Arynes halogen-metal exchange

SCHEME 12.5 Halogen-metal exchange for aryne generation. 

Metal-halogen exchange in o-haloaryltriflates (19, X = Br, I) occurs at -78 °C with BuLi to produce arynes. Mesylate or tosylate in place of triflate gave unsatisfactory results. Addition of alkoxyarynes produced this way to 2-methoxyfuran (23) is regioselective and proceeds head-to-head. 

Aryl triflates have been used to generate arynes via other routes than metal-halogen exchange. For example, fluoride ion displacement of the trimethylsilyl group in 26 provides a convenient route to benzyne under mild conditions. The required benzyne precursor 26 was prepared from o-trimethylsilylphenoxytrimethylsilane by sequential treatment with BuLi and (Tf)20. Analogous aryne precursors have also been prepared less directly, as in the case of amide benzyne 31. Examples of 32 include various methylfurans, diphenylsobenzofuran and tetraphenylcyclopentadienone. Examples of nucleophiles include methanol, phenol, lithium thiophenoxide and others. 

With few exceptions arynes used in the nucleophilic additions discussed so far are generated either by removing with base an aryl proton adjacent to a leaving group (Type A2, Section III.A.2), or by decomposing an anthranilic acid derivative (Type Bl, Section III.A.3). Reactions described in the remainder of this section are initiated instead by metal-halogen exchange (Type Al, Section IILA.l). 

Although there are some mechanistic uncertainties, there is evidence that the reaction occurs via two successively formed arynes produced after metal-halogen exchange at both iodines. If arynes were formed independently at each halogen pair, one would expect a mixture of m- and p-terphenyls as products. It is thought that the regioselectivity in the nucleophilic additions to aryne intermediates 638 and 639 is a consequence of the need to keep the two carbanionic sites on the benzene ring remote (i.e. para) to each other. 

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