Showing papers on "Heck reaction published in 2012"

Imparting Catalyst-Control upon Classical Palladium-Catalyzed Alkenyl C–H Bond Functionalization Reactions

Abstract: The functional group transformations carried out by the palladium-catalyzed Wacker and Heck reactions are radically different, but they are both alkenyl C–H bond functionalization reactions that have found extensive use in organic synthesis. The synthetic community depends heavily on these important reactions, but selectivity issues arising from control by the substrate, rather than control by the catalyst, have prevented the realization of their full potential. Because of important similarities in the respective selectivity-determining nucleopalladation and β-hydride elimination steps of these processes, we posit that the mechanistic insight garnered through the development of one of these catalytic reactions may be applied to the other. In this Account, we detail our efforts to develop catalyst-controlled variants of both the Wacker oxidation and the Heck reaction to address synthetic limitations and provide mechanistic insight into the underlying organometallic processes of these reactions.In contrast ...

Magnetic Nanoparticles-Supported Palladium: A Highly Efficient and Reusable Catalyst for the Suzuki, Sonogashira, and Heck Reactions

Abstract: A highly efficient, air- and moisture-stable and easily recoverable magnetic nanoparticle-supported palladium catalyst has been developed for the Suzuki, Sonogashira and Heck reactions. A wide range of substrates was coupled successfully under aerobic conditions. In particular, the performance of the magnetic separation of the catalyst was very efficient, and it is possible to recover and reuse it at least eight times without significant loss of its catalytic activity.

Copper-catalyzed alkene arylation with diaryliodonium salts.

Abstract: Alkenes and arenes represent two classes of feedstock compounds whose union has fundamental importance to synthetic organic chemistry. We report a new approach to alkene arylation using diaryliodonium salts and Cu catalysis. Using a range of simple alkenes, we have shown that the product outcomes differ significantly from those commonly obtained by the Heck reaction. We have used these insights to develop a number of new tandem and cascade reactions that transform readily available alkenes into complex arylated products that may have broad applications in chemical synthesis.

Mild and efficient nickel-catalyzed Heck reactions with electron-rich olefins.

Abstract: A new efficient protocol for the nickel-catalyzed Heck reaction of aryl triflates with vinyl ethers is presented. Mild reaction conditions that equal those of the corresponding palladium-catalyzed Heck reaction are applied, representing a practical and more sustainable alternative to the conventional regioselective arylation of vinyl ethers. A catalytic system comprised of Ni(COD)2 and 1,1′-bis(diphenylphosphino)ferrocene (DPPF) in combination with the tertiary amine Cy2NMe proved effective in the olefination of a wide range of aryl triflates. Both electron-deficient and electron-rich arenes proved compatible, and the corresponding aryl methyl ketone could be secured after hydrolysis in yields approaching quantitative. Good functional group tolerance was observed matching the characteristics of the analogous Pd-catalyzed Heck reaction. The high levels of catalytic activity were explained by the intermediacy of a cationic nickel(II) complex potentially responsible for the successive β-hydride elimination a...

Catalyst-controlled regioselectivity in the synthesis of branched conjugated dienes via aerobic oxidative Heck reactions.

Abstract: Pd-catalyzed aerobic oxidative coupling of vinylboronic acids and electronically unbiased alkyl olefins provides regioselective access to 1,3-disubstituted conjugated dienes. Catalyst-controlled regioselectivity is achieved by using 2,9-dimethylphenanthroline as a ligand. The observed regioselectivity is opposite to that observed from a traditional (nonoxidative) Heck reaction between a vinyl bromide and an alkene. DFT computational studies reveal that steric effects of the 2,9-dimethylphenanthroline ligand promote C–C bond formation at the internal position of the alkene.

Preparation of Allyl and Vinyl Silanes by the Palladium‐Catalyzed Silylation of Terminal Olefins: A Silyl‐Heck Reaction

Abstract: A high-yielding protocol for the palladium-catalyzed silylation of terminal alkenes using silyl halides is reported. This method allows facile conversion of styrenes to E-β-silyl styrenes using either TMSI or TMSCl/LiI. Terminal allyl silanes with good E:Z ratios are also readily accessed from α-olefins by this method. When combined with existing technology, this transformation provides a powerful strategy to selectively functionalize the vinyl or allylic position of terminal alkenes.

Brønsted Acid Catalyzed Asymmetric Propargylation of Aldehydes

Abstract: Enantiomerically pure homopropargylic alcohols are highly useful intermediates, with broad synthetic utility. The terminal alkyne functionality serves as a synthetic handle for cross-coupling, metathesis, and heterocycle synthesis.[1] The addition of allenic or propargylic reagents to carbonyl compounds is mechanistically similar to the analogous reaction with allylic reagents. Though many useful and innovative methods exist for the synthesis of homoallylic alcohols,[2] the enantio-selective synthesis of homopropargylic alcohols remains arduous. Two main complications are 1) the lower reactivity of the allenylic and propargylic substrates in comparison to allylic substrates, and 2) the difficulties associated with controlling the reaction regioselectivity.[3] Herein, we describe a highly enantioselective catalytic method for the preparation of homopropargylic alcohols. Computational studies of the reaction provide insight into the catalysis and stereochemistry of the reaction. Many current methods for enantioselective propargylation reactions rely upon the use of chiral reagents.[4] Alternative catalytic methods have been developed, but are limited to the use of allenylic or propargylic metal-based reagents or intermediates.[2a,5] Despite notable work, many of these methods are restricted by one or more limitations. Among them are 1) the use of reagents that are relatively difficult to prepare or are unstable to air and/or moisture, 2) the use of undesirable metal reagents or catalysts, and 3) regioselectivity concerns. In the past decade, Lewis and Bronsted acid-catalyzed allylboration reactions have fascinated the synthetic community.[6,7] However, this methodology remains relatively undeveloped for the more challenging allenylboration of aldehydes. Following our recent report on the development of a chiral phosphoric acid-catalyzed allylboration,[7] we examined the extension of our methodology to the enantioselective propargylation of aldehydes. We began our investigation with the reaction of benzaldehyde and allenyl boronic acid pinacol ester. Boronate 2 is a relatively stable, non-toxic and commercially available reagent. The C–C bond formation proceeded smoothly in the presence of various chiral acid catalysts,[8] with complete control over the regioselectivity (Table 1). PA5[9] afforded product 3 with the highest enantio-selectivity, when toluene was used as the reaction solvent. An increase to 87% ee was seen with the use of higher catalyst loading, in the presence of 4A M.S. (entry 13). The enantio-selectivity could be further increased, when the reaction was conducted at lower reaction temperatures of 0°C (entry 14) and −20°C (entry 15), albeit with longer reaction times. Table 1 Catalyst screening and optimization for the propargylation of benzaldehyde.[a] With the optimized conditions in hand,[10] a variety of aldehydes with different electronic and steric properties were tested to study the scope and limitation of the developed methodology (Table 2). The reaction proved tolerant to electron-donating and electron-withdrawing groups (1a–1j), giving excellent yields and enantioselectivities (92–96% ee). The methodology was extended to aliphatic aldehydes (1k–1m), furnishing the corresponding homopropargylic alcohol products 3k–m in 77–82% ee. Table 2 Enantioselective propargylation of aldehydes.[a] We prepared several important synthetic scaffolds, previously unavailable from enantioenriched homopropargylic alcohols (Scheme 1). Chiral dihydrofuran-3-ones, such as 4, are important building blocks[11] for the synthesis of biologically active compounds. Despite their importance, a general enantioselective synthesis for this class of molecule has yet to be reported. We successfully transformed 3a[12] into dihydrofuran-3-one 4, by employing gold-catalyzed reaction methodology developed by Zhang and co-workers,[13] with complete preservation of the enantiomeric excess. Crabbe homologation of 3a provided optically active 3,4-allenol 5, which has the potential to serve as a substrate in natural product synthesis.[14] Chiral dihydrofuran 6, currently dependent on the Heck reaction for its synthesis,[15] was obtained through a molybdenum-mediated cycloisomerization of 3a, based on methodology developed by McDonald and co-workers.[16] Scheme 1 Synthesis of important chiral moieties. It is our belief that the propargylation proceeds through a six-membered cyclic transition state, where catalyst activation operates by hydrogen-bonding of the boronate oxygen. To further understand the mechanism and stereoselectivity of this phosphoric acid-catalyzed propargylation reaction, we performed theoretical calculations. Calculated energies of different pathways for allylboration[17] and propargylation showed that Bronsted acids form a strong hydrogen bond with the pseudo-equatorial oxygen of the allenyl boronate.[18] A computed transition state structure involving protonation is shown in Figure 1. Figure 1 Transition state structure for the Bronsted acid-catalyzed propargylation reaction. To explore the origins of the enantioselectivity, we studied the transition state structures for the propargylation reaction, where the phosphoric acid catalyst activates the pseudo-equatorial oxygen of the allenyl boronate. Biphenol(bipol)-derived phosphoric acid was used as the model, in place of the fully derived binol phosphoric acid, to reduce the computational time. Catalyst PA5, bearing a 2,4,6-triisopropylphenyl group at the 3,3′-positions, provides high experimental enantioselectivity. Thus, the diastereomeric transition states of the re-face and si-face attack involving the bipol model of PA5 were compared. Transition states TSr1 and TSs1 are represented in Figure 2. Re-face attack (TSr1) is predicted to be more favored than si-face attack (TSs1) by 1.3 kcalmol−1. This is in agreement with the 74% ee obtained experimentally. Figure 2 Optimized structures of TSr1 and TSs1. Relative energies (kcal mol−1) are shown in parentheses. Figure 2 shows a lack of obvious steric differences in the transition states. H–H distances are 2.4 A or more. However, the distortion of the catalyst is larger in TSs1 than in TSr1 by about 1.2 kcalmol−1. This distortion relieves steric repulsions that would otherwise occur. The preference for re-facial selectivity is therefore the result of the larger distortion of the catalyst–boronate complex in TSs1. The origins of the differences in distortion energies of the catalyst–boronate complex in the two TSs can be visualized from geometries of the catalyst in the TSs. Figure 3a shows the catalyst–boronate complex structure in TSr1. Here, the dioxaborolane ring has no significant steric interaction with the catalyst, and the dihedral angle between the 2,4,6-triisopropylphenyl substituent and the bipol core is 74°, almost the same as the dihedral angle of 72° in the optimized catalyst. Figure 3b shows the catalyst–boronate complex structure in TSs1, with the dioxaborolane ring on the left. The methyl groups (circled in Figure 3b) of the dioxaborolane ring and the isopropyl groups of the catalyst (circled in Figure 3b) are close to each other. In order to minimize such steric repulsions, the 2,4,6-triisopropylphenyl substituent is rotated around the bond to the bipol phenyl core with a dihedral angle of 78°. This is a 6° rotation away from the dihedral angle in the optimized catalyst (72°). The asymmetric induction can be rationalized by differences in distortion energies originating from the steric interactions between the substrates and the bulky 3,3′-substituents on the catalyst. Figure 3 a) 3D structure of TSr1 without benzaldehyde. b) 3D structure of TSs1 without benzaldehyde. For other catalysts screened experimentally, calculations showed the absence of an energy difference between re- and si-attack diastereomeric transition states, suggesting why these catalysts gave low enantioselectivities. In summary, we have developed the first Bronsted acid-catalyzed propargylation of aldehydes, for the synthesis of chiral homopropargylic alcohols. The reaction is simple and highly efficient, demonstrating broad synthetic utility. Mechanistic studies show the catalyst activating the reaction by forming a strong hydrogen bond with the pseudo-equatorial oxygen of the boronate. The high enantioselectivity obtained with catalyst PA5 originates from steric interactions between the methyl groups of the allenylboronate, the bulky catalyst substituents, and the resulting distortion of the catalyst.

Palladium-catalyzed oxidative Heck coupling reaction for direct synthesis of 4-arylcoumarins using coumarins and arylboronic acids.

Abstract: An efficient protocol for the direct synthesis of 4-arylcoumarins via palladium-catalyzed oxidative Heck coupling reaction of coumarins and arylboronic acids was developed. 4-Arylcoumarins were obtained in moderate to excellent yields, and the reaction also showed tolerance toward functional groups such as hydro, methoxy, diethylamino, nitro, and chloro groups.

A Mild, Palladium-Catalyzed Method for the Dehydrohalogenation of Alkyl Bromides: Synthetic and Mechanistic Studies

Abstract: We have exploited a typically undesired elementary step in cross-coupling reactions, β-hydride elimination, to accomplish palladium-catalyzed dehydrohalogenations of alkyl bromides to form terminal olefins. We have applied this method, which proceeds in excellent yield at room temperature in the presence of a variety of functional groups, to a formal total synthesis of (R)-mevalonolactone. Our mechanistic studies have established that the rate-determining step can vary with the structure of the alkyl bromide and, most significantly, that L(2)PdHBr (L = phosphine), an intermediate that is often invoked in palladium-catalyzed processes such as the Heck reaction, is not an intermediate in the active catalytic cycle.

Bacteria Cellulose Nanofibers Supported Palladium(0) Nanocomposite and Its Catalysis Evaluation in Heck Reaction

Abstract: Bacteria cellulose (BC) nanofibers supported palladium(0) nanocomposites were prepared and fully characterized in terms of morphology, crystallinity, composition, and thermal stability. The as-prepared catalyst was further successfully explored in Heck coupling reaction between aryl halide and styrene or acrylates, with a yield over 86–96% for the first coupling reaction. With coupling yields decreased less than 10% for the fifth reaction cycle, Pd/BC catalyst exhibits great potential as recyclable catalyst for Heck coupling.

Organochalcogen ligands and their palladium(ii) complexes: Synthesis to catalytic activity for Heck coupling

Abstract: Heck cross coupling reactions have been catalyzed with several palladium(II)-complexes of organochalcogen ligands. The complexes applied in molecular and tethered forms appear to be dispensers of catalytically active species, but this aspect has not been thoroughly looked at in all cases. The thermal stability, air and moisture insensitivity and ease of handling and synthesis have made them viable alternatives to phosphine/carbene based Pd-catalysts. This review covers developments from the design of organochalcogen ligands and their palladium(II)-complexes to the applications of these complexes in catalyzing Heck reactions.

Palladium nano-particles supported on agarose as efficient catalyst and bioorganic ligand for CC bond formation via solventless Mizoroki–Heck reaction and Sonogashira–Hagihara reaction in polyethylene glycol (PEG 400)

Abstract: In this study, abundant naturally occurring agarose has been used as a support and ligand for palladium nanoparticles. In the presence of this catalytic system, Mizoroki–Heck and Sonogashira–Hagihara coupling reactions were performed successfully. The catalyst exhibits high activity in Mizoroki–Heck reaction under phosphane and solvent-free conditions for the reaction of iodo- and bromoarenes with butyl acrylate and styrene. This catalytic system also showed high catalytic activity for Sonogashira–Hagihara coupling reaction of various aryl halides (I, Br, Cl) under copper and ligand-free conditions in polyethylene glycol (PEG 400) as an ecofriendly and non-poisonous media. The catalyst can be separated from the reaction mixture and reused for the similar batches of the reaction. High efficiency of the catalyst along with its recycling ability and the rather low Pd-loading which are demonstrated in both Mizoroki–Heck and Sonogashira–Hagihara reactions are the merits of the presented catalyst system.

Palladium Nanoparticles Supported on Mixed-Linker Metal–Organic Frameworks as Highly Active Catalysts for Heck Reactions

Abstract: Well-dispersed palladium nanoparticles (Pd NPs) supported on amine-functionalized, mixed-linker metal–organic frameworks (MIXMOFs) based on MIL-53(Al) were prepared by using the ion-exchange method. Pd NPs were characterized by powder X-ray diffraction (XRD), N2 adsorption, transmission electron microscopy (TEM), inductively coupled plasma atomic emission spectroscopy (ICP-AES), and X-ray photoelectron spectroscopy (XPS). The mean diameter of Pd NPs is approximately 3.2 nm. It was found that the Pd NPs supported on amine-functionalized MIXMOFs are stable at high temperature. The Pd NPs exhibit efficient catalytic activity for Heck reaction and can be easily recovered and reused.

Palladium-catalyzed, asymmetric Mizoroki–Heck reaction of benzylic electrophiles using phosphoramidites as chiral ligands

Abstract: We report herein the first examples of asymmetric Mizoroki–Heck reactions using benzyl electrophiles. A new phosphoramidite was identified to be an effective chiral ligand in the palladium–catalyzed reaction. The reaction is compatible with polar functional groups and can be readily scaled up. Several cyclic olefins worked well as olefin components. Thirty-one examples are included.

Total synthesis of cyrneine A.

Abstract: Keywords: cross-coupling ; natural products ; neurochemistry ; stereoselective synthesis ; total synthesis ; Ring Enlargement Reaction ; Asymmetric-Synthesis ; Tricyclic Core ; Cyathin Diterpenoids ; Heck Reaction ; Intermediate ; Cyclization Reference EPFL-ARTICLE-177265doi:10.1002/anie.201200515View record in Web of Science Record created on 2012-05-18, modified on 2017-05-12