Regioselective Heck Vinylation of Electron-Rich Olefins with Vinyl Halides: Is the Neutral Pathway in Operation? (original) (raw)
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Terminal Heck Vinylations of Chelating Vinyl Ethers
Advanced Synthesis & Catalysis, 2004
Terminal chelation-controlled Heck vinylations of electron-rich amino-functionalized vinyl ethers were performed with high regioselectivity furnishing moderate to good isolated yields of the corresponding 1-alkoxy-1,3-butadienes. DFT calculations support an amine-palladium(II) coordination strength reactivity/selectivity rationale, where the dimethylamino group was the preferred metal presenting functionality. Controlled microwave heating effectively accelerated these palladium-catalyzed reactions and full conversion could be achieved within 30 minutes. Subsequent Diels-Alder reactions with dimethyl acetylenedicarboxylate under microwave irradiation resulted exclusively in partly aromatized bi-and tricyclic compounds by elimination of the aminoalkoxy group. Thus, the selected dimethylamino auxiliary both controlled the regiochemistry in the palladiumcatalyzed vinylation and was easily displaced in the aromatization process.
Chemistry - A European Journal, 2008
FULL PAPER ly commercially unavailable in addition to being base sensitive and thermally labile. It is now generally accepted that the regioselectivity issue exists because there are two competing reaction pathways in the Heck reaction, as illustrated in Scheme 2. [3, 5, 6, 10] The cationic pathway (Scheme 2, pathway A) yields the a product, whereas the neutral pathway (Scheme 2, pathway B) produces the b product. Pathway A has a distinguishing feature compared with pathway B: the former involves halide dissociation from Pd II , whereas the latter features phosphorus dissociation. Given the electrophilic nature of cationic Pd II , pathway A is expected to favour electron-rich olefins. [11] Silver and thallium salts act as halide scavengers, thereby promoting pathway A. Similarly, the lability of the PdÀOTf bond facilitates the formation of the cationic Pd II-olefin species, thus leading to regioselective production of the branched product. [12] It is also apparent that a monodentate phosphorous ligand would favour pathway B, whereas a bidentante ligand would be necessary for pathway A. Recent DFT calculations have given more insight into the mechanisms and show that when following pathway A electron-rich olefins indeed tend to afford the a-arylated olefin, and this is driven primarily by electrostatic and frontier orbital interactions. [13] In fact, the C À C bond forming olefin insertion step may be viewed as an intramolecular nucleophilic attack of the migrating aryl group at the olefin. [13a] More recently, Amatore, Jutand and co-workers showed that isobutyl vinyl ether reacts with
Pd-catalyzed Heck reactions of aryl bromides with 1,2-diarylethenes
Journal of the Brazilian Chemical Society, 2011
Um sistema catalítico composto por Pd(OAc) 2 e P(o-tol) 3 foi aplicado na reação de Heck entre brometos de arila e diariletenos. Utilizando-se K 2 CO 3 como base e DMF como solvente, olefinas triarilsubstituídas foram obtidas com rendimentos de bons a excelentes. Brometos de arila com substituintes eletroretiradores foram menos ativos para a reação de acoplamento Heck e levaram à formação de produto de homoacoplamento em quantidades substanciais, indicando que a adição oxidativa não deve ser a etapa lenta da reação. A presença de substituintes no diarileteno afetou drasticamente a seletividade da reação. Realizou-se também a dupla arilação do estireno, levando diretamente à olefina triarilsubstituída, com rendimento de 73%. A catalytic system composed of Pd(OAc) 2 and P(o-tol) 3 was found to be effective for the Heck reaction of aryl bromides with diarylethylenes. Using K 2 CO 3 as a base and DMF as a solvent, trisubstituted olefins were obtained in good to excellent yields. Aryl bromides containing an electron-withdrawing group in para position were less reactive for the Heck coupling reaction and gave substantial amount of homocoupling by-product suggesting that oxidative addition is not the rate-determining step. Electron withdrawing group substituent in the para position of stilbene affects the regioselectivity of the reaction. In this case, the phenyl group from the Ph-Pd complex migrates preferentially to the same carbon of the double bond to which the phenyl is bonded. Finally, a one pot sequential double Heck arylation of styrene was performed, giving trisubstituted olefin with an overall yield of 73%.
Organic Letters, 2003
r,-Unsaturated acetals afford, in the presence of the LIC−KOR superbase, 1-alkoxybuta-1,3-dienes. These substrates cross couple with aryl derivatives in the presence of Pd catalyst (Heck conditions) in a regio-and stereoselective mode. With dialkyl acetals, the reaction affords arylated dienes; on the other hand, in the case of 1,3-dioxane derivatives, the final outcome of the process formally corresponds to the direct γ-arylation reaction of the starting r,-unsaturated material. Metal-catalyzed coupling reactions are very efficient and reliable procedures for the construction of new carboncarbon bonds. 1 In particular, the Heck reaction has been used extensively over the past three decades for the elaboration of alkenes. 2 The reaction is a straightforward way to achieve substituted alkenes, dienes, and other unsaturated structures, many of which are important intermediates for the preparation of dyes, UV screens, and drugs. 3 Although arylation of two-carbon vinyl fragments might sometimes result in scarcely regioselective reactions, 4,5 highly regioselective R-arylation and R-vinylation procedures have been reported under specific experimental conditions. 6 In particular, 100% regioselective R-functionalization of vinyl ethers can be achieved by favoring the coordination of the Pd complex to
Tetrahedron Letters, 2008
A highly efficient palladium-catalyzed Heck coupling reaction of heteroaryl halides with electron-rich vinyl ether and hydroxyalkyl vinyl ethers is described. It was found that the choice of solvent, ligand, and reaction temperature had a fundamental influence on the regioselectivity and reactivity of the reaction, and the combination of Pd(OAc) 2 and DPPF in ethylene glycol led to the most effective catalytic system. Under these conditions, a variety of heteroaryl halides reacted very quickly with electron-rich olefins to afford exclusively the branched products in good to excellent yields without employing triflates, halide scavengers, or ionic liquids.
Highly efficient Heck olefin arylation in the presence of iminophosphine–palladium(0) complexes
Journal of Molecular Catalysis A: Chemical, 2005
The Heck coupling of aryl bromides with olefins such as styrene or butyl acrylate is efficiently catalysed by the iminophosphine-palladium(0) complex [Pd(dmfu)(P-N)] (dmfu = dimethyl fumarate; P-N = 2-(PPh 2 )C 6 H 4 -1-CH NC 6 H 4 OMe-4) (1) in polar solvents. With activated aryl bromides such as 4-bromoacetophenone turnover numbers of up to 20,000 can be achieved at 140 • C in 2 h. The presence of electron-donating groups leads to decreased reaction rates, nevertheless, high substrate conversions can be obtained in reasonable reaction times. Kinetic studies indicate that complex 1 is only a precursor of the actual catalytic species. Experiments aimed to demonstrate the intervention of metallic palladium did not lead to conclusive findings.
Ionic Liquid-Promoted, Highly Regioselective Heck Arylation of Electron-Rich Olefins by Aryl Halides
Journal of the American Chemical Society, 2005
Palladium-catalyzed regioselective Heck arylation of the electron-rich olefins, vinyl ethers 1ad, enamides 1e-g, and allyltrimethylsilane 1h, has been accomplished in imidazolium ionic liquids with a wide range of aryl bromides and iodides instead of the commonly used, but commercially unavailable and expensive, aryl triflates. The reaction proceeded with high efficiency and remarkable regioselectivity without the need for costly or toxic halide scavengers, leading exclusively to substitution by aryl groups of diverse electronic and steric properties at the olefinic carbon R to the heteroatom of 1a-g and to the heteroatom of 1h. In contrast, the arylation reaction in molecular solvents led to mixtures of regioisomers under similar conditions. Several lines of evidence point to the unique regiocontrol stemming from the ionic environment provided by the ionic liquid that alters the reaction pathway. The chemistry provides a simple, effective method for preparing branched, arylated olefins and contributes to the extension of Heck reaction to a wider range of substrates.
Accounts of Chemical Research, 2011
T he Pd-catalyzed MizorokiÀHeck reaction of olefins with aryl halides, more often simply called the Heck reaction, was recently recognized with the 2010 Nobel Prize in chemistry. Although highly selective with electron-deficient olefins, which generally yield the linear β-arylated product exclusively, the Heck reaction is less satisfactory with electron-rich olefins. This substrate typically generates a mixture of both rand β-arylated regioisomeric products, hampering wider application of the reaction in chemical synthesis. Pioneering studies by a number of researchers revealed that high r-regioselectivity could be obtained under PdÀdiphosphine catalysis either through (i) the substitution of aryl triflates for halides or (ii) the addition of stoichiometric silver or thallium salts when aryl halides are used. Under these conditions, the arylation is believed to proceed via an ionic pathway. However, silver introduces added cost, thallium salts are toxic, and triflates are generally commercially unavailable, base sensitive, and thermally labile. Believing that the ionic pathway would be promoted in an ionic medium, in the early 2000s, we attempted the Pd-catalyzed arylation of the benchmark electron-rich olefin butyl vinyl ether with aryl bromides in an imidazolium ionic liquid. We were delighted to observe that highly regioselective r-arylation could readily be accomplished, with no need for silver additives, thallium additives, or aryl triflates. A range of other electron-rich olefins has since been shown to be viable as well. The high r-selectivity probably results from the high ionic strength of the medium, which facilitates the dissociation of halide anions from the [L 2 Pd(Ar)X] intermediate, channeling the arylation into the ionic pathway. Hydrogen bonding interactions may also play a role, however. We subsequently discovered that the r-arylation can indeed be significantly accelerated by a hydrogen bond donor salt, in both ionic liquids and common solvents. Evidence shows that the concentration of the cationic Pd(II)Àolefin species along the ionic pathway is increased as a result of hydrogen bonding between the hydrogen bond donor and the halide anion. More recently, we reported that cheaper and greener alcohols allow the Heck arylation of electron-rich olefins to proceed in a much faster, productive, and totally r-regioselective manner, circumventing the need for an ionic medium or hydrogen bond donor salt. In particular, aryl chlorides with diverse properties have been demonstrated to be viable substrates for the first time. Significantly, it appears that ethylene glycol facilitates both the oxidative addition of ArCl to Pd(0) and the subsequent dissociation of chloride from Pd(II). A closely related reaction, acylation of aryl halides with aldehydes, was also developed. Proceeding via the intermediacy of an electron-rich enamine, this PdÀpyrrolidine cooperative catalysis affords alkyl aryl ketones in a straightforward manner, extending the Heck reaction from olefins to aldehydes.