Diels ortho-benzyne

In 1953, Robert s experiments on the conversion of C-labeled chlorobenzene with KNH2 into aniline gave strong support to the intermediacy of ortho-benzyne in this and related reactions. Additional direct evidence for the existence of ortho-benzyne was provided by the observation of its IR spectrum, sohd-state dipolar NMR spectrum, and NMR in a molecular container, and by UV photoelectron spectroscopy. Even at low temperatures, arynes are extraordinary reactive. The reactions of arynes can be divided into three groups (i) pericyclic reactions, (ii) nucleophilic additions, and (iii) transition-metal catalyzed reactions. The pericyclic reactions can be divided into several categories such as Diels-Alder reactions, [2-f2] cycloadditions, 1,3- and l,4-dipolar cycloadditions, and the ene reactions. Arynes react with practically aU kinds of nucleophiles. More recently, the transition-metal catalyzed reactions of arynes have been studied, in particular those involving palladium. 

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). 

Scheme 7.34 Diels-Alder reaction of ortho-benzyne in the synthesis of a polycyclic system.

A neat intramolecular trap for benzyne works in this way. A standard benzyne-generating reaction—the diazotization of an ortho-amino benzoic acid (Chapter 23) gives a zwitterion that loses nitrogen and CO2 to release the benzyne. A furan tethered to the next ortho position traps the benzyne in an intramolecular Diels-Alder reaction. The yield is impressive and the trap is very efficient. 

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,... 

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