Cyclization Of Alkynes Research Articles

Photochemical difluoromethylation of alkynes: synthesis of CF2H-substituted seven-membered dioxodibenzothiazepines and dibenzazepines

A general and efficient photochemical strategy for difluoromethylation/radical cascade cyclization of alkynes with sodium difluoromethylsulfinate (NaSO2CF2H) has been disclosed.

Computational insight into gold(I)-catalyzed intramolecular regioselectivity of tryptamine-ynamide cycloisomerizations.

The regioselectivity for gold(I)-catalyzed intramolecular cycloisomerizations of tryptamine-ynamides has long been elusive despite various synthetic examples of similar substrates being available. Computational studies were carried out to provide insight into the mechanisms and the origin of the substrate-dependent regioselectivity of these transformations. Based on the analyses of non-covalent interactions, distortion/interaction, and energy decomposition on the interactions between the terminal substituent of alkynes and the gold(I) catalytic ligand, the electrostatic effect was determined to be the key factor for α-position selectivity while the dispersion effect was determined to be the key factor for β-position selectivity. Our computational results were consistent with the experimental observations. This study provides useful guidance for understanding other similar gold(I)-catalyzed asymmetric alkyne cyclization reactions.

Facile synthesis of 2-aza-9,10-diphenylanthracene and the effect of precise nitrogen atom incorporation on OLED emitters performance.

Polycyclic aromatic hydrocarbons (PAHs) are important compounds in materials chemistry, particularly for optoelectronic applications. One strategy for tuning PAH properties involves the net exchange of carbon atoms for heteroatoms, such as nitrogen. We report a comparative study of the well-known fluorophore 9,10-diphenylanthracene with an aza analog. The latter compound is accessed using a short sequence involving the use of two strained cyclic alkynes, benzyne and a 3,4-piperidyne, in Diels-Alder cycloaddition sequences. Comparative studies of 9,10-diphenylanthracene and the aza-analog show how the addition of a single nitrogen atom impacts electrochemical and optical properties. Organic light-emitting diode (OLED) devices were prepared using both compounds, which showed that nitrogen substitution leads to an unexpected red shift in electroluminescence, likely due to exciplex formation between the active layer and the 4,4'-N,N'-bis[N-(1-naphthyl)-N-phenylamino]biphenyl (NPB) hole-transport layer. These studies highlight a unique approach to accessing heteroatom-containing PAHs, while underscoring the impact of heteroatoms on OLED device performance.

Palladium(0)-Catalyzed Anti-Selective Addition-Cyclizations of Alkynyl Electrophiles.

Palladium(0)/monophosphine complexes catalyze anti-selective alkylative, arylative, and alkynylative cyclizations of alkynyl electrophiles with organometallic reagents. The remarkable anti-selectivity results from novel oxidative addition, that is, the nucleophilic attack of electron-rich palladium(0) on the electrophile across the alkyne followed by transmetalation and reductive elimination ("anti-Wacker"-type cyclization). With regard to 5-alkynals, triphenylphosphine (PPh3 )-ligated palladium(0) catalyzes the cyclization of terminal alkynes and conjugated alkenyl- or alkynyl-substituted ones to afford 2-cyclohexen-1-ol and 2-alkylidene-cyclopentanol derivatives, respectively. For 6-alkyl- or 6-aryl-5-alkynals, the cyclization does not proceed with the palladium/PPh3 catalyst; however, it does proceed with palladium/tricyclohexylphosphine (PCy3 ), to yield the former products predominantly. Remarkably, the latter catalyst completely switches the regioselectivity in the cyclization of the conjugated diyne-aldehydes. Notably, palladium/PPh3 -catalyzed cyclizations also proceed with other organometallics or even without them.

Modular PET Agent Construction Strategy through Strain-Promoted Double-Click Reagent with Efficient Photoclick Step.

An efficient modular strategy for rapid assembly of positron emission tomography (PET) agents has been developed. The use of a sequential, rapid, and selective double-click reaction allows for a combinatorial approach to the cross-linking of positron emitter-bearing prosthetic groups with various ligands. The strain-promoted azide alkyne cyclization (SPAAC) coupling of 18F-labeled azide synthon with MC-DIBOD, a cyclooctadiyne with one of the triple bonds caged as a cyclopropenone moiety, produces a stable intermediate. A brief exposure of the latter to 350-420 nm light removes protection of the second triple bond allowing for the addition of an azide-tagged biomolecule. The utility of this strategy has been demonstrated by the construction of several PET agents. The value of modularity was demonstrated in the preparation of PSMA PET agents, where the hydrophilicity was easily modified to improve tumor to background contrast.

Direct Electrooxidative Selenylation/Cyclization of Alkynes: Access to Functionalized Benzo[b]furans.

A mild, practical, metal and oxidant-free methodology for the synthesis of various C-3 selenylated benzo[b]furan derivatives was developed through the intramolecular cyclization of alkynes promoted with diselenides via electrooxidation. A wide range of selenium-substituted benzo[b]furan derivatives were obtained in good to excellent yields with high regioselectivity under constant current in an undivided cell equipped with carbon and platinum plates as the anode and cathode, respectively. Moreover, the convergent approach exhibited good functional group tolerance and could be easily scaled up with good efficiency, providing rapid access to a diverse range of selenylated benzo[b]furans derivatives from simple, readily available starting materials.

Photoinduced Tandem Cyclization of Alkynes with Phenylsulfinic Acids: Access to Sulfone-Substituted Dioxodibenzothiazepines or Dibenzazepines

AbstractPhotoinduced tandem cyclization of alkynes with phenylsulfinic acids has been accomplished, which gives a mild strategy for the preparation of sulfone-substituted seven-membered N-heterocycles. A variety of scaled-up experiments, further transformations, and mechanistic studies were also operated in the follow-up work.

Cu‐catalyzed synthesis of 1‐naphthols with terminal alkynes and 2‐bromoaryl ketones

A Cu‐catalyzed straightforward synthesis of 1‐naphthols via an 6‐endo‐dig cyclization of terminal alkynes with 2‐bromoaryl ketones in water is reported. The Cu(I) catalytic system tolerates various electron‐withdrawing and electron‐donating functional groups on both substrates and exhibits unique 6‐endo‐dig selectivity to give 1‐naphthols in moderate to good yields.

Alkyne‐Based Syntheses of Carbo‐ and Heterohelicenes

Abstract[n]Helicenes are polycyclic aromatic molecules in which n ortho‐condensed benzene or other aromatic rings give rise to helical chiral and highly conjugated structures. The unique screw shape, helically extended π‐system and intriguing electronic and chirooptical properties of these molecules have attracted scientific interest for decades. The applications of helicenes have now expanded into several fields including material science, nanoscience, biochemistry, supramolecular and polymer chemistry. Despite the great theoretical and practical interest in helicenes, their synthesis remains a challenge. Among synthetic approaches to helicenes, alkyne cyclizations have great potential, since carbon‐rich high‐energy alkynes can form aromatic rings via cycloisomerizations. These processes are atom‐economic. In addition, alkyne reactions are highly favorable thermodynamically. This review focuses on alkyne‐based syntheses of carbo‐ and heterohelicenes (2000–2022). These syntheses are obviously multistage. In the review, they are systematized in terms of the key step leading to the formation of a helical shape. The methods are grouped into two categories: (a) metal‐free syntheses and (b) transition‐metal‐catalyzed syntheses. This division is very arbitrary, since catalytic Sonogashira and Suzuki‐Miyaura reactions and others are often used to prepare starting materials in the syntheses of the first group. Most of the publications on the topic are related to transition‐metal‐catalyzed syntheses of helicenes.magnified image

Copper-Catalyzed Diastereo- and Enantioselective Borylative Cyclization

Copper-catalyzed enantioselective borylative cyclization with various electrophiles via difunctionalization of unsaturated hydrocarbons is a powerful tool for the generation of interesting boron-containing carbocycles and heterocycles processes involving a chiral organocopper intermediate. Alkenes, allenes, and alkynes are versatile and easily accessible substrates that can be subjected to a wide range of reactions to produce densely functionalized, enantioenriched products. In this chapter, I discuss copper-catalyzed alkenes, allenes, and alkynes borofunctionalization and enantioselective cyclization via chiral organocopper intermediate. Copper-catalyzed enantioselective borylative cyclization and regiodivergent functionalization of alkenes, allenes, and alkynes, as well as the current mechanistic understanding of such processes, are given special attention in this review.

Photochemical assisted novel formation of δ-lactone utilizing trimethylsilylacetylene, isopropanol and ironpentacarbonyl

As evidenced by previous research, photochemical reaction of terminal acetylene and ironpentacarbonyl produces a variety of products with slight changes in reaction conditions. The time of UV-irradiation is one of the most important parameter which decide the selectivity of the product of the reaction. In this report, a novel method for the synthesis of a (tricarbonyl)iron complex of δ-lactone/2-pyranone has been achieved by photochemical reaction of trimethylsilyl acetylene, ironpentacarbonyl and iso-propanol. The pyranone ring was formed by the cyclization of acetylene, iso-propanol and carbonmonoxide. Further, the Fe(CO)3 moiety coordinatively attaches to the π-electron clouds of lactone ring. The successful transformation of 2-pyranone from the (tricarbonyl)iron complex of 2-pyranone was also established by following the demetalation of Fe(CO)3. The formation of (tricarbonyl)iron complex and 2-pyranone were confirmed by various spectroscopic techniques, which includes the 1H, 13C and mass spectrometry. Moreover, the molecular structure of (tricarbonyl)iron complex of δ-lactone or 2-pyranone was established by the single crystal X-ray diffraction analysis.

Visible-Light-Induced Organocatalyzed [2+1] Cyclization of Alkynes and (Trifluoroacetyl)silanes

AbstractThe synthesis of common cyclopropenes has been widely studied, but the synthesis of cyclopropenols is a significant challenge. Here, we highlight our recent work on the synthesis of trifluoromethylated cyclopropenols through a [2+1] cycloaddition reaction between alkynes and (trifluoroacetyl)silanes under visible-light-induced organocatalysis. The novel amphiphilic donor–acceptor carbenes derived from (trifluoroacetyl)silanes can react effectively with both activated and nonactivated alkynes. A broad substrate scope and a good functional-group tolerance have been achieved. Moreover, the synthetic potential of this reaction was highlighted by a gram-scale reaction and the one-pot diastereoselective synthesis of trifluoromethylated cyclopropanols.

Retracted: Direct synthesis of 1‐naphthylamines enabled by 6‐endo‐dig cyclization strategy using copper catalysis

Here, we describe a facile approach for the synthesis of substituted 1‐naphthylamines via three‐component 6‐endo‐dig cyclization of terminal alkynes with 2‐bromoaryl ketones, primary or secondary amines in water under Pd‐free conditions. The Cu(I) catalytic system avoids a fundamental problem related to these substrates, which competitively evolve through 5‐endo‐dig cyclization pathways under metal catalysis. This unique performance unlocks a rapid access to a diverse 1‐naphthylamines library that previously required longer synthetic routes. The synthetic potential of this method was further demonstrated by the gram‐scale synthesis, and the mechanism study showed that the reaction experienced sequential halide exchange, imine‐enamine tautomerization and 6‐endo‐dig cyclization.

Theoretical study on the mechanism of Ni−Al bimetallic catalyzed dual C−H cyclization of amides and alkynes

The reaction mechanism of Ni−Al bimetallic catalyzed dual C−H cyclization of amides and internal alkynes has been studied theoretically. Four reactions were considered with N-phenylformamide (S1) and (2Ph)-N,N-bis(1-phenylethyl)formamide (S2) as amides, second phosphine oxide (SPO) and PMe3 as ligands, respectively. For two reactions with SPO as ligand and the reaction of S2 with PMe3, the reaction mechanism mainly includes formyl C(sp2)−H bond activation, phenyl C(sp2)−H or benzylic methyl C(sp3)−H bond activation, release of alkene, alkyne coordination and insertion, isomerization, and reductive elimination steps generating the cyclization product. The reaction of S1 with PMe3 proceeds via formyl C(sp2)−H bond activation, isomerization, and reductive elimination steps giving the alkyne addition product. In addition, the influence of substituent in SPO on reaction mechanism and the regio-selectivity of phenylpropyne in reaction have been calculated in detail.

In Situ Allene Formation via Alkyne Tautomerization to Promote [4 + 2]-Cycloadditions with a Pendant Alkyne or Nitrile.

We have explored the net-[4 + 2]-cycloadditions of a variety of aryl (or alkenyl) alkynes. Tautomerization via base-catalyzed alkyne-to-allene isomerization produces a transient allene, which undergoes stepwise cyclization with not only a pendant alkyne but also a nitrile. The operative mechanisms for these reactions were studied by density functional theory and compared with the slower thermal cyclization of the precursor alkyne.

Supported palladium-catalyzed carbonylative cyclization of 2-bromonitrobenzenes and alkynes to access quinolin-4(1H)-ones

A palladium supported on graphitic carbon nitride (Pd/g-C3N4) catalyzed carbonylative cyclization of 2-bromonitrobenzenes and alkynes has been developed for the expedite construction of quinolin-4(1H)-one scaffolds. By using a low loading heterogeneous palladium catalyst, Mo(CO)6 as both the CO surrogate and the reductant, and nitroarenes as the nitrogen source, the reaction proceeded well to give a variety of quinolin-4(1H)-ones in good to excellent yields.

Photocatalytic Markovnikov-type addition and cyclization of terminal alkynes leading to 4-sulfonyl quinoline-2(1H)-ones.

A new and expedient photocatalytic protocol for the construction of quinolin-2(1H)-ones via Markovnikov-type sulfonylation/6-endo-trig cyclization/selective C(O)-CF3 bond cleavage starting from N-alkyl-N-(2-ethynylphenyl)-2,2,2-trifluoroacetamides and sulfinic acids has been developed. It is as an unprecedented protocol for the preparation of 4-sulfonylquinoline-2(1H)-ones with high efficiency, mild reaction conditions, acceptable yields and a wide range of substrates.

Synthesis of 1-pyrroline derivatives via cyclization of terminal alkynes with 2-azaallyls.

An efficient transition-metal-free cyclization reaction to prepare 1-pyrroline derivatives bearing various functional groups is described. In this method, a simple combination of a base and a solvent allows the cyclization reaction of terminal alkynes and 2-azaallyls to be carried out efficiently under mild and metal-free conditions. This cyclization reaction will provide an efficient method for the synthesis of medicinally relevant polysubstituted and multifunctionalized pyrrolines.

Visible light-induced deoxygenation/cyclization of salicylic acid derivatives and aryl acetylene for the synthesis of flavonoids

A visible-light-induced photocatalytic strategy for the synthesis of flavonoids has been developed through the deoxygenative/cyclization reaction of salicylic acid derivatives with aryl acetylene using diphenyl sulfide as an O-transfer reagent. Based on the controlled experiments, the mechanism of visible-light-induced free radical coupling cyclization was proposed. The protocol obtained 51 flavonoids in good yields and has been successfully applied to the synthesis of some natural flavones.

Synthesis of 2,5-disubstituted selenophenes via a copper-catalyzed regioselective [2+2+1] cyclization of terminal alkynes and selenium.

Herein, a straightforward method for the synthesis of 2,5-disubstituted selenophenes via [2+2+1] cyclization of easily accessible terminal alkynes and elemental selenium has been developed. This reaction features high atom- and step-economy, excellent regioselectivity, good functional group tolerance and the use of stable and non-toxic selenium as a selenium source. A series of control experiments suggests that the reaction might undergo Glaser coupling reaction of two molecules of alkynes, followed by insertion of H2Se and subsequent cyclization. Moreover, the newly formed products can be further converted to diverse conjugated selenophene-based derivatives, demonstrating their potential applications in organic synthesis and materials science.