Aryl Alkenes Research Articles

Visible Light-Induced Three-Component Alkoxyalkylation of Alkenes with α-Halocarbonyls and Alcohols.

A visible-light-induced three-component alkoxyalkylation of alkenes has been developed under the photocatalysis of fac-Ir(ppy)3. The alkene substrate scope included aryl and aliphatic alkenes as well as electron-rich and electron-deficient alkenes, allowing the facile coupling with a diverse array of α-halocarbonyl compounds. The redox potential-guided orchestration of radical processes with precision allows rapid access to highly functionalized products that are useful building blocks in organic synthesis.

Silver-Mediated Allylation of Aryl Alkenes to Synthesize 1,4-Dienes.

An efficient silver-mediated allylation of aryl alkenes is described, which provides a variety of skipped 1,4-dienes.Without the need for other traditional transition metals or gold, this AgOTf-mediated allylation proceeds smoothly with high regio- and stereoselectivity. Mechanistic and computational studies suggest that this silver-mediated allylation takes place via a Friedel-Crafts-type pathway of aryl alkenes to the silver-activated allyl acetates.

Photocatalytic generation of alkyl carbanions from aryl alkenes

AbstractOrganometallic reagents are routinely used as fundamental building blocks in organic chemistry to rapidly diversify molecular fragments via carbanion intermediates. However, the catalytic generation of carbanion equivalents, particularly from sp3-hybridized alkyl scaffolds, remains an underdeveloped goal in chemical synthesis. Here we disclose an approach for the generation of alkyl carbanions via single-electron reduction of aryl alkenes, enabled by multi-photon photoredox catalysis. We demonstrate that photocatalytically induced alkyl carbanions engage in intermolecular C–C bond-forming reactions with carbonyl electrophiles. Central to this method is the controlled formation of an alkene distonic radical anion intermediate that undergoes nucleophilic addition, followed by a kinetically favoured reductive polar crossover to produce a second carbanion available for further diversification. The versatility of this protocol was illustrated by the development of four distinct intermolecular C–C bond-forming reactions with aromatic alkenes (hydroalkoxylation, hydroamidation, aminoalkylation and carboxyaminoalkylation) to generate a range of valuable and complex scaffolds.

Photoinduced Asymmetric Alkene Aminohetarylation with Chiral Sulfoximine Reagents.

Given the pivotal role of β-(het)arylethylamine moiety in bioactive molecules, the direct amino(het)arylation of alkenes occupies a privileged position in the construction of (het)arylethylamine derivatives. Herein we devise chiral sulfoximines as novel bifunctional reagents which exhibit remarkable efficiency in the challenging asymmetric alkene aminohetarylation reaction, particularly in terms of reactivity and stereo-control. The chiral reagents can be conveniently accessed in gram scale, and efficiently generate N-centered radicals under mild photochemical conditions. The transformation proceeds through enantioselective 1,4-hetaryl migration, ensuring precise chirality transfer from sulfur- to carbon-centers, rendering wide applicability to both aromatic and aliphatic alkenes. Furthermore, the method is straightforward to operate and does not require transition metals or photosensitizers, making it an attractive and practical option.

Nickel‐Catalyzed α‐selective Hydroalkylation of Vinylarenes

AbstractC(sp3) centers adjacent to (hetero) aryl groups are widely present in physiologically active molecules. Metal‐hydride‐catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)−C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel‐hydride‐catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α‐selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand‐free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio‐ and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α‐branched alkylated pyrrole derivatives.

Nickel-Catalyzed α-selective Hydroalkylation of Vinylarenes.

C(sp3) centers adjacent to (hetero) aryl groups are widely present in physiologically active molecules. Metal-hydride-catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)-C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel-hydride-catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α-selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand-free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio- and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α-branched alkylated pyrrole derivatives.

Synthesis of Dinuclear Cobalt Silylene Complexes and Their Catalytic Activity for Alkene Hydrosilylation Reactions.

A novel dinuclear silylene cobalt complex [((Me3P)2Co)(PMe2)(CoCl(PMe3))(Si(NCH2PPh2)2C6H4)] (1) supported by the [PSi(silylene)P] ligand was prepared through the reaction of N-heterocyclic [PSiP] pincer ligand L1 (HSiCl(NCH2PPh2)2C6H4) with Co(PMe3)4. Complex [((Me3P)2Co)2(Si(NCH2PPh2)2C6H4)] (2) was formed through the reaction of complex 1 with MeLi. To the best of our knowledge, complexes 1 and 2 are the first examples of dinuclear silylene cobalt complexes supported by the [PSi(silylene)P] ligand. A new preligand L2 (SiCl2(NCH2PPh2)2C6H4) was synthesized, and the reaction of preligand L2 with Co(PMe3)4 afforded silyl cobalt complex [((Me3P)2Co)(SiCl(NCH2PPh2)2C6H4)] (3). The reaction of 3 with CO delivered cobalt carbonyl complex [((Me3P)(CO)Co)(Si(NCH2PPh2)2C6H4)]2O (4). The catalytic activity of cobalt complexes 1-4 on the hydrosilylation of alkenes was explored. Among the four complexes, complex 1 has the best catalytic activity. The catalytic process could be promoted with NaBHEt3 as an additive, and a complete conversion with an excellent selectivity of 98:2 (b/l) could be reached at 120 °C within 8 min for aryl alkenes. A possible catalytic cycle was proposed on the basis of the experimental results and literature reports, with a cobalt hydride complex as an active intermediate. The molecular structure of complexes 1-4 was determined by single-crystal X-ray diffraction analysis.

1,5-Diaza-3,7-diphosphacyclooctanes (P2N2): An Underappreciated Ligand Class for Nickel- and Palladium-Catalyzed Heck-Type Cross-Couplings

Abstract1,5-Diaza-3,7-diphosphacyclooctane (P2N2) scaffolds represent a readily accessible, tunable ligand class for transition metals. However, despite their prevalence in areas such as electrocatalysis and coordination chemistry, P2N2 ligands have been rarely used to make catalysts for organic synthesis. Research into Mizoroki–Heck-type aldehyde, alcohol, and alkene arylation reactions has revealed that the P2N2 family outperforms many commonly used phosphines. This Synpacts article summarizes our work and provides a broad overview on the preparation and application of P2N2 ligands in organic synthesis. It also serves to highlight how a simple, modular class of ligands can solve contemporary challenges with transition-metal catalysis, including novel reactivity and exceptional regioselectivity.

Photoinduced Palladium-Catalyzed Radical Germylative Arylation of Alkenes with Chlorogermanes.

We describe a visible light-induced palladium-catalyzed radical germylative arylation of alkenes with easily accessible chlorogermanes. This protocol provides expedient access to germanium-substituted indolin-2-ones in good to excellent yields under mild reaction conditions. The key step for this strategy lies in the reductive activation of germanium-chloride bonds with an excited palladium complex under visible light irradiation. The involvement of germanium radicals was evidenced by electron paramagnetic resonance spectroscopy experiments.

Light-promoted AIBN-catalyzed oxidative cleavage of aryl olefins to aryl ketones

A convenient light-promoted 2,2-azobis(isobutyronitrile) (AIBN)-catalyzed synthesis of aryl ketone from aryl alkenes with molecular oxygen as the oxidant was developed. A series of aryl ketone were obtained in moderate to good yields. The new protocol features mild conditions and relatively broad substrate scope. The reaction was successfully applied for the synthesis of Fenofibrate in good yield. Based on previous documents and current experimental results, a plausible mechanism is proposed.

Cobalt(II)-Catalyzed Proficient Synthesis of Enaminones from Aryl Alkenes and Amines

AbstractA simple, cost-effective, and modular strategy has been developed to synthesize synthetically and pharmaceutically active enaminones by oxidative amination of aryl alkenes with amines and CHCl3, using tert-butyl hydroperoxide as an oxidant. We describe the synthesis of enaminones from vinyl arenes and sterically hindered N,N-diisopropylethylamine (DIPEA) by employing an Earth-abundant cobalt salt as a catalyst within a very short reaction period for the first time. Furthermore, nitrogen- and oxygen-containing heterocyclic compounds have been synthesized from these highly functionalized enaminones. Moreover, various control experiments, such as radical trapping reaction, along with a Hammett analysis with various types of substituents on the styrene ring unraveled the detailed mechanism of this reaction pathway.

Paired Electrolysis Enables Reductive Heck Coupling of Unactivated (Hetero)Aryl Halides and Alkenes.

The formation of carbon-carbon (C-C) bonds is a cornerstone of organic synthesis. Among various methods to construct Csp2-Csp3 bonds, the reductive Heck reaction between (hetero)aryl halides and alkenes stands out due to its potential efficiency and broad substrate availability. However, traditional reductive Heck reactions are limited by the use of precious metal catalysts and/or limited aryl halide and alkene compatibility. Here, we present an electrochemically mediated, metal- and catalyst-free reductive Heck reaction that tolerates both unactivated (hetero)aryl halides and diverse alkenes such as vinyl boronates and silanes. Detailed electrochemical and deuterium-labeling studies support that this transformation likely proceeds through a paired electrolysis pathway, in which acid generated by the oxidation of N,N-diisopropylethylamine (DIPEA) at the anode intercepts an alkyl carbanion formed after radical-polar crossover at the cathode. As such, this approach offers a sustainable method for the construction of Csp2-Csp3 bonds from (hetero)aryl halides and alkenes, paving the way for the development of other electrochemically mediated olefin difunctionalization reactions.

Paired Electrolysis Enables Reductive Heck Coupling of Unactivated (Hetero)Aryl Halides and Alkenes

AbstractThe formation of carbon‐carbon (C−C) bonds is a cornerstone of organic synthesis. Among various methods to construct Csp2−Csp3 bonds, the reductive Heck reaction between (hetero)aryl halides and alkenes stands out due to its potential efficiency and broad substrate availability. However, traditional reductive Heck reactions are limited by the use of precious metal catalysts and/or limited aryl halide and alkene compatibility. Here, we present an electrochemically mediated, metal‐ and catalyst‐free reductive Heck reaction that tolerates both unactivated (hetero)aryl halides and diverse alkenes such as vinyl boronates and silanes. Detailed electrochemical and deuterium‐labeling studies support that this transformation likely proceeds through a paired electrolysis pathway, in which acid generated by the oxidation of N,N‐diisopropylethylamine (DIPEA) at the anode intercepts an alkyl carbanion formed after radical‐polar crossover at the cathode. As such, this approach offers a sustainable method for the construction of Csp2−Csp3 bonds from (hetero)aryl halides and alkenes, paving the way for the development of other electrochemically mediated olefin difunctionalization reactions.

Flavin-catalyzed, TBHP-promoted oxidation of (het)aryl alkane to ketone

A protocol of flavin-catalyzed, TBHP-promoted aerobic oxidation of (het)aryl alkane to ketones has been developed and the products were provided in moderate-to-excellent yields with broad functional group tolerance. Flavin was first employed as a catalyst to oxidize (het)aryl alkane to ketones. The methodology were applied to the synthesis of many biologically active, pharmaceutical molecules and natural products. Mechanistic investigation reveals that a radical pathway may be involved in the transformation.

Selective nitrogen insertion into aryl alkanes

Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit the development of synthetic chemistry, pharmaceutical research, and materials science. Substituted amines, especially nitrogen-containing alkyl heterocyclic compounds, are widely found in nature products and drugs. Generally, accessing these compounds requires multiple steps, which could result in low efficiency. In this work, a molecular editing strategy is used to realize the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials. Using derivatives of O-tosylhydroxylamine as the nitrogen source, this method enables precise nitrogen insertion into the Csp2-Csp3 bond of aryl alkanes. Notably, further synthetic applications demonstrate that this method could be used to prepare bioactive molecules with good efficiency and modify the molecular skeleton of drugs. Furthermore, a plausible reaction mechanism involving the transformation of carbocation and imine intermediates has been proposed based on the results of control experiments.

Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

Asymmetric carbohydroxylation of alkenes via sequential photocatalytic oxo-alkylation and enzymatic reduction

Asymmetric carbohydroxylation of alkenes offers an efficient approach to access chiral alcohols, a class of versatile building blocks in pharmaceutical and agrochemical industries, from abundant simple alkenes. Herein we reported a sequential photo-biocatalysis protocol for the asymmetric carbohydroxylation of alkenes, involving a stepwise photocatalytic decarboxylative radical addition/Kornblum oxidation and enzymatic reduction. A series of chiral alcohols with bulky structures were synthesized in up to 75 % isolated yields and 99 % ee from N-hydroxyphthalimide esters and aryl alkenes.

Mechanochemical Synthesis of α-halo Alkylboronic Esters.

α-halo alkylboronic esters, acting as ambiphilic synthons, play a pivotal role as versatile intermediates in fields like pharmaceutical science and organic chemistry. The sequential transformation of carbon-boron and carbon-halogen bonds into a broad range of carbon-X bonds allows for programmable bond formation, facilitating the incorporation of multiple substituents at a single position and streamlining the synthesis of complex molecules. Nevertheless, the synthetic potential of these compounds is constrained by limited reaction patterns. Additionally, the conventional methods often necessitate the use of bulk toxic solvents, exhibit sensitivity to air/moisture, rely on expensive metal catalysts, and involve extended reaction times. In this report, a ball milling technique is introduced that overcomes these limitations, enabling the external catalyst-free multicomponent coupling of aryl diazonium salts, alkenes, and simple metal halides. This approach offers a general and straightforward method for obtaining a diverse array of α-halo alkylboronic esters, thereby paving the way for the extensive utilization of these synthons in the synthesis of fine chemicals.

Pd-Catalyzed Hydroboration of Vinylarenes with B2pin2.

A palladium(II)-catalyzed Markovnikov hydroboration of aryl alkenes with readily available bis(pinacolato)diboron (B2pin2) is reported. The reaction proceeded with low catalyst loading (0.5 mol %) in the absence of N- or P-containing ligands, affording the products in up to 90% yield. Trifluoracetic acid serves as the hydrogen source, enabling the synthesis of benzylic boronic esters under mild ambient conditions.

Multicomponent Heteroarylphosphorothiolation of Alkenes for Accessing β‐Phosphorothiolated Quinoxalinones

AbstractHerein, we present a (NH4)2S2O8 mediated difunctionalization reaction of aryl alkenes with quinoxalinones and P(O)SH compounds. This method enables the synthesis of various phosphorothioate‐containing quinoxalin‐2(1H)‐one derivatives (46 examples) in 37–79% yields. The reaction is compatible with a range of functional groups and is easily adaptable to large‐scale synthesis. Preliminary studies suggest the involvement of phosphorothioate radicals in these transformations.