Arylation Reactions Research Articles

Single-atom copper catalyst for the S-arylation reaction to produce diaryl disulfides.

Single-atom Cu supported on CeO x nanorod catalysts (Cu1/CeO x ) have been synthesized through the anchoring of copper by terminal hydroxyl groups on the CeO x surface. The oxygen defect characteristics of the CeO x nanorods promote electron transfer between Cu and CeO x through a Ce-O-Cu interface, which realizes flexible electronic regulation of the Cu sites. Single-atom Cu species with an oxidation state of between +1 and +2 were formed, which was confirmed by X-ray photoelectron spectroscopy, X-ray fine structure spectroscopy, and electron paramagnetic resonance spectroscopy. Cu1/CeO x emerged as a catalyst with advanced catalytic performance for elemental sulfur in S-arylation using aryl iodides, achieving 97.1% iodobenzene conversion and 94.8% selectivity toward diphenyl disulfide. The substituted iodobenzene with different electronic or steric groups successfully realized S-arylation and produced the corresponding diaryl disulfides with high selectivity. The fully exposed single-atom Cu with flexible electronic characteristics successively realized oxidative addition or coordination of multiple substrates, making it possible to obtain diaryl disulfide with high selectivity.

Synthesis and characterization of enantiopure chiral NH2/SO palladium complexes.

A series of enantiopure chiral NH2/SO palladium complexes have been synthesised with high yields by treating the corresponding tert-butylsulfinamide/sulfoxide derivatives with Pd(CH3CN)2Cl2. The enantiopure chiral ligands were prepared by stereoselective addition of tert-butyl or phenyl methylsulfinyl carbanions to different tert-butylsulfinylimines. In all cases, coordination occurs with concomitant desulfinylation. X-ray studies of the Pd complexes showed a higher trans influence of the phenylsulfinyl group in comparison to that of the tert-butylsulfinyl group. Furthermore, we have obtained and characterised two possible palladium amine/sulfonyl complexes, epimers at sulfur, resulting from N-desulfinylation and coordination of palladium with both oxygens of the prochiral sulfonyl group. The catalytic activity and enantioselectivity of the new Pd(II) complexes of acetylated amine/tert-butyl- and phenylsulfoxides in the carboxylated cyclopropanes arylation reaction has been studied, obtaining the best results with the phenylsulfoxide ligand 25(SC,SS) that produced the final arylated product in a 93 :7 enantiomeric ratio.

Novel oxoisochromene synthesisviachemoselective O–H insertion of 1,3-dicarbonyl compounds and subsequent Pd-catalyzed intramolecular arylation reaction

Chemoselective O–H insertion of 1,3-diketones under transition metal-free conditions gives rise to vinyl ethers; Subsequent Pd-catalyzed intramolecularO-arylation of vinyl ethers leads to novel oxoisochromenes.

Enantioselective construction of triaryl-substituted all-carbon quaternary stereocenters via organocatalytic arylation of oxindoles with azonaphthalenes.

Azonaphthalenes have been verified as a class of effective arylation reagents in a variety of asymmetric transformations. Here a highly efficient approach to construct triaryl-substituted all-carbon quaternary stereocenters through chiral phosphoric acid-catalyzed enantioselective arylation of 3-aryl-2-oxindoles with azonaphthalenes is disclosed. This chemistry is scalable and displays excellent functional group tolerance, furnishing a series of 3,3-disubstituted 2-oxindole derivatives in good yields with excellent enantiocontrol. Preliminary mechanistic data suggest that the initially formed direct addition intermediate undergoes intramolecular annulation under acidic reaction conditions.

A heptazine-based polymer photocatalyst with donor-acceptor configuration to promote exciton dissociation and charge separation

Polymeric carbon nitride (PCN) is an emerging class of polymer semiconductor photocatalysts, but bulk PCN typically suffers from low visible-light-harvesting ability, high activation energy, and rapid charge recombination. In this context, using the same core building block, a donor-acceptor (D-A) type heptazine-based polymer, namely BPCN, was proposed via Friedel-Crafts arylation reaction to tackle these issues. Comparatively, the affording BPCN features extended light absorption, reduced activation energy, and suppressed charge recombination, triggered by the electron push-pull interactions as a consequence of the D-A configuration. BPCN is elucidated to be an effective heterogeneous photocatalyst for aerobic organic transformations and a wide range of substrate scopes and reactions were realized. Besides, BPCN also showed an advantage in mediating the photocatalytic water oxidation reaction, achieving a nearly 10-fold oxygen evolution reaction (OER) rate over PCN. These findings demonstrate the great potential of the rational design of heptazine-based polymers with D-A configurations for artificial photosynthesis.

Rational ligand modification maximizes turnover rate in a model Pd-catalyzed C-H arylation

The direct cross-coupling of (hetero)aromatics without prior functionalization is a promising reaction for the chemical and pharmaceutical industries, enabling the conversion of inexpensive feedstocks in a highly step-efficient manner. However, many C-H arylations rely on high loadings of a Pd catalyst that preclude their use in low-cost applications. In this work, we have maximized the turnover rate of a Pd-catalyzed C-H arylation reaction through rational tuning of the ligands. Starting from a computational study of the catalytic mechanism, a kinetic model was derived that accurately explains the experimental time profiles. Quantitative structure-activity relationships between the substituents on the ligands and the resulting catalytic activity for various C-H arylations were obtained. This study demonstrates that, depending on the coupling partner, the C-H activation is not the sole rate-limiting step, and that the ligands can be adapted accordingly to further accelerate catalytic turnover.

Catalyst-free, One-pot Synthesis of 2-Aryl Benzimidazoles from Orthophenylenediamine and Aryl Aldehyde in Acetonitrile

Aim: The study aims to optimize and synthesize benzimidazole derivatives. Background: Benzimidazoles are essential intermediates and scaffolds for biological activity and drug substances. The reported syntheses of benzimidazoles suffer from disadvantages like longer reaction time using a catalyst, which makes the method costly, and the use of strong corrosive acids and toxic reagents that increase environmental hazards. Objectives: One-pot synthesis of 2-aryl benzimidazole from ortho-phenylenediamine and aryl aldehyde. Method: Herein disclosed a catalyst-free, one-pot synthesis of 2-aryl benzimidazole. Results: Different 2-aryl benzimidazoles were synthesized in good yields via the condensation reaction of aryl aldehyde and ortho-phenylenediamine in acetonitrile as a solvent at room temperature. The method is very simple and convenient, with good yields. The formation of the desired product is affected by the substituent of aryl aldehydes. Electron donating substituents are shown to have a higher time in the completion of a reaction than electron-withdrawing substituents. Conclusions: One-pot synthesis of benzimidazole was found to be simpler and economical.

Overcoming the low reactivity of biobased, secondary diols in polyester synthesis

Shifting away from fossil- to biobased feedstocks is an important step towards a more sustainable materials sector. Isosorbide is a rigid, glucose-derived secondary diol, which has been shown to impart favourable material properties, but its low reactivity has hampered its use in polyester synthesis. Here we report a simple, yet innovative, synthesis strategy to overcome the inherently low reactivity of secondary diols in polyester synthesis. It enables the synthesis of fully biobased polyesters from secondary diols, such as poly(isosorbide succinate), with very high molecular weights (Mn up to 42.8 kg/mol). The addition of an aryl alcohol to diol and diacid monomers was found to lead to the in-situ formation of reactive aryl esters during esterification, which facilitated chain growth during polycondensation to obtain high molecular weight polyesters. This synthesis method is broadly applicable for aliphatic polyesters based on isosorbide and isomannide and could be an important step towards the more general commercial adaption of fully biobased, rigid polyesters.

Utility of 4‐Amino‐2,1,3‐benzothiadiazole Directing Group in the Pd(II)‐catalyzed Arylation of γ‐C−H Bonds of Carboxamides and β‐C‐H Bonds of Amino Acid Carboxamides

AbstractExpanding the availability, scope, and limitations of directing groups (DGs) for executing the site‐selective C−H activation and functionalization and substrate scope development are valuable efforts. This paper reports the scope and extension of the utility of the 4‐amino‐2,1,3‐benzothiadiazole (ABTD) directing group in the Pd(II)‐catalyzed arylation of remote sp2/sp3 γ‐C−H bonds of aromatic carboxamides and sp3 β‐C−H bonds of amino acid carboxamides. The performance of the ABTD DG in the arylation of remote γ‐C−H bonds of carboxamides and sp3 β‐C−H bonds of amino acid carboxamides was compared with other known DGs. For example, we have observed that the mono arylation of the methyl sp3 β‐C−H bonds of alanine carboxamide possessing the ABTD DG with iodopyridine yielded the pyridylalanine derivative. Conversely, the same reaction using 8‐AQ DG did not yield the expected pyridylalanine derivative. Furthermore, 2,1,3‐benzothiadiazole moiety‐containing compounds are an important class of molecules in materials chemistry and medicinally relevant molecules. While this work reveals the utility of ABTD as the DG in the Pd(II)‐catalyzed C−H arylation of carboxamides including amino acid derivatives. On the other hand, indirectly the process of ABTD‐aided C−H arylation reactions has enabled to accomplish the synthesis of a library of 2,1,3‐benzothiadiazole moiety containing new carboxamides.

Isolation and Reactivity of Stannylenoids Stabilized by Amido/Imino Ligands.

The reaction of the lithium aryl(silyl)amide Dipp(i Pr3 Si)NLi (Dipp=2,6-i Pr2 C6 H3 ) with one equivalent of SnCl2 in THF gave a novel stannylenoid Dipp(i Pr3 Si)NSnCl⋅LiCl(THF)2 . Heating the solution of amidostannylenoid in toluene to 80 °C resulted in dimeric amido(chloro)stannylene [Dipp(i Pr3 Si)NSnCl]2 , which can be converted to bis(amido)stannylene Sn[N(Dipp)(i Pr3 Si)]2 and amido(imino)stannylene Sn[N(Dipp)(i Pr3 Si)][IPrN] (IPrN=bis(2,6-diisopropylphenyl)imidazolin-2-imino). Treatment of bis(imino)stannylenoid [IPrN]2 Sn(Cl)Li with N2 O resulted in the dimeric complex [IPrNSn(Cl)OLi]2 . All compounds were characterized by NMR, elementary analysis, and X-ray structural determination.

An Expedient Iodine‐Catalyzed Synthesis of Unsymmetrical Thiosulfonates by Sulfonylation of Thiols using Sulfonyl hydrazides in the Presence of Oxone

AbstractA metal‐free and green iodine‐catalyzed protocol is described herein for the synthesis of unsymmetrical thiosulfonates by sulfonylation of thiols using I2/Oxone. It's shown that oxidative cross‐coupling of thiyl radicals with sulfonyl radicals – generated from thiols and sulfonyl hydrazides, respectively, by the redox chemistry between thiol/Oxone and I2/Oxone – occurs in a facile manner at rt, providing access to unsymmetrical thiosulfonates. Diverse unsymmetrical thiosulfonates are synthesized in good‐to‐excellent isolated yields by the reactions of aryl/(hetero)aryl/alkyl thiols with a variety of aryl/(hetero)aryl/alkyl/benzyl sulfonyl hydrazides. The protocol can be further extended to the synthesis of alkyl/aryl sulfonate esters by the reactions of sulfonyl hydrazides with alcohols/phenols using I2/Oxone.

Unusual Formation of 1,2,4-Oxadiazine Core in Reaction of Amidoximes with Maleic or Fumaric Esters.

We have developed a simple and convenient method for the synthesis of 3-aryl- and 3-hetaryl-1,2,4-oxadiazin-5-ones bearing an easily functionalizable (methoxycarbonyl)methyl group at position 6 via the reaction of aryl or hetaryl amidoximes with maleates or fumarates. The conditions for this reaction were optimized. Different products can be synthesized selectively in good yields depending on the base used and the ratio of reactants: substituted (1,2,4-oxadiazin-6-yl)acetic acids, corresponding methyl esters, or hybrid 3-(aryl)-6-((3-(aryl)-1,2,4-oxadiazol-5-yl)methyl)-4H-1,2,4-oxadiazin-5(6H)-ones. The reaction is tolerant to substituents' electronic and steric effects in amidoximes. As a result, a series of 2-(5-oxo-3-(p-tolyl)-5,6-dihydro-4H-1,2,4-oxadiazin-6-yl)acetic acids, their methyl esters, and 1,2,4-oxadiazoles based on them were prepared and characterized by HRMS, 1H, and 13C NMR spectroscopy. The structures of three of them were elucidated with X-ray diffraction.

Radical Fluorosulfonyl Arylation of Alkenes: Accessing FSO2-Functionalized Chromanes via Formal Endo and Exo Cyclization.

The introduction of sulfonyl fluoride groups into bioactive molecules can often bring about enhanced biological activity, which has attracted more research interest in chemical biology and drug development in recent years. Here, we report the development of a radical fluorosulfonylation of alkenes/intramolecular arylation cascade for the construction of chromanes with sulfonyl fluoride groups attached. The radical 1,2-fluorosulfonyl arylation reactions proceed well in both endo and exo cyclization fashions, allowing for further variation of the distance between the chromane core and the sulfonyl fluoride group.

Regioselective Benzylic C–H Alumination and Further Functionalization of 2-Alkylpyridines by Yttrium Catalyst

The regioselective benzylic C–H alumination of various symmetrical and nonsymmetrical 2,6-alkylpyridines catalyzed by a half-sandwich yttrium complex has been developed. The resulting alkylaluminum species bearing a pyridyl ring moiety can be transformed to the corresponding alcohols by oxidation. Moreover, the Cu-catalyzed allylation and benzylation and Pd-catalyzed arylation reactions can be applied to the resulting alkylaluminum species, giving the corresponding α-mono-allylated, α-mono-benzylated, and α-mono-arylated 2-alkylpyridine derivatives, respectively, in good to high yields. Unsymmetrically substituted 2,6-dialkylpyridines can be synthesized from simple symmetrical substrates by repeating such C–H alumination/C–C bond formation processes. Because of the high regioselectivity of the present C–H alumination and the subsequent C–C bond formation, this protocol may serve as a desirable method for the synthesis of nonsymmetrically-2,6-disubstituted pyridine derivatives.

Thiophene-based conjugated ultra-micropore rigid polymers for selective xenon capture

Radioactive isotopes of krypton (Kr) and xenon (Xe) are produced from the fission reaction of nuclear reactors. The separation of Xe/Kr from the nuclear off-gas is important for the spent fuel reprocessing. Compared with the industrial method of cryogenic distillation, physical adsorption is a simple and energy-saving method for Xe/Kr separation. Here, three rigid conjugated micropore polymers, including thiophene containing CMP-PY-BTP, TBTP and fluorine-containing CMP-PY-TFB, were prepared in high yield through direct CH arylation reaction, and their structure–function relationship with Xe/Kr separation was described. CMP-PY-TFB, BTP, and TBTP all possessed rigid micropores with Brunauer-Emmett-Teller specific surface areas of 786.25, 141.64 and 488.30 m2/g, respectively. Among three polymers, CMP-PY-TBTP exhibited the highest Xe/Kr selectivity (11.9 for ideal adsorption solution theory selectivity and 9.3 for Henry selectivity), owing to the combined effect of stronger polarization of its thiophene structural unit and micropore confinement (5.4 Å). The density functional theory (DFT) calculation revealed that Xe was more strongly adsorbed in thiophene-containing units than that of fluorine-containing unit which verified the stronger interaction caused by thiophene group’s polarization. Though having weaker polarization to Xe, fluorine-containing CMP-PY-TFB exhibited the highest Xe uptake of 43.59 cm3 g−1 due to its largest specific surface area (786.25 m2/g).

Recent Advances in Room-Temperature Direct C–H Arylation Methodologies

AbstractIn recent decades, direct C–H arylation has become a preferred tool for biaryl coupling over traditional cross-coupling methods owing to its operationally simple protocol, inherent atom and step economy, and reduced metallic waste. Several elegant methods have been developed that offer the facile transformation of usually inert Csp2–H bonds into Csp2–Csp2 bonds in a single synthetic operation. Despite many merits, a major drawback to this chemistry comes from the low reactivity of aryl C–H bonds, which often mandate harsh reaction conditions compromising sustainability. Hence, developing reaction protocols that require milder conditions has become an important goal in this area of research. This review article comprehensively highlights the synthesis and mechanistic aspects of direct C–H arylation reactions, which proceed at or below room temperature.1 Introduction2 Concepts and Examples2.1 Transition-Metal-Catalyzed Procedures2.1.1 Pd Catalysis2.1.2 Other Metal-Based Procedures2.1.3 Additive-Free Procedures2.2 Direct Arylation Polymerization2.3 Photocatalyzed Procedures2.3.1 Organometallic C–H-Activation-Based Procedures2.3.2 Radical-Addition-Based Procedures2.4 Transition-Metal-Free Procedures2.4.1 Base-Mediated Procedures2.4.2 Iodonium- and Diazonium-Salt-Based Procedures2.5 Electrocatalyzed Procedures3 Summary and Outlook

Direct Arylation: A Greener Synthesis of Anthraquinone-Naphthalene diimide-Based Small Chromophores for Applications in Organic Thin Film Transistors.

In this paper, we report the design and synthesis of three naphthalene diimide- (NDI) and anthraquinone- (AQ) based organic chromophores derived from direct arylation reactions; NDI-AQ, AQ-NDI-AQ and NDI-AQ-NDI. Compared to classic cross-coupling reactions, this method reduced the number of synthetic and purification steps. The chemical structures, photophysical and electrochemical properties of these molecules were characterized using UV-vis spectroscopy, fluorescence emission spectroscopy and cyclic voltammetry (CV). The optoelectronic properties of the three dyes enabled the fabrication of organic thin film transistors (OTFTs). The fabricated OTFTs displayed good n-type semiconducting properties, with electron mobilities ( ) of 1.5-4.2×10-4 cm2 V-1 s-1 .

Shining Visible Light on Reductive Elimination: Acridine-Pd-Catalyzed Cross-Coupling of Aryl Halides with Carboxylic Acids.

Despite the recent tremendous progress on transition-metal/photoredox dual catalysis in organic synthesis, single transition-metal catalysis under visible-light irradiation, which can utilize light energy more efficiently, is still underdeveloped. Herein, we report the design of photosensitizing phosphinoacridine bidentate ligands for visible-light-induced transition-metal catalysis, expecting that the electron-accepting acridine moiety would create a highly reactive electron-deficient metal center toward reductive elimination via metal-to-ligand charge transfer (MLCT). Using these ligands, we have achieved a palladium-catalyzed cross-coupling reaction of aryl halides with carboxylic acids under visible-light irradiation. Electronic tuning of the phosphinoacridine ligands not only enabled the use of a variety of aryl halides as the coupling partner, including less reactive aryl chlorides, under blue light irradiation, but also realized the employment of lower-energy green and red light for the cross-coupling. Experimental mechanistic studies have proved that the reductive elimination of aryl esters is induced by photoirradiation of phosphinoacridine-ligated arylpalladium(II) carboxylate complexes. The theoretical calculation suggests that the reductive elimination in the excited state is promoted by decreasing the electron density of the Pd center through photoinduced intramolecular electron transfer, i.e., MLCT, in the transition state owing to the electron-deficient acridine scaffold. This is a very rare example of photoinduced reductive elimination on palladium(II) complexes.

Enantioselective Synthesis of N−N Bisindole Atropisomers

AbstractN−N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of N−N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of N−N bisindole atropisomers via the palladium‐catalyzed de novo construction of one indole skeleton is presented. A wide variety of N−N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N‐arylation reaction. Structurally diverse indole‐pyrrole, indole‐carbazole, and non‐biaryl‐indole atropisomers possessing a chiral N−N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol.

Temperature-Controlled Selective Mono- vs. Di-ortho-Arylation for the Synthesis of Arylhydrazine Derivatives.

A method of palladium-catalyzed C-H arylation assisted with a 3,4,4-trimethylpyrazol-5-on directing group, selectively providing mono- and di-ortho-arylated products is reported. Steric hindrance appearing between the directing group and the already introduced aryl substituent enables control of mono- vs. diarylation selectivity by the temperature of the reaction. Taking advantage of this, a series of monosubstituted and disubstituted derivatives were obtained in good yields. Moreover, unsymmetrical double-arylation in a one-pot procedure was developed to give corresponding products in reasonable yields. Additionally, synthesis and X-ray study of intermediate palladium metallacycles of both, the first and second arylation reactions, were conducted. X-ray structure comparison emphasizes the geometrical differences that were consistent with the observed reactivity. Finally, decarboxylative cleavage of the pyrazolone directing group under mild conditions gave synthetically useful hydrazones. The presented solution opens the alternative synthetic way to such ortho arylated derivatives of arylhydrazines.