Transition-Metal-Free Synthesis of Benzo-Fused Five- and Six-Membered Heterocycles Employing Arynes

Kaicharla, Trinadh; Biju, Akkattu T.

doi:10.1016/b978-0-12-800070-0.00003-7

Cited by 5 publications

(3 citation statements)

References 137 publications

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“…Aryne chemistry has witnessed a resurgence of interest in the last three decades for the synthesis of various 1,2-disubstituted benzenes . Employing arynes is a convenient method for double functionalization of arenes and the synthesis of benzo-fused heterocycles . The existence of these highly reactive intermediates was speculated in 1902 by Stoermer and Kahlert in the reaction of 3-bromobenzofuran to 2-ethoxybenzofuran under basic conditions, and the reaction was assumed to proceed via the 2,3-didehydrobenzofuran intermediate.…”

Section: Introductionmentioning

confidence: 99%

Employing Arynes in Diels–Alder Reactions and Transition-Metal-Free Multicomponent Coupling and Arylation Reactions

2016

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Arynes are highly reactive intermediates having several applications in organic synthesis for the construction of various ortho-disubstituted arenes. Traditionally, arynes are generated in solution from haloarenes under strongly basic conditions. However, the scopes of many of the aryne reactions are limited because of the harsh conditions used for their generation. The renaissance of interest in aryne chemistry is mainly due to the mild conditions for their generation by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates. This Account is focused on the Diels-Alder reaction of arynes and their transition-metal-free application in multicomponent couplings as well as arylation reactions. The Diels-Alder reaction of arynes is a powerful tool for constructing benzo-fused carbocycles and heterocycles. In 2012, we developed an efficient, broad-scope, and scalable Diels-Alder reaction of pentafulvenes with arynes affording benzonorbornadiene derivatives. Subsequently, we accomplished the Diels-Alder reaction of arynes with dienes such as 1,2-benzoquinones and tropones. Moreover, we uncovered a transition-metal-free protocol for the synthesis of 9,10-dihydrophenanthrenes by the reaction of arynes with styrenes that proceeds via a Diels-Alder/ene-reaction cascade. In addition, we demonstrated the reaction of arynes with indene/benzofurans, which proceeds via a tandem [4 + 2]/[2 + 2] sequence. Multicomponent coupling (MCC) involving arynes mainly comprises the initial addition of a nucleophile to the aryne followed by interception of the aryl anion intermediate with an electrophile (provided the nucleophilic and electrophilic moieties do not belong to the same molecule). We have disclosed aryne MCCs initiated by N-heterocycles such as (iso)quinoline, pyridine, and aziridines. When (iso)quinoline is used as the nucleophilic trigger and N-substituted isatin as the third component, the reaction affords spirooxazino(iso)quinolines via 1,4-dipolar intermediates. Unexpectedly, using pyridine affords indolin-2-ones, where the reaction proceeds via the pyridylidene intermediate. Additionally, we developed the phosphine-triggered aryne MCCs for the synthesis of functionalized benzooxaphospholes. In another phase of our work, we studied the synthetic utility of CO2 as a one-carbon synthon in aryne MCCs for the synthesis of phthalimides. Engaging arynes as an aryl source is one of the transition-metal-free methods for arylation reactions. We have demonstrated the N-arylation of aromatic tertiary amines and O-arylation of aliphatic alcohols using arynes. It is anticipated that the chemistry of arynes will continue to prosper and will lead to surprising developments for the synthesis of various 1,2-disubstituted arenes of molecular complexity and structural diversity. Future challenges in this area include the utility of arynes in enantioselective transformations and the synthesis and reactions of exotic heterocyclic arynes.

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Section: Introductionmentioning

confidence: 99%

Employing Arynes in Diels–Alder Reactions and Transition-Metal-Free Multicomponent Coupling and Arylation Reactions

2016

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“…Arynes are one of the most important classes of transient species that have emerged as powerful synthons and widely used in the synthesis of various functionalized arenes, heterocycles, and complex natural products . This versatile reactive intermediate could be achieved in situ from its corresponding precursors using appropriate reagents and conditions.…”

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confidence: 99%

Three-Component Coupling Reactions of Aryne, DMSO, and Activated Alkyne: Stereoselective Synthesis of 2-[(o-Methylthio)aryloxy]-Substituted Dialkyl Maleates

et al. 2019

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A transition-metal-free coupling reaction of aryne, DMSO, and activated alkyne for the synthesis of 2-[(o-methylthio)aryloxy]-substituted dialkyl maleates is reported. This cascade process is associated with several bond cleavage as well as bond formation reactions in one pot. One of our synthesized maleates has been unambiguously established by single-crystal XRD studies. This methodology allows preparation of trisubstituted vinyl ethers with excellent stereospecificity.

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“…One reason for the resurgence of interest in this area is the development of a mild and functional group tolerant method for generating arynes using fluoride induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates demonstrated by Kobayashi and co-workers . Because of the low-lying LUMO of arynes, they are excellent dipolarophiles, and consequently, a series of 1,3-dipoles can add across the CC triple bond to form various benzo-fused five-membered heterocycles . For instance, the 1,3-dipoles such as nitrones, nitrile oxides, nitrile imines, azomethine imines, diazo compounds, aromatic azides, , and sydnones, are known to add to arynes resulting in the formation of benzo-fused five-membered heterocycles (Scheme , eq 1).…”

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

et al. 2019

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The synthetic utility of NaN3 as the azide component in the [3 + 2] annulation with arynes generated from 2-(trimethylsilyl)aryltriflates resulting in the transition-metal-free synthesis of N-H and N-aryl benzotriazoles has been demonstrated. Using CsF as the fluoride source in CH3CN, the N-H benzotriazoles are formed in high selectivity instead of the expected azidobenzene. Interestingly, N-aryl benzotriazoles are formed using KF and THF as solvent in an open-flask reaction. Moreover, a method for the N1-arylation of benzotriazole is also presented.

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Transition-Metal-Free Synthesis of Benzo-Fused Five- and Six-Membered Heterocycles Employing Arynes

Cited by 5 publications

References 137 publications

Employing Arynes in Diels–Alder Reactions and Transition-Metal-Free Multicomponent Coupling and Arylation Reactions

Employing Arynes in Diels–Alder Reactions and Transition-Metal-Free Multicomponent Coupling and Arylation Reactions

Three-Component Coupling Reactions of Aryne, DMSO, and Activated Alkyne: Stereoselective Synthesis of 2-[(o-Methylthio)aryloxy]-Substituted Dialkyl Maleates

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

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