Benzynes as dienophiles

For a review of benzynes as dienophiles, see Hoffmann Dehydrobenzene and Cycloalkynes, Academic Press New York, 1967, pp. 200-239. For a review of the reactions of benzynes with heterocyclic compounds see Bryce Vernon Adv. Helerocycl. Chem. 1981,2, 183-229. 

Diels-Alder reactions of furans were the subject of a recent review (1986). Their intermolecular versions profit notably from high-pressure conditions (Section 4.1.4.2.1) or the use of benzynes as dienophiles (Section 4.1.7). 

The high reactivity of benzynes as dienophiles in Diels-Alder reactions has also been observed in reactions with aromatic hydrocarbons, a class of compounds usually considered as inert as dienes. In a two-step synthesis of triptycene di- and tetracarboxylic acids, arynes generated in situ from anthranUic adds 158 cydized with anthracenes 159 affording di- or tetramethyltriptycenes 160 in 41-69% yields (Scheme 12.47) [85], Acids 161 were obtained after subsequent oxidation of the cycloadducts 160 with potassium permanganate. 

Benzynes, as dienophiles 13 Bridgehead olefin, formation in the intramolecular Diels-Alder reaction 2, 7 Butressing, effect of, on intramolecular Diels-Alder reaction 41-42... 

Incidentally, a 1,3-cycloaddition of benzyne to thiophene has been postulated (81CC124) to account for the small, but reproducible amount of benzo[ >]thiophene formed in this reaction (Scheme 79). Reactive alkynes have been successfully used as dienophiles to cycloadd with thiophenes benzene derivatives are obtained after extrusion of sulfur from the adduct (Scheme 80) (72TL605, 72TL1909, 73CB674). 

Two novel mono- and bisoxadisilole-fused benzo [fjfurans were prepared and isolated. They were shown to undergo facile Diels-Alder cycloaddition reactions with dienophiles such as the oxadisilole-fused benzyne, as illustrated in Equations (115) and (116), to form acene precursors <2006JOC3512>. 

Arynes have functioned as dienophiles in this type of Diels-Alder reaction. The reaction of 2-pyrone with benzyne to yield naphthalene, as shown in the accompanying scheme, was first reported in 1962. ... 

Pyridyne is formed and reacts as a dienophile in reactions analogous to those described by Wittig and Pohmer and by Stiles and Miller in benzyne chemistry. ... 

Because of their strong aromatic character, benzene and naphthalene are very unreactive as dienes however anthracene 19 reacts with highly reactive dienophiles, such as dehydrobenzene (benzyne) 20 ... 

When benzyne is generated in the absence of another reactive molecule it dimerizes to biphenylene.132 In the presence of dienes, benzyne is a very reactive dienophile and [4+2] cycloaddition products are formed. The adducts with furans can be converted to polycyclic aromatic compounds by elimination of water. Similarly, cyclopentadienones can give a new aromatic ring by loss of carbon monoxide. Pyrones give adducts that can aromatize by loss of C02, as illustrated by Entry 7 in Scheme 11.9. 

The [2+4] cycloaddition proceeds with retention of dienophile configuration, as was clearly demonstrated by carrying out the reaction with /ra .r-l, 2-dicyanocthync leading to 148 (Scheme 58). When benzyne generated in situ was utilized, reactions gave rise to 1-borabenzobarrelene derivatives 149 and 150 (Scheme 59). 

Whenever benzyne is expected to undergo a [2+2] cycloaddition as with ketones,109 it behaves as a dienophile with aromatic thioketones. Reaction of thiobenzophenones with benzyne yields the [4+2] cycloadducts and 1H-2-benzothiopyrans.110,111 Sterically congested thiones,111 thiopivalophenones and 2, react with benzyne to give the [2+2] adducts, 2H-l-benzothietes. 

Finally, it should be pointed out that the diaryne reactions of 1,2,4,5-tetrabromobenzene are stepwise. Thus the procedure described here, but using half the amounts of furan and butyllithium, can be used to prepare 6,7-dibromonaphthalene 1,4-endoxide (mp 115-117°C) in 70% yield.17 This versatile intermediate can then be used as a benzyne precursor, to make unsymmetric adducts 7 13 17 it also can be used as a dienophile.15 18... 

Reactivity with benzyne Even with the good dienophile ben2yne Cjq does not react as diene but rather forms a [2+2] cycloadduct [85-87]. One reason for such reactivity is certainly due to the fact that in a hypothetical [4+2]-adduct one unfavorable [5,6]-double bond in the lowest energy VB structure is required. 

Photooxygenations of 1,4-dioxins and their benzo- and naphtho derivatives as well as the ozonolyses of 1,4-benzo-dioxins and the cycloaddition of dithiins and 1,4-benzodithiins have been reported <1996CHEC-II(6)447>. In more recent reports, 2-chloro-l,4-benzodithiin-l,l,4,4-tetraoxide 67 was employed as a very reactive dienophile <19970393, 2005JOC5221> and was suggested as a mild alternative to the use of benzyne in [4-1-2] cycloaddition reactions (Scheme 7) <1996T14247>. 

L in Scheme 11.3) departs. Nucleophilic addition to the intermediate benzyne (step D) is readily explained by perturbative MO arguments. The extra and orbitals of benzyne are compared to those of ethylene in Figure 11.7. The aromatic n system is not involved in the special properties of benzyne. The third benzyne n bond is due to the overlap in fashion of the two sp2 hybrid orbitals which lie in the nodal plane of the intact 6 electron system. Two factors contribute to a very low LUMO for benzyne. First, the sp2 hybrid orbitals are lower in energy than the 2p orbitals from which the ethylene orbitals are constructed. Second, the intrinsic interaction between the two sp2 orbitals is less than the normal / cc since the orbitals have less p character and are tipped away from each other. The low LUMO of benzyne makes the molecule a strong Lewis acid, susceptible to attack by bases, and a reactive dienophile in Diels-Alder reactions, as we shall see later. 

Aromatic compounds can also behave as dienes.858 Benzene is very unreactive toward dienophiles very few dienophiles (one of them is benzyne) have been reported to give Diels-Alder adducts with it.859 Naphthalene and phenanthrene are also quite resistant, though naphthalene has given Diels-Alder addition at high pressures.860 However, anthracene and other compounds with at least three linear benzene rings give Diels-Alder reactions readily. The interesting compound triptycene can be prepared by a Diels-Alder reaction between benzyne and anthracene 861... 

The benzyne route to 1-cyanobenzocyclobutenes has been employed for the synthesis of a myriad of complex natural products. The cyano group in (74) was used to attach the dienophile as well as for building die imino bridge of (75), an important precursor for some diterpene alkaloids (Scheme 15).110... 

The benzyne functions as a dienophile towards reactive diene systems. The reactivity of the 9,10-positions in anthracene is well known (Diels-Alder reaction, Section 7.6), and addition of benzyne to 9-bromoanthracene yields the interesting cage-ring alkyl halide 9-bromotriptycene (9-bromo-9,10-o-benzenoanthracene). The reaction is incomplete and some unreacted 9-bromoanthracene remains in the crude reaction products, but may be removed by virtue of its ready conversion into a maleic anhydride adduct in a further Diels-Alder-type reaction. 

Benzyne in solution reacts as a dienophile Wittig (1957) first demonstrated this in the reaction of benzyne with furan. Corbett and Porter (1965) obtained further supporting evidence by isolating 1,4-addition products from benzyne with 1-vinylnaphthalene and 3-vinylbenzo[b]-thiophene Dilling (1966) did the same with styrene. 

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