(Iso)quinoline compounds represent a critically important class of pharmaceutical molecules, including antimicrobial drugs and kinase inhibitors. Recently, heteroarynes with formally strained triple bonds have been extensively used to construct biologically active heteroaromatic scaffolds. Despite the importance of (iso)quinolines, their application in (iso)quinolyne chemistry for organic syntheses has been rare owing to their low regioselectivity. In this study, we report a novel method for the regiocontrol of (iso)quinolynes via the formation of unique cationic aryne species. These cationic species are generated by the protonation of (iso)quinolynes using o-triazenylarylboronic acids as precursors and camphorsulfonic acid as the proton source. These cationic intermediates underwent cycloaddition with organic azides, exhibiting significantly higher distal selectivity (up to distal : proximal = 14.3 : 1) than neutral (iso)quinolynes (distal : proximal = approximately 4 : 1). Density functional theory calculations supported the participation of cationic aryne species in the solution-phase reaction for the first time and enabled the prediction of their regioselectivity. By transforming the electronic nature of the aryne through site-specific protonation, this method overcomes a long-standing challenge in heteroaryne reactivity, providing a robust synthetic toolkit for the regioselective functionalization of complex, biologically relevant (iso)quinolines.

Arynes are important synthetic intermediates that are usually generated under alkaline conditions. We developed a method for generating arynes using two hydroxy compounds as activators. o-Triazenylarylboronic acids generate (hetero)arynes when activated by a combination of ethylene glycol, pinacol, and p-nitrophenol; these arynes then react with a range of arynophiles under slightly acidic conditions that complement the conventional basic conditions with unique chemoselectivities observed even in the presence of excess hydroxy compounds.

For developing a biomimetic synthetic route for bioactive hybrid isoprenoid indotertine and drimentine derivatives, we investigated acid-mediated cyclization/isomerization reactions of 3a-prenyl and 3a-geranyl pyrroloindolines. In the case of the 3a-prenyl derivatives, we discovered a skeletal rearrangement reaction initiated by the opening of pyrrolidine rings. For 3a-geranyl derivatives, we successfully constructed a tetracyclic framework corresponding to the substructure of the indotertines.

We explored the synthesis and reactivity of C(sp3)-substituted sulfonium salts derived from sulfoxides and silyl enol ethers. We successfully isolated sulfonium salts as stable solids by modifying sulfoxide substituents and exchanging counterions. The reactivity of these sulfonium salts was demonstrated through α-halogenation and carbon-carbon bond formation reactions. These reactions represent Umpolung processes mediated by sulfonium groups, enabling the coupling of two nucleophiles. Notably, the characteristic reactivity of enone-containing sulfonium salt was demonstrated by the generation of an oxyallyl cation intermediate through the addition of β-dicarbonyl compounds under basic conditions.

Herein, we report the functionalization of polyhedral oligosilsesquioxanes (POSS) and related siloxanes with arynes. Using o-triazenylarylboronic acids as aryne precursors and silica gel as the activator, the transformation of siloxane bearing various arynophilic moieties on the side chains was achieved with high yields without touching the siloxane core. This method was applied to the conjugation of POSS and pharmaceutical cores using an aryne derived from the synthetic intermediate of cabozantinib. Furthermore, orthogonal dual functionalization of POSS was realized by combining the aryne reaction with Huisgen cyclization.

Herein, a novel aryne species, 3-triazenylaryne, was developed and its regioselectivity was revealed. Based on the regioselectivity, various alkyne moieties were introduced by iodoalkynylation, and further derivatization to o-triazenylarylboronic acids as 3-alkynylaryne precursors was enabled. Therefore, 3-triazenylaryne was developed as a divergent platform for the generation of various 3-alkynylarynes.

Alkyldiarylsulfonium salts were synthesized by a combination of active sulfonium species, prepared through the activation of diarylsulfoxide, and alkyl nucleophiles. The isolated sulfonium salts were subjected to the allylation and cyclopropanation of the active methylene compounds and metal-free C(sp3)-C(sp2) couplings via oxyallyl cation intermediates under mild conditions. The series of reactions included an umpolung strategy for the coupling of alkyl nucleophiles and metal-free C-C bond formation using sulfonium salts.

We have developed an improved method for generating aryne from o-triazenylarylboronic acids. Unlike the previous method that required excess o-triazenylarylboronic acids as aryne precursors, we used corresponding boronates as limiting reagents, which resulted in high yields. By combining the formation of boronates and aryne generation through silica gel treatment in one-pot, we were able to effectively use a wide range of o-triazenylarylboronic acids in reactions with various arynophiles. This one-pot method was particularly suitable for transforming complex aryne precursors with different functional groups.

We developed o-triazenylarylboronic acids as stable solid aryne precursors, which generate arynes under mild conditions using silica gel as the sole reagent and undergo reactions with a range of arynophiles both in solution and in the solid-state.

We report aryne generation from 2-triazenylarylboronic acids using an activator such as Brønsted acids, Lewis acids, and solid acids. With the use of (±)-Camphorsulfonic acid [(±)-CSA], the aryne precursors provided cycloadducts with a range of arynophiles in high yields. Aryne generated under the acidic conditions underwent chemoselective cycloaddition with a furan in the presence of a basic arynophile, namely an amine. Hammett plot analyses revealed that an aryne generation mechanism induced by (±)-CSA is distinct from the mechanism induced by silica gel.

AbstractThis study reports the development of Rh(II)-catalyzed N–N bond-forming reaction of amino acid derivatives or aliphatic amines to provide hydrazine derivatives through the combined use of Rh2(esp)2 and [(3,4-dimethoxyphenyl)sulfonylimino]-2,4,6-trimethylphenyliodinane (3,4-(MeO)2C6H3SO2N=IMes). This is the first report of N–H amination of aliphatic amines with metal–nitrene species.

We studied the selective formation of 3,5-and 2,5-pyrazinone via a transamidation-cyclization reaction.The equilibrium between acyl amides changed depending on the solvent, acidity, and substituents.Furthermore, selective transformation of 2,5-pyrazinone was accomplished by using a substrate with a secondary amine.

Dirhodium(ii)-catalyzed ortho C-H amination of N,N-dialkylanilines has been developed. Sterically congested 1,2-diaminobenzenes were obtained in high yields with excellent chemo- and regioselectivities from para-substituted anilines and even from para-unsubstituted anilines. The ortho selectivity observed was rationalized in terms of the interaction between the dialkylamino group and a Rh(II)-nitrene intermediate.

Acid anhydride-activated sulfoxides can undergo a variety of cascade reactions after reacting with nucleophiles on its sulfur atom. Originally regarded as an abnormal phenomenon that occurs under Pummerer reaction conditions, the reports of the reaction increased gradually, and research regarding sulfoxide reactivity has advanced. In recent years, the term 'interrupted Pummerer reaction' has been introduced, and the transformation has been actively incorporated into the development of new research areas. Such studies have yielded numerous valuable sulfoxides, which contribute to the precise reaction control and to the generation of practical products. Notably, the outcome of the interrupted Pummerer reaction is characteristic for each nucleophile.

Propellanes are polycyclic compounds in which tricyclic systems share one carbon–carbon single bond. Propellane frameworks that consist of larger sized rings are found in a variety of natural products. As an approach to the stereoselective synthesis of the propellane framework, one of the efficient methods is forming several rings in a single operation. Lapidilectine B (1) is composed of a propellane framework and was synthesized through the oxidative cyclization of trisubstituted alkenes. When the alkene with an ester moiety was treated with N-iodosuccinimide (NIS), iodocyclization proceeded to give the cyclic carbamate. On the other hand, when PhI(OAc)2 was allowed to react in the carboxyl form, a furoindolin-2-one structure corresponding to the A-B-C ring of lapidilectine B (1) was produced. Furthermore, when Pd(OAc)2 catalyst was used for cyclization under oxidative conditions, the product yield was improved.

Rh(ii)-Nitrene-mediated N–H amination of 2-aminophenylboronates triggered a cascade of oxidation/elimination processes resulting in the generation of benzynes.

Herein, we report the application of 1,3-dipolar cycloaddition reaction toward the synthesis of a variety of 8-oxa-2-azabicyclo[3.2.1]octane compounds, the core structure of atkamine. The target compounds were obtained using a combination of a vinyl ether and carbonylylide, which was generated from a diazo compound and rhodium catalyst, in the presence of a Lewis acid.

A metal-free biaryl coupling reaction of phenol or aryl ethers mediated by a sulfonium salt formed from diphenyl sulfoxide and trifluoromethanesulfonic anhydride has been developed. The method is a rapid, one-pot reaction, leaving no traces of the sulfonium moiety in the product.

A sulfonium species generated from sulfoxide and acid anhydride is a useful reagent for organic synthesis owing to its powerful electrophilicity. Among the various sulfonium-mediated reactions, interrupted Pummerer reaction has been well-investigated recently, which progresses the nucleophilic attack of substrate on sulfur atom of sulfonium such as Swern-type oxidation. Although interrupted Pummerer reactions are reported with various substrate such as alcohols, alkenes, enol ethers, the application to aromatics is limited because of the stability of initially generated arylthionium salts. In contrast, we previously developed intramolecular reaction via arylthionium intermediate for installing nucleophile to indole 2 alpha-position in a one-pot procedure. This reaction was proceeded with special substrate by intramolecular reaction, therefore, it was unexplored as a general synthetic method. This article describes the details of the development of sulfonium species mediated reactions to functionalize indoles by intermolecular interrupted Pummerer reaction.

A single‐step synthesis of N‐aryl‐N′‐tosyldiazenes from primary aromatic amines was developed. A wide range of aromatic amines provided the corresponding products in high yields by N–N bond formation with RhII–nitrene intermediates, which were generated in situ from dirhodium(II) complex catalysts and (tosylimino)‐2,4,6‐trimethylphenyliodinane, followed by oxidation. The synthesized N‐aryl‐N′‐tosyldiazenes were successfully demonstrated to serve as potent and stable surrogates for diazonium salts in the two‐step deaminative transformation of primary aromatic amines.