Cycloaddition Of Arynes Research Articles

Bifunctional Lewis Base-Catalyzed (3 + 2) Cycloadditions of Pyrazolone-Derived MBH Carbonates with Arynes.

The (3 + 2) cycloaddition of arynes with allylic ylides remains a formidable challenge because both intermediates are highly reactive and prone to spontaneous quenching. Here, we report a (3 + 2) cycloaddition of pyrazolone MBH carbonates with arynes, enabling the efficient synthesis of diverse indene-fused spiropyrazolones. The key is employing a new bifunctional Lewis base catalyst to facilitate the cycloaddition of in situ generated allylic pyridinium ylides with arynes.

Syn-1,2-Diaminobenzocyclobutenes from [2+2] cycloaddition of 2-imidazolones with arynes.

Formal [2+2] cycloaddition of arynes with 2-imidazolones affords syn-1,2-diaminobenzocyclobutenes. The transformation can also be conducted as a one-pot, three-stage process direct from simple propargyl amines and isocyanates to afford the new stereochemically defined benzocyclobutene frameworks.

A Sydnone-Based Route to Indazolo[2,3-a]quinoxaline Derivatives

AbstractA new synthetic route to indazolo[2,3-a]quinoxaline derivatives is described. The strategy is based on the 1,3-dipolar cycloaddition of arynes to quinoxaline–sydnone derivatives as a key step. The polyaromatic sydnones were prepared through a copper-promoted intramolecular cyclization of the C-4 position of sydnones on imines.

Scalable Synthesis of Benzotriazoles via [3+2] Cycloaddition of Azides and Arynes in Flow

AbstractA method for the metal‐free synthesis of benzotriazoles in flow is reported. Using azides and in situ generated arynes, benzotriazoles are formed in a [3+2] cycloaddition within minutes. Employing different substitution patterns of the azide and aryne coupling partners, a modular access to benzotriazoles is provided. Thermal strain of hazardous azides and accumulation of reactive intermediates is minimized by short reaction times in flow, improving the safety profile of the process. The scalability of the reaction is demonstrated.

Aryne cycloaddition reaction as a facile and mild modification method for design of electrode materials for high-performance symmetric supercapacitor

Covalent modification of graphene-based materials can be considered as one of the most promising methods for tailoring their electrochemical properties and extending their application as electrode materials for supercapacitors. In this contribution, we report a facile and mild approach for the covalent functionalization of reduced graphene oxide (rGO) via aryne cycloaddition using pseudocyclic iodoxoborole as an aryne source. The structure and chemical composition of the functionalized rGO (f-rGO) were assessed by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), ultraviolet–visible (UV–vis) spectrophotometry, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS), which revealed the negligible influence of covalent modification on the rGO structure. Transmission electron microscopy (TEM) imaging showed an increase of the interlayer distance from 0.38 to 0.46 nm upon functionalization. The electrochemical performance of f-rGO material was studied by cyclic voltammetry (CV), galvanostatic charge-discharge (GCD) and electrochemical impedance spectroscopy (EIS) techniques in 2 M KOH aqueous solution as the electrolyte. Under optimized conditions, the f-rGO displayed a high specific capacitance of 297 F g−1 at a current density of 1 A g−1, which is much higher than that of unmodified rGO (170 F g−1 at 1 A g−1). Therefore, the f-rGO was used to construct a symmetric supercapacitor device, exhibiting an energy density of 6.7 Wh kg−1 at a power density of 685.8 W kg−1. The device exhibited good cycling stability and ability to maintain about 96% of the initial capacitance value after 10,000 cycles. Furthermore, two symmetric supercapacitor devices were successfully applied to power a home-designed windmill device for 3 s. The results obtained in the present study highlight the importance of graphene functionalization as an effective route to fabricate rGO-based materials with enhanced properties in energy storage devices.

A straightforward access to 3-trifluoromethyl-1H-indazoles via (3+2)-cycloaddition of arynes with nitrile imines derived from trifluoroacetonitrile

In situ generated arynes react with nitrile imines derived from trifluoroacetonitrile at 0 °C in THF solutions yielding 3-trifluoromethyl-1H-indazole derivatives as the only intermolecular products. The reaction corresponds the expected (3 + 2)-cycloadditions which belong to the Type III (inverse-electron-demand) of Sustmann’s classification. Subsequent CAN-mediated dearylation of the model N-(p-methoxy)phenyl indazole leads to N-unsubstituted analogue, which easily undergoes alkylation and acylation reactions. Presented protocol offers a superior method for preparation of the 3-CF3 substituted indazole derivatives.

Enantiospecific Generation and Trapping Reactions of Aryne Atropisomers

Enantioenriched aryne atropisomers having a biaryl stereogenic axis vicinal to the reactive triple bond are demonstrated to exist. These reaction intermediates are easily produced in situ and can undergo the standard aryne cycloaddition chemistry in an enantiospecific manner. Notably, the aryne atropisomers herein have allowed the practical syntheses of a small nanographene as well as some triptycene and anthracene derivatives that embed stereogenic axes of controlled absolute configurations.

Synthesis of Nanographenes, Starphenes, and Sterically Congested Polyarenes by Aryne Cyclotrimerization.

In recent years, synthetic transformations based on aryne chemistry have become particularly popular, mostly due to the spread of methods to generate these highly reactive intermediates in a controlled manner under mild reaction conditions. In fact, aryne cycloadditions such as the Diels-Alder reaction are nowadays widely used for the efficient preparation of polycyclic aromatic compounds. In 1998, our group discovered that arynes can undergo transition metal-catalyzed reactions, a finding that opened new perspectives in aryne chemistry. In particular, Pd-catalyzed [2 + 2 + 2] cycloaddition of arynes allowed the straightforward synthesis of triphenylene derivatives such as starphenes or cloverphenes. We found that this reaction is compatible with different substituents and sterically demanding arynes as starting materials. This transformation is especially useful to increase the molecular complexity in one single step, transforming molecules formed by n cycles in structures with 3n + 1 cycles. In fact, we took advantage of this protocol to prepare a large variety of sterically congested polycyclic aromatic hydrocarbons such as helicenes or twisted polyarenes. Soon after the discovery of the reaction, the co-cyclotrimerization of arynes with other reaction partners, such as electron deficient alkynes, significantly expanded the potential of this transformation. Also the use of catalysts based on alternative metals besides Pd (e.g., Ni, Cu, Au) or the use of other strained intermediates such as cycloalkynes or cycloallenes added value to this reaction. In addition, we realized that the Pd-catalyzed aryne cyclotrimerization reaction is particularly useful for the bottom-up preparation of well-defined nanographenes by chemical methods. Although the extreme insolubility of these planar nanographenes hampered their manipulation and characterization by conventional methods, recent advances in single molecule on-surface characterization by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) with functionalized tips under ultrahigh vacuum (UHV) conditions, permitted the impressive visualization of these nanographenes with submolecular resolution, together with the examination of the corresponding molecular orbital densities. Moreover, arynes have been shown to possess a rich on-surface chemistry. In particular, arynes have been generated and studied on-surface, showing that the reactivity is preserved even at cryogenic temperatures. On-surface aryne cyclotrimerization was also demonstrated to obtain large starphene derivatives. Therefore, it is expected that the combination of aryne cycloadditions and on-surface synthesis will provide notable findings in the near future, including the "à la carte" preparation of graphene materials or the synthesis of elusive molecules with unique properties.

Group 4 Diarylmetallocenes as Bespoke Aryne Precursors for Titanium-Catalyzed [2 + 2 + 2] Cycloaddition of Arynes and Alkynes.

Despite the ubiquity of reports describing titanium (Ti)-catalyzed [2 + 2 + 2] cyclotrimerization of alkynes, the incorporation of arynes into this potent manifold has never been reported. The in situ generation of arynes often requires fluoride, which instead will react with the highly fluorophilic Ti center, suppressing productive catalysis. Herein, we describe the use of group 4 diarylmetallocenes, CpR2MAr2 (CpR = C5H5, C5Me5; M = Ti, Zr), as aryne precursors for the Ti-catalyzed synthesis of substituted naphthalenes via coupling with 2 equiv of an alkyne. Fair-to-good yields of the desired naphthalene products could be obtained with 1% catalyst loadings, which is roughly an order of magnitude lower than similar reactions catalyzed by palladium or nickel. Additionally, naphthalenes find broad applications in the electronics, photovoltaics, and pharmaceutical industries, urging the discovery of more economic syntheses. These results indicate that aryne transfer from a CpR2M(η2-aryne) complex to another metal is a viable route for the introduction of aryne fragments into organometallic catalytic processes.

Sequential cycloaddition and ring expansion reaction of arynes and methylenebenzothiopheneones: synthesis of a benzo-fused eight-membered ring via sulfonium ylides.

A sequential cycloaddition and ring expansion of arynes and methylenebenzothiopheneones has been disclosed. This strategy proceeds through a sulfonium ylides intermediate and allows for the efficient synthesis of a sulfur-containing benzo-fused eight-membered ring.

Formal [7 + 2] Cycloaddition of Arynes with N-Vinyl-α,β-Unsaturated Nitrones: Synthesis of Benzoxazonines and Their N-O Bond Cleavage.

Various benzoxazonines were synthesized through a formal [7 + 2] cycloaddition of arynes with N-vinyl-α,β-unsaturated nitrones under mild conditions. Controllable N-O bond cleavage of benzoxazonines afforded polysubstituted pyrrole-tethered benzopyrans and acyclic ketone-substituted phenols in moderate to good yields. Further transformations provided a facile approach to access useful building blocks with specific stereoselectivity.

Tandem nucleophilic addition-cycloaddition of arynes with α-iminoesters: two concurrent pathways to imidazolidines.

The tandem nucleophilic addition-cycloaddition reaction has been developed for the synthesis of functionalized imidazolidine derivatives. A variety of α-iminoesters and aryne precursors were well tolerated under the mild reaction conditions. This asymmetric cycloaddition afforded imidazolidine derivatives with high yields, complete regioselectivities, and excellent diastereo- and enantioselectivities. Aryne-induced ylides working as 1,3-dipoles for asymmetric cycloaddition are the notable feature of the present reaction. In the tandem reaction, the [3+2] cycloaddition of aryne-induced ylides with metallized α-iminoesters and metal-catalyzed [3+2] cycloaddition of azomethine ylide with α-iminoesters are two concurrent pathways to imidazolidines.

Synthesis of Spiro[indazole-3,3'-indolin]-2'-ones via [3 + 2] Dipolar Cycloaddition of Arynes with 3-Diazoindolin-2-ones and Indazolo[2,3-c]quinazolin-6(5H)-ones by Subsequent Thermal Isomerization.

An efficient protocol for facile construction of spiro[indazole-3,3'-indolin]-2'-ones was developed via [3 + 2] dipolar cycloaddition of arynes with 3-diazoindolin-2-ones under mild conditions in excellent yields. Subsequent thermal isomerization of the spiro[indazole-3,3'-indolin]-2'-ones readily afforded indazolo[2,3-c]quinazolin-6(5H)-ones.

A Photocatalyzed Synthesis of Naphthalenes by Using Aniline as a Traceless Directing Group in [4 + 2] Annulation of Amino-benzocyclobutenes with Alkynes

We report a visible-light-promoted synthesis of substituted naphthalenes via [4 + 2] annulation of amino-benzocyclobutenes with alkynes. Amino-benzocyclobutenes, which are conveniently synthesized by [2 + 2] cycloaddition of arynes with ketenes followed by reductive amination, undergo regioselective opening of the cyclobutenyl ring to reveal a presumably distonic radical cation upon photooxidation by an excited iridium complex. The distonic radical cation undergoes the annulation with terminal and internal alkynes as well as diynes to afford structurally diverse naphthalenes. The regiochemistry of the annulation follows the pattern displayed in the addition of nucleophilic carbon radicals to alkynes. The aniline group plays a dual role in which it not only directs the initial photooxidation to generate the amine radical cation but also serves as a leaving group to complete aromatization.

Diastereoselective Synthesis of Chiral 2,3-Disubstituted Indolines via Formal [3+2]-Cycloaddition of Arynes with γ-Amino-α,β-unsaturated Esters.

A one step formal [3+2]-annulation protocol for the synthesis of 2,3-disubstituted indolines is described. The in situ generated aryne acts as a two-atom component, and γ-amino-α,β-unsaturated esters acting as a three-atom component to construct indoline units in a highly regio- and diastereoselective manner with yields ranging from 63 to 80%.

Synthesis of spiro-3H-indazoles via 1,3-dipolar cycloaddition of arynes with 6-diazocyclohex-2-en-1-one derivatives and fused-2H-indazoles by subsequent rearrangement

Rare spiro-3H-indazoles bearing a carbonyl group adjacent to the spirocyclic quarternary carbon were prepared via 1,3-dipolar cycloaddition reaction of arynes with 6-diazocyclohex-2-en-1-one derivatives under mild conditions.

Aryne cycloaddition reactions of benzodioxasilines as aryne precursors generated by catalytic reductive ortho-C[sbnd]H silylation of phenols with traceless acetal directing groups

Diversely substituted arylsilyl triflates, as aryne precursors for aryne cycloaddition reactions, were accessed from benzodioxasilines. Catalytic reductive CH ortho-silylation of phenols with traceless acetal directing groups was exploited to prepare benzodioxasilines. Sequential addition of MeLi and then trifluoromethanesulfonic anhydride to benzodioxasilines provided arylsilyl triflates in a single pot. Notably, this approach was successfully utilized to prepare sterically hindered 1,2,3-trisubstituted arylsilyl triflates, which ultimately underwent fluoride-mediated aryne cycloaddition.

Sulfonium Ylides by (3+2) Cycloaddition of Arynes with Vinyl Sulfides: Stereoselective Synthesis of Highly Substituted Alkenes.

The reaction of in situ generated arynes with vinyl sulfides provides benzannulated sulfonium ylides in a (3+2) cycloaddition. Trapping of the intermediate ylides with electrophiles (proton transfer or a second aryne addition) and subsequent β-elimination give rise to di-, tri-, or tetrasubstituted alkenes with high stereoselectivity. Experimental studies and DFT calculations provide insight into the mechanisms of these cascade reactions.

ChemInform Abstract: Synthesis of Carbazolequinones by Formal [3 + 2] Cycloaddition of Arynes and 2‐Aminoquinones.

A formal cycloaddition reaction for the synthesis of biologically and pharmaceutically important carbazolequinones via the annulation of aminoquinones with arynes has been developed. This practical and metal-free cascade reaction proceeds through successive C–C/C–N bond formations. Moreover, this novel method has been utilized for the concise synthesis of bioactive murrayaquinone A and koeniginequinone B and their analogues.

Synthesis of Diverse Benzotriazoles from Aryne Precursors Bearing an Azido Group via Inter- and Intramolecular Cycloadditions

A diverse range of benzotriazoles were synthesized from various 3-(azidoalkoxy)aryne precursors, which were easily prepared by Mitsunobu etherification. Various bis-1,2,3-triazoles containing a benzotriazole skeleton were obtained via sequential azide–alkyne and azide–aryne cycloadditions. Intramolecular azido–aryne cycloaddition, conducted using the same starting materials, afforded new types of ring-fused benzotriazoles. In the latter case, the reaction proceeded efficiently even though the regioorientation of the azido group was the reverse of that usually observed in intermolecular reactions between 3-alkoxyarynes and an azide.