Coupling Cyclization Reaction Research Articles

BF3 ⋅ OEt2 as a Versatile Reagent: Applications in Organic Synthesis

AbstractBoron trifluoride diethyl etherate, commonly referred to as BF3 ⋅ OEt2, plays a crucial role as a potent reagent in various organic transformations, particularly in the synthesis of heterocyclic systems through the establishment of carbon‐carbon & carbon‐heteroatom bonds. Its Lewis acid properties, reactivity, and stability at room temperature make it essential for a wide range of chemical reactions. BF3 ⋅ OEt2 demonstrates remarkable efficacy in processes such as hydroxylation of double bonds, epoxide cleavage, acid esterification, cyanation, coupling, and diverse cyclization reactions, surpassing other Lewis acids in performance. Its significant impact on organic synthesis extends to the formation of natural products, highlighting its profound significance in the realm of chemistry. The unique properties and versatility of boron trifluoride diethyl etherate make it a fundamental tool for a diverse array of chemical transformations. The numerous applications of this reagent in organic synthesis have prompted the development of a comprehensive review, focusing on its various roles and contributions in this field.

Benzo[4,5]imidazo[1,2-a]pyrimidine-based structure-inherent targeting fluorescent sensor for imaging lysosomal viscosity and diagnosis of lysosomal storage disorders

Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines, pesticides, tracers and photoelectric materials. However, their synthesis approach still needs to be optimized, and their fluorescent properties in intracellular microenvironment are unclear. Here, a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions, broad substrate scopes and high yields. After a system study, we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement (102-fold) for glycerol at 490 nm. Particularly, 4aa possessed excellent structure-inherent targeting (SIT) capability for lysosome (P = 0.95) with high pH stability and large Stokes shift. Importantly, 4aa was validated for its effectiveness in diagnosing lysosomal storage disorders (LSD) in living cells. The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish. This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives, reveals this skeleton has excellent SIT features for lysosome, but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.

Synthesis of N‐Sulfonyl Amidines and 1,3,4‐Oxadiazoles through Electrochemical Activation of DMF

AbstractElectrochemical routes for the synthesis of N‐sulfonyl amidines and 1,3,4‐oxadiazoles are reported through the activation of DMF molecule. Successful implementation of electro‐redox on dehydrative coupling and oxidative cyclization reactions eliminates the necessity of stoichiometric chemical oxidants and minimizes the generation of reagent waste. Both protocols exhibited broad functional group tolerance, permitting a widespread substrate scope with 47–94% isolated yield. Several control experiments and cyclic voltammetry studies were performed and mechanistic details of these transformations are thoroughly outlined.magnified image

Visible Light-Induced Coupling Cyclization Reaction of α-Diazosulfonium Triflates with α-Oxocarboxylic Acids or Alkynes.

A photocatalyst-free radical cleavage of α-diazo sulfonium salts has been developed for the first time. The reaction provides an efficient method for the generation of diazomethyl radicals from α-diazosulfonium triflates under photochemical conditions. Utilizing the in situ generated diazomethyl radicals as key intermediate, the coupling cyclization reaction of α-diazosulfonium triflates with α-oxocarboxylic acids or alkynes has been achieved. The method affords a diverse set of important 2,5-disubstituted 1,3,4-oxadiazoles and 3,5-disubstituted-1H-pyrazoles with excellent regioselectivity in a single step. A reaction mechanism involving a radical pathway was further supported by control experiments and DFT calculations.

The Synthesis of 2-substituted Benzo[b]furans Catalyzed by Ni/5-Bromo- 2,2’-bipyridine

Abstract: A tandem system that enabled the synthesis of 2-substituted benzo[b]furans from 2- halophenols and aryl acetylenes catalyzed by Ni/5-bromo-2,2’-dipyridine was explored. The protocol was found effective for one-pot cascade coupling cyclization reaction producing benzo[b]furan compounds, and heteroaryl substrates were observed to be compatible for this system as well, giving corresponding products in 20-70% yields.

Copper-Catalyzed 6-endo-dig Cyclization-Coupling of 2-Bromoaryl Ketones and Terminal Alkynes toward Naphthyl Aryl Ethers in Water.

The cyclization-coupling reaction of 2-bromoaryl ketones and terminal alkynes is first realized by copper catalysis, which produces polyfunctional naphthyl aryl ethers in moderate to excellent yields with broad substrate scope and good functional group tolerance. This reaction proceeds via 6-endo-dig cyclization and C(sp2)-O coupling using green H2O as the unique solvent and 5-bromopyrimidin-2-amine as the critical additive. Mechanistically, a unique Cu(III)-acetylide probably is the key intermediate, which allows exclusive 6-endo-dig selectivity.

Synthesis and crystal structures of unsymmetrical wave-shaped heptathienoacenes.

Three unsymmetrical wave-shaped heptathienoacenes (UHT-1, UHT-2 and UHT-3) with sulfur atoms at different isomeric locations in the two terminal thiophene rings were designed and synthesized. The synthetic strategy contains two crucial steps, including the cross-coupling of two different dithienothiophene isomers (DTT) from dithieno[2,3-b:3',2'-d]thiophene (bb-DTT), dithieno[2,3-b:2',3'-d]thiophene (bt-DTT) and dithieno[2,3-b:3',4'-d]thiophene (bs-DTT) as building blocks through the Negishi coupling and intramolecular cyclization reactions with (SnBu3)2S. X-ray crystal structures of UHT-1, UHT-2 and UHT-3 show that the molecules adopt a wave-shaped geometry with multiple intermolecular interactions, such as S-S, S-C and S-H, which result in different crystal packing patterns. The isomeric location of the sulfur atoms of the two terminal thiophene rings of UHT-1, UHT-2 and UHT-3 plays an important role in tuning π-electronic conjugation and spectroscopic behaviors.

Electrochemical synthesis for benzisothiazol-3(2H)-ones by dehydrogenative N[sbnd]S bond formation

Herein, we report an electrochemical method for the synthesis of benzisothiazol-3(2H)-ones from 2-mercaptobenzamides. The electrochemical reaction proceeds through intramolecular NH/SH coupling cyclization reaction by generating H2 as the nonhazardous side product. Moreover, the developed procedure is highly advantageous due to its short reaction time, mild conditions and wide substrate scope without the employment of metal catalyst and exogenous-oxidant.2009 Elsevier Ltd. All rights reserved.

Enantioselective Reductive Divinylation of Unactivated Alkenes by Nickel-Catalyzed Cyclization Coupling Reaction.

Catalytic asymmetric dicarbofunctionalization of tethered alkenes has emerged as a promising tool for producing chiral cyclic molecules; however, it typically relies on aryl-tethered alkenes to form benzene-fused compounds. Herein, we report an enantioselective cross-electrophile divinylation reaction of nonaromatic substrates, 2-bromo-1,6-dienes. The approach thus offers a route to new chiral cyclic architectures, which are key structural motifs found in various biologically active compounds. The reaction proceeds under mild conditions, and the use of chiral t-Bu-pmrox and 3,5-difluoro-pyrox ligands resulted in the formation of divinylated products with high chemo-, regio-, and enantioselectivity. The method is applicable for the incorporation of chiral hetero- and carbocycles into complex molecules.

Synthesis of C3-Symmetric Triazine-Based Derivatives: Study of their AIEE, Mechanochromic Behaviors, and Detection of Picric Acid and Uric Acid in Aqueous Medium

A smart accessible D-A with a tripod shape of triazine derivatives such as TZOME, TZSET, and TZNET was synthesized through simple Suzuki–Miyaura coupling and cyano cyclization reaction. Remarkably, TZNET has excellent optical properties compared to TZOME and TZSET. In particular, TZNET exhibits enhanced emission, induced through aggregation and mechanochromic luminescence. More interestingly, AIEE-fluorescent TZNET has a turnoff fluorescence sensor for picric acid with an LOD of 203 nM and a turn-on sensor for uric acid with an LOD of 209 nM. To the best of our knowledge, this is the first dual-coupled sensor for picric acid and uric acid in an aqueous medium.

Metal-Free Indole-Phenacyl Bromide Cyclization: A Regioselective Synthesis of 3,5-Diarylcarbazoles.

A metal-free, simultaneous triple C-C coupling cyclization reaction between phenacyl bromides and indoles is discovered in a highly regioselective fashion to furnish 3,5-diarylcarbazoles. DMAP is utilized as the only reagent for the unusual and rapid cyclization reaction to furnish all new carbazole compounds through installation of a great diversity of substituents. A plausible radical mechanism for the new reaction is predicted by conducting various control experiments, competitive reactions, furoindole formation, and ESI-MS analyses of the ongoing cyclization reaction.

Rhodium/copper-cocatalyzed coupling-cyclization of o-alkenyl arylisocyanides with vinyl azides: one-pot synthesis of α-carbolines

A novel rhodium/copper-cocatalyzed coupling–cyclization reaction of o-alkenyl arylisocyanides with vinyl azides has been developed. The reaction provides a new route to α-carbolines by the formation of two C–C bonds, one C–N bond and two aromatic rings in a single step.

One‐Step Synthesis of Trifluoroethylated Chromones via Radical Cascade Cyclization–Coupling of 2‐(Allyloxy)arylaldehydes

A transition‐metal‐free synthetic protocol involved with trifluoromethyl radical addition–cyclization of 2‐(allyloxy)arylaldehydes for a series of CF3‐containing 3‐substituted chromenones formation has been developed. The radical cascade cyclization–coupling reaction can be run in a one‐step manner with Langlois′ reagent (CF3SO2Na) and K2S2O8. Broad scopes of substrates with various functional groups are evaluated in moderate to good efficacy under operational simplicity and mild reaction conditions. A plausible mechanism for the construction of trifluoroethylated chromones is proposed based on mechanistic studies.

Metal-Free Cascade [4 + 1] Cyclization Access to 4-Aryl-NH-1,2,3-triazoles from N-Tosylhydrazones and Sodium Azide.

A molecular iodine-mediated coupling cyclization reaction for the synthesis of 4-aryl-NH-1,2,3-triazoles has been developed from N-tosylhydrazones and sodium azide. This metal-free cascade [4 + 1] cyclization reaction could rapidly synthesize valuable compounds via a sequential C-N and N-N bond formation. Mechanistic studies demostrate that the nitrogen atoms of the 1,2,3-triazoles are not entirely from sodium azide.

Palladium(II) Acetate Catalyzed Cyclization–Coupling of (o-Ethynylphenyl)phosphonic Acid Monoesters with Allyl Halides

A Pd(OAc)2-catalyzed tandem cyclization–coupling reaction of (o-ethynylphenyl)phosphonic acid monoesters and allyl halides has been developed. This reaction provides an efficient, mild, general and regioselective way to synthesize 4-allylphosphaisocoumarins.

Rhodium-Catalyzed Coupling-Cyclization of Alkenyldiazoacetates with o-Alkenyl Arylisocyanides: A General Route to Carbazoles.

A rhodium-catalyzed coupling-cyclization reaction of alkenyldiazoacetates with o-alkenyl arylisocyanides has been developed. In this reaction, the highly reactive alkenylketenimine intermediates generated by coupling reaction of alkenyldiazoacetates with o-alkenyl arylisocyanides undergo intramolecular [4 + 2] cycloaddition and provide a novel, highly efficient method for the one-step synthesis of carbazoles by formation of three new bonds and two rings from readily available acyclic starting materials.

Synthesis and coupling of ABx polysiloxane macromonomers to form highly branched polysiloxanes

This work focuses on the synthesis of polysiloxane ABx macromonomers with functional groups (A [Si-H] and B [vinyl]) incorporated on to the polymer backbone, and the coupling of these functionalities to form randomly, but highly, branched polymers. The synthesis of the ABx macromonomers was performed by the anionic copolymerization of hexamethylcyclotrisiloxane (D3) and 1,3,5-trivinyl-1,3,5-trimethylcyclotrisiloxane (V3) monomers, followed by an end-capping/termination reaction with chloro(methyl)phenylsilane. The resulting macromonomers were coupled by a Pt(0) catalyzed hydrosilylation reaction, to yield highly branched polysiloxanes. The coupling reaction was investigated at different solution concentrations and using macromonomers with different extents of vinyl content. It was shown that a higher solution concentration resulted in higher degrees of chain coupling and branching, arising from efficient intermolecular coupling in preference to (the competing) intramolecular coupling (cyclization) reaction. Moreover, an increase in the mole fraction of vinyl monomer also resulted in higher levels of branching. With the ability to control the degree of branching, the strategy reported here provides a facile route to synthesize branched polysiloxanes (silicones) with varying flexibility and elasticity.

A Diindole-fused Corannulene Imide Derivative: Synthesis and Properties

A diindole-fused corannulene imide derivative was synthesized through two steps, Suzuki coupling and subsequent reductive cyclization reaction. Fusing indole rings to corannulene imide led to significantly red-shifted absorption, a lower HOMO–LUMO band gap, and a lower bowl-to-bowl inversion barrier than those of corannulene imide. The heterocycles also decreased the aromaticity of the rings of corannulene moiety adjacent to heterocycles.

(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2/CuI as Cocatalyst for Coupling-Cyclization of 2-Iodophenol with Terminal Alkynes in Water

A new and efficient [(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2/CuI-co-catalyzed coupling-cyclization reactions of 2-iodophenol with terminal alkynes is described. Different 2-substitued benzo[b]furan derivatives are obtained in good to excellent yields. This protocol employs a relatively low palladium(II) catalyst loading in water under air conditions.

Investigating the stereochemical outcome of a tandem cyclization-coupling reaction leading to a 3-arylideneisobenzofuran-1-one

Investigating the stereochemical outcome of a tandem cyclization-coupling reaction leading to a 3-arylideneisobenzofuran-1-one