Electron-deficient Aryl Groups Research Articles

Discovery of tetrazole thioethers: An efficient, environmentally friendly and metal-free S-arylation using diaryliodonium salts

An efficient, environmentally friendly, and metal-free method for the synthesis of functionalized tetrazole thioethers via the S-arylation of tetrazole-5-thiones using diaryliodonium salts as aryl transfer reagents has been developed. This novel methodology provides rapid access to tetrazole thioether derivatives under facile conditions. Our study underscores the chemoselectivity of unsymmetrical diaryliodonium salts, emphasizing their preference for the transfer of sterically hindered and electron-deficient aryl groups. Notably, the synthesized compound 3h exhibits antitumor activity against A2789 (ovarian cancer) and MDA-MB-231 (breast cancer) tumor cells. In silico studies predict these compounds to possess good drug-likeness and low toxicity risk. These findings highlight the potential of functionalized tetrazole thioethers as antiproliferative agents and pave the way for further development and optimization in future investigations.

Metal-Free Regioselective N2-Arylation of 1H-Tetrazoles with Diaryliodonium Salts.

We describe a simple, metal-free regioselective N2-arylation strategy for 5-substituted-1H-tetrazoles with diaryliodonium salts to access 2-aryl-5-substituted-tetrazoles. Diaryliodonium salts with a wide range of both electron-rich and previously challenged electron-deficient aryl groups are applicable in this method. Diversely functionalized tetrazoles are tolerable also. We have devised a one-pot system to synthesize 2,5-diaryl-tetrazoles directly from nitriles. The synthetic utility of this method is furthered extended to late-stage arylation of two biologically active molecules.

Silylcyclopropanes by Selective [1,4]-Wittig Rearrangement of 4-Silyl-5,6-dihydropyrans.

4-Silyl-5,6-dihydropyrans undergo remarkably selective [1,4]-Wittig rearrangements to give silylcyclopropanes in good yields. The selectivity is independent of the silyl group, but it is influenced by the electronic character of the migrating center. Electron-rich and electron-neutral (hetero)aryl groups and aliphatic substituents at the migrating center lead to exclusive [1,4]-migration, whereas electron-deficient aryl groups predominantly afford [1,2]-Wittig products.

Chiral Cobalt(II) Complex Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Selenides with α-Diazo Pyrazoleamides

Organoselenium compounds, due to their high structural diversity, special function, and biological activities, have drawn attention in synthetic chemistry. Herein, a novel example of chiral N,N′-di...

Synthesis of Aryldiphenylphosphine Oxides by Quaternization of Tertiary Diphenylphosphines with Aryl Bromides Followed by the Wittig Reaction.

A two-step method for the synthesis of aryldiphenylphosphine oxides from tertiary diphenylphosphines and aryl bromides is developed. The first step is the quaternization of methyldiphenylphosphine or benzyldiphenylphosphine with aryl bromides. This quaternization can be nickel-catalyzed (metal-free in some cases), and tolerate of a variety of functional groups, furnishing quaternary phosphonium salts in 48–90% yields. The second step is Wittig reactions of these quaternary phosphonium salts with furan-2-carbaldehyde or p-chlorobenzaldehyde to provide aryldiphenylphosphine oxides in 27–90% yields. The use of the Wittig reaction for the synthesis of tertiary phosphine oxides is in contrast to its traditional use for the synthesis of olefins, leaving tertiary phosphine oxide as a byproduct. This quaternization–Wittig method can be applied to synthesize aryldiphenylphosphine oxides that are difficult to access by the alkaline hydrolysis of aryltriphenylphosphonium salts, especially those bearing an electron-deficient aryl group. The ligand-coupling mechanism for the alkaline hydrolysis of (p-acylphenyl)triphenylphosphonim salts is also discussed.

Self-assembly of amphiphilic aryl-squaramides in water driven by dipolar π-π interactions.

Squaramides are versatile compounds with a great capacity to interact via non-covalent interactions and therefore of interest for the development of supramolecular systems and functional materials. In the present work, a new series of aryl-squaramide amphiphiles (1-5) were prepared to form supramolecular polymers in water. Interestingly, only compounds 1 and 2 that contain electron-deficient aryl groups are capable of forming hydrogels (∼10-2 M) upon treatment with a base (NaOH or PBS). The aggregation behaviour of 1 and 2 was studied by static light scattering, UV-Vis, 1H NMR, FT-IR, and atomic force microscopy, and it was found that these compounds aggregate forming well-defined 1D nanofibers below the critical gelation concentration (<10-3 M). Moreover, the combination of these experiments with 1D and 2D NMR studies and theoretical calculations revealed that 1 and 2 self-assemble via an unprecedented interaction motif showing dipolar π-π interactions between the squaramide rings and the 4-nitrophenyl or 3,5-bis(trifluoromethyl)phenyl rings of 1 and 2, respectively. Such kinds of assemblies are stabilized by the compensation of the dipole moments of the stacked molecules. This interaction mode contrasts with those typically driving squaramide-based assemblies based on either hydrogen bonds or antiparallel stacking. We believe that this interaction motif is of interest for the design and development of new squaramide nanomaterials with free hydrogen bonding groups, which might be useful in drug delivery applications.

Thioureas as Highly Active Catalysts for Biomimetic Bromocyclization of Geranyl Derivatives.

Thioureas bearing electron-deficient aryl groups show high catalytic activity in the biomimetic bromocyclization of geranyl derivatives. The reaction of geranyl derivatives with N-bromosuccinimide (NBS) proceeds rapidly in CH2Cl2 to give the corresponding bromocyclization products in high yields as a ca. 1:1 mixture of endo- and exo-isomers. The reactivity of geranyl derivatives highly depends on the terminal substituent: electron-donating substituents increase the reactivity, while electron-withdrawing substituents decrease the reactivity.

Organocatalytic Arylation of α-Ketoesters Based on Umpolung Strategy: Phosphazene-Catalyzed SN Ar Reaction Utilizing [1,2]-Phospha-Brook Rearrangement.

An organocatalytic arylation of α-ketoesters was developed on the basis of umpolung strategy. Phosphazene P2-tBu efficiently catalyzes the three-component coupling reaction of α-ketoesters, a silylated secondary phosphite, and electron-deficient fluoroarenes to provide α-hydroxyester derivatives possessing an electron-deficient aryl group at the α-position. The reaction involves the catalytic generation of α-oxygenated ester enolates from α-ketoesters through the [1,2]-phospha-Brook rearrangement followed by the SN Ar reaction.

Nucleophilic Ring Opening of Donor-Acceptor Cyclopropanes Catalyzed by a Brønsted Acid in Hexafluoroisopropanol.

A general, Brønsted acid catalyzed method for the room temperature, nucleophilic ring opening of donor-acceptor cyclopropanes in fluorinated alcohol solvent, HFIP, is described. Salient features of this method include an expanded cyclopropane scope, including those bearing single keto-acceptor groups and those bearing electron-deficient aryl groups. Notably, the catalytic system proved amenable to a wide range of nucleophiles including arenes, indoles, azides, diketones, and alcohols.

Copper-Catalyzed Regioselective Monodefluoroborylation of Polyfluoroalkenes en Route to Diverse Fluoroalkenes.

Monodefluoroborylation of polyfluoroalkenes has been achieved in a regioselective manner under mild conditions via copper catalysis. The method has shown an extremely broad scope of substrates, including (difluorovinyl)arenes, tetrafluoroethylene (TFE), (trifluorovinyl)arenes, and trifluoromethylated monofluoroalkenes. The choice of boron source was important for the efficient transformation of (difluorovinyl)arenes; (Bpin)2 was suitable for substrates with an electron-deficient aryl group and (Bnep)2 for those with an electron-rich aryl group. Derivatization of the (fluoroalkenyl)boronic acid esters to the corresponding potassium trifluoroborate salts has rendered the products easily isolable, which greatly improved the synthetic practicality of the monodefluoroborylation reaction. Stoichiometric experiments indicate that the fate of the regioselectivity depends on the mode of β-fluorine elimination, which depends on the substrate. Further transformation of the boryl group has allowed facile preparation of fluoroalkene derivatives as exemplified by the synthesis of a fluoroalkene mimic of atorvastatin, which potently inhibited the enzyme activity of HMG-CoA reductase.

Ferrocenyl-based unsymmetrical azines as multisignaling sensors for Hg2+, Cu2+ in aqueous environment

Seven ferrocenyl-based unsymmetrical azines 3a–3f and 5a were synthesized under metal-free conditions in good yields. Ferrocene-based unsymmetrical azines 3f and 5a have shown to be excellent multichannel chemosensors for Hg2+ and Cu2+ ions in aqueous environment. The color of the solution containing chemosensor 3f changed from yellow to colorless, upon the addition of Hg2+ and Cu2+ ions. Quantification of the absorption titration analysis shows that the detection limit was 6.77×10−7M for 3f-Cu2+ and 7.19×10−7M for 3f-Hg2+, respectively. For 5a, the detection limit can reach 1.29×10−7M and 2.40×10−7M for Cu2+ and Hg2+, respectively. Moreover, 1-substituted ferrocene-based unsymmetrical azines 3a–3e with electron-rich, electron-neutral, and electron-deficient aryl groups have significant influence on the sensitivity.

Gold(I)-Catalyzed Tandem Reactions Initiated by Hydroamination of Alkynyl Carbamates: Application to the Synthesis of Nitidine

As a convenient and direct synthesis of 1,2-dihydroisoquinolines, the gold(I)-catalyzed intramolecular hydroamination of (2-alkynyl)benzyl carbamates has been developed. The reaction with cationic gold(I) complex [AuCl(PPh(3))/AgNTf(2)] proceeded at room temperature, giving the desired 6-endo adducts. The addition of alcohol efficiently promoted the reaction, and the amount of the catalyst could be reduced to 1 mol %. However, the alkynes bearing either an electron-deficient aryl group or an alkyl group resulted in predominant production of 5-exo adducts. In such cases, use of a bulky gold catalyst, AuCl[(o-biPh)((t)Bu)(2)P]Cl/AgNTf(2), improved the regioselectivity, giving the 6-endo adducts in better yields. Furthermore, the hydroamination of alkynyl carbamates bearing an acetal or enone was successfully applied to the concise synthesis of tetracyclic heterocycles such as nitidine via the single catalyst-mediated tandem cyclization which consists of a condensation or a Michael addition of the resulting enecarbamates.

Brønsted Acid Catalyzed Enantioselective 1,3-Dipolar Cycloaddition

An asymmetric 1,3-dipolar cyclo­addition of nitrones with ethyl vinyl ether catalyzed by chiral phosphoramides is reported. The presented reaction yields the endo products as the major diastereomer. Several phosphoramides bearing different aryl groups at the 3,3′-positions of the binol backbone were screened, with catalyst 1 giving the best results. A variety of diaryl nitrones could be employed in this reaction. High enantioselectivities were obtained only with electron-deficient aryl groups.

Lewis‐Acid‐Catalyzed Rearrangement of Arylvinylidenecyclopropanes: Significant Influence of Substituents and Electronic Nature of Aryl Groups.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Palladium‐Catalyzed C—H Arylation of Thieno[2,3‐b]thiophene: An Approach to Novel 2,5‐Diaryl/Heteroaryl Thieno[2,3‐b]thiophenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Lewis-Acid-Catalyzed Rearrangement of Arylvinylidenecyclopropanes: Significant Influence of Substituents and Electronic Nature of Aryl Groups

Lewis-acid-catalyzed reactions of arylvinylidenecyclopropanes having three substituents at the corresponding cyclopropyl rings have been investigated thoroughly. The reaction products are highly dependent on the substituents at the corresponding cyclopropyl rings and the electronic nature of the aryl groups. For arylvinylidenecyclopropanes bearing two alkyl groups at the C-1 position (R1, R2, R3=aryl; R4=H; R5, R6=alkyl), naphthalene derivatives were formed in the presence of Lewis-acid Eu(OTf)3 in DCE at 40 degrees C. For arylvinylidenecyclopropanes in which R1, R2, R3=aryl and R4, R5=alkyl (syn/anti isomeric mixtures), the corresponding 6aH-benzo[c]fluorine derivatives were formed in the syn-configuration via a double intramolecular Friedel-Crafts reaction when all of the aryl groups do not have electron-withdrawing groups or the corresponding indene derivatives were obtained via an intramolecular Friedel-Crafts reaction as long as one electron-deficient aryl group was attached. For arylvinylidenecyclopropanes in which R1, R2, R3, R4=aryl and R5=alkyl or H, the corresponding indene derivatives were obtained exclusively via a sterically demanding intramolecular Friedel-Crafts reaction. Lewis-acid effects and mechanistic insights have been discussed on the basis of experimental investigations.

Palladium-Catalyzed C-H Arylation of Thieno[2,3-b]thiophene: An Approach to Novel 2,5-Diaryl/Heteroaryl Thieno[2,3-b]thiophenes

Direct C-H arylation of thieno[2,3-b]thiophene is reported under Pd(OAc) 2 /n-Bu 4 NBr catalysis and provides rapid entry into the first examples of 2,5-diaryl thienothiophenes. The reaction works well with either electron-deficient or electron-rich halo-arenes, giving satisfactory yields of diarylation products. Novel push-pull thienothiophenes bearing electron-deficient aryl groups (λ max 318-373 nm and λ cut-off 430 nm) are potentially interesting for their photonic properties.

Electronic and Steric Effects on the Reductive Elimination of Diaryl Ethers from Palladium(II)

Arylpalladium aryloxide complexes containing sterically and electronically varied phosphine ligands were prepared, and the rates for reductive elimination of diaryl ethers from these complexes were studied to determine the ligand properties that most strongly accelerate this unusual reaction. Electronic and steric effects were probed by preparing monomeric palladium complexes of the type (L)Pd(Ar)(OAr‘), in which L = DPPF (1,1‘-bis-diphenylphosphinoferrocene), CF3-DPPF (1,1‘-bis[di(4-(trifluoromethyl)phenyl)phosphino]ferrocene), and D-t-BPF (1,1‘-bis(di-tert-butylphosphino)ferrocene) and Ar = electron-deficient and electron-neutral aryl groups. Direct C−O bond-forming reductive elimination to form diaryl ethers in high yield was observed after warming the complexes that contained an electron-deficient aryl group bound to palladium. The rate constant for C−O bond-forming reductive elimination from the CF3-DPPF-ligated palladium complex was twice that obtained for the analogous DPPF-ligated complex. Reductive elimination of diaryl ether from the more bulky D-t-BPF complex occurred roughly 100 times faster than from the DPPF complex. Thermolysis of DPPF and CF3-DPPF complexes containing an electron-neutral aryl group did not form diaryl ether. Thermolysis of (D-t-BPF)Pd(Ph)(OC6H4-4-OMe) also did not form diaryl ether and generated the two monophosphines PhP(t-Bu)2 and FcP(t-Bu)2 (di-tert-butylphosphinoferrocene). However, heating of a FcP(t-Bu)2-ligated aryloxide complex containing an electron-neutral, palladium-bound aryl group generated diaryl ether in 10−25% yield. Moreover, heating of this complex in the presence of an excess of P(t-Bu)3 or Ph5FcP(t-Bu)2 or 1 equiv of 2-di-tert-butylphosphino-1,1‘-binaphthyl generated diaryl ether in higher, 58−95%, yields. The effect of ligand concentrations on reaction yields implied that exchange of the bulkier ligands with FcP(t-Bu)2 induced the reductive elimination of diaryl ether.

Novel C−C Bond Cleavage under Mild, Neutral Conditions: Conversion of Electron-Deficient Aryl Alkyl Ketones to Aryl Carboxylic Esters

A novel, unique way to cleave the carbon-carbon bond in aryl alkyl ketones under mild, neutral conditions is described. Treatment of aryl alkyl ketones in a refluxing mixture of N,N-dimethylformamide dimethyl acetal and methanol for 16 h provided aryl carboxylic esters. The scope and limitations of the reaction are discussed. Useful yields of the reaction can be obtained with electron-deficient aryl groups, and the yields are higher when the alkyl group is larger than a methyl group. Studies toward elucidation of the reaction mechanism led to a proposed mechanism that is consistent with all the observations.

Tetrathiafulvalenes as π-Electron Donors for Intramolecular Charge-Transfer Materials

Although tetrathiafulvalene (TTF) and its derivatives have been extensively studied for more than 25 years as π-electron donors in intermolecular charge-transfer materials, the intriguing potential of TTF as a donor in an intramolecular sense has only recently been developed. Many versatile, functionalized TTF building blocks are now readily available, and this article will review a range of compounds in which TTF is covalently linked to an electron acceptor moiety by a variety of linking units, sometimes giving rise to an intramolecular charge-transfer (ICT) interaction, which is most frequently manifested in the optical and electrochemical properties. In this context, acceptor subunits include: tetracyano-p-quinodimethane, quinones, electron-deficient aryl groups, pyridinium and bipyridinium units, fullerenes, phthalocyanines, and mesomerically conjugated carbonyl, thiocarbonyl, ester, and related groups. This work paves the way for more systematic and detailed studies of TTF–spacer–A molecules (where A is an acceptor) in which there is increased control of the structural, electronic, optical, and magnetic properties arising from ICT interactions in the ground state, or in the excited state.