Synthesis of Trisubstituted Oxazoles via Aryne Induced [2,3] Sigmatropic Rearrangement-Annulation Cascade.

A transition-metal-free, [2,3] sigmatropic rearrangement-annulation cascade of 2-substituted thio/amino acetonitriles with arynes allowing the synthesis of 2,4,5-trisubstituted oxazoles under mild conditions has been demonstrated. The key sulfur/nitrogen ylides were generated by the initial S/N arylation followed by proton transfer, which was followed by the selective [2,3] sigmatropic rearrangement involving the -CN moiety and a subsequent annulation to afford the desired products in reasonable yields.

Three-Component, Diastereoselective [6 + 3] Annulation of Tropone, Imino Esters, and Arynes.

A transition-metal-free, three-component, and diastereoselective [6 + 3] annulation reaction employing tropone, imino esters, and arynes allowing the synthesis of bridged azabicyclo[4.3.1]decadienes is demonstrated.

An Umpolung Oxa-[2,3] Sigmatropic Rearrangement Employing Arynes for the Synthesis of Functionalized Enol Ethers.

An oxa-[2,3] sigmatropic rearrangement involving arynes is reported featuring the umpolung of ketones, where the C═O bond polarity is reversed. The in situ-generated sulfur ylides from β-keto thioethers and arynes undergo efficient rearrangement allowing the facile and robust synthesis of functionalized enol ethers in high yields and excellent functional group compatibility. Preliminary mechanistic studies rule out the possibility of Pummerer-type rearrangement operating in this case.

Thiophenols as Protic Nucleophilic Triggers in Aryne Three-Component Coupling.

The synthetic potential of thiophenols as a protic nucleophilic trigger in the transition-metal-free and Grignard-reagent-free three-component coupling involving arynes is demonstrated. Employing aldehydes as the third component, the reaction allowed the mild and broad scope synthesis of 2-arylthio benzyl alcohol derivatives in good yields. Moreover, selenophenol could be used as the nucleophilic trigger, and activated ketones could be used as the third component in this reaction.

Rapid Synthesis of Zwitterionic Phosphonium Benzoates by a Three-Component Coupling Involving Phosphines, Arynes and CO.

A mild and easy to perform multicomponent coupling involving phosphines, arynes generated from 2-(trimethylsilyl)aryl triflates, and CO allowing the transition-metal-free synthesis of zwitterionic phosphonium benzoates has been developed. The reaction proceeds via the generation of 1 : 1 zwitterionic intermediates from phosphines and arynes followed by the interception with CO to deliver the carboxylates in moderate to good yields instead of the anticipated benzooxaphosphol-3(1H)-ones.

Lewis Acid Catalyzed Ring-Opening 1,3-Aminothiolation of Donor-Acceptor Cyclopropanes Using Sulfenamides.

Yb(OTf) catalyzed mild and regioselective ring-opening 1,3-aminothiolation of donor-acceptor (D-A) cyclopropanes using sulfenamides has been demonstrated. The insertion of the C-C σ-bond of D-A cyclopropanes into the S-N σ-bond of sulfenamides allows the synthesis of diverse γ-aminated α-thiolated malonic diesters in moderate to good yields (up to 87%) with good functional group compatibility. The stereospecificity of the reaction was demonstrated using enantiomerically pure D-A cyclopropane.

Three-Component Aminoselenation of Arynes.

The three-component coupling of tertiary amines, arynes, and aryl selenium bromide or diaryl diselenide as an electrophilic selenium source allowing the synthesis of 2-selanyl aniline derivatives is reported. This aminoselenation reaction of arynes installs a C-N and C-Se bond under mild conditions, and the products are formed in moderate to good yields. This reaction is compatible with various functional groups, and the preliminary studies on the mechanism of the reaction is also provided.

Selective Synthesis of -H and -Aryl Benzotriazoles by the [3 + 2] Annulation of Sodium Azide with Arynes.

The synthetic utility of NaN as the azide component in the [3 + 2] annulation with arynes generated from 2-(trimethylsilyl)aryltriflates resulting in the transition-metal-free synthesis of -H and -aryl benzotriazoles has been demonstrated. Using CsF as the fluoride source in CHCN, the -H benzotriazoles are formed in high selectivity instead of the expected azidobenzene. Interestingly, -aryl benzotriazoles are formed using KF and THF as solvent in an open-flask reaction.

Iodide as a Nucleophilic Trigger in Aryne Three-Component Coupling for the Synthesis of 2-Iodobenzyl Alcohols.

The synthetic potential of KI as the iodide source in aryne three-component coupling has been demonstrated using aldehydes as the third component. This mild and transition-metal-free coupling reaction allowed the straightforward synthesis of 2-iodobenzyl alcohols in moderate to good yields with good functional group compatibility. Moreover, KBr and KCl could be used as the nucleophilic trigger in this aryne multicomponent coupling (MCC) and N-methylisatin and CO could be used as the electrophilic third components.

The aryne Sommelet-Hauser rearrangement.

An aryne induced transition-metal-free and mild Sommelet-Hauser rearrangement of tertiary benzylamines for the synthesis of α-aryl amino acid derivatives in moderate to good yields is presented. Unlike the conventional Sommelet-Hauser rearrangement of ammonium salts, the methodology developed herein requires neither harsh conditions nor strong bases. Moreover, a temperature dependent switchable selectivity for the Sommelet-Hauser and Stevens [1,2] rearrangements has been observed.

Transition-Metal-Free Thioamination of Arynes Using Sulfenamides.

The insertion of arynes into the S-N σ-bond of sulfenamides allowing the synthesis of o-sulfanylaniline derivatives with reasonable functional group compatibility is presented. The aryne generated from 2-(trimethylsilyl)aryl triflates using CsF in DME was the key for the success of this transition-metal-free thioamination reaction, which involves new C-N and C-S bond formations in a single step under mild conditions. Moreover, the synthetic potential of this method was demonstrated by the synthesis of the antidepressant drug vortioxetine.

Employing Arynes for the Generation of Aryl Anion Equivalents and Subsequent Reaction with Aldehydes.

Arynes are highly reactive intermediates, which are utilized for the electrophilic arylation of various X-H bonds (X = O, N, S etc.). Herein, a new synthetic strategy is demonstrated, where arynes are converted into aryl anion equivalents by treatment with phosphines and a base.

Synthesis of Functionalized β-Keto Arylthioethers by the Aryne Induced [2,3] Stevens Rearrangement of Allylthioethers.

A mild and transition-metal-free synthesis of β-keto arylthioethers has been developed by the aryne triggered [2,3] Stevens rearrangement of allylthioethers. The key sulfur ylide intermediate for the rearrangement was formed by the S-arylation of allylthioethers with arynes generated from 2-(trimethylsilyl)aryl triflates using CsF. Later, the reaction products are converted into valuable heterocycles in two steps.