Diels-Alder reactions of arynes

A Diels-Alder reaction of arynes with 1,2,4-triazines 102 allows the preparation of isoquinolines substituted with electron-withdrawing groups in the nitrogen-containing ring. The isoquinoline-1-carboxylic esters bearing additional substituents are of particular interest because they are not readily available by the usual routes [100,101] (Scheme 2.42). 

Scheme 43. Synthesis of the pentiptycene 85 by a typical Diels-Alder reaction of aryne intermediates with anthracene [137b]...

It should be noted that because of the extreme reactivity of arynes, other reactions such as 2+2 cycloaddition or the ene reaction may complete with the Diels-Alder mode of addition more frequently than is the case with less reactive dienophiles. This is especially true if the diene component is not conformationally predisposed to the 4+2 cycloaddition mode. Also, as with other dienophiles, Diels-Alder reactions of arynes are stereoselective. 

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]. 

An extensive review of recent advances in transition-metal-ffee carbon-carbon and carbon-heteroatom cycloadditions of arynes, generated from 2-(trimethylsilyl)aryl triflates, has been presented. The Diels-Alder reaction of arynes, generated from... 

New Diels-Alder reactions of 3-vinylindoles with an aryne selective access to functionalized [a]anellated carbazoles [145]... 

The reaction of benzyne with furan was the first example of a Diels-Alder reaction of benzyne to be studied b. No authenticated examples of arynes are known which fail to give cyclo-adducts with furan i38>. The tetrahalogenobenzynes all form the expected adducts 103, X = F 6), Cl 57>i39)j gr 59) or i 59)). d0 other highly fluorinated arynes i40,i4i>. The isomeric adducts (104) and (105) have been detected by 19F n.m.r. spectroscopy when the dilithio-compound (12) was allowed to decompose in the presence of furan 28 103). 

The reaction of benzyne with cyclohexadiene has been known for some time 4>, but although a number of steroidal cis-dienes are readily available no reactions with arynes had been reported prior to our beginning such investigations 145>. This was somewhat surprising in view of the number of reports concerning the modification of steroids by means of reactions with carbenes 146 i49) and the known Diels-Alder reactions of steroidal dienes and trienes iso.isi). 

Diels-Alder reaction of 3-vinylindole 131 with aryne in the presence of air gives, besides primary Diels-Alder product 132, the methyl 12-methyl-12H-[3]-benzoxepino[l,2-l7]indole-5-carboxylate 135. This can be explained by the formation of 1,2-dioxetane 133, its cyclo reversion and final intramolecular cyclization of dienol 134 or its tautomers (Scheme 26 (1996JCS(P1)1767)). 

Furan has generally been observed to be a good diene in Diels-Alder reactions with arynes, and has been widely used in trapping aryne intermediates. Upon treatment with one equivalent of lanthanum, l-halo-2-iodobenzenes effectively generate benzynes, which are trapped with furan to afford the Diels-Alder product 99 (Equation 12.35) [58]. 

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... 

The Diels-Alder reaction ([4+2] cycloaddition) [8] provides one of the most powerful methods for the constmc-tion of PAHs because it affords one-step formation of the six-membered ring framework, the basic unit of these derivatives. This chapter, based on the results of our work, will highUght the synthesis of substituted oligoacenes including anthracene (1), tetracene (2), and pentacene (3) cores by Diels-Alder reactions using arynes and quinones as dienophile components and furans, thiophene-1,1-dioxides, and o-quinodimethane as diene components. The synthetic methodology will be accompanied by discussions on molecular and packing stmctures as weU as solid-state optical properties. 

Species such as 5 and 6 are called benzynes (sometimes dehydrobenzenes), or more generally, arynes, and the mechanism is known as the benzyne mechanism. Benzynes are very reactive. Neither benzyne nor any other aryne has yet been isolated under ordinary conditions, but benzyne has been isolated in an argon matrix at 8 where its IR spectrum could be observed. In addition, benzynes can be trapped for example, they undergo the Diels-Alder reaction (see 15-58). It should be noted that the extra pair of electrons does not affect the aromaticity. The... 

Similar alkene formations via dealkoxycarbonylation and denitration have been reported for the synthesis of novel heterocycles. Heterocyclic nitro compounds such as 4-nitroisoxazole undergo the Diels-Alder reaction subsequent dealkoxycarbonylation and denitration give the products, which are regarded as the Diels-Alder adducts of five-membered heterocyclic arynes (Eq. 7.142).121... 

The first steroidal examples of Diels-Alder reaction in which the dienophile is an aryne have been reported in fulL Thus, cholesta-2,4-diene affords two adducts with benzyne, in low yield, as the result of both a- and -face attack... 

Best and Wege59have reported the first total synthesis of Mansonone F and this is described in Scheme 10. Phenol (111)60 was made to react with 2-chloroacetyl-5-methylfuran (112) in dimethylsulfoxide and sodium methoxide to yield (113). Ketalization of (113) followed by catalytic reduction and basic hydrolysis afforded anthranilic acid (114). Diazotization followed by pyrolysis with propene oxide in 1,2-dichloroethane probably yielded aryne (115), which undergoes intramolecular Diels-Alder reaction producing the adduct (116). Deoxygenation and then acid hydrolysis afforded the product (117). This was subjected to Grignard reaction. The resulting tertiary alcohol on nitration yielded the nitro compound (118) which was subjected to reduction and oxidation respectively to obtain (119). It yielded Mansonone F (120) on dehydration. 

Thiophenes undergo Diels-Alder reactions, but their diene reactivity is lower than that of furans. The [4+2] cycloaddition occurs, therefore, only with very reactive dienophiles (arynes and alkynes with acceptor substituents) or under high pressure (example 3). 1,2-Disubstituted benzene derivatives 2 are formed with alkynes, as the primary Diels-Alder adduct 1 eliminates sulfur ... 

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