Three-Component Interrupted Radical Heck/Allylic Substitution Cascade Involving Unactivated Alkyl Bromides (original) (raw)
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Journal of Organometallic Chemistry, 1999
The palladium-catalyzed arylation and alkenylation of alkenes, generally called the Heck reaction, has been applied to a number of new concepts. Starting from simple, oligohalogenated alkenes and arenes, the synthesis of a variety of highly functionalized carbon skeletons has been established. The domino-type combination of an intramolecular Heck with an inter-or intramolecular Diels-Alder reaction has been shown to provide facile access to interesting bicyclic and tetracyclic frameworks. While intramolecular Heck reactions on trisubstituted, cyclopropylidene-terminated alkenes proceeded with retention of the cyclopropyl moiety, tetrasubstituted alkenes with methylenecyclopropane end groups reacted with ring opening to yield cross-conjugated trienes. The study of the palladium-catalyzed oligocyclizations of 2-bromoalka-1,(v-1)-diene-n-ynes has revealed interesting and useful systematics as to achievable ring size combinations and skeletal types. Highly functionalized methylenecyclopropanes are conveniently accessible via palladium-catalyzed allylic substitution reactions of 1-ethenylcyclopropyl sulfonates and chlorides as well as cyclopropylideneethyl esters which proceed with complete regioselectivity in most cases.
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
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.
The Journal of Organic Chemistry
Nitroalkanes undergo decarboxylative allylation in the presence of vinyl-substituted cyclic carbonates providing a wide variety of functionalized homoallylated compounds with exquisite stereocontrol. This Pd-mediated procedure features operational simplicity, versatile substrate combinations and also allows for the sequential introduction of different allyl groups in the nitroalkane scaffolds with high levels of stereocontrol through the intermediacy of a (Z)-configured palladacyclic intermediate. As far as we know, the developed protocol is the first general Pd-mediated methodology towards (Z)-configured homoallylic nitroalkanes with attractive functional group diversity. ∎ RESULTS AND DISCUSSION Screening Studies. Various conditions were screened towards the formation of the targeted (Z)-product 3a taking vinyl cyclic carbonate 1a and nitroethane as benchmark substrates. The nature of the Pd precursor, ligand, solvent, relative amount of nitroethane and catalyst loading were optimized (see Table 1 and Tables S1-S5, see the Supporting Information: SI). The optimized conditions reported in Table 1 gave the best NMR yield (Table 1, entry 1; 85%, isolated 50%) 14 and stereoselectivity (Z/E>99:1) of homoallylic nitroalkane product 3a. The presence of other Pd-precursors, solvents or ligands (Table 1, entries 29) gave inferior results in terms of yield and/or stereocontrol, and are not discussed in detail here. Scheme 2. Variation of Nitroalkane Reagent to afford Homoallylic Compounds 3a-3q Scheme 4. Stereoselective Synthesis of Mono-, Bis-and Trisallylated Compounds.
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%.
A unique Pd-catalysed Heck arylation as a remote trigger for cyclopropane selective ring-opening
Combining functionalization at a distant position from a reactive site with the creation of several consecutive stereogenic centres, including the formation of a quaternary carbon stereocentre, in acyclic system represents a pinnacle in organic synthesis. Here we report the regioselective Heck arylation of terminal olefins as a distant trigger for the ring-opening of cyclopropanes. This Pd-catalysed unfolding of the strained cycle, driving force of the chain-walking process, remarkably proved its efficiency and versatility, as the reaction proceeded regardless of the molecular distance between the initiation (double bond) and termination (alcohol) sites. Moreover, employing stereodefined polysubstituted cyclopropane vaults allowed to access sophisticated stereoenriched acyclic scaffolds in good yields. Conceptually, we demonstrated that merging catalytically a chain walking process with a selective C–C bond cleavage represents a powerful approach to construct linear skeleton possessing two stereogenic centres.