Aryne/furan Diels-Alder cycloadducts

Interestingly, when the number of equivalents of t-butyllithium was reduced from 4.0 to 1.1, all three benzyne-furan cycloadducts (i.e., 97a, 102, and 103) resulting from the three possible dibromoindole starting materials (lOOa-c) were isolated in excellent yields (Scheme 28). It is noteworthy that while the ortho dichlOTO- and dibromo-substituted indoles (94, lOOa-c) resulted in clean formation of the aryne species, the ortho difluoro derivatives lOOd-f did not behave in the same way. The attempted Diels-Alder reactions with 4,5 and 6,7-difluoroindoles lOOe and lOOf resulted only in the recovery of starting material. However, in the case of 5,6-difluoroindole lOOd, the cycloaddition resulted in the formation of 103,... 

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. 

Arynes with their reactive triple bond would be expected to participate readily in cycloaddition reactions. However, as demonstrated in the previous section, the addition of nucleophiles is extremely facile, and therefore reactions with non-nucleophilic reagents cannot usually be observed unless the aryne is generated in the absence of nucleophiles. In practice this usually means that routes involving the treatment of aryl halides with nucleophilic bases cannot be used. The first cycloaddition reaction of ortho-benzyne, the Diels-Alder reaction with furan was observed in 1955 by Wittig and used 2-fluorobromobenzene as the precursor. The cycloadduct was obtained in almost 90% yield, and the reaction has formed the basis for numerous synthetically useful Diels-Alder cycloadditions involving arynes. Tetrabromobenzene reacts with butyllithium to give the diaryne intermediate with furan to form a tetrahydroanthracene. The mixture of syn and anti conformers can be separated based on differences in methanol solubility (Scheme 7.26). 

Other Cyclic Dienes. Besides furan, the Diels-Alder reaction of arynes with other cyclic dienes has been also reported. Tautens etal. have prepared azabicycle 20 from Af-Boc-pyrrole and an aryne intermediate derived from dibromide 19. The prepared cycloadduct has been nsed in the total synthesis of (+)-homochelidonine (Scheme 12.13) [21]. 

The Diels-Alder reactions of -deficient 2//-pyran-2-ones with vinyl moiety containing dienophiles under microwave and high pressures have been extensively reviewed. The microwave-initiated intramolecular Diels-Alder reaction of an alkynol with a furan (80) formed a cycloadduct (81) that readily converted to 3,4-disubstituted 5-hydroxyindoles (82) in 15-74% yields in a one-pot reaction (Scheme 23). ° The treatment of < rt/io-(trifluoromethanesulfonyloxy)aryl boronic acid pinacol ester (83) with t- or i-butyllithium generates arynes (85) via boronate intermediate (84) at... 

Benzyne (28) (a representative of the short-lived reactive intermediates of the aryne type) can be trapped by Diels-Alder reachon with furan to give the cycloadduct 29, which is isomerized to a-naphthol by acid ... 

The unusual benzodifuran quinone 166 is formed by the retro-Diels— Alder elimination of ethane from 165, itself obtained by hydrogenation of a bis(aryne-furan) cycloadduct (Scheme 33) a similar approach gives the analogs 167-169 (2007T12621). 

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