Arynes intramolecular

An unusual case of addition of a carbanion to an unconjugated carbon-carbon double bond is shown in Scheme 47a. The subsequent transfer of the amide group is also noteworthy (80CC1042). The intramolecular addition of a carbanion to an aryne is a more widely established process. Such reactions have been applied to the synthesis of indoles (Scheme 47b) (75CC745> and oxindoles (Scheme 47c) (63JOC1,80JA3646). 

The first benzazetidine (243) was isolated from the photolysis of 3-phenyldihydroben-zotriazine (242) (66JA1580). Another route to benzazetidines involving formation of the N to aryl-C bond utilizes intramolecular nucleophilic substitution via aryne (287). It is not general, however, and is only satisfactory when R and/or are alkoxy groups. The reaction also fails for iV-alkylamines (78LA608). 

One of the most interesting reactions of this type involves the intramolecular addition of the organolithium derivative to the aryne (13) which is derived from the dilithio-compound (12) 28>. This leads to the remarkably stable organolithium compound (14) which reacts with water to form the expected heptafluorobiphenylene, and with bromine to form 1-bromoheptafluorobiphenylene. 

The anion-radical mechanism for these syntheses is based on the following facts. The reactions require photo- or electrochemical initiation. Oxygen inhibits the reactions totally, even with photoirradiation. Indoles are formed from o-iodoaniline only the meta isomer does not give rise to indole. Hence, the alternative aryne mechanism (cine-substitution) is not valid. What remains as a question is the validity of the ion-radical mechanism exclusively to the substitution of the acetonyl group for the halogen atom in o-haloareneamine or also for intramolecular condensation. 

Diels-Alder reaction of 3-vinylindole 131 with aryne in the presence of air gives, besides primary Diels-Alder product 132, the methyl 12-methyl-12H-[3]-benzoxepino[l,2-l7]indole-5-carboxylate 135. This can be explained by the formation of 1,2-dioxetane 133, its cyclo reversion and final intramolecular cyclization of dienol 134 or its tautomers (Scheme 26 (1996JCS(P1)1767)). 

Carbanions derived from side chain tertiary amides have also been cyclized to provide isoquinolones and isoindoles (equation 36).125 126 While benzyne intermediacy in the formation of the former is likely, the latter seems to arise through a SrnI reaction pathway. Synthesis of indole from the meta bromo compound (87), on the other hand, clearly involves an aryne cyclization. 27 A more versatile route to indoles is based on intramolecular addition of aminyl anions to arynes (equation 38).128 A somewhat similar dihydroindole preparation constitutes the first step in a synthesis of lycoranes (equation 39).129 The synthesis of (88) also falls in the same category of reactions, but it is noteworthy because only a few examples of ring closure of heteroarynes are mentioned in literature.27 28... 

An important discovery in recent years has been that under the fairly high temperatures required for their formation from anhydrides, arynes are in equilibrium with the corresponding cyclopentadienylidenecarbenes which may be trapped by an intramolecular insertion. This is illustrated by FVP of 297 at 800 °C where the aryne 298 rearranges to the... 

Methyl thiosalicylate provides both electrophilic and nucleophilic sites for annulation of arynes generated from silylaryl triflates in the presence of CsF. An initial intermolecular nucleophilic coupling to afford a diaryl sulfide 529 is followed by an intramolecular electrophilic cyclization and thioxanthones result. The use of THF as solvent suppresses the competitive proton abstraction which leads to methyl 2-thiophenoxybenzoate (Scheme 211) <2005OL4273>. 

Tetrachlorophthalic anhydride gave a relatively low yield of products derived from tetrachlorobenzyne. The pyrolysis tube was badly carbonized evidently extensive decomposition of the anhydride, the aryne, or the chlorinated products had occurred. Tetrabromophthalic anhydride gave a still lower yield of products. These are not listed in the table because none of them retained all four bromine atoms and could be definitely ascribed to reactions of tetrabromobenzyne, although tri-bromo- and dibromonaphthalene were present in appreciable amounts. Tetraphenylphthalic anhydride also gave low yields of products of the reaction of tetraphenylbenzyne with pyridine. This was not because of the stability of the anhydride and its reluctance to form the aryne, but rather because the aryne preferred to stabilize itself intramolecularly. The behavior of tetraphenylphthalic anhydride is discussed in another Section. 

Bond formation through carbanions of type B has been much more widely used. A versatile isoindole synthesis (Scheme 24a) proceeds through intramolecular carbanion addition to an aryne. The subsequent aromatization is effected by base promoted elimination of hydrogen cyanide (77T2255). 

Both xanthones and thioxanthones are available through CsF-promoted coupling of arynes with salicylates and thiosalicylates. The synthesis proceeds through sequential intermolecular nucleophilic substitution and intramolecular electrophilic cyclisation (Scheme 39) <07JOC583>. The Pd-catalysed annulation of 3-iodoflavone with the same triflate results in the dibenzo[a,c]xanthone (Scheme 39) <07JOC223>. 

Intramolecular aryne arylation in synthesis of heterocycles 89ACR275. 

More remarkable are the reactions between ketone enolate ions and arynes generated by a complex base. Products derived using the aprotic solvent system differ considerably from those involving enolate ions in ammonia. In the protic solvent the aryl anion resulting from the addition of an enolate ion to an aryne is protonated and continued reaction is thereby prevented. Such protonation does not occur in the aprotic medium further reactions occur by intramolecular addition of the aryl anion to a carbonyl group, Scheme 5. Products obtained from acyclic ketones include... 

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