Arynes aryl triflates

Aryl triflates have been used to generate arynes via other routes than metal-halogen exchange. For example, fluoride ion displacement of the trimethylsilyl group in 26 provides a convenient route to benzyne under mild conditions. The required benzyne precursor 26 was prepared from o-trimethylsilylphenoxytrimethylsilane by sequential treatment with BuLi and (Tf)20. Analogous aryne precursors have also been prepared less directly, as in the case of amide benzyne 31. Examples of 32 include various methylfurans, diphenylsobenzofuran and tetraphenylcyclopentadienone. Examples of nucleophiles include methanol, phenol, lithium thiophenoxide and others. 

Aryl triflates 35, generated from the corresponding phenols, react with lithium diisopropylamide (EDA) in diisopropylamine (DIA) to give 36 in good yield. The reaction was demonstrated (via substitution pattern in the products) to proceed via an aryne intermediate. The choice of LDA as the base is critical BuLi, NaNH2, sodium acetylide and 2-lithiofuran all failed to generate an aryne from 35 (R = p- h). Application of the method to other nucleophiles than DIA, or to cycloadditions, has not yet been demonstrated. 

The synthesis of HBT (73), which contains three [5]helicene units, illustrates the power of the cyclotrimerization of polycyclic arynes for the synthesis of he-licenes. More examples are shown in Table 2. Again, Pd2(dba)3 is the catalyst of choice for trimerization of the asymmetric arynes 77-79, which are generated from the corresponding o-(trimethylsilyl)aryl triflates 74-76. In the reactions of 1,2-didehydronaphthalene (77) and 1,2-didehydrophenanthrene (78), mixtures of regioisomers are obtained, whereas 84 is the only isomer isolated from the cyclotrimerization of 79. Compounds 80 and 82 contain a [5]helicene unit, while compound 84 is the first example of a double helicene formed by a pen-tahelicene and a heptahelicene with two rings in common. 

An interesting new addition to the methods available for constructing arylthiophenes is the addition of thienyllithium to arynes generated from aryl triflates and LDA <93JOC4722>. Both ipso-and c/ne-substitution are possible. o-Tolyl triflate gave the ortho- and we/a-substituted products in the ratio 43 57, but 2-methoxyphenyl triflate gave exclusively the weta-substituted product. 

Arynes can be prepared and used as isoquinoline precursors in a formal [4 + 2] reaction with enamides or amidoacrylates. Arynes are liberated from fluoride anion reaction of silyl aryl triflates with cesium fluoride. 

Finally, the same group carried out a mono and a double annulation of arynes to synthesize fluoren-2-ones 60 and polycyclic aromatic systems 62 respectively [40]. These methods involve the in situ formation of highly reactive arynes by reaction of 2-(trimethylsilyl)aryl triflates 58 and CsF. In the presence of Pd(dba)2 (dba = dibenzylideneacetone), a crosscoupling and cyclization with a 2-halobenzaldehyde occur in the former case and C—H activation and cyclization occur in the latter case (Scheme 8.13). 

In 1983, Kobayashi developed a convenient approach to arynes by the fluoride-induced 1,2-elimination of o-(trimethylsilyl)aryl triflates (Equation 12.6) [5]. The mild reaction conditions involved in this protocol are compahble with a variety of reagents, substrates, functionalities and even transition metal catalysts. Today, this approach is the most widely used and the most efficient method for aryne generation. 

A wide variety of reagents have been used in 1,3-dipolar cycloadditions with arynes. For example, a general method for the preparation of Al-unsubstituted indazoles 27 and 1 -arylindazoles 28 by the [3+2] cycloaddition of aiynes generated from o-(silyl)aryl triflates and diazomethane daivatives has been developed. The selective formation of 27 or 28 depends on the relative amounts of the... 

By using the fluoride-induced generation of arynes from o-(silyl)aryl triflates, Larock and Liu have developed the aryne-mediated A-arylation of amines, sulfonamides, and carbamates as well as the O-arylation of phenols and carboxylic acids. Remarkably, a wide variety of functional... 

Keywords o-(Trimethylsilyl)aryl triflates, iodine, cesium fluoride, acetonitrile, room temperature, aryne, insertion reaction, substituted and polycyclic o-diiodoarenes... 

Aryne Annulation. Treatment of o-(trimethylsilyl)aryl triflates with TBAT results in the formation of ben-zyne intermediates. Fluoride-induced 1,2-eliminations of o-(trimethylsilyl)aryl triflates, which are readily prepared from phenols, have been shown to provide the respective aryne products, which, at room temperature, precipitously undergo cycloaddition in the presence of Diels-Alder adducts, including, but not limited to, tethered acyclic dienes, tethered enynes (eq 15), azomethine imines (eq 16),ene carbamates, and acetamidoacry-lates (eq 17). ... 

An extensive review of recent advances in transition-metal-ffee carbon-carbon and carbon-heteroatom cycloadditions of arynes, generated from 2-(trimethylsilyl)aryl triflates, has been presented. The Diels-Alder reaction of arynes, generated from... 

The reactive zwitterions arising from the nucleophilic attack of imines 479 on the benzyne generated in situ from 2-(trimethylsilyl)phenyl triflate 478 proved to be an appropriate molecular scaffold for the capture of CO2 with sufficient electrophilicity to yield 2-aryl-3,l-benzoxazin+-ones 480 (Equation 53). Both substituents of the C=N bond affected the course of the reaction considerably the best yields were achieved by using imines with electron-rich or neutral aryl groups on the carbon, and benzyl or nonbranched chain alkyl substituents on the nitrogen atom. With substituted derivatives of 478, the unsymmetrically substituted arynes led to regioisomeric products <2006JA9308>. 

There has been a summary of the use of insertion reactions of arynes into a-bonds to prepare nrt/io-disubs tituted arenes. A key to the success of these processes is the ability to generate benzyne under mild conditions by the reaction of readily available o-(trimethylsilyl)phenyl triflate with fluoride ions.61 Reaction of amines and their derivatives with benzynes generated in this way has been shown to be an efficient method for the production of N-arylated derivatives, as illustrated in Scheme 8. The method also works well in the O-arylation reactions of phenols and carboxylic acids 62... 

By employing o-(trimethylsilyl)phenyl triflate derivatives (11) as the aryne precursors, Larock and coworkers have developed a facile transition metal-free N-arylation method for amines, sulfonamides and carbamates under very mild reaction conditions (Scheme 12.4) [11]. Aromatic and aliphatic, as well as primary and secondary amines, react well, afTording good to excellent yields of the desired products. Secondary amines generally react faster than primary amines in... 

In 2010, Biju and Glorius [62] reported the NHC-catalyzed hydroacylation of arynes. A variety of aldehydes reacted with the arynes, generated in situ from 2-trimethylsilylaryl triflate and KF, to give benzophenones, a,p-unsaturated and other aryl ketones (Scheme 7.42). 

Heteroarenes and Benzannulated Heterocycles. The heteroatom arylation methods involving 2-(trimethylsilyl)phenyl triflates have been extended to the preparation of heterocycles. Acridones, xanthones, and thioxanthones are readily obtained by reacting methyl 2-aminobenzoate, methyl salicylate, or methyl thiosalicylate, respectively, with the aryne generated from 2-(tri-methylsilyl)phenyl triflate (eq 8). The ar3me is also used to prepare various benzannulated heterocycles via a three-component coupling process where at least one other cort5)onent is an imine or carbonyl compound. This procedure provides simple entry to racemic substituted benzoitninofurans, 2-iminoisoindolines, ... 

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