Electron-rich Aromatic Systems Research Articles

Aromatic C-H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel-Crafts reaction: a recent update.

The aza-Friedel-Crafts reaction allows an efficient coupling of electron-rich aromatic systems with imines for the facile incorporation of aminoalkyl groups into the aromatic ring. This reaction has a great scope of forming aza-stereocenters which can be tuned by different asymmetric catalysts. This review assembles recent advances in asymmetric aza-Friedel-Crafts reactions mediated by organocatalysts. The mechanistic interpretation with the origin of stereoselectivity is also explained.

Divergent synthesis of fused Benzo-xanthene and oxazine derivatives via Cu-catalyst

Cu-Cu2O combination showed synergic effects in catalyzing intramolecular Ullmann coupling reaction for halo-Betti bases to afford fused benzo-xanthenes from both electron-rich and electron-deficient aromatic systems in good yield under mild reaction conditions. The sterically hindered halo-Betti bases also provided products in excellent yield. Under optimized condition, a gram scale reaction was also performed to afford the product in excellent yield. However, without ortho-halo substituted Betti-bases failed to afford fused benzo-xanthene derivatives. Exploring the reaction optimization without Cu metal, serendipitously it was produced 1,3-oxazine derivatives in excellent yield via intramolecular cross-dehydrogenative coupling (CDC) reaction. Similarly, electron-rich, electron-deficient and sterically hindered Betti-bases provided the products in good to excellent yield under mild condition.

Influence of Electronic Environment on the Radiative Efficiency of 9-Phenyl-9H-carbazole-Based ortho-Carboranyl Luminophores.

The photophysical properties of closo-ortho-carboranyl-based donor–acceptor dyads are known to be affected by the electronic environment of the carborane cage but the influence of the electronic environment of the donor moiety remains unclear. Herein, four 9-phenyl-9H-carbazole-based closo-ortho-carboranyl compounds (1F, 2P, 3M, and 4T), in which an o-carborane cage was appended at the C3-position of a 9-phenyl-9H-carbazole moiety bearing various functional groups, were synthesized and fully characterized using multinuclear nuclear magnetic resonance spectroscopy and elemental analysis. Furthermore, the solid-state molecular structures of 1F and 4T were determined by X-ray diffraction crystallography. For all the compounds, the lowest-energy absorption band exhibited a tail extending to 350 nm, attributable to the spin-allowed π–π* transition of the 9-phenyl-9H-carbazole moiety and weak intramolecular charge transfer (ICT) between the o-carborane and the carbazole group. These compounds showed intense yellowish emission (λem = ~540 nm) in rigid states (in tetrahydrofuran (THF) at 77 K and in films), whereas considerably weak emission was observed in THF at 298 K. Theoretical calculations on the first excited states (S1) of the compounds suggested that the strong emission bands can be assigned to the ICT transition involving the o-carborane. Furthermore, photoluminescence experiments in THF‒water mixtures demonstrated that aggregation-induced emission was responsible for the emission in rigid states. Intriguingly, the quantum yields and radiative decay constants in the film state were gradually enhanced with the increasing electron-donating ability of the substituent on the 9-phenyl group (‒F for 1F < ‒H for 2P < ‒CH3 for 3M < ‒C(CH3)3 for 4T). These features indicate that the ICT-based radiative decay process in rigid states is affected by the electronic environment of the 9-phenyl-9H-carbazole group. Consequently, the efficient ICT-based radiative decay of o-carboranyl compounds can be achieved by appending the o-carborane cage with electron-rich aromatic systems.

Shifted Selectivity in Protonation Enables the Mild Deuteration of Arenes Through Catalytic Amounts of Bronsted Acids in Deuterated Methanol.

Taking advantage of the "differentiating effect" of the solvent methanol, deuterations of electron-rich aromatic systems can be carried out under mild acid catalysis and thus under far milder conditions than known so far. The exceptional functional group tolerance observed under the optimized conditions, which even includes highly acid-labile groups, results from a hitherto unexploited shifted selectivity in protonation, and enabled simple and straightforward access to complex deuterium-labeled compounds.

Molecular engineering of pyrene carbazole dyes with a single bond and double bond as the mode of linkage

Both carbazole and pyrene are electron-rich aromatic systems and are expected to be potential donors when used in push–pull dye architecture in the field of DSSC.

One-Pot Synthesis of Structurally Diverse Iminosugar-Based Hybrid Molecules.

A one-pot iminium-ion-based strategy has been developed for the synthesis of structurally novel iminosugar-based hybrid molecules. Iminium ion derived from l-rhamnose lactol-mesylate reacted with electron-rich aromatic systems in an inter/intra molecular fashion to furnish pyrrolidine-based iminosugar C-aryl glycosides with a high degree of stereoselectivity. Iminium ion also reacted readily with active methylene compounds such as 4-hydroxycoumarin, 4-hydroxyquinolinone, and lawsone to provide iminosugar C-coumarin/quinolinone/naphthoquinonyl glycosides in very good yields. Azomethine ylide generated from an iminium ion derivative underwent dipolar cycloaddition reaction with 1,4-quinones to furnish novel isopyrrolonaphtho/anthroquinon-based iminosugar-hybrids. The preliminary cytotoxic activities of some of the synthesized iminosugar-hybrids have been assayed against various human cancer cell lines and some of the hybrid molecules exhibited promising anticancer activities.

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent.

An alternative method for forming sulfonates through hypervalent iodine(III) reagent-mediated oxidation of sodium sulfinates has been developed. This transformation involves trapping reactive sulfonium species using alcohols. With additional optimization of the reaction conditions, the method appears extendable to other nucleophiles such as electron-rich aromatic systems or cyclic ethers through a ring opening pathway.

Thoughts about the electrophilic aromatic substitution mechanism: the Friedel-crafts alkylation and acylation of benzene with acetyl and t-butyl cations in the gas phase

The mechanism of electrophilic aromatic substitution (SEAr) is still matter of debate and interest in the literature. In this work, the Friedel-Crafts alkylation and the acylation in the gas phase were investigated in the context of the unified mechanism for SEAr. In this unified proposal three kinds of intermediates can potentially be formed: oriented and unoriented π-complexes, intimate single electron transfer (SET) intermediates and σ-complexes. Quantum chemical calculations at M06-2X/6–311++G(d,p) level were carried out for the investigation of the reaction of benzene with acetyl and tert-butyl ions as model non-oxidant electrophiles for acylation and alkylation, respectively, in the gas phase. It was found that both the tert-butyl and the acetyl cations prefer to form oriented π-complexes. Both electrophiles do not react through a SET pathway with benzene. The π-complex between tert-butyl cation and benzene can evolve to a σ-complex, while in the case of the acetyl cation and benzene the σ-complex was not found as a minimum on the potential energy surface. Instead, it corresponds to a transient species or a very shallow minimum. The outcome of this is that the π-complex would only react with the aromatic ring evolving to the product with nucleophilic assistance by a species of the reaction medium, in either through a concerted mechanism or a specific interaction. This is also observed for aromatics with low ionization energies/nucleophilicities. However, very electron rich aromatic systems afford σ-complexes, and as their ionization energies increases (i.e., less nucleophilic), the more the resulting complex resembles a π-complex, more or less continuously. This suggests out that electrophilic aromatic substitution reactions cannot be rationalized within a single mechanistic framework. Instead, a continuum of mechanistic possibilities may be involved.

Turn-On Sulfide π Donors: An Ultrafast Push for Twisted Mechanophores.

Attached to electron-rich aromatic systems, sulfides are very weak acceptors; however, attached to electron-poor aromatics, they turn into quite strong donors. Here, we show that this underappreciated dual nature of sulfides deserves full consideration for the design of functional systems. Tested with newly designed and synthesized planarizable push-pull mechanophores, sulfide acceptors in the twisted ground state are shown to prevent oxidative degradation and promote blue-shifting deplanarization. Turned on in the planar excited state, sulfide donors promote red-shifting polarization. Impressive Stokes shifts are the result. Demonstrating the usefulness of time-resolved broadband emission spectra to address significant questions, direct experimental evidence for the ultrafast (3.5 ps), polarity-independent and viscosity-dependent planarization from the twisted Franck-Condon S1 state to the relaxed S1 state could be secured.

Acid catalyzed nitrile thiolysis of 3-amino-acrylonitriles, toward the synthesis of 3,4-substituted-5-amino-isothiazoles

Application of an acid-catalyzed thioamidation of β-amino-acrylonitriles to the corresponding β-amino-thioacrylamides toward the synthesis of 3,4-substituted-5-amino-isothiazoles is described. The greatest yields were observed for examples with electron rich aromatic systems. This method uses inexpensive and easily handled reagents.

ChemInform Abstract: Visible‐Light‐Driven Difluoroacetamidation of Unactive Arenes and Heteroarenes by Direct C—H Functionalization at Room Temperature.

AbstractThe mild, scalable method tolerates a broad scope of electron‐rich and electron‐deficient aromatic and heteroaromatic systems.

ChemInform Abstract: Regioselective Thiolation of Arenes and Heteroarenes: C—H Functionalization Strategy for C—S Bond Formation.

A facile transition-metal-free oxidative cross-dehydrogenative coupling reaction involving selective formation of a C-S bond leading to the synthesis of arylthiobenzoxazoles, heteroarylthiobenzoxazoles, and arylthiobenzothiazoles has been described. This highly regioselective C-H functionalization reaction with electron-rich aromatic systems including heteroaromatics is achieved by reversing the reactivity of sulfur in the presence of a suitable oxidant and strong acid.

Aromaticity and amyloid formation: Effect of π-electron distribution and aryl substituent geometry on the self-assembly of peptides derived from hIAPP22–29

A comprehensive investigation of peptides derived from the 22–29 region of human islet amyloid polypeptide (hIAPP) that contain phenylalanine analogs at position 23 with a variety of electron donating and withdrawing groups, along with heteroaromatic surrogates, has been employed to interrogate how π-electron distribution effects amyloid formation. Kinetic aggregation studies using turbidity measurements indicate that electron rich aromatic ring systems consistently abolish the amyloidogenic propensity of hIAPP22–29. Electron poor systems modulate the rate of aggregation. Raman and Fourier transform infrared spectroscopy confirm the parallel β-sheet secondary structure of aggregates derived from peptides containing electron poor phenylalanine analogs and provide direct evidence of ring stacking. Transmission electron microscopy confirms the presence of amyloid fibrils. The effect of aryl substituent geometry on peptide self-assembly reveals that the electronic nature of substituents and not their steric profile is responsible for failure of the electron donating group peptides to aggregate. Non-aggregating hIAPP22–29 peptides were found to inhibit the self-assembly of full-length hIAPP1–37. The most potent inhibitory peptides contain phenylalanine with the p-amino and p-formamido functionalities. These novel peptides may serve as leads for the development of future aggregation inhibitors. A potential mechanism for inhibition of amylin self-assembly by electron rich hIAPP22–29 peptides is proposed.

Regioselective thiolation of arenes and heteroarenes: C-H functionalization strategy for C-S bond formation.

A facile transition-metal-free oxidative cross-dehydrogenative coupling reaction involving selective formation of a C-S bond leading to the synthesis of arylthiobenzoxazoles, heteroarylthiobenzoxazoles, and arylthiobenzothiazoles has been described. This highly regioselective C-H functionalization reaction with electron-rich aromatic systems including heteroaromatics is achieved by reversing the reactivity of sulfur in the presence of a suitable oxidant and strong acid.

ChemInform Abstract: Visible‐Light‐Triggered Direct Benzoyloxylation of Electron‐Rich Arenes at Room Temperature Without Chelation Assistance.

A RuII photocatalytic method was developed for the direct mono-benzoyloxylation of electron-rich aromatic and heteroaromatic systems even with an excess amount of benzoyl peroxide. The reaction was conducted at room temperature under visible light. The direct ArC–H benzoyloxylations occur without the assistance of any directing groups and can also tolerate various functional groups that have already shown diverse reactivities in transition-metal catalysis.

ChemInform Abstract: Supramolecular Assemblies Based on Dative Boron—Nitrogen Bonds

AbstractReview: 31 refs.

Supramolecular Assemblies Based on Dative Boron–Nitrogen Bonds

Dative boron-nitrogen bonds were found to be a useful binding motif in structural supramolecular chemistry. Crystalline cages were formed using a diboronate ester and 2,4,6-tri(4-pyridyl)-1,3,5-triazine. These cages can act as hosts for electron-rich planar aromatic systems such as triphenylene. Further, crystalline two-dimensional polymers were formed via dative B-N bonds between a triboronic ester and a ditopic pyridyl ligand. Use of an extended triboronate ester resulted in formation of a gel in toluene with a minimum gelation concentration of 0.5 wt%.

ChemInform Abstract: Synthesis of Triethyl Arylmethanetricarboxylates by the Manganese(III)- Promoted Reaction of Electron-Rich Aromatic Systems with Triethyl Methanetricarboxylate.

Electron-rich aromatic systems undergo tri(ethoxycarbonyl)-methylation, in fair to excellent yields, on reaction with triethyl methanetricarboxylate (2) in the presence of manganese(III) acetate at 60-65 o C in acetic acid solution

Fullerenes: Chemical structure and properties

Fullerenes: Chemical structure and properties

C–H bond functionalizations with palladium(II): intramolecular oxidative annulations of arenes

Oxidative annulations for the synthesis of carbocycles were developed using a catalytic palladium(II) system. Indoles with pendant olefin tethers were oxidatively cyclized to form annulated products. Electron-rich aromatic systems were also investigated, culminating in the synthesis of benzofurans and dihydrobenzofurans by a similar protocol. These reactions were demonstrated to proceed by an initial C–H bond functionalization event, followed by olefin insertion and β-hydride elimination.