Insertion reactions arynes

An aryne insertion reaction occurs when the electrophilic and nucleophilic groups are linked by a o-bond [9] these processes will be discussed in Section... 

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

H. Yoshida, K. Takaki, Aryne insertion reactions into carboiKarbon o-Bonds, Synlett 23 (2012) 1725-1732. 

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... 

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]. 

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. 

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). 

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. 

However, most of the reported examples in this field refer to the insertion into the C=0 re-bond of formamides. Miyabe et al. pioneered the use of DMF as a useful component in aryne-mediated reactions reporting the synthesis of 6-methoxysalicylaldehyde from 3-methoxybenzyne. Interestingly, they were also able to trap the four-membered ring intermediate 39 with dialkylzincs to afford o-aminoalkylphenols 40 (Scheme 12.23) [36]. 

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]. 

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]

Yoshida, Kunai et al. have reported some reactions of this type, complementing the transition metal-free aryne insertion into o-bonds. Mechanistically, these reactions could proceed via carbopalladation of arynes by the palladium complex arising from the initial oxidative... 

Nickel(0)-aryne complexes readily undergo insertion reactions with unsaturated substrates such as CO, CO2, olefins, and alkynes. " The latter often undergo double insertions. For instance, the complex Ni(r7 -C6H4)(PEt3)2 undergoes double insertion of alkynes to form substituted naphthalenes (Scheme Z) while double insertion of thioalkynes gives various 2,3-thioether naphthalenes, as shown in Scheme 13. A recent report has also demonstrated the application of this insertion reaction to various diynes such as dialkynyl naphthalenes. The factors that determine the regiochemistry of these insertions have been reviewed. 

Type of reaction C-I bond formation Reaction conditions Acetonitrile, room temperature Synthetic strategy Aryne insertion into I-I o-bonds Catalysts/reagents Cesium fluoride (CsF)... 

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... 

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. 

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. 

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. 

The first step in the reaction is therefore addition of the nitrene to the aromatic double bond forming an aziridine 26 71>. This intermediate can now collapse to the sulphonamide 27 and an aryne which produces tars 68>. Ring opening to form an aniline derivative 28 — a formal insertion product — is another possibility of stabilization. 

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