Arynes aryl anions

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... 

Benzyne also reacts with compounds containing nucleophilic carbon atoms such as enolates and aryl anions. Intramolecular nucleophilic addition to an aryne by the ortho ring carbon atom of another benzene ring substituted... 

Table 1. Generation of Arynes via Aryl Anion Intermediates...

Different carbon- or heteroatom-centered nucleophilic positions a-bonded to a suitable electrophilic functionality can undergo facile cleavage by adding to arynes and by further intramolecular nucleophilic substitution in the initially formed aryl anion or zwitterion intermediate. The overall process results in the insertion of an aryne into a nucleophilic-electrophilic o-bond. 

Another important aspect of aryne chemistry that has found application in benzo-fused heterocycles synthesis is MCRs, which generally include the first addition of nucleophiles to arynes and subsequent interception of the aryl anion intermediate with other electrophiles. If the nucleophile and electrophile are not part of the same molecule, the overall process is a unique multicomponent coupling, where the aryne is inserted between the other two coupling partners to afford the final product 85 (Scheme 39). This highly efficient transition-metal-free methodology has been applied to the S5mthesis of valuable benzo-fused heterocycles and has foxmd application in natural product synthesis. 

A variety of substituted aromatic compounds have been prepared through addition of anionic nucleophiles to arynes generated from readily accessible precursors.1 Most of the laboratory preparations start with aryl halides. The coupling yields are usually good to modest (equations 13-15) but can be poor (equation 16).83 Sometimes, a dramatic improvement in reaction efficiency can be achieved by the change of the base/solvent pair or other reaction conditions. For instance, in arylation of phenoxides and benzenethiolates, a switch over to DMSO as the solvent boosted the yield considerably (equation 17).86 Another example, illustrative of this point, is the reaction of N-methylpyrrolidone with aryl halides where an acceptable yield could not be obtained under a variety of conditions except with LICA in THF (equation 18).71... 

Anions derived from unsaturated amides or acids have recently been used as nucleophiles toward arynes . The products are 4-aryl unsaturated amides (520, 521) or acids thought to arise as shown. A variety of alkoxy substituted arynes were used. With methylsubstituted arynes, rearranged structures appeared in the products. For example, with 522 (R = H) indan 528 was obtained (51%) together with a small amount of 526 (R = H). With 522 (R = Me), however, the major product (55%) was 526 (R = Me), and no indan derivative was produced. A possible mechanism is shown. 

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