Heteroarylation Reactions Research Articles

RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

Electrochemical Synthesis of Dimeric λ3-Bromane: Platform for Hypervalent Bromine(III) Compounds.

A straightforward and scalable approach to a previously unreported class of cyclic hypervalent Br(III) species capitalizes on the anodic oxidation of aryl bromide to dimeric benzbromoxole that serves as a versatile platform to access a range of structurally diverse Br(III) congeners such as acetoxy-, alkoxy-, and ethynyl-λ3-bromanes as well as diaryl-λ3-bromanes. The synthetic utility of dimeric λ3-bromane is exemplified by photoinduced Minisci-type heteroarylation reactions and benzylic oxidation.

Synthesis, Chemical Reactivities, and Biological Properties of Pyrazolone/ Pyrazolinone as a Blocking Unit for Building Various Heterobicyclic Systems: A Review

: This review reports various synthetic routes of pyrazolone/ pyrazolinone derivatives via the addition of cycloaddition, condensation, cyclocondensation, modification, alkylation, as well as formylation, regioselective, and ring-opening reactions under reflux, microwave irradiation, and/ or ultrasonication conditions. It also presents critical chemical behaviors towards nucleophilic and electrophilic reagents. The chemical reactivities of pyrazolone/ pyrazolinone derivatives involve alkylation, acylation, condensation, catalyzed diazo coupling, oxidation, heteroarylation, phosphorylation, stereoselective alkenylation, enantioselective alkylation, addition, and complexation reactions. The review also summarizes the significant biological activity of pyrazolone/ pyrazolinone derivatives as antibacterial, antifungal, anti-inflammatory, anticancer, antitumor, anthelmintic, analgesic, as well as antioxidant, anthelmintic, antibiofilm, and anti-HIV. Moreover, some pyrazolone/ pyrazolinone derivatives used to remove various metal or soft metal ions from the wastewater. Besides, they exhibited stable complexes with some metals, for example, Ag (I), Cu (I), Cu (II), Hg (II), Pb (II), Sn (II), and Sb (V) as new materials, catalysis, and precursors for CVD in the microelectronic industry and as potential antitumoral.

Two-step direct heteroarylation reaction towards 2,5-bis(alkoxy)benzene polymer for organic field-effect transistors processed with tetrahydrofuran

A 2,5-bis(alkoxy)benzene polymer POB-TNT has been newly designed and synthesized via very convenient two-step direct heteroarylation reaction. Its physicochemical properties have been investigated. POB-TNT demonstrates typical [Formula: see text]-type carrier transport characteristic in unencapsulated bottom-gate and top-contact organic field-effect transistors (OFETs) processed with relatively green tetrahydrofuran solvent. The results highlight a readily accessible and low-cost-oriented polymer semiconductor for non-halogenated solvent-processed OFET application.

Mechanistic insights into the C(sp3)-H heteroarylation of amides and Fukui function analysis of regioselectivity

• The underlying mechanism of visible-light-enabled C(sp 3 )-H heteroarylation of amides. • Protonated heteroarenes promoting coupling reaction. • Fukui functions predicting the reactive sites of the protonated heteroarenes in heteroarylation of amides. A computational study is carried out to understand the mechanism and excellent regioselectivity in metal-free heteroarylation of amides reported by Zhu’s group. The heteroarylation reaction started with the initial generation of key nitrogen-centered radicals via ligand exchange between reactant 1a and initiator PIFA under visible-light irradiation. Following, this reaction undergoes four-stages: 1,5-hydrogen atom transfer, C C coupling, single electron transfer and proton transfer. The C C coupling step is identified as the selectivity-determining step in which the carbon-centered radical ( C ) selectively only attacks the carbon atom adjacent to nitrogen of lepidine ( 2a ). And the radical C more easily attacks the protonated 2a , compared with unprotonated 2a , due to significantly lowered SOMO/LUMO energy difference between them to promote this nucleophilic radical addition. From the calculated result, we can see that the positive effect of the acidity of the reaction substrates on the nucleophilic addition to heteroarenes. Fukui functions of different types of heteroarene substrates are calculated to predict the favorable nucleophilic sites. The calculated most favorable reactive sites of heteroarene substrates are well consistent with the experimental observed ones. This theoretical research provides deeper understandings for the underlying mechanism and the origin of exclusive regioselectivity of the heteroarylation of amides.

Photoredox-Mediated Remote C(sp3)-H Heteroarylation of N-Alkyl Sulfonamides.

A Minisci-type δ-selective C(sp3)-H heteroarylation of sulfonyl-protected primary aliphatic amines with N-heteroarenes under photoredox-catalyzed conditions was developed. The reaction typically uses a slight excess of amine reactant. The use of benziodoxole acetate (BI-OAc) oxidant and hexafluoroisopropanol solvent is critical to achieve high yield. Besides methylene C-H bonds, heteroarylation reactions of δ methyl C-H bonds also worked under more forced conditions. The reactions show a broad scope for both amine and N-heteroarene substrates, offering a straightforward method for synthesis of complex δ-heteroarylalkylmines from simple precursors.

Direct Heteroarylation versus Stille Polycondensation Reaction for the Synthesis of TQ1 Conjugated Polymer

ABSTRACTWe report a facile synthesis of the well‐known and highly promising conjugated polymer TQ1 using eco‐friendly direct heteroarylation reaction. Optimization of the reaction conditions yielded the target polymer with good optoelectronic and charge‐transport characteristics. The TQ1 polymer obtained in the direct heteroarylation reaction delivered power conversion efficiency of ∼5% in organic bulk heterojunction solar cells, which matches well the characteristics of the reference devices assembled using TQ1 batch synthesized via conventional Stille polycondensation reaction. The obtained results highlight the potential of the direct heteroarylation reaction as an efficient and environment‐friendly alternative to Stille cross‐coupling in the design of high‐quality semiconductor materials for organic electronics. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 776–782

Stereoselective synthesis of 2,5-disubstituted pyrrolidines via gold-catalysed anti-Markovnikov hydroamination-initiated tandem reactions.

A series of gold-catalysed intramolecular anti-Markovnikov hydroamination-initiated azidation, allylation and heteroarylation reactions of chiral homopropargyl sulfonamides have been developed. Various enantioenriched 2,5-disubstituted pyrrolidines are obtained in moderate to excellent yields with excellent enantioselectivities and generally high diastereoselectivities.

Synthesis and characterization of low bandgap conjugated poly[(3-alkylylthiophene-2,5-diyl)-alt-(3-cyanothiophene-2,5-diyl)] by direct heteroarylation polymerization

A series of novel conjugated copolymers of poly[(3-alkylthiophene-2,5-diyl)-alt- (3-cyanothiophene-2,5-diyl)]s, (PACTs), containing electron-releasing 3-alkylyl thiophene-2,5-diyl (AT) and electron-withdrawing dibromo 3-cyanothiophene- 2, 5-diyl (CT) were synthesized by the polycondensation of a direct heteroarylation reaction. The regular alteration of the electron donor and electron acceptor unit in a polymer backbone led to a decrease in the energy bandgap of conjugated poly(3-alkylylthiophene-2,5-diyl)s (P3HT). To accelerate the polycondensation reaction, microwave-assisted heating was used to reduce the reaction time and increase the molecular weight of the polymers. Owing to the strong intermolecular interactions between the neighboring 3-cyanothiophene-2,5-diyl units in the polymer backbone, the lamellar and edge-on structures of the polymer chains were induced on the substrate. The photovoltaic performance of these conjugated copolymers was also evaluated by preparing bulk heterojunction solar cell devices of ITO/PEDOT: PSS/PACT:PC71BM/Al.

Sequential one pot double C[sbnd]H heteroarylation of thiophene using bromopyridines to synthesize unsymmetrical 2,5-bipyridylthiophenes

We present CH heteroarylation reactions between thiophene and variously substituted bromopyridines. The objective was to synthesize unsymmetrical 2,5-bipyridylthiophenes. We studied the reaction conditions allowing to a sequential one-pot double CH heteroarylation, in a view to introduce two different pyridyl moieties at positions 2 and 5 of the thiophene ring using bromopyridines. 11 original unsymmetrical 2,5-bipyridylthiophenes were synthesized and characterized, including 2,5-di(pyridin-2-yl)thiophenes for which the preparation by classical cross-coupling reactions is challenging. Finally, with the additional synthesis of both an unsymmetrical 2,5-biarylthiophene and an original pyrimidin-thiophene-furan scaffold, we shown that our methodology was also an efficient tool to access to new heterocyclic sequences.

Optimized synthesis of π-extended squaraine dyes relevant to organic electronics by direct (hetero)arylation and Sonogashira coupling reactions.

This study reports on the synthesis and characterization of four molecular π-extended squaraine compounds relevant to the field of organic electronics. The compounds each consist of a bis-indole squaraine core end-capped with indoloquinoxaline units employing three different bridging units, namely thiophene, thiazole, and acetylene. Compound 10 bears a thiophene bridge, 11 consists of a thiophene bridge and fluorinated indoloquinoxaline terminal units, and compounds 12 and 13 are bridged by thiazole and acetylene, respectively. The final compounds are constructed using the atom economical direct (hetero)arylation or the classic Sonogashira carbon-carbon bond formation protocols. Each carbon-carbon bond forming reaction employing thiophene bridges (i.e. synthesis of compounds 10 and 11) has been optimized using the stable and reusable silica supported Pd catalyst, SiliaCat® DPP-Pd, streamlining the synthetic procedure. While compounds 12 and 13 were also accessible using the SiliaCat® DPP-Pd catalyst, the use of Herrmann-Beller and Pd(PPh3)4 catalysts, respectively, lead to improved isolated yields of the final materials. Compounds 10-13 were characterized by thermal gravimetric analysis, cyclic voltammetry, optical absorption spectroscopy, photoluminescence spectroscopy, and each structure was analysed using density functional theory. All compounds exhibit high thermal stability and good solubility in common organic solvents, including in the greener alternative 2-methyl tetrahydrofuran. The reported compounds display stable ambipolar redox behaviour, furthermore, we have demonstrated that the frontier molecular energy levels can be effectively tuned by changing the bridging unit as predicted by density functional theory. Most striking is the drastic optical absorption profile changes observed from this class of materials upon post-deposition film annealing, suggesting molecular rearrangement in the solid-state. The induced changes and fine structure observed upon post-deposition annealing is unique to these π-extended squaraines with nothing like it reported in the literature for related squaraine based materials.

Metal-Free Photocatalyzed Cross Coupling of Bromoheteroarenes with Pyrroles

The excited radical anion of rhodamine 6G reduces heteroaryl bromides and chlorides to generate heteroaryl radicals that were successively trapped by pyrroles for the synthesis of heteroaromatic biaryls in moderate to excellent yields. The synthetically important photoredox catalytic C–H heteroarylation reaction works for a broad range of brominated electron-rich heteroarenes and chlorinated heteroarenes bearing electron withdrawing groups. In addition, this methodology was applied to the formal synthesis of a benzimidazole derivative II with interesting pharmacological properties.

ChemInform Abstract: Achievement of Regioselectivity in Transition Metal‐Catalyzed Direct C—H (Hetero)Arylation Reactions of Heteroarenes with One Heteroatom Through the Use of Removable Protecting/Blocking Substituents or Traceless Directing Groups

AbstractReview: [175 refs.

ChemInform Abstract: Base‐Mediated Cyclocondensation of Salicylaldehydes and 2‐Bromoallyl Sulfones for the Synthesis of 3‐Sulfonylchromene Derivatives and Their Regioselective Friedel—Crafts Heteroarylation Reactions.

AbstractA transition metal‐free, vinylic bromide displacement reaction of bromoallyl sulfones (II) with phenolate nucleophiles is reported.

Transition Metal‐Free Direct CH (Hetero)arylation of Heteroarenes: A Sustainable Methodology to Access (Hetero)aryl‐Substituted Heteroarenes

AbstractIn recent years, environmental and economic reasons have motivated the development of transition metal‐free carbon‐carbon bond forming reactions and some excellent reviews have covered this research area of particular interest for the pharmaceutical industry. However, none of these reviews has been specifically dedicated to summarize and discuss the results achieved in the rapidly growing field of the transition metal‐free direct (hetero)arylation reactions of heteroarenes. This review, which covers the literature from 2008 to 2014, aims to provide a thorough insight into the synthetic and mechanistic aspects of these atom economic and environmentally benign reactions also highlighting their advantages and possible disadvantages compared to conventional methods for the synthesis of arylheteroarenes and biheteroarylsviatransition metal‐catalyzed reactions.magnified image

Base-Mediated Cyclocondensation of Salicylaldehydes and 2-Bromoallyl Sulfones for the Synthesis of 3-Sulfonylchromene Derivatives and Their Regioselective Friedel-Crafts Heteroarylation Reactions.

Cesium carbonate-mediated reaction of 2-hydroxybenzaldehydes and 2-bromoallyl sulfones afforded 2H- and 4H-chromenol derivatives endowed with a 3-arylsulfonyl group. 2-Bromoallyl sulfones functioned as synthetic equivalents of allenyl sulfones under these conditions. The 2H- and 4H-chromenol derivatives underwent regioselective Friedel-Crafts reactions with heteroarenes in the presence of p-toluenesulfonic acid to afford 4-heteroaryl-4H-chromene derivatives in excellent yields.

ChemInform Abstract: Copper‐Mediated C6‐Selective Dehydrogenative Heteroarylation of 2‐Pyridones with 1,3‐Azoles.

AbstractThe Cu(OAc)2‐mediated heteroarylation reactions use a pyridyl substituent on the nitrogen atom of the pyridone ring as directing group.

Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives.

Conditions allowing the one pot 2,5-diheteroarylation of 2,5-dibromothiophene derivatives in the presence of palladium catalysts are reported. Using KOAc as the base, DMA as the solvent and only 0.5–2 mol % palladium catalysts, the target 2,5-diheteroarylated thiophenes were obtained in moderate to good yields and with a wide variety of heteroarenes such as thiazoles, thiophenes, furans, pyrroles, pyrazoles or isoxazoles. Moreover, sequential heteroarylation reactions allow the access to 2,5-diheteroarylated thiophenes bearing two different heteroaryl units.

ChemInform Abstract: Cross‐Coupling of Heteroarenes by C—H Functionalization: Recent Progress Towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

AbstractReview: results obtained from January 2009 to February 2013 in the area of transition metal‐catalyzed title arylation reactions; 430 refs.

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

AbstractIn recent years, transition metal‐catalyzed direct (hetero)arylation reactions of heteroarenes with (hetero)aryl halides and pseudohalides have received significant attention as eco‐friendly and economic alternatives to classical methods for the construction of heteroaryl‐(hetero)aryl CC bonds by transition metal‐catalyzed cross‐couplings involving the use of stoichiometric amounts of organometallic reagents. This critical review with 430 references covers the results obtained in the period January 2009 to February 2013 in the area of the transition metal‐catalyzed direct inter‐ and intramolecular (hetero)arylation reactions of heteroarenes containing one heteroatom. Particular attention has been given to illustrate chemo‐ and site selectivity aspects of these reactions as well applications of these CC bond forming reactions in the synthesis of pharmaceutically relevant compounds, natural products and their analogues and precursors. The most recent advancements into the mechanism(s) of these reactions have also been briefly reported.magnified image