Insertion reaction of arynes

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... 

Two different carbon functional groups can be introduced simultaneously into 1,2-positions of aromatic skeletons based on a novel insertion reaction of arynes (101) into a carbonyl-cyanomethyl a-bond of a-cyanocarbonyl compounds (102) to produce 1,2-disubstituted aromatics (103).134... 

Finally, transition metal-catalyzed reactions of arynes have been explored as a useful method for the construction of a wide variety of carbo- and heteocycles. These reactions include cyclotrimerization of arynes, cocyclization of arynes with alkynes or alkenes, and carbopaUadation of arynes with Pd-complexes. Moreover, some insertion reactions of arynes into a-bonds are also catalyzed by metal complexes. 

SCHEME 12.46 Other a-bonds insertion reactions of arynes. 

When the nucleophilic and the electrophilic positions of the reagent confronted to the aryne are not c-bonded, a cascade intermolecular nucleophilic addition-intramolecular electrophilic cycUzation of arynes can take place. The fragmentation step, which is cmcial for the insertion reaction of arynes into a-bonds, is not involved in annulation processes because the intermediate obtained from the cyclization is usually a stable five- or six-membered ring system. 

Catalytic Insertion Reactions of Arynes into [Pg.330]

In 2001, Yoshida et al. demonstrated that the insertion reaction of arynes into a C—Sn CT-bond of alkynyl- and vinylstannanes 42 took place smoothly using a... 

The major products from the reaction of arynes with thiophene and benzothiophene by addition and insertion are shown in Table 11. Benzyne from phthalic anhydride reacted with thiophene at 690° to give naphthalene and benzothiophene by 1,4-addition and loss of sulfur, and by 1,2-addition and loss of acetylene, respectively, as well as phenyl-thiophene by insertion (Fields and Meyerson, 1966d, 1967e) (Scheme 19). The ratio of naphthalene to benzothiophene was about 9 1, nearly the same preference for 1,4-over 1,2-addition as was inferred from the reaction of benzyne with dichlorobenzenes and pyridine at the same temperature, and again reflects the strong tendency of benzyne to act as a dienophile. 

It has been shown that carbon monoxide can insert into a nickel-aryne bond in a stoichiometric manner [134]. The catalytic carbonylation reaction of arynes induced by transition metals was first reported in 2001 (Equation 12.68) [135], and cobalt carbonyl complexes have since been found to be the catalysts of choice in this transformation. For example, anthraquinone was obtained in 82% yield in the presence of 2mol% of Co4(CO)i2. 

Photolysis of the mercury compound 286 in benzene leads to 3-phenyl-thiophene (291) and 3-iodothiophene (287). The former could arise from an insertion reaction of the aryne (4) with benzene if it is assumed that the expected but missing 2-phenylthiophene 292 completely isomerizes to the 3-isomer (291) under the reaction conditions. The argument is not convincing, however, since the 3-iodothiophene (287) formed as a coproduct, presumably by homolysis of the C-Hg bond, also yields 3-phenylthiophene (291) on photolysis in benzene, albeit in very low yield. Furthermore, by analogy with the reaction of benzyne the major products should be those of cycloaddition, which, in the case of 4, might lead, after loss of acetylene, to thianaphthene (293). No such products were reported from the photolysis of the mercury compound (286), but they have been observed from other possible sources of the aryne (4) (Section III.3.A.f). 

In this field, Yoshida et al. have also made interesting contributions describing some insertion reaction of aiynes into C—C a-bonds. IMth /i-toluenesulfonylacetonitrile or malononitrile two equivalents of the corresponding arynes react with the starting material. The overall process, which takes place through an initial C—C a-bond insertion, involves the formation of three C—C and one C—H bonds, and affords diverse diarylmethane derivatives 82 in a straightforward manner (Schane 12.43) [72]. 

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

The reactions of this study involved insertion of the aryne, as well as 1,2- and 1,4-addition followed by rearomatization (Scheme (18. 

Zirconium-benzyne complexes have been used rather extensively in organic synthesis.8 45 For this purpose, one particularly important characteristic of zirconium-aryne complexes is that olefin insertion into the Zr—C bond occurs stereospecifically. Thus, when generated in situ, the zirconium-benzyne complex (45) reacts with cyclic alkenes to give exclusively the cis-zirconaindanes (46), which upon treatment with electrophiles provide access to a variety of m-difunctionalized cycloalkanes (47-49) (Scheme 5).46 For example, carbonylation of intermediate 46 affords tricyclic ketone 49, reaction with sulfur dichloride gives thiophene 48, and reaction of 46 with tert-butylisocyanide followed by I2 gives 47 via 50 and, presumably, intermediate 51 [Eq. (12)]. 

Zirconium-aryne complexes have also found application in the regiose-lective synthesis of halophenols.62 Reaction of 101 with methyl diethylbori-nate or triethylborate leads to insertion of a boron-oxygen bond into a Zr-benzyne bond with formation of 102 and 104, respectively (Scheme 12). Further reactions of 102 and 104 with bromine or iodine followed by excess NaOH and 30% hydrogen peroxide gives halomethyl(methoxy)phe-nols 103 and 105 in good yields. In most cases only one regioisomer of the halophenol was observed. 

Aryne complexes of late transition metals are very reactive towards both nucleophiles (amines, alcohols, water) and electrophiles (iodine). They also undergo insertion reactions with CO, alkenes and alkynes,but while the behaviour of ruthenium complexes is somewhat similar to that of titanium or zirconium complexes, the reactivity of nickel complexes is rather different [6,8]. Examples of these reactions that are particularly interesting for the purposes of this chapter are shown in Schemes 8 and 9. Ruthenium complex 33 undergoes insertion of a molecule of benzonitrile,benzaldehyde or di(p-tolyl)acetylene to yield met-allacycles 40,41 and 42, respectively (Scheme 8). Further insertion of a second unsaturated molecule into these metallacycles has not been observed [25,27]. 

Aryne-nickel complexes, which were carefully studied by Bennett [6, 7], show a different reactivity, since following the insertion of a first unsaturated species, the metallacycles so formed usually undergo a second insertion and subsequent reductive elimination (Scheme 9). Thus, complex 44 undergoes the insertion of two molecules of 3-hexyne to afford 43 in good yield, and double insertion of the asymmetric alkyne t-butylacetylene into complex 44 yields naphthalene 45 with a high regioselectivity attributed to steric factors. Interestingly, the reaction of 44 with the more electron-deficient alkyne hexafluoro-... 

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. 

Under similar reaction conditions, arynes can also insert into the N—Si o-bond of aminosilanes, leading to 2-silylanihne derivatives in a straightforward manner (Equation 12.17) [23]. Both, cyclic and acychc amine-derived silanes work weU in this reachon, which is initiated by a nudeophihc attack of the nitrogen moiety of the aminosilane on the aryne triple bond, forming a zwitterion which subse-... 

In addition to the examples discussed above, arynes have also been found to insert into C-C single bonds. The reaction of either 2- or 3-bromophenol with arylacetonitriles in the presence of a strong base, such as lithium 2,2,6,6-tetramethylpiperidide (LiTMP), led to the same major products, 2-arylmethyl-6-hydroxybenzenecarbonitriles 23 (Scheme 12.9) [26]. In both cases, lithium 2,3-didehydrophenoxide (21) was generated. The anion of nitrile 20 then adds solely at the 3-position of 21 to afford adduct 22, which subsequently leads to the final product 23 after intramolecular rearrangement. When 2-bromo-l-naphthol was used instead of 2-bromophenol, a similar reachvity was observed [27]. 

The insertion of arynes into a-cyanocarbonyl compounds occurs smoothly under the same mild reaction conditions, and by a similar reaction pathway [37]. In the case of the sterically hindered substrate pivaloylacetonitrile, a single product 41 is formed in excellent yield (Equation 12.25), whereas a mixture of 42 and the double addition product 43 were usually obtained when other a-cyanocarbonyl compounds were used (Equation 12.26). 

The reaction, initiated by carbopalladation of the aryne by stable ir-allylpalladium intermediates, is followed by the insertion of a second molecule of aryne into the arylpalladium bond and subsequent intramolecular carbopalladation of the alkene by the newly formed biarylpalladium species. When the second equivalent of aryne is replaced with an internal alkyne, naphthalene 236 is formed in a 47% yield (Equation 12.61). 

Under the same reaction conditions, the Sn—Sn o-bond of a distarmane also readily adds to the triple bond of arynes, yielding diverse 1,2-distannylarenes which have the potential to act as bis-anion equivalents (Equation 12.73) [141]. Moreover, highly strained cyclohexynes undergo this Sn-Sn a-bond insertion smoothly under the reaction conditions in yields up to 90%. 

A significant ligand effect was observed in the palladium-catalyzed distannylation of arynes (Equation 12.74) [142]. While the reaction with t-OctNC yielded 254 as the major product, the insertion of two molar equivalents of aryne into the Sn-Sn O-bond predominated in the presence of the bicycUc phosphite EXPO (4-ethyl-2,6,7-trioxa-l-phosphabicyclo[2.2.2]octane). 2,2 -Bis(trimethylstannyl)biaryls 253 were thus generated alongside l,2-bis(trimethylstaimyl)benzenes 254 such 2,2 -distannylbiaryls 253 are synthetically useful compounds and can be readily converted to various substituted biaryls. 

Insertion into Carbon-Carbon o-Bonds. First examples of this concept were reported with anionic nucleophiles in the context of the addition of a-lithioalkyl and a-lithioarylacetonitriles to arynes. In 1984, Meyers and Pansegrau proposed a cyclization rearrangement mechanism to account for the formation of products 77 in the reaction of a-lithioacetonitriles to 3-oxazolylbenzyne. Initial attack of the nucleophile takes place at C-2 probably due to chelation of the lithium atom from the lithiated nitrile to the oxazoline moiety (Scheme 12.40) [67]. 

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