number (TON) and turnover frequency (TOF) addressed with these new monolith catalysts are reaching values comparable with the ones obtained with powdered catalysts. Considering the fact that the catalysts in use are not powders but rather monoliths bearing hierarchical porosities, the series of Pd@organo−Si(HIPE) compounds combine heterogeneous catalysis efficiency and facile reusability where catalyzed species and catalyst support...