Coupling Cyclization Reaction Research Articles

Novel π-conjugated molecules based on diimidazopyridine: Significantly improved the photophysical, thermal and electrochemical properties bearing different aryl substituents

A series of π-conjugated molecules based on diimidazolepyridine derivatives were designed, synthesized by Suzuki coupling reaction and cyclization reaction and characterized. Diimidazolepyridine motif as the main structure could improve the thermal stability and optical property of the materials. All of the target compounds exhibited good thermal stabilities with Td values in the range of 416–490 °C. These compounds showed steady blue light emissions in the range of 424–478 nm and high quantum yields (0.33–0.69) in solution. Especially, compound 4f achieved appropriate energy gap (Eg = 2.69 eV) and high fluorescence quantum yields (Φf = 0.69) because of introducing electron-donating group, such energy gap was helpful to electronic transfer and transport. The materials have great potential for good electronic-transmission materials in OLEDs.

1‐Phenyl‐1,2‐benziodoxol‐3‐(1H)‐one as Synthon for Phthalide Synthesis through Pd‐Free, Base‐Free, Sonogashira‐Type Coupling Cyclization Reaction

Hypervalent iodine(III) five‐membered heterocycles have found broad application as atom‐transfer reagents for organic synthesis. Among them, 1‐phenyl‐1,2‐benziodoxol‐3‐(1H)‐one is known as a traditional benzyne precursor, but no further synthetic applications have been reported. Herein, we report the first synthetic application of 1‐phenyl‐1,2‐benziodoxol‐3‐(1H)‐one to the synthesis of phthalides by using only CuI as catalyst. High selectivity and yields were achieved under mild reaction conditions with good functional group tolerance. During our investigations, the efficiency of different CuI and CuII catalysts under various reaction conditions were studied. The nature of the leaving group, the substituents on the substrate, and the temperature play an important role on both yield and selectivity. Moreover, a plausible mechanistic pathway for this transformation was proposed based on our observations and previous literature reports.

Synthesis of substituted benzofurans and indoles by Zn-catalyzed tandem Sonogashira-cyclization strategy

Transition metal catalyzed cross-coupling reactions are one of the predominant strategies for the construction of heterocyclic structures which possess wide applications in the synthesis of natural products, pharmaceuticals, polymers, etc. Due to the vast importance of substituted benzofurans and indoles, numerous synthetic methodologies have been introduced for their synthesis. Among these methods, transition metal catalyzed cyclization reactions possess a unique position. In this manuscript, we disclose the first and efficient zinc-catalyzed protocol for the cyclization reactions of alkynes with 2-iodophenol and 2-iodoaniline leading to benzofurans and indoles respectively via a tandem Sonogashira coupling-cyclization process. Among the different metal catalysts, zinc has enormous potential due to its great availability, non-toxicity, eco-friendly and inexpensive nature.Zn(II) with N,N′-dimethylethylenediamine represents a suitable and efficient catalytic system for the desired tandem CC coupling-cyclization reactions, and a broad spectrum of functional groups are tolerated during the catalysis. A variety of substituted benzofurans and indoles have been successfully prepared in moderate to good yields under this new protocol.

Multifold C-C Coupling and Unorthodox Cyclization Catalysis for Selective Synthesis of Indolotriarylmethanes, Indolocarbazoles, and Their Analogues: A Control Experiment Study.

The selective construction of medicinally and synthetically important indole-based unsymmetrical triarylmethanes using indoles and aldehydes is challenging because the significant nucleophilicity of indole leads to C-C coupling with an azafulvene intermediate to build up the alternative bis(indolyl)methane products, which may be useful synthons. A new, straightforward, ligand-free CuII catalytic strategy for easy syntheses of unsymmetrical indolotriarylmethanes and new bisindolylbenzoyl analogues is established through the dual C-C coupling of an assembly of three reaction partners comprising aldehydes, indoles, and arylboronic acids. More importantly, this approach is exploited for multifold C-C coupling cyclization reactions with C-C cleavage using symmetrical bisindolylbenzoylmethanes in the presence of an organic base and aerial molecular oxygen as a stoichiometric oxidant. In contrast to the formation of a simple cyclocondensation product indolocarbazole, it undergoes unprecedented selective pseudo-four-component tandem oxidative cyclization with fragmentation from a 1,3-dicarbonyl compound to produce valuable fused 5,7-dihydroindolo[2,3-b]carbazoles through the functionalization of two indole C(sp2)-H and one C(sp3)-H bond of the active methylene residue. For a better understanding of the new reactions, we have studied various competition experiments and ESI-MS and 3D Mid-IR-ATR spectral analyses of the ongoing reactions. The predicted DFT transition state model is also in agreement with the experimental results.

ChemInform Abstract: Palladium‐Catalyzed Dehydrogenation Coupling—Cyclization Reactions of Acetylenic Acids with Iodonium Ylides for the Synthesis of 2(5H)‐Furanones.

A new route for the synthesis of 2(5H)-furanones is presented via Pd(PPh3)4-catalyzed cascade reaction of acetlenic acids with iodonium ylides using K2CO3 as the base. The cascade proceeds through dehydrogenation coupling and cyclization under mild conditions.

ChemInform Abstract: Multicomponent Coupling Cyclization Access to Cinnolines via in situ Generated Diazene with Arynes, and α‐Bromo Ketones.

AbstractThe reaction tolerates various aryl substituted α‐bromo ketones, but no heterocyclic or alkyl substituted α‐bromo ketones.

Synthesis of novel 1,2,3-triazole derivatives of 2,3-dihydroquinazolin-4(1H)-one

This work reports an efficient route for the synthesis of novel 1,2,3-triazole derivatives of 2,3-dihydroquinazolin-4(1H)-one starting from isatoic anhydride via a three-step reaction. The resulting 2-amino-N-substituted benzamides from the reaction of isatoic anhydride and benzylamines underwent coupling cyclization reaction with 4-(prop-2-yn-1-yloxy)benzaldehyde, and then click reaction with in situ prepared organic azides afforded the title compounds in good yields.

Copper-catalyzed Ullmann reaction for the synthesis of fused hexacyclic heterocycles containing naphthyridine, acridine, and pyrazole (imidazole) moieties

Consecutive Knoevenagel condensation, Michael addition, cyclization, and Ullmann Csp2-N coupling reactions took place in the Domino reaction of o-halogenated benzaldehydes, tert-butyl 2,4-dioxopiperidine-1-carboxylate, and 1H-indazol-6-amine or 3H-benzo[d]imidazol-5-amine catalyzed by CuI. It gave series of fused hexacyclic heterocycles containing naphthyridine, acridine, and pyrazole (imidazole) moieties in one-pot under ligand-free conditions.

Cu–Pd/γ-Al2O3catalyzed the coupling of multi-step reactions: direct synthesis of benzimidazole derivatives

Catalyzed by the synergy effects of Cu–Pd bimetal and acidity of γ-Al2O3, the transfer hydrogenation and successive cyclization coupling reaction fromo-nitroaniline and alcohol to afford benzimidazole derivatives in high yield was realized.

Multicomponent Coupling Cyclization Access to Cinnolines via in Situ Generated Diazene with Arynes, and α-Bromo Ketones.

A transition-metal-free multicomponent coupling cyclization reaction was explored involving arynes, tosylhydrazine, and α-bromo ketones. The reaction proceeds via a formal [2 + 2 + 2] cycloaddition, giving access to cinnoline derivatives in moderate yields under mild conditions. Three chemical bonds were formed-two C-N bonds and one C-C bond-in a single step.

Palladium-Catalyzed Dehydrogenation Coupling–Cyclization Reactions of Acetylenic Acids with Iodonium Ylides for the Synthesis of 2(5H)-Furanones

A new route for the synthesis of 2(5H)-furanones is presented via Pd(PPh3)4-catalyzed cascade reaction of acetlenic acids with iodonium ylides using K2CO3 as the base. The cascade proceeds through dehydrogenation coupling and cyclization under mild conditions.

ChemInform Abstract: A Simple Access to N‐(Un)substituted Isoquinolin‐1(2H)‐ones: Unusual Formation of Regioisomeric Isoquinolin‐1(4H)‐ones.

AbstractThe coupling—cyclization reaction of 2‐iodobenzamides (I) with terminal alkynes (II) in the presence of a catalytic amount of cupric acetate leads to isoquinolin‐1(2H)‐ones (III), whilst the reaction of amide (Ia) with alkynes (II) in the presence of excess Cu(O‐Ac)2 affords regioisomeric isoquinolin‐1(4H)‐ones (IV).

ChemInform Abstract: A Cyclization—Carbonylation—Cyclization Coupling Reaction of (ortho‐Alkynyl Phenyl) (Methoxymethyl) Sulfides with the Palladium(II)‐Bisoxazoline Catalyst.

A cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of (o-alkynylphenyl) (methoxymethyl) sulfides, catalyzed by (box)PdII complexes, afforded symmetrical ketones bearing two benzo[b]thiophene groups in good to excellent yields. This method is applicable to a broad range of substrates.

ChemInform Abstract: Palladium‐Catalyzed Cyclization Reactions of Allenes in the Presence of Unsaturated Carbon—Carbon Bonds

AbstractReview: 60 refs.

A Practical Synthesis of Chiral Oxazolines through a Highly Diastereoselective Coupling–Cyclization Reaction of N‐(Buta‐2,3‐dienyl)amides and Aryl Iodides

AbstractA highly trans diastereoselective synthesis of 2,4,5‐trisubstituted oxazoline derivatives is described that proceeds through a palladium‐catalyzed coupling–cyclization reaction of N‐(buta‐2,3‐dienyl)amides with aromatic iodides. The reaction with optically active substrates provides convenient access to highly enantioenriched oxazoline derivatives with excellent 1,2‐induction.

Facile regioselective synthesis and antimicrobial activity of heterocycle-phosphor esters

Several heterocycle-phosphor esters of moderate to good antimicrobial activity were efficiently obtained via applying different phosphorus reagents to the substrate 6-hydroxy-1,3-benzoxathiol-2-one. Benzothiophene-3-diethoxyphosphonates were obtained from the condensation reaction between the substrate and methyl, ethyl diethyl-phosphorylacetates, and diethyl cyanomethylenephosphonate. A coupling cyclization reaction of our substrate with vinyl- and allylphosphonates led to the corresponding benzoxathiaphosphinin-3(2H)-one oxides. On the other hand, an addition-cyclization reaction of dialkyl hydrogenphosphonates and tris(dialkylamino)phosphines with the oxathiolone substrate resulted in the formation of a series of 1,4,2-benzoxathiaphosphinin-3(2H)-one oxides. Screening results of antibiotic potency for the products were reported. .

Palladium-Catalyzed Cyclization Reactions of Allenes in the Presence of Unsaturated Carbon–Carbon Bonds

Modern synthetic chemists have looked for rapid and efficient ways to construct complex molecules while minimizing synthetic manipulation and maximizing atom-economy. Over the last few decades, researchers have made considerable progress toward these goals by taking full advantage of transition metal catalysis and the diverse reactivities of allenes, functional groups which include two cumulative carbon-carbon double bonds. This Account describes our efforts toward the development of Pd-catalyzed cyclization reactions of allenes in the presence of compounds that contain unsaturated carbon-carbon bonds such as alkenyl halides, simple alkenes, allenes, electron-deficient alkynes, or propargylic carbonates. First, we discuss the coupling-cyclization reactions of allenes bearing a nucleophilic functionality in the presence of alkenyl halides, simple alkenes, functionalized and nonfunctionalized allenes, or electron-deficient alkynes. These processes generally involve a Pd(II)-catalyzed sequence: cyclic nucleopalladation, insertion or nucleopalladation, and β-elimination, reductive elimination, cyclic allylation or protonation. We then focus on Pd(0)-catalyzed cyclization reactions of allenes in the presence of propargylic carbonates. In these transformations, oxidative addition of propargylic carbonates with Pd(0) affords allenylpalladium(II) species, which then react with allenes via insertion or nucleopalladation. These transformations provide easy access to a variety of synthetically versatile monocyclic, dumbbell-type bicyclic, and fused multicyclic compounds. We have also prepared a series of highly enantioenriched products using an axial-to-central chirality transfer strategy. A range of allenes are now readily available, including optically active ones with central and/or axial chirality. Expansion of these reactions to include other types of functionalized allenes, such as allenyl thiols, allenyl hydroxyl amines, and other structures with differing steric and electronic character, could allow access to cyclic skeletons that previously were difficult to prepare. We anticipate that other studies will continue to explore this promising area of synthetic organic chemistry.

Copper-catalysed intramolecular O-arylation: a simple and efficient method for benzoxazole synthesis.

A wide range of 2-substituted benzoxazoles can be efficiently synthesized from N-(2-iodo-/bromo-phenyl)benzamides, and even the less reactive N-(2-chlorophenyl)benzamides, via Cu-catalysed intramolecular coupling cyclization reactions using methyl 2-methoxybenzoate as the ligand under mild reaction conditions. In addition, the benzoxazoles can be easily prepared from the primary amides coupling with o-dihalobenzenes in a single step.

Divergent Total Synthesis of the Lycopodium Alkaloids Huperzine A, Huperzine B, and Huperzine U

Huperzine A, huperzine B, and huperzine U are congeners isolated from the Chinese herb Huperzia serrata (= Lycopodium serratum ) in minuscule amounts. The most efficient total synthesis of huperzine A, the first asymmetric total syntheses of huperzine B, and the first total synthesis of huperzine U have been achieved efficiently in overall yields of 17%, 10%, and 9%, respectively, each spanning 10-13 steps from (R)-pulegone. The featured steps include palladium-catalyzed Buchwald-Hartwig coupling and Heck cyclization reactions and an Ir-catalyzed olefin isomerization reaction. This work has established the absolute configurations of huperzine B and huperzine U and revealed that natural huperzine A, huperzine B, and huperzine U possess the same set of absolute stereochemistries, thus providing support for the potential role of huperzine B and huperzine U in the biosynthesis of huperzine A.

Novel Four-Step Synthesis of Thioxo-quinazolino[3,4-a]quinazolinone Derivatives

A novel synthesis of thioxo-quinazolino[3,4-a]quinazolinone framework was developed through a four-step reaction starting from isatoic anhydride. The resulting 2-aminobenzamides from the reaction of isatoic anhydride and different amines underwent coupling–cyclization reaction with 2-nitrobenzaldehydes, reduction of nitro group, and then cyclization reaction with carbon disulfide (CS2). All steps were carried out under easy and user-friendly conditions in a short time without using expensive catalysts or reagents. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]