Electron-rich Styrenes Research Articles

Mechanistic investigation of sustainable heme-inspired biocatalytic synthesis of cyclopropanes for challenging substrates

Engineered heme proteins exhibit excellent sustainable catalytic carbene transfer reactivities toward olefins for value-added cyclopropanes. However, unactivated and electron-deficient olefins remain challenging in such reactions. To help design efficient heme-inspired biocatalysts for these difficult situations, a systematic quantum chemical mechanistic study was performed to investigate effects of olefin substituents, non-native amino acid axial ligands, and natural and non-natural macrocycles with the widely used ethyl diazoacetate. Results show that electron-deficient substrate ethyl acrylate has a much higher barrier than the electron-rich styrene. For styrene, the predicted barrier trend is consistent with experimentally used heme analogue cofactors, which can significantly reduce barriers. For ethyl acrylate, while the best non-native axial ligand only marginally improves the reactivity versus the native histidine model, a couple of computationally studied macrocycles can dramatically reduce barriers to the level comparable to styrene. These results will facilitate the development of better biocatalysts in this area.

Organo‐Mediator Enabled Electrochemical Deuteration of Styrenes

AbstractDespite widespread use of the deuterium isotope effect, selective deuterium labeling of chemical molecules remains a major challenge. Herein, a facile and general electrochemically driven, organic mediator enabled deuteration of styrenes with deuterium oxide (D2O) as the economical deuterium source was reported. Importantly, this transformation could be suitable for various electron rich styrenes mediated by triphenylphosphine (TPP). The reaction proceeded under mild conditions without transition‐metal catalysts, affording the desired products in good yields with excellent D‐incorporation (D‐inc, up to >99 %). Mechanistic investigations by means of isotope labeling experiments and cyclic voltammetry tests provided sufficient support for this transformation. Notably, this method proved to be a powerful tool for late‐stage deuteration of biorelevant compounds.

Organo-Mediator Enabled Electrochemical Deuteration of Styrenes.

Despite widespread use of the deuterium isotope effect, selective deuterium labeling of chemical molecules remains a major challenge. Herein, a facile and general electrochemically driven, organic mediator enabled deuteration of styrenes with deuterium oxide (D2O) as the economical deuterium source was reported. Importantly, this transformation could be suitable for various electron rich styrenes mediated by triphenylphosphine (TPP). The reaction proceeded under mild conditions without transition-metal catalysts, affording the desired products in good yields with excellent D-incorporation (D-inc, up to > 99%). Mechanistic investigations by means of isotope labeling experiment and cyclic voltammetry tests provided sufficient support for this transformation. Notably, this method proved to be a powerful tool for late-stage deuteration of biorelevant compounds.

Organophotocatalytic [2+2] Cycloaddition of Electron-Deficient Styrenes.

A visible-light organophotocatalytic [2+2] cycloaddition of electron-deficient styrenes is described. Photocatalytic [2+2] cycloadditions are typically performed with electron-rich styrene derivatives or α,β-unsaturated carbonyl compounds, and with transition-metal-based catalysts. We have discovered that an organic cyanoarene photocatalyst is able to deliver high-value cyclobutane products bearing electron-deficient aryl substituents in good yields. A range of electron-deficient substituents are tolerated, and both homodimerisations and intramolecular [2+2] cycloadditions to fused bicyclic systems are available by using this methodology.

(Digital Presentation) TiO2 Photoelectrochemical Radical-Cation Vinylcyclopropane Rearrangements

In the field of synthetic organic chemistry, photochemical and electrochemical methods are often considered to be competing techniques that induce single electron transfer (SET). Recently, metal complexes and organic dyes have been extensively used as molecular sensitizers that can induce homogeneous bidirectional SET. On the other hand, heterogeneous monodirectional SET can be induced by electrodes, which differs from the photochemical methods. In this context, semiconductors are unique alternatives, since they can induce heterogeneous but bidirectional SET, potentially enjoying advantages of both photochemical and electrochemical methods. Such semiconductor "photoelectrochemical" methods may trigger the reactions that are otherwise difficult to achieve.We have been developing electrochemical SET-triggered cycloadditions in lithium perchlorate (LiClO4)/nitromethane (CH3NO2) solution, which facilitates the generation of radical cations from electron-rich alkenes and styrenes. Recently, we also have been focusing on TiO2 photoelectrochemical SET-triggered cycloadditions, expanding a scope of the electrochemical versions. During the course of our study to develop new TiO2 photoelectrochemical SET-triggered cycloadditions, we unexpectedly found that vinylcyclopropane rearrangements was also possible in LiClO4/CH3NO2 solution. The reactions are initiated by oxidative SET by hole, which is followed by immediate ringopening of the cyclopropanes to generate distonic radical cations. It is expected that reductive SET by excited electron is also involved to realize effective net redox-neutral transformations. Experimental details, including preliminary mechanistic studies, will be presented in this talk.

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

Lewis Base Catalyzed, Sulfenium Ion Initiated Enantioselective, Spiroketalization Cascade.

A Lewis base catalyzed, enantioselective sulfenocyclization of alkenes to afford [6,6]spiroketals has been developed. The method uses a chiral Lewis base catalyst with an electrophilic sulfur source to generate enantioenriched thiiranium ion with alkenes. Upon formation, the thiiranium ion is subsequently captured in a cascade-type reaction, wherein a ketone oxygen serves as the nucleophile to open the thiiranium ion and an alcohol provides the secondary cyclization to form biorelevant spiroketals. A variety of electron-rich and electron-neutral E-substituted styrenes form the desired spiroketals in good yields with excellent enantio- and diastereoselectivities. Alkyl-substituted and terminal alkenes participate in the cascade reaction, but with a limited scope compared to the styrenyl substrates. This method allows for rapid formation of highly substituted spiroketals in good yield and excellent enantioselectivity.

The synthesis of atalantrenes B, C and D, styrene-dimers from the seeds of Atalantia monophylla

Concise syntheses of three recently reported natural products from Atalantia monophylla are reported. The syntheses required the preparation and careful dimerization of highly electron rich styrenes under acidic conditions. The present work adds to a growing body of evidence that demonstrates that synthetic utility of chiral phosphoric acids in asymmetric reactions using styrene-type compounds.

Preparation of branched polystyrene via atom transfer radical polymerisation using diene with electron-rich double bond

ABSTRACT Self-designed bis(4-vinylbenzyl)-oxalate (DBE) was synthesized successfully. The branched polystyrene was prepared by using an atom transfer radical polymerization method with copper bromide (CuBr)/2,2'-bipyridine (Bpy) as a catalyst, the DBE as a branched monomer and tert-butyl α-bromoisobutyrate (t-BBiB) as an initiator. The structure of the synthesized branched monomer was determined by nuclear magnetic resonance (NMR) spectroscopy. The conversion of monomer during the polymerization was measured by gas chromatography (GC) while the molecular weight, molecular weight distribution and degree of branching of the polystyrene were characterized by three-detection volume exclusion chromatography (TD-SEC). The results show that bis(4-vinylbenzyl)-oxalate with electron-rich double bond and styrene with electron-rich double bond can be successfully obtained branched polystyrene. The branched structure developed as the reaction proceeded. At the same time, the molecular weight of the branched polystyrene gradually increased as the reaction progressed, and the molecular weight distribution widened consistent with the increased degree of branching.

Redox Potential Controlled Selective Oxidation of Styrenes for Regio- and Stereoselective Crossed Intermolecular [2 + 2] Cycloaddition via Organophotoredox Catalysis.

A redox potential controlled intermolecular [2 + 2] cross-cycloaddition has been developed in the presence of a thioxanthylium photoredox catalyst. Electron-rich styrenes such as β-bromostyrene (Ep/2 = +1.61 V vs SCE) were selectively oxidized by a thioxanthylium photoredox catalyst (E1/2 (C*/C•-) = +1.76 V vs SCE) to styryl radical cations and reacted with styrene (Ep/2 = +1.97 V vs SCE) to furnish polysubstituted cyclobutanes in high yields. The present reaction can be successfully applied to intermolecular [2 + 2] cross-cycloaddition of β-halogenostyrenes, which cannot be effectively achieved by the hitherto reported representative organophotoredox catalysts.

Iron-Catalyzed Meerwein Carbooxygenation of Electron-Rich Olefins: Studies with Styrenes, Vinyl Pyrrolidinone, and Vinyl Oxazolidinone.

The arylative oxygenation of the electron-rich olefins styrene, α-methylstyrene, vinyl pyrrolidinone, and vinyl oxazolidinone was accomplished using arenediazonium salts and catalytic amounts of FeSO4 in an effective single electron transfer radical process. A broad range of aryldiazonium salts was tolerated using water, methanol, or their combination with acetonitrile to furnish the corresponding carbohydroxylated and carbomethoxylated products (42 examples), including functionalized dihydroisocoumarin and dihydrobenzofuran systems in good to excellent yields (up to 88%). The protocols developed for the Fe(II)-catalyzed carbohydroxylation were also compared to Ru(II) and Ir(III) photoredox carbooxygenations of these electron-rich olefins. The Fe(II)-catalyzed process proved to be highly competitive compared to the photoredox and the uncatalyzed processes. The proposed mechanism for the Fe(II)-catalyzed reactions involves the synergic combination with an effective Fe+2/Fe+3 redox system and a radical polar crossover mechanism featuring an unprecedented capture of the reactive N-acyliminium in the case of vinyl pyrrolidinone and vinyl oxazolidinone.

Ligand-Controlled Regioselective Hydrocarboxylation of Styrenes with CO2 by Combining Visible Light and Nickel Catalysis.

The ligand-controlled Markovnikov and anti-Markovnikov hydrocarboxylation of styrenes with atmospheric pressure of CO2 at room temperature using dual visible-light-nickel catalysis has been developed. In the presence of neocuproine as ligand, the Markovnikov product is obtained exclusively, while employing 1,4-bis(diphenylphosphino)butane (dppb) as the ligand favors the formation of the anti-Markovnikov product. A range of functional groups and electron-poor, -neutral, as well as electron-rich styrene derivatives are tolerated by the reaction, providing the desired products in moderate to good yields. Preliminary mechanistic investigations indicate the generation of a nickel hydride (H-NiII) intermediate, which subsequently adds irreversibly to styrenes.

Photoinduced oxidative activation of electron-rich arenes: alkenylation with H2 evolution under external oxidant-free conditions.

The dehydrogenative cross-coupling of arenes and alkenes is a particularly ideal approach for the synthesis of aryl alkenes. Herein, we report a photo-induced C-H/C-H cross-coupling between electron-rich arenes and styrene derivatives using a dual catalytic system containing an acridinium photosensitizer and a cobaloxime proton-reducing catalyst. This catalytic system enables the Csp2-Csp2 bond formation accompanying H2 evolution. Various substituted aryl alkenes can be afforded with good to excellent yields and high β-regioselectivity.

Photocatalytic E → Z Isomerization of Alkenes

The current renaissance of organic photochemistry and photocatalysis has emboldened non-specialists to explore this rich landscape in search of solutions to long-standing challenges in synthesis. Many iconic stoichiometric photochemical transformations that were often platforms for mechanistic explorations have found limited application in contemporary synthesis, likely due to a perceived difficulty in reaction execution and the dearth of scope. Fortunately, many of these valuable processes are now being translated into robust methods, often with the aid of catalysis. The selective E → Z photochemical isomerization of olefins exemplifies this growing trend. Whilst examples of photochemical isomerization reactions are ubiquitous in physical organic textbooks, their intricate mechanistic delineations often contrast starkly with highly restricted substrate scopes: In the case of carbogenic scaffolds, electron-rich styrenes and stilbenes continue to dominate despite their limited synthetic potential. In this Account , our recent development of a photocatalytic isomerization of activated olefins is discussed. Inspired by the antipodal Z → E process with retinal that constitutes the basis of the mammalian visual system, and a qualitative report describing the reverse E → Z directionality enabled by crystalline (–)-riboflavin localized in the eye, critical noncovalent interactions have been distilled allowing this latter biological process to be reengineered. The result is an expansive, operationally trivial isomerization of substrates containing the cinnamyl motif using an inexpensive, readily available photocatalyst. Reliant on a selective excitation mechanism, this process complements the pioneering work of Hammond, Arai, and others by expanding the scope of olefin isomerization. In the case of carboxylic acids, it was possible to generate the coumarin scaffold directly by exploiting the two discrete activation modes of riboflavin sequentially, namely energy transfer (E T ) followed by single electron transfer (SET). This first example of a “ one catalyst, two activation modes ” strategy constitutes a photocatalytic variant of covalent cascade catalysis and provides a new entry to an important class of pharmaceutical building blocks. Reaction development is placed in an historical context, and key findings from other laboratories that facilitated the study are highlighted. 1 Introduction 2 A Brief Introduction to Photochemistry 3 Photochemical Isomerization of Olefins 4 The Bioinspired Isomerization of Activated Olefins 5 Emulating Coumarin Biosynthesis with (–)-Riboflavin 6 Conclusions

Photoinitiation with boron clusters

Polymer Chemistry Nonmetallic photoinitiators of polymerization are gaining interest for biomedical and electronics applications in which metal compounds are toxic or their presence reduces performance. Messina et al. report on boron clusters [B12(OR)12, where R is a phenyl or pentafluorophenyl group] that act as photoinitiators with blue light for the polymerization of olefins. These compounds photoionize and can initiate the reaction via one-electron transfer (creating a cluster radical anion and a monomer radical cation) to both electron-rich and electron-deficient styrene monomers at very low loadings (0.005 mol %). Even monomers such as isobutylene yielded highly branched polymers when the highly electron-withdrawing fluorinated initiator was used. J. Am. Chem. Soc. 10.1021/jacs.6b03568 (2016).

Visible-Light-Induced Olefin Activation Using 3D Aromatic Boron-Rich Cluster Photooxidants.

We report a discovery that perfunctionalized icosahedral dodecaborate clusters of the type B12(OCH2Ar)12 (Ar = Ph or C6F5) can undergo photo-excitation with visible light, leading to a new class of metal-free photooxidants. Excitation in these species occurs as a result of the charge transfer between low-lying orbitals located on the benzyl substituents and an unoccupied orbital delocalized throughout the boron cluster core. Here we show how these species, photo-excited with a benchtop blue LED source, can exhibit excited-state reduction potentials as high as 3 V and can participate in electron-transfer processes with a broad range of styrene monomers, initiating their polymerization. Initiation is observed in cases of both electron-rich and electron-deficient styrene monomers at cluster loadings as low as 0.005 mol%. Furthermore, photo-excitation of B12(OCH2C6F5)12 in the presence of a less activated olefin such as isobutylene results in the production of highly branched poly(isobutylene). This work introduces a new class of air-stable, metal-free photo-redox reagents capable of mediating chemical transformations.

Styrene Aziridination by Iron(IV) Nitrides.

Thermolysis of the iron(IV) nitride complex [PhB(tBuIm)3Fe≡N] with styrene leads to formation of the high-spin iron(II) aziridino complex [PhB(tBuIm)3Fe-N(CH2CHPh)]. Similar aziridination occurs with both electron-rich and electron-poor styrenes, while bulky styrenes hinder the reaction. The aziridino complex [PhB(tBuIm)3Fe-N(CH2CHPh)] acts as a nitride synthon, reacting with electron-poor styrenes to generate their corresponding aziridino complexes, that is, aziridine cross-metathesis. Reaction of [PhB(tBuIm)3Fe-N(CH2CHPh)] with Me3SiCl releases the N-functionalized aziridine Me3SiN(CH2CHPh) while simultaneously generating [PhB(tBuIm)3FeCl]. This closes a synthetic cycle for styrene azirdination by a nitride complex. While the less hindered iron(IV) nitride complex [PhB(MesIm)3Fe≡N] reacts with styrenes below room temperature, only bulky styrenes lead to tractable aziridino products.

ChemInform Abstract: I2‐Catalyzed Divergent Regioselective Addition of Methoxybenzenes with Ethenylbenzenes under Microwave Irradiation.

Abstract1,2,2‐Triarylethanones (III) are efficiently obtained starting from simple and commercially available electron‐rich arenes and styrenes.

Synthesis of 2-Aminooxazolines and Spiro-2-aminooxazolines by Using a Convenient Two-Step INCO-Mediated Reaction

A two-step reaction sequence yielding 2-aminooxazolines under mild conditions was developed. Both electron-rich and electron-deficient styrenes as well as functionalized primary and secondary amides could be used in the reaction to afford 2-aminooxazolines in reasonable yields.

Regio‐ and Diastereoselective CC Coupling of α‐Olefins and Styrenes to 3‐Hydroxy‐2‐oxindoles by Ru‐Catalyzed Hydrohydroxyalkylation

Regio‐ and Diastereoselective CC Coupling of α‐Olefins and Styrenes to 3‐Hydroxy‐2‐oxindoles by Ru‐Catalyzed Hydrohydroxyalkylation