Aryne Concept

The first didehydroaromatic species for which a structural formula was proposed was the flve-membered hetaryne, 2,3-didehydrobenzofuran (22). This intermediate was postulated to explain the formation of 2- as well as 3-substitution products from the reaction of 3-bromobenzofuran with NaOEt or alcoholic KOH [equation (3)]. The authors recognized that such an aryne, analogous to alkynes, could add ethanol in either direction, thus accounting for the isomeric product mixture. They furthermore ascribed a very high, strain-induced instability to 22 which they held responsible for the failure of all 

Attempts to generate a related didehydrospecies, the anhydride of acetylene dicarboxylic acid (23), ended in failure, although the authors were sufficiently optimistic to reserve future studies in this area to themselves. A few years later the intermediacy of 23, along with the four-membered cycloalkyne 24, was claimed during the pyrolysis of acetoxymaleic acid anhydride. 

Didehydroaromatic species apparently were considered as possible intermediates only twice during the next 30 years and in one of those instances rejected as being too unlikely. A dipolar formulation (lb) of dehydrobenzene was suggested almost simultaneously by Wittig and Morton as an intermediate in the reactions of halobenzenes with alkali metal derivatives of hydrocarbons. A symmetrical structure (la) for dehydrobenzene was specifically rejected by Wittig based on some earlier erroneous experimental work.  

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Belief in the existence of flve-membered hetarynes has waxed and waned since they were first postulated in the early part of this century. As described above, most of the development of the aryne concept took place with benzenoid compounds. Once this central idea became well established, however, it was natural to examine the scope of its application to other ring systems including flve-membered heterocycles. The first experiments in this direction in the early 1960s appeared to prove the existence of didehydromaleic anhydride (23), ° both 2,3-didehydrothiophene and 3,4-didehydrothiophene, 4 and 25 respectively, and even the patriarchal 2,3-didehydrobenzofuran (22). Older experimental results were reinterpreted in the light of these new claims to suggest that 2,3-didehydrobenzothiophene (26) and its dioxide (27) were probably known. The first reviews of these early results were generally optimistic about the existence of flve-membered hetarynes and doubtless... 

Concerning our own work on arynic ketone phenylations, we first performed experiments in the mixture HMPA—THF9,39. They led us to the concept of complex bases. After that we generally used THF or DME, reserving HMPA to only a few special cases. 

Intermolecular aminopaUadation with arynes or alkynes leads to the vinylpalla-dium species 70. A key C-H activation foUowed by reductive elimination furnishes the heterocycle 71. This concept was successfuUy applied in the synthesis of phenanthridines 73 and isoquinoHnes 75 using acyloxime 72 in the reactions with benzyne precursor 61a and alkyne 74, respectively (Scheme 3.19). 

Following the same concept, Akai et al. have used the bulky and robust TBS group for controlling theregioselectivity of aryne-furan Diels-Alder reactions. Thus, 3-TBS-arynes react with a wide variety of substituted furans to give preferentially the and-adducts 16, which become the only isomers observed (anti/syn> 50/1) when the C-2 substituent of the furan is also a relatively bulky group (f-Bu, TMS, or SnBUj). Interestingly, this reaction saves as a method for the selective synthesis of substituted 1-naph-thol derivatives 17 by treatment of and-adducts 16 with p-toluenesulfonic acid (Scheme 12.11) [19]. 

Insertion into Carbon-Carbon o-Bonds. First examples of this concept were reported with anionic nucleophiles in the context of the addition of a-lithioalkyl and a-lithioarylacetonitriles to arynes. In 1984, Meyers and Pansegrau proposed a cyclization rearrangement mechanism to account for the formation of products 77 in the reaction of a-lithioacetonitriles to 3-oxazolylbenzyne. Initial attack of the nucleophile takes place at C-2 probably due to chelation of the lithium atom from the lithiated nitrile to the oxazoline moiety (Scheme 12.40) [67]. 

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