Cycloaddition Of Arynes Research Articles

Total synthesis of calothrixins and their analogues via formal [3+2] cycloaddition of arynes and 2-aminophenanthridinedione

Bioactive indolo[3,2-j]phenanthridine alkaloids, calothrixin A, B, and their analogues have been synthesized via formal cycloaddition of arynes and 2-aminophenanthridinedione as the key step, which proceeds through successive C–C/C–N bond formation and subsequent oxidation under transition-metal-free and mild conditions in the final stage of the synthesis.

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.

ChemInform Abstract: [3 + 2] Cycloaddition of Arynes with CF3CHN2: Access to 3‐Trifluoromethyl‐1H‐indazoles.

AbstractA general and practical methodology for the formation of 3‐trifluoromethylindazoles under mild reaction conditions is developed.

ChemInform Abstract: Cycloaddition of Arynes and Cyclic Enol Ethers as a Platform for Access to Stereochemically Defined 1,2‐Disubstituted Benzocyclobutenes.

AbstractThe reaction is investigated for various substrate types to produce the desired fused ring system.

A practical, multi-gram synthesis of (±)-herbindole A, (±)-herbindole B, and (±)-herbindole C from a common intermediate via 6,7-indole aryne cycloaddition and Pd(0)-catalyzed cross-coupling reactions

A practical, multi-gram 10-step synthesis of racemic herbindole A, B, and C from a common intermediate is described. The key step features a remarkably regioselective C-7 metal–halogen exchange and elimination from a Bartoli-generated N-t-butyldimethylsilyl-4,6,7-tribromo-5-methylindole scaffold to afford the 6,7-indole aryne. Cycloaddition with cyclopentadiene, oxidative cleavage, and Fujimoto reduction gave a common intermediate from which all three herbindoles were readily derived. A final Pd(0)-catalyzed Negishi and Stille cross-coupling reaction at the C-4 bromide afforded each of the herbindoles on a multigram scale.

Cycloaddition of Arynes and Cyclic Enol Ethers as a Platform for Access to Stereochemically Defined 1,2-Disubstituted Benzocyclobutenes.

Benzocyclobutenes (BCBs) are important entities in a multitude of areas, such as complex organic synthesis, materials and polymer chemistry, and electronics. Whereas reactions between arynes and ketene acetals have been well studied, reactions with cyclic enol ethers are unknown. A cis olefin geometry in cyclic enol ethers makes them well suited for formal [2 + 2] cycloaddition with arynes than for competing ene reactions, making them effective reactants. Reactions of 2,3-dihydrofuran, 2,3-dihydro-3H-pyran, 5-butyl-2,3-dihydrofuran, (S)-2-((benzyloxy)methyl)-2,3-dihydrofuran, and 1,4-dioxene with various arynes were successful. An advantage of the use of cyclic enol ethers is that despite the plausible intermediacy of zwitterionic intermediates, the products are limited to a cis ring junction. This can be exploited for potential access to stereochemically-defined 1,2-disubstituted BCBs. As a demonstration, ether ring cleavage with BBr3 provided trans-functionalized BCBs and displacement with azide then provided cis derivatives. DFT computations have been utilized to understand the structures of three arynes in relation to the cycloadditions and for a predictive evaluation of product ratios in two cases. A comparative evaluation of the HOMO energies of a related series of cyclic olefins has also been performed by DFT computations.

ChemInform Abstract: The Reaction of Arynes with Muenchnones: Synthesis of Isoindoles and Azaisoindoles.

Abstract1,3‐Dipolar cycloaddition of arynes derived from silyl triflates with muenchnones, generated in situ from precursors (II), affords isoindole derivatives in moderate to high yields.

ChemInform Abstract: Transition‐Metal‐Free Synthesis of Multisubstituted N‐Arylindoles via Reaction of Arynes and α‐Amino Ketones.

Abstract A simple transition-metal-free protocol for the synthesis of indoles has been developed using aryne cycloaddition. The in situ-generated arynes couple with α-amino ketones through a one-step N-arylation–nucleophilic addition process under mild conditions and efficiently produce multisubstituted N-arylindoles.

ChemInform Abstract: Aryne Cycloaddition with Stable Muenchnones: Synthesis of 9,10‐Dihydro‐9,10‐epiminoanthracenes and Isoindoles.

AbstractStable muenchnones react with an excess of in situ generated arynes to afford the bis‐adducts (III) in good yields.

Transition-metal-free synthesis of multisubstituted N-arylindoles via reaction of arynes and α-amino ketones

A simple transition-metal-free protocol for the synthesis of indoles has been developed using aryne cycloaddition. The in situ-generated arynes couple with α-amino ketones through a one-step N-arylation–nucleophilic addition process under mild conditions and efficiently produce multisubstituted N-arylindoles.

ChemInform Abstract: Modular Synthesis of N‐Vinyl Benzotriazoles.

AbstractA new approach to the title compounds by azide—aryne cycloaddition and Julia—Kocienski reaction is described.

ChemInform Abstract: Aryne Cycloaddition Reactions in the Synthesis of Large Polycyclic Aromatic Compounds

AbstractReview: 141 refs.

Aryne Cycloaddition with Stable Münchnones: Synthesis of 9,10‐Dihydro‐9,10‐epiminoanthracenes and Isoindoles

AbstractArynes react with stable münchnones in a [3+2] cycloaddition/[4+2] cycloreversion sequence under mild conditions. The reaction initially affords isoindoles, but in the presence of excess arynes, these isoindole intermediates readily undergo a further aryne [4+2] cycloaddition to afford 9,10‐dihydro‐9,10‐epiminoanthracenes in good to excellent yields. Controlling the reaction conditions to stop at the isoindole stage was attempted but proved difficult and limited. This chemistry further expands aryne dipolar cycloaddition chemistry with mesoionic substrates.

Aryne Cycloaddition Reactions in the Synthesis of Large Polycyclic Aromatic Compounds

AbstractCycloaddition reactions involving arynes provide privileged strategies for the convergent synthesis of polycyclic compounds containing aromatic rings. This review focuses on the application of aryne chemistry, in particular [4+2] and palladium‐catalysed [2+2+2] cycloaddition reactions, in the synthesis of large polycyclic aromatic hydrocarbons (PAHs) containing five or more fused benzene rings. Many of the polycyclic compounds included in this report display properties of interest in the field of materials science and some can be considered as nano‐sized graphene substructures or nanographenes.

Efficient cycloaddition of arynes to carbon nanotubes under microwave irradiation

The functionalization of single-wall carbon nanotubes (SWCNT) by cycloaddition reactions with arynes under microwave irradiation has been studied. The efficiency of the functionalization was monitored by XPS, FTIR and Raman spectroscopies, TGA and HR-TEM. All experimental results point to the formation of SWCNT with a high degree of functionalization, with mass increases ranging from 6.4% to 15.1% depending on the aryne substitution.

Further Investigations into the Regioselectivity of 6,7-Indole Aryne Cyclo­additions with 2-Substituted Furans: Remarkable Contrasteric Preference Depends­ on Pyrrole and Benzene Ring Substitution

A series of related 6,7-dibromoindole compounds were prepared to study the effects of pyrrole and benzene ring substitution patterns on the regioselectivity of 6,7-indole aryne cycloadditions with 2-<i>tert</i>-butylfuran. The arynes were generated by our metal–halogen exchange/elimination protocol. The results of this investigation reveal that substitution at the 3-position on the indole ring in particular results in remarkable regiocontrol that favored the contrasteric products. Aromatic conjugation at this site significantly enhanced this effect. However, the presence of most 4- or 5-substituents generally resulted in markedly reduced selectivity. Exceptions in this latter series included the 4-ethyl and 4-iodo cases both of which also gave predominantly contrasteric products even in the absence of a beneficial C-3 substituent.

ChemInform Abstract: Aryne Cycloaddition with 3‐Oxidopyridinium Species.

AbstractThis is a [3+2] cycloaddition affording bicyclo[3.2.1] skeletons.

One-pot synthesis of dihydrobenzisoxazoles from hydroxylamines, acetylenedicarboxylates, and arynes via in situ generation of nitrones

Aryne [3 + 2] cycloaddition with nitrones generated in situ from the addition of hydroxylamines to acetylenedicarboxylates affords moderate to good yields of dihydrobenzisoxazoles. This reaction extends the current scope of aryne cycloaddition to include in situ generated nitrones and produces functionalized dihydrobenzisoxazoles with a quaternary center.

Total synthesis of (±)-cis-trikentrin B via intermolecular 6,7-indole aryne cycloaddition and Stille cross-coupling

An efficient total synthesis of the annulated indole natural product (±)-cis-trikentrin B was accomplished by means of a regioselectively generated 6,7-indole aryne cycloaddition via selective metal–halogen exchange from a 5,6,7-tribromoindole. The unaffected C-5 bromine was subsequently used for a Stille cross-coupling to install the butenyl side chain and complete the synthesis. This strategy provides rapid access into the trikentrins and the related herbindoles, and represents another application of this methodology to natural products total synthesis. The required 5,6,7-indole aryne precursor was prepared using the Leimgruber–Batcho indole synthesis.

Synthesis of benzisoxazolines by the coupling of arynes with nitrones.

A variety of substituted benzisoxazolines have been synthesized by the [3 + 2] cycloaddition of nitrones and arynes. The reaction scope is broad, the reaction conditions are mild, and the process tolerates a variety of functional groups.