Ni-catalysed regioselective 1,2-diarylation of unactivated olefins by stabilizing Heck intermediates as pyridylsilyl-coordinated transient metallacycles (original) (raw)
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Journal of the American Chemical Society, 2017
We disclose a strategy for Ni-catalyzed regioselective dicarbofunctionalization of olefins in styrene derivatives by intercepting Heck C(sp 3)-NiX intermediates with arylzinc reagents. This approach utilizes a readily removable imine as a coordinating group that plays a dual role of intercepting oxidative addition species derived from aryl halides and triflates to promote Heck carbometallation, and stabilizing the Heck C(sp 3)-NiX intermediates as transient metallacycles to suppress -hydride elimination and facilitate transmetalation/reductive elimination steps.
Chemistry (Weinheim an der Bergstrasse, Germany), 2018
Highly diastereo and enantioselective non-covalent substrate directable Heck desymmetrizations of cyclopentenyl olefins bearing hydroxymethyl and carboxylate functional groups are presented. These conformationally unbiased cyclic olefins underwent effective arylations in yields of up to 97%, diastereoselectivity up to >20:1, and enantiomeric excesses of up to 99%. Non-covalent directing effects were shown to be present in Heck-Matsuda and oxidative Heck reactions allowing the preferential formation of cis-substituted aryl cyclopentenes containing two stereocenters, including quaternary stereocenters. These results validate the internal out-of-coordination-sphere ion-dipole interaction concept directing the reaction diasteroselectivity to the cis-Heck product. This approach is complementary to existing methods using bisphosphine monoxide giving the opposite trans-diastereoisomer. The applicability of the method is showcased by a straightforward synthesis of a potent phosphodiester...
Organic letters, 2017
We disclose a Pd-catalyzed reaction protocol that regioselectively difunctionalizes unactivated olefins with aryl iodides and tethered enolates. The current method allows the rapid synthesis of a variety of 1,3,4-trisubstituted pyrrolidinones from simple and readily available amides. We further demonstrate this new method's application by postsynthetically modifying the arylacetic acid side chains of two commercial nonsteroidal anti-inflammatory drugs, indomethacin and tolmetin, to highly decorated 4-benzylpyrrolidinone frameworks. Mechanistic studies reveal that the reaction proceeds via a Heck reaction/enolate cyclization cascade, a process that exploits β-H elimination in a constructive mode for regioselective 1,2-difunctionalization of unactivated olefins.
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%.
Advanced Synthesis & Catalysis, 2012
Aryl alcohols are employed as feedstock for the Heck reaction. Keggin-type heteropolyacids catalyse the selective dehydration of the alcohols to styrenes, which, in one-pot, undergo palladium-catalysed Heck arylation with aryl bromides, affording broadly functionalised stilbenes. The choice of solvent is critical for the cascade dehydration-Heck reaction, with electron-rich aryl alcohols preferring a basic medium while electron-deficient ones demanding solvents of lower basicity.
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.
Developing efficient and selective strategies to approach complex architectures containing (multi-)stereogenic centers has been a long-standing synthetic challenge in both academia and industry. Catalytic cascade reactions represent a powerful means of rapidly leveraging molecular complexity from simple feedstocks. Unfortunately, carrying-out cascade Heck-type reactions involving unactivated (tertiary) alkyl halides remains an unmet challenge owing to unavoidable βhydride elimination. Herein, we show that a modular, practical and general palladium catalyzed, radical three-component coupling can indeed overcome the aforementioned limitations through an interrupted Heck/allylic substitution sequence mediated by visible light. Selective 1,4-difunctionalization of unactivated 1,3-dienes, such as butadiene, has been achieved by employing different commercially available nitrogen-, oxygen-, sulfur-or carbon-based nucleophiles and unactivated alkyl bromides (>130 examples, mostly >95:5 E/Z, >20:1 rr). Sequential C(sp 3)-C(sp 3) and C-X (N, O, S) bonds have been constructed efficiently with a broad scope and high functional group tolerance. The flexibility and versatility of the strategy has been illustrated in a gram-scale reaction and streamlined syntheses of complex ether, sulfone and tertiary amine products, some of which would be difficult to access via currently established methods.