Arynes addition reactions

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

The chemistry of dehydrobenzene, the parent aryne, has become well established during the past almost twenty years 4>. It is essentially the chemistry of a short lived (half-life ca. 10-4 sec.), and highly electrophilic intermediate. It reacts with a large number of nucleophiles, and undergoes cyclo-addition reactions with a wide variety of compounds. A number of observations have led us, and others, to concentrate our efforts on the tetrahalogenobenzynes. It seemed reasonable to predict that the presence of four electron withdrawing substituents on the aryne (1) would result in a significant increase in the electrophilicity compared with that of benzyne. 

Addition chemistry has developed into a promising tool for the modification and derivatization of the surface of nanotubes [24, 26], However, it is difficult to achieve chemoselectivity and regioselectivity control of addition reactions, requiring hot addends such as arynes, carbenes, radicals, nitrenes or halogens under drastic reaction conditions. 

Insertion and Addition Reaction Products of Arynes with Pyridine... 

From the addition reactions of phthalic anhydride with pyridine, naphthalene was formed in much greater quantity than quinoline isoquinoline was either totally absent or present in only minute amounts. These facts indicated (a) if there were much 1,2-addition of benzyne, it occurred predominantly at the 1,2 and 3,4 atoms in pyridine (b) 1,4-addition took place at carbon atoms in preference to a nitrogen and a carbon atom. Studies with other systems indicate that arynes have a decided preference for 1,4- over 1,2-addition. 

Addition reactions of the Si-Si cr-bonds of disilanes 121, 131, and 133 to the C=C bonds of various arynes were found to be promoted by a palladium-1,1,3,3-tetramethylbutyl isocyanide complex. Diverse 1,2-disilylated arenes 130, 132, and 134 were obtained from five-membered and benzo-condensed six-membered cyclic disilanes (Equations 21-23). The H, 13C, and z9Si NMR spectroscopic data as well as X-ray crystallographic analysis were used to confirm the above structures <20050M156>. 

The imidazole aryne l-methyl-4,5-dehydroimidazole undergoes ready addition reactions at the 4,5-bond.465... 

IV.2.1. Aromatic Elimination-Addition Reactions (Arynic Condensations). . 65... 

On the basis of the addition reactions already described in Sections III, B and C, this interpretation is not as improbable as at first might be thought. In this connection the trapping of benzocyclobutadiene and some seven-membered arynes by furan, to give normal adducts, is worth mentioning ... 

It should be noted that because of the extreme reactivity of arynes, other reactions such as 2+2 cycloaddition or the ene reaction may complete with the Diels-Alder mode of addition more frequently than is the case with less reactive dienophiles. This is especially true if the diene component is not conformationally predisposed to the 4+2 cycloaddition mode. Also, as with other dienophiles, Diels-Alder reactions of arynes are stereoselective. 

The scope of multiple and tandem aryne additions, which as we have seen are useful for forming two or more carbon-carbon bonds in a one-pot reaction, remains to be further explored. 

Buszek and coworkers next conducted additional studies to further understand the regioselectivity of these indole-aryne cycloaddition reactions [54], They chose to generate the indole-aryne systems either from the 4,5- or 5,6-ort/io-dibromo species 100c and 100b by treatment with n-BuLi (2.2 equiv) in toluene, or from the corresponding o-trimethylsilyl triflates 104 and 108 by treatment with tetrabuty-lammonium triphenyldifluorosilicate (TBAT, 2.5 equiv) in THF or CsF (3 equiv) in acetonitrile. It was observed that for either the 4,5- or 5,6- indolyne systems thus prepared, there are no regiochemical preferences in the cycloaddition reactions with t-butylfuran (105a) (Scheme 29). 

Arynes, such as benzyne (1,2-dehydrobenzene), also undergo Diels-Alder cycloaddition reactions. Benzyne, CelTj, is a highly reactive species and can be prepared by elimination of a suitably substituted benzene derivative. It reacts in situ with various dienes such as furan, cyclopentadiene, cyclohexadiene and even benzene and naphthalene to give bicyclic or polycyclic cycloadducts (3.15). Analogous addition reactions are shown by dehydroaromatics in the pyridine and thiophene series. 

Scheme 7.36 shows a further example of the use of aryne in alkaloid synthesis, involving intramolecular nucleophilic addition reaction as a key step in the synthesis of lysergic acid ester. 

The major application of arynes in synthesis is in the construction of polycyclic systems using either the Diels-Alder or intramolecular nucleophilic addition reactions. 

During an investigation into the addition reactions of element-element o-bonds to the C—C triple bonds of arynes, Yoshida et al. observed aryne insertion into the S—Sn o-bond of stannyl sulfides (Equation 12.16) [22]. The reaction is initiated by nudeophihc attack of the sulfur atom of the stannyl sulfide on the aryne triple bond, resulhng in the formation of a zwitterion, which undergoes intramolecular nudeophihc substitution at the stannyl moiety. This affords the corresponding 2-(arylthio)arylstannane 19. 

In Section 12.3.1, an addition reaction of N-alkylimidazoles to arynes was described by Yoshida et al. (Equation 12.12) [14], which led to the synthesis of N-alkyl-N -arylimidazolium salts. Xie and Zhang, however, have recently reported a completely different result from the reaction between benzyne and N-substituted imidazoles (Scheme 12.44) [78]. 

The first of these possibilities can occur if the addition reaction to the aryne is regiospecific and leads only to the normal substitution product 126 - 1 - 127. Such regiospecific reactions are known and are due to electronic and/or steric effects in either the aryne or the entering nucleophile. For example, m-chlorobenzotrifluoride (130) and m-bromoanisole (131) give only the respective m-substituted anilines (132) upon amination in spite of the demonstrated intermediacy of arynes. Similar regiospecificity might be expected even in unsubstituted hetarynes because of electronic directing effects of the heteroatom. 

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