Ionic Liquid-Promoted, Highly Regioselective Heck Arylation of Electron-Rich Olefins by Aryl Halides (original) (raw)
Related papers
Journal of Organometallic Chemistry, 2005
Palladium-catalyzed Heck reactions of the heteroaryl halides, halopyridines, bromoquinoline and bromothiophenes, with the electron-rich olefins vinyl ethers and allyl alcohol were shown to give essentially only the branched olefins in an imidazolium ionic liquid, whereas in molecular solvents a mixture of regioisomers was formed. The method obviates the need for aryl triflates and stoichiometric inorganic salt additives, providing an easy entry to functionalized heteroaromatics incorporating acetyl and 2-allyl alcohol functionalities.
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.
Journal of Molecular …, 2007
γ-Arylated γ,δ-unsaturated ketones have been prepared in good to excellent yields via the Pd-catalyzed Heck arylation of an electron-rich olefin, 5-hexen-2-one (1), with aryl bromides (2a-2l) in the ionic liquid [bmim][BF 4 ]. The reaction is highly regioselective, leading predominantly to branched, γ-arylated products with Pd-DPPP [DPPP = 1,3-bis(diphenylphosphino)propane] catalysis. However, the choice of ligand is found to be crucial for regiocontrol; a change of ligand from DPPP to 1,1-bis(diphenylphosphino)ferrocene (DPPF) affords predominantly the (E)-type, δ-arylated γ,δ-unsaturated ketones. The method is simple, effective, and applicable to the coupling of both electron-rich and electron-deficient aryl bromides with no need for any halide scavengers.
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
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.
The Journal of Organic Chemistry, 2009
Highly regioselective vinylation of electron-rich olefins by bromo-as well as chlorostyrenes is effected by palladium catalysis with either mono-or bidentate phosphines in a molecular solvent, with no need for halide scavengers, ionic liquids, or ionic additives. The use of the hemilabile 1,3-bis(diphenylphosphino)propane monoxide (dpppO) as a ligand led to faster reactions of more challenging 2-substituted vinyl ethers and reduced Pd loadings. In contrast to the related arylation reaction, evidence suggests that the vinylation may proceed via the neutral Heck mechanism.
Journal of Molecular …, 2008
Regioselective Heck arylation of ␣-substituted allylic alcohols by aryl bromides was achieved by Pd-DPPP catalysis in ionic liquids, affording a /␥ ratio of up to 78/22 in the case of the coupling of 1-bromonaphthalene with but-1-en-3-ol. In addition to the effects of both ligands and reaction media, the regiocontrol toward the formation of branched products was significantly affected by the steric properties of allylic alcohols; with the increasing bulkiness of the substituent on allylic alcohol, the /␥ regioselectivity decreased. For comparison, arylation by aryl triflates in a molecular solvent was also demonstrated, which showed the same trend in regioselectivity.
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%.
Journal of the Brazilian Chemical Society, 2010
Novos líquidos iônicos aquirais e quirais foram preparados utilizando-se rotas sintéticas inéditas e/ou otimizadas. Estas séries de líquidos iônicos do tipo imidazolínico, imidazólico e piridínico foram totalmente caracterizadas, incluindo-se análises por calorimetria diferencial de varredura (DSC). O desempenho desses líquidos iônicos (LIs) foi demonstrado empregando-se a arilação de Heck de aza-acrilato endocíclicos com sais de arenodiazônio ou iodetos de arila. As arilações de Heck realizadas na presença destas entidades iônicas quirais, seja como um solvente ou um aditivo, foram eficazes levando à completa conversão do substrato, em bons a excelentes rendimentos do aduto de Heck na maioria dos casos, apesar de não ser observada indução assimétrica em nenhum dos casos estudados. Dois novos complexos quirais de paládio do tipo carbeno N-heterocíclico foram preparados em bons rendimentos a partir de um sal imidazólico quiral e suas estruturas caracterizadas por difração de raios-X. De modo geral, a arilação de Heck empregando tetrafluoroboratos de arenodiazônio em líquidos iônicos demonstrou ser mais eficiente do que os protocolos tradicionais em termos de reatividade e rendimentos de reação. New achiral and chiral RTILs were prepared using novel and/or optimized synthetic routes. These new series of imidazolinium, imidazolium, pyridinium and nicotine-derived ionic liquids were fully characterized including differential scanning calorimetry (DSC) analysis. The performance of these achiral and chiral room temperature ionic liquids (RTILs) was demonstrated by means of the Heck arylation of endocyclic acrylates employing arenediazonium salts and aryl iodides. The Heck arylations performed in the presence of these ionic entities, either as a solvent or as an additive, were effective leading to complete conversion of the substrate and good to excellent yield of the Heck adduct. In spite of the good performances, no asymmetric induction was observed in any of the cases studied. Two new diastereoisomeric NHC-palladium complexes were prepared in good yields from a chiral imidazolium salt and their structure characterized by X-ray diffraction. Overall, the Heck arylations employing arenediazonium tetrafluoroborates in RTILs were more effective than the traditional protocols employing aryl iodides in terms of reactivity and yields.