Arynes precursors

Carbene precursors such as a-halogenoalkylmagnesium compounds and aryne precursors such as o-halogenoarylmagnesium compounds are on the whole less readily accessible than the corresponding organolithium compounds, and more thermally stable, so that carbenoid and arynoid reactions based on the organomagnesium intermediates are much less used [1]. ... 

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. 

Aminobenzotriazole and related triazoles, all of which are aryne precursors, are autocatalytic inactivators of cytochrome P-450 and related oxidases. Evidence has been presented that the enzyme oxidizes these substrates to benzyne which then binds covalently to the heme prosthetic group of the enzyme, possibly as in 120, thus deactivating it. 

These studies have been extended to a variety of other aryne precursors and nitrilesOne of the more interesting examples involves the one-step synthesis of aminoisoquinoline 519 from precursors 517 and 518, thought to occur by the mechanism shown. Some of this work has been reviewed. ... 

Entry Aryne precursor Reagent Catalyst (0.1 equiv) Additives Yield (%)>>... 

The palladium-catalyzed cyclotrimerization reaction is not limited to mono-cyclic arynes. On the contrary, a very interesting field of application of this reaction is the synthesis of extended PAHs from polycyclic aryne precursors. 

The triple bond of arynes reacts with bis-71-allylpalladium in an amphiphilic fashion (Eq. 16) [14]. The reaction of the aryne precursors 38 with allyl-tributylstannane 3a and allyl chloride 12b in acetonitrile in the presence of 2 equivalents of CsF and 2.5 mol% of Pd2(dba)3 CHCl3-dppf catalyst at 40 °C for 12 h affords the 1,2-diallylbenzenes 39 in good to high yields. The reaction proceeds through the addition of two allyl groups of bis-71-allylpalladium to the benzyne triple bond as shown in 40. 

Although arynes are recognized as highly reactive dienophiles there are relatively few reports of IMDA reactions where those reactive intermediates are tethered to a furan. A three or four atom tether linking the aryne precursor to the furan leads to efficient reactions <86AJC635>. The use of a... 

The interconversion of the 1,2-, 1,3-, and 1,4-didehydrobenzenes has been studied. A 1,2- to 1,3-didehydrobenzene conversion has been postulated to occur during pyrolysis (900 °C) of the phenyl substituted aryne precursors as shown in Scheme 7.4. Extremely high temperatures are required for benzyne interconversion. 

The only other useful aryne precursor of the zwitterionic type is diphenyliodonium-2-carboxylate, prepared from 2-iodobenzoic acid. It is much more thermally stable than benzenediazonium-2-carboxylate, decomposing in the range 160-200 °C with elimination of carbon dioxide and iodobenzene (Scheme 7.15). 

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... 

When one molecule of aryne precursor is replaced with a bicycUc alkene in the previous process, the carbocycUzation of an aryl iodide, a bicydic alkene and an aryne takes place, giving exclusively the eoco isomer of an annulated 9,10-dihydrophenanthrene 240 (Equation 12.65) [132]. 

Scheme 8 Synthesis of PAHs 28 and 29 using an aryne precursor [29]...

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. ... 

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,... 

Of the final two entries in Table 2, o-aminophenylboronic acid (4 Ip) is a promising aryne precursor whose detailed chemistry awaits further examination, and hence no information on the mechanism of its decomposition is available. Thermolysis of o-benzenedisulfonyl azide (41q) gives some evidence of benzyne formation, presumably via a nitrene and the cyclic azodisulfone 48. ""... 

One of the best routes to arynes is the oxidation of aminotriazoles (49j) with lead tetraacetate. Variations involve generating the intermediate nitrene 57 or nitrenoid with other oxidizing agents or from other precursors (49k-49n). By analogy the nitrene 58 or nitrenoid obtained by oxidation of 1-aminoindazole (59) might be expected to fragment to arynes by loss of Nj and a nitrile. In fact this reaction constitutes an excellent synthesis of the previously discussed aryne precursors, the 1,2,3-benztriazines (49e). A vibrationally excited form of 49c is presumably an intermediate in the pyrolysis of sulfoximides of 2-aminoindazoles (60) to arynes. 

In the last aryne precursor to be discussed in this section the nitrogen to be eliminated is exclusively exocyclic to the cleaving cyclic system. Photolysis of the diazobenzofuranone (61) gives benzyne (1) by the sequential loss of Nj and CO as shown. Each of the numbered species was detected by infrared spectroscopy in an argon matrix at... 

Finally, several likely aryne precursors in this category fail. Neither thermolysis nor photolysis of the tosylhydrazone derivative 64 yields any benzyne-derived products.Instead, the rearranged benzoxazolone (65) forms and, like... 

The failure to obtain such a furan adduct from an aryne precursor which yields other aryne-diene adducts (148) does not necessarily indicate the absence of arynes, however. One example of precisely this phenomenon was traced to the unique ability of furan to preferentially consume the aryne precursor 411 in a nonaryne pathway leading to 2-phenylfuran (172). Other examples are due to the instability of the benzyne-furan adduct 148a to strong bases. ... 

With some aryne precursors it is experimentally not possible to isolate, synthesize, or kinetically test for the Diels-Alder adduct (150). It is also conceivable that no such stable adduct exists, but that the aryne pathway is avoided by an addition-elimination process involving only reactive arynoid intermediates (175) [equation (27)]. In such cases a free aryne can be tested for... 

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