Trimethylsilyl phenyl Triflate

Handling, Storage, and Precautions stable liquid. Incorrqiati-ble with fluoride, hydroxide, or alkoxides, especially upon warming. 

Kobayashi and co-workers introduced 2-(trimethylsilyl)phenyl triflate as an aryne precursor subject to benzyne formation without the need of a strong base. Fluoride-induced desilylation and rapid elimination of the sulfonate provide efficient access to benzyne in acetonitrile at room temperature (eq 1). Other solvents such as THF, acetone, dichloromethane, DME, and toluene may be used, but such conditions may require heating for benzyne formation and frequently afford diminished yields. Preparation of the benzyne intermediate is even possible in protic media, albeit with decreased efficiency and limited applicability in subsequent reaction steps.  

orKF/18-C-6 MeCN, THF, DME, PhCHj (CHjtjCO, or CHCI2 0-110 C 

Various fluoride sources are employed for benzyne generation. Cesium fluoride or TBAF are most commonly used however, the combination of potassium fluoride and 18-crown-6 also works weU. The use of excess fluoride, typically 2 to 4 equiv, tends to provide superior results. 

Polycyclic Arenes. Trimethylsilylphenyl triflates have found widespread use as benzyne precursors in the preparation of polycyclic arenes. Triphenylenes are made via paUadium-catalyzed [2 + 2 + 2] cyclotrimerization of arynes, by paUadium-catalyzed annulation of the aryne and 2-halobiaryls, or via carbopalladation/carbocycUzation of arynes with substituted iodobenzenes (eq 2). All three approaches furnish substituted triphenylenes in high reported yields. Substituted phenanthrenes or naphthalenes are similarly prepared using 2-(trimethylsilyl) phenyl triflate as an aryne precursor. Treatment of the reagent with fluoride, a palladium catalyst, and a deactivated alkene, allyl halide, or internal aIk5Tie provides 9-substituted or 9, 

This route has been used to synthesize lignan-containing natural products. Extended fused polycyclic arenes are also accessible using related approaches.  

The palladium-catalyzed annulation of arynes, derived from 2-(trimethylsilyl)phenyl triflate, by 2-halobenzaldehydes provides variably substituted fluoren-9-ones in good yields (eq 4). Catalytic dicobalt octacarbonyl under CO pressure furnishes anthraquinones in the presence of the aryne derived from 2-(trimethylsilyl)phenyl triflate.  

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Benzyne, which is generated in situ from 2-(trimethylsilyl)phenyl triflate and KF, acts as an alkyne congener in distannation in the presence of palladium-/ r/-alkyl isocyanide complex.157 A variety of substituted benzyne derivatives inserts into the Sn-Sn bond to give l,2-bis(stannyl)benzenes (Equation (59)). The reaction fails to occur in the presence of other palladium catalysts such as Pd(PPh3)4. 

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... 

In unpublished work, shown in Scheme 5.6.22, we have shown that 33b, 2-(trimethylsilyl) phenyl triflate and 2-thienyl tri-n-bntylstannane, in the presence of Pd(0) in MeCN at 80 °C for 16 h, afford 63 in 40% yield." Work is in hand to optimize the process. 

The high efficiency of the present precursor 2 is demonstrated by comparison with a similar precursor, 2-(trimethylsilyl)phenyl triflat (4), which generates benzyne under mild conditions (room temperature and neutral).7 Benzyne precursor 2 gives the adduct, 1,4-epoxy-1,4-dihydronaphthalene 3, quantitatively in the reaction with furan, while the reaction of benzyne precursor 4 under the same conditions leads to a lower yield of adduct 3 and needs longer reaction time. 

Acyclic dienes bearing Oppolzer s sultam auxiliary 261 have been utilized in the synthesis of functionalized 1,4-dihydronaphthalenes <05JA15028>. Cycloaddition of dienes 261 with benzynes, generated from 2(trimethylsilyl)phenyl triflate 263 using cesium fluoride, provides cycloadducts 263 with excellent diastereoselectivities. 

A limitation of the scope of this reaction has been observed when attempting its application to 6-nitro-2-(trimethylsilyl)phenyl triflate. The excessively strong electron-withdrawing effect of the nitro group promotes nucleophilic attack by the fluoride on the sulphur atom of the triflate, cleaving the S-0 bond and expelling the phenoxide. 

The use of precursors of asymmetrically substituted arynes introduces the question of regioselectivity, since two products of cyclotrimerization are possible. However, the cyclotrimerization of asymmetrically substituted aryne 2, generated from 3-methoxy-2-(trimethylsilyl)phenyl triflate (64), proceeds in good yield and with high regioselectivity, affording a 93 7 mixture of regioiso-mers 65 and 66 (Scheme 14) [39]. 

Trimethylsilyl)phenyl triflate (55) is commercially available (Aldrich), but can in any case easily be prepared from o-bromophenol, both by the procedure described by Kobayashi (60% yield, see ref. 41) and by the modified method described on page 121 (92% yield, ref 42)... 

The cross-coupling of o-(trimethylsilyl)phenyl triflate, allyl chloride, and... 

Arynes are novel reaction intermediates that react with dienes or 1,3-dipoles to give the corresponding cycloadducts. Recently, many researchers have reported the reaction of benzyne prepared from 2-(trimethylsilyl)phenyl triflate or benzenedia-zonium carboxylate with imines, aminobenzoate, 2-aminobenzophenones, azides, and diazo compounds, which provides various N-containing cycloadducts, such as acridines, acridones, triazoles, and indazoles. Formally, the reaction proceeds in a [2-1-2], [3-1-2], or [4-1-2] manner. Benzyne is an extremely reactive species because of the presence of a strained triple bond and undergoes polar and pericycHc reactions. The lifetime of benzyne in the gas phase has been estimated to around 20 ns (2 X 10" s) by mass spectroscopic techniques. Some spectroscopic properties of benzyne have been determined by Orville Chapman using matrix isolation techniques (Scheme 7.20). 

C for 5 hours, 2,6-bis(trimethylsilyl)phenyl triflate (105) gave a quantitative yield of the trifluoromethyl ether 106. The reaction was found to be first order in 105 and zero order in 2,6-lutidine. The AH and AS values for the reaction were found to be 26.5 kcal/ mol and —5.5 eu, respectively. Propose a mechanism and give a mechanistic label for the reaction. 

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... 

The first example of a transition metal-catalyzed cycUzation of arynes was reported in 1998 [112], when benzyne generated from o-(trimethylsilyl)phenyl triflate was shown to undergo cyclotrimerization in the presence of a catalytic amount of Pd(PPh3)4 to afford triphenylene (208) (Scheme 12.60). 

Benzynes, generated from 2-(trimethylsilyl)phenyl triflates, react with P-alkenyl-X(5)-phosphazenes via a formal r-insertion into the PN bond. A subsequent retro 2 - -2-cycloaddition/6 r electrocyclization-protonation cascade rationalizes the formation of the resulting 1,4-benzazaphosphorinium triflates (Scheme 21). 

A three component coupling reaction involving carbopallada-tion of the aryne followed by a Fleck coupling with tert-butyl acrylate affords oFtAo-substituted cinnamic acids in good yields (eq 11). An ene reaction between the aryne, generated in THF at room temperature, and an alkyne creates allenylbenzenes in moderate yields. The reaction of jr-allylpalladium species with the benzyne created from 2-(trimethylsilyl)phenyl triflate provides access to several types of products in multicomponent... 

The benzyne created from 2-(trimethylsilyl)phenyl triflate was used in a highly diastereoselective aryne Diels-Alder reaction with a diene bearing Oppolzer s sultam. This approach to cis-functionalized 1,4-dihydronaphthalenes was reportedly the first aryne Diels-Alder reaction to provide enantioenriched cyclo-adducts. An unusual route to /3-aminoketones involves the treatment of 2-(trimethylsilyl)phenyl triflate with TBAF and an asymmetric vinyldihydropyridone. The resultant aryne Diels-Alder cycloadduct undergoes aromatization/eUmination to create the )V-acyl-/3-aminoketone (eq 13). This method was featured in a multistep synthesis of an unnatural a-amino acid. 

Fluoride-Induced Elimination. 2-(Trimethylsilyl)phenyl triflate (6), first reported by Kobayashi et al. in 1983 [11], and now commercially available, has turned into the most widely used benzyne... 

The use of benzyne derivatives in intermolecular carbo-palladation processes has stood out as a powerful tool for the preparation of 1,2-functionalized arenes in the last decade. Since the pioneering work by Yamamoto in 2000 [34], which introduced arynes as reactive partners in palladium-catalyzed reactions, several groups have exploited the carbopallada-tion of benzyne in three-component couplings. In general, 2-(trimethylsilyl)phenyl triflate derivatives, in combination with a fluoride salt such as CsF, are used as benzyne precursors. 

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