Furan reaction with benzyne derivatives

A new cathodic cyclodimerisation of 4-pyrones yields either (90) or (91) depending on conditions,88 2-Benzopyran-3-one has been isolated at low temperature and intercepted by NPM as the adduct (92) 88 high-pressure cycloaddition reactions of 2H-pyran-3-ones with a variety of dienophiles have been recorded.88 Cycloaddition reactions of furans and isobenzofurans continue to dominate this section. Dienophiles whose reactions with furan have been studied recently include phenylsulphonylpropadiene (giving predominantly the endo-adduct (93) 8b. benzynes (derived from aryloxazoli nesJ.8 and... 

Benzyne formation and their reactions are not limited to simple benzene derivatives. Heterocyclic mole-ules can also be used for benzene reactions. One important use of benzyne derivatives is in the Diels-Alder caction (see sec. 11.4.A). When 3-bromo-2-methoxypyridine (394) was treated with EDA at -78°C, for. ample, lithium-hydrogen exchange occurred to give 395. Loss of LiBr led to benzyne (396), which reacted with furan to give the Diels-Alder product (397) in 74% yield. ... 

The Diels-Alder reaction of benzynes offers a route to the synthesis of fused azepine derivatives. Thus it is possible to convert the furan (15) into the fused system (16) in approximately 50% yield by reaction with LiTMP in THF at -78 °C... 

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,... 

Benzynes generated by the fluoride-induced elimination of TMS and OTf groups from o-trimethylsilyl [6]- and [7]-heUcenol triflates selectively undergo an intramolecular Diels-Alder reaction with one of the benzene rings within the hehcenes, rather than an external furan molecule, giving rise to bridged derivatives of coro-nene (Equation 12.42) [86). 

In a model synthetic study that focused on the CD-D fragment of angelmicin B (548), Narayan and Roush reported that furan 173 reacted readily with the transient benzyne derived from tribromide 541 (Scheme 13.109) [173]. Upon mUd acid workup, a mixture (1 1) of regioisomers 542 and 543 was produced, although each was found to be very air sensitive. Reaction of the mixture with NaH, BnBr, and TBAF provided 544 in 75% yield. Deprotection and CAN mediated oxidation afforded quinone 545. A palladium-catalyzed cross-coupling of boronic acid 546 and 545 then... 

Hydroxy-THISs react with electron-deficient alkynes to give nonisol-able adducts that extrude carbonyl sulfide, affording pyrroles (23). Compound 16 (X = 0) seems particularly reactive (Scheme 16) (25). The cycloaddition to benzyne yields isoindoles in low- yield. Further cyclo-addition between isoindole and benzyne leads to an iminoanthracene as the main product (Scheme 17). The cycloadducts derived from electron-deficient alkenes are stable (23, 25) unless highly strained. Thus the two adducts, 18a (R = H, R = COOMe) and 18b (R = COOMe, R = H), formed from 7, both extrude furan and COS under the reaction conditions producing the pyrroles (19. R = H or COOMe) (Scheme 18). Similarly, the cycloadduct formed between 16 (X = 0) and dimethylfumarate... 

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. 

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