Coupling Of Arynes Research Articles

A novel three-component coupling reaction of aryne, CN derivatives, and acrylonitrile

A three-component aryne coupling reaction with CN derivatives as a nucleophile, and acrylonitrile as a third component, acting as both a proton donor and a nucleophile, has been developed.

The Versatility of the Aryne–Imine–Aryne Coupling for the ­Synthesis of Acridinium Photocatalysts

AbstractThe increasing use of acridinium photocatalysts as sustainable alternative to precious metal-based counterparts encourages the design and efficient synthesis of distinct catalyst structures. Herein, we report our exploration of the scope of the aryne–imine–aryne coupling reaction combined with a subsequent acridane oxidation for a short two-step approach towards various acridinium salts. The photophysical properties of the novel photocatalysts were investigated and the practical value was demonstrated by a cation-radical accelerated nucleophilic aromatic substitution reaction.

The Winding Road towards an Atropo‐enantioselective ‘ARYNE Coupling’

AbstractFor the first time, the challenging atropo‐enantioselective coupling of in‐situ generated arynes and aryllithiums in the presence of a chiral ligand of lithium was investigated. This preliminary study demonstrates the feasibility of this concept, by affording enantioenriched axially chiral biaryls even in the case of products showing a high degree of steric congestion around the newly created aryl−aryl bond.

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.

Transition‐Metal‐Free Heterobiaryl Synthesis via Aryne Coupling

We disclose, for the first time, an efficient route for the construction of various heterobiaryl backbones in fair to excellent yields using the Aryne coupling methodology. This study outlined the remarkable effect of external chelating ligands and salt additives on the heterocyclic partner reactivity in the aryne coupling reaction.

A cascade process for the synthesis of ortho-formyl allyl aryl ethers and 2H-chromen-2-ol derivatives from arynes via trapping of o-quinone methide with an activated alkene.

A transition-metal free synthetic strategy has been developed for the direct synthesis of ortho-formyl substituted allyl aryl ethers via a cascade three-component coupling of arynes, activated alkene and N,N-dimethylformamide. The reaction proceeds via C-O and C-C bond cleavage as well as C-C and two new C-O bond formations in a single reaction vessel. The methodology provides a good yield of ortho-formyl substituted allyl aryl ethers. Moreover, the synthetic strategy has been utilized for the one-pot synthesis of 2H-chromen-2-ol derivatives.

Transition‐Metal‐Free Approach for the Direct Arylation of Thiophene: Experimental and Theoretical Investigations towards the (Het)‐Aryne Route

This paper presents the results of our investigations on the arylation of thiophene using the transition‐metal‐free “aryne coupling” methodology. The reaction was studied by both experiment and computation (density functional theory) and comparison with phenyllithium was established. In parallel, the effects of the ligand and the salt on the coupling reaction were examined. The results underline the remarkable effect of such additives on the coupling reaction and the potency of the method to construct hetaryl–aryl backbones which open up promising access to a wide range of heterobiaryl structures using the novel “Het‐Aryne” route.

Inside Cover: Aryne–Imine–Aryne Coupling Reaction via [4+2] Cycloaddition between Aza‐o‐Quinone Methides and Arynes (Asian J. Org. Chem. 8/2017)

Aryne–imine–aryne coupling: Two molar amounts of arynes have been formally inserted into carbon−nitrogen double bonds of imines. This aryne–imine–aryne coupling reaction selectively produces acridane derivatives via intermediary generation of transient aza-o-quinone methides. The use of imines with steric bulk at the imine carbon, which leads to preferential formation of ‘outward’ aza-o-quinone methides, is the key for this reaction. More information can be found in the Communication by Hiroto Yoshida et al. on page 973 in Issue 8, 2017 (DOI: 10.1002/ajoc.201700251).

Aryne–Imine–Aryne Coupling Reaction via [4+2] Cycloaddition between Aza‐o‐Quinone Methides and Arynes

AbstractA direct method for the synthesis of acridane derivatives based upon a 2:1 coupling reaction between arynes and imines was developed. The reaction proceeds through formation of transient aza‐ortho‐quinone methides arising from a net [2+2] cycloaddition between arynes and imines. Introduction of steric bulk into an imine carbon has proven to be vital for this facile coupling.

Control of axial chirality in absence of transition metals based on arynes

The modular construction of enantioenriched biaryl derivatives is presented. This approach is based on (1) an almost quantitative access to polybrominated precursors via a transition metal-free aryl–aryl coupling, the ARYNE coupling, (2) the regioselective introduction of a traceless chiral auxiliary (an enantiopure para-tolylsulfinyl group), (3) the chemoselective functionalization of this auxiliary, and (4) subsequent regioselective functionalization of the remaining bromine atoms without any racemization during these steps. Next, the atroposelective coupling of in situ generated arynes and aryllithiums bearing various chiral auxiliaries (tert-butyl sulfoxide, para-tolyl sulfoxide, and tartrate-derived chiral diethers and oxazolines) is described and applied to the formal synthesis of (−)-steganacin. La construction modulaire de dérivés biaryliques énantioenrichis est présentée. Cette approche est basée sur (a) un accès quasi quantitatif aux précurseurs polybromés via un couplage aryle–aryle sans métaux de transition, le couplage ARYNE, (b) l'introduction régiosélective d'un auxiliaire chiral (un groupe para-tolylsulfinyl énantiopur), (c) la fonctionnalisation chimiosélective de cet auxiliaire et (d) la fonctionnalisation régiosélective subséquente des atomes de brome restants sans racémisation au cours de ces étapes. Ensuite, le couplage atropo-sélectif à l'aide d'arynes générés in situ et d'aryllithiums portant divers auxiliaires chiraux (tert-butyl sulfoxyde, para-tolyl sulfoxide, diéthers dérivés du tartrate et des oxazolines chirales) est décrit et appliqué à la synthèse formelle de la (−)-stéganacine.

Transition‐Metal‐Free Synthesis of a Known Intermediate in the Formal Synthesis of (–)‐Steganacin

The formal synthesis of the two enantiomers of a natural, axially chiral biaryl, steganacin, is reported. The previously developed atropo‐diastereoselective coupling of an aryne and an aryllithium (“aryne coupling”) allows for this synthesis. In each step, the axial configuration of the biaryl could be maintained. The key intermediate, identified previously, was accessed without using transition metals, which demonstrates the potential of the aryne coupling reaction as a complementary or alternative to transition‐metal‐catalyzed coupling reactions.

Synthesis of Dihydrophenanthridines and Oxoimidazolidines from Anilines and Ethylglyoxylate via Aza Diels-Alder Reaction of Arynes and KF-Induced Annulation.

The transition-metal-free multicomponent coupling of arynes, anilines, and ethylglyoxylate, proceeding via an inverse electron-demand aza Diels-Alder cycloaddition and N-arylation, has been demonstrated. This protocol allows rapid access to N-aryl dihydrophenanthridine derivatives in moderate to high yields at room temperature from readily available starting materials. In addition, an unprecedented fluoride induced annulation of ethyl(arylimino)acetates led to the formation of highly functionalized oxoimidazolidine derivatives in good yields under mild conditions.

Lithium/Element Exchange as an Efficient Tool for Accessing Atropo-enriched Biaryls via Arynes.

This account documents the development of transition metal-free, aryne-mediated aryl-aryl coupling, the 'ARYNE coupling', which began in 2001 in Lausanne. ortho,ortho'-Di-, tri- and even tetrasubstituted biphenyls have now become accessible on a multi-gram scale. The reaction is perfectly regioselective and the obtained polybromobiphenyls can be submitted to regioselective bromine/lithium interconversions. The access to enantiopure biphenyls is now possible using enantiopure sulfoxides as chiral auxiliaries, which allow for subsequent chemoselective sulfoxide/metal exchange on each atropo-diastereoisomer with configurational stability of the intermediate biaryllithiums. Direct atropo-diastereoselective ARYNE coupling has been reported more recently.

Synthesis of functionalized amino epoxides by a three-component coupling involving aziridines, arynes and aldehydes.

A transition-metal-free three-component coupling involving N-substituted aziridines, arynes and aldehydes resulting in the formation of trisubstituted N-aryl α-amino epoxides has been demonstrated. The reaction likely proceeds via the highly strained cyclic nitrogen ylide intermediates generated from aziridines and arynes.

Three-Component Coupling Involving Arynes, Aromatic Tertiary Amines, and Aldehydes via Aryl-Aryl Amino Group Migration.

The transition-metal-free multicomponent coupling of arynes, aromatic tertiary amines, and aldehydes proceeding via the aryl to aryl amino group migration has been demonstrated. This protocol allows rapid access to ortho-functionalized tertiary amines in moderate to good yields. Moreover, activated ketones can also be used as the aldehyde component in the present reaction. The similarity of the aryl-aryl tertiary amino group migration with the Smiles rearrangement is striking.

Metal-free synthesis of ortho-CHO diaryl ethers by a three-component sequential coupling.

A practical, metal-free, and highly chemoselective approach was developed for the synthesis of ortho-CHO diaryl ethers by a three-component sequential coupling of arynes, N,N-dimethylformamide (DMF), and diaryliodonium salts. Diverse functional groups including halo, nitryl, and bulky substituents and heteroaromatics are well tolerated. Mechanistically, isotopic tracer experiments reveal that the diaryliodonium salt serves as an electrophile to trap the transient intermediates generated from the [2 + 2] cyclization of an aryne and DMF.

ChemInform Abstract: Diastereoselective Synthesis of N‐Aryl Tetrahydroquinolines and N‐Aryl Indolines by the Tandem Reaction of Arynes.

A tandem reaction of arynes with α- or β-amino ketones has been revealed. Arynes react with β-amino ketones through a cascade insertion–cyclization process to afford N-aryl tetrahydroquinolines in good yield with excellent anti-selectivity. Meanwhile, the coupling of arynes with α-amino ketones produces multisubstituted indolines in high yield with syn-selectivity. A quaternary carbon center can be constructed in this process, and the reaction can be easily scaled up.

New Entry to the Synthesis of α-Iminonitriles by Lewis Acid Mediated Isomerization of Cyano-Substituted Iminoisobenzofurans Prepared by Palladium-Catalyzed Three-Component Coupling of Arynes, Isocyanides, and Cyanoformates

A variety of α-iminonitriles were formed as the minor products of three-component coupling reactions of arynes, isocyanides, and cyanoformates in the presence of the cationic palladium complex [Pd(NCPh)2(dppf)](BF4)2 as the catalyst, along with cyano-substituted iminoisobenzofurans as the major products. α-Iminonitriles obtained from this process are hardly accessible by conventional methods. In addition, when the isolated iminoisobenzofurans were treated with diisobutylaluminum hydride (DIBAL-H) or AlMe3, the transformation of cyano-substituted iminoisobenzofurans into α-iminonitriles was observed.

Diastereoselective Synthesis of N-Aryl Tetrahydroquinolines and N-Aryl Indolines by the Tandem Reaction of Arynes

A tandem reaction of arynes with α- or β-amino ketones has been revealed. Arynes react with β-amino ketones through a cascade insertion-cyclization process to afford N-aryl tetrahydroquinolines in good yield with excellent anti-selectivity. Meanwhile, the coupling of arynes with α-amino ketones produces multisubstituted indolines in high yield with syn-selectivity. A quaternary carbon center can be constructed in this process, and the reaction can be easily scaled up.

ChemInform Abstract: Synthesis of Benzisoxazolines by the Coupling of Arynes with Nitrones.

AbstractA facile, mild, and general method to prepare benzisoxazolines is reported.