Quinodimethane derivatives

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

Furthermore, it was shown that porphyrin Id can also react with a pyrazine o-quinodimethane derivative (... 

Scheme 3 DA reaction of porphyrin Id with pyrazine o-quinodimethane derivative.

An analogy with reductive dimerization of diphenyl cyclopropenone (p. 58) was found on polarography of l,2-diphenyl-4,4-dicyano triafulvene (64)289. In a one-electron reduction step the cyclopropenyl radical anion 469 is likely to be generated and dimerized to the dianion of tetraphenyl-l,4-dicyanomethyl benzene (470) the dianion 471 could be successively oxidized via the anion radical 472 to the 1,4-quinodimethane derivative 473. 

A. Issaris, D. Vanderzande, and J. Gelan, Polymerization of a p-quinodimethane derivative to a precursor of poly (p-phenylene vinylene) — indications for a free radical mechanism, Polymer, 38 2571-2574, 1997. 

Table 4.2 [4+2]-Cycloaddition of C q with different o-quinodimethane derivatives.

Quinodimethane derivatives of terthiophene and other oligomers showed an absorption maximum at 583-688 nm (02JOC6015 03OL1535). Bis(dicyanoethylene) oligothiophene derivatives have been characterized and the compound with four thienyl rings showed an absorption band at 790 nm (02JA12380). This type of compounds was used in thin film transistors (see below) (02JA4184). 

When 1,3-diphenyl-l,3-dihydrobenzo[c]thiophene 2,2-dioxide is heated at 250° in diethyl phthalate, 1,2-diphenylbenzocyclobutene is not formed. Instead, rearrangement [Eq. (6)] of the initially formed o-quinodimethane derivative (96) occurs to give 9-phenyl-9,10-... 

Thus, the ease of desulfonylation of a l,3-dihydrobenzo[c]thiophene 2,2-dioxide and therefore the products obtained is dependent on the stability of the intermediate o-quinodimethane. The photochemical decomposition of l,3-dihydrobenzo[c]thiophene 2,2-dioxide probably involves an excitation energy of >74 kcal/mole and is not possible under the conditions already mentioned, whereas its 1,3-diphenyl derivative may be photochemically desulfonylated under these conditions because the intermediate o-quinodimethane derivative (96) is stabilized relative to o-quinodimethane itself (see also Cava and Shirley96).101... 

Dimethyl-l,3-dihydrobenzo[c]thiophene 2,2-dioxide also fails to give a benzocyclobutene on being heated. In this case the intermediate o-quinodimethane derivative (97) undergoes a rapid 1,5-hydride shift to give o-ethylstyrene [Eq. (7)]. 88,89... 

Only one 1,4-quinodimethane derivative incorporating cyclopropenylidene and cyclopentadi-enylidene groups (the [3.6.5]quinarene derivative 3) is known, which was synthesized in an essentially similar way to the quinocyclopropenes. Compound 3 was stable in the solid state and in dry aprotic solvents, but extremely unstable in wet solvents. ... 

Scheme 3.42). Di-tert-butyl phosphonates are too bulky to be fluorinated cleanly by this procedure, and side reactions such as elimination of phosphate or formation of isobutylene are observed. The electrophilic fluorination of a dimethyl benzylphosphonate having a (benzy-loxycarbonyl)methyl moiety in the para position was unsuccessful, with only unidentified nonfluorinated products being isolated. This may be a consequence of the elimination of fluorine from the first formed monofluorinated products, yielding quinodimethane derivatives, which may undergo further reaction. ... 

A significant application of this procedure has been described for [GOjfiillerene cycloaddition under microwave conditions by Langa et al. [17]. More recently, Chi et al. have applied the concept to the Diels-Alder reaction of [60]fiillerene with o-quinodimethane derivatives, generated in situ from 4,5-benzo-3,6-dihydro-l,2-oxathiine-2-oxide derivatives (thienosultines) under reflux in 1,2-dichlorobenzene solution the reaction was highly accelerated by microwave irradiation giving comparable yields of the mono and bis cycloadducts [18]. 

There is still little, if any, substantive data on the structure-reactivity profile of different heterocyclic -quinodimethanes, but the expected trends are supported by experience. The stability of the -quinodimethanes appears to be related to the loss of aromatic character o-quinodimethanes derived from the more stable aromatic heterocycles are the most reactive. Thus, when generated by flash vacuum pyrolysis and condensed at low temperatures, some heterocyclic rt-quinodimethanes can be isolated. It is clear that the furan derived. species 7 is considerably more stable than the thiophene analogue 2. The species 7 is sufficiently. stable for NMR spectra to be recorded at -60 °C and Diels-Alder adducts can be obtained by adding dienes to the cold finger <81JA669I>. In contrast, the species 2 can be observed directly only in an argon matrix <88CB791> and it readily polymerises even in the presence of dienophiles. Similar qualitative trends are observed with other heterocyclic o-quinodimethanes. 

Toxicity and lack of stability is also a problem in the use of bis(halomethyl) heterocycles as precursors to o-quinodimethanes. Another drawback is lack of flexibility in that the dihalides are not amenable to further modification to produce substituted o-quinodimethane derivatives. Nevertheless, in spite of these problems, its directness and simplicity have made this one of the most widely used approaches to o-quinodimethanes. It is also interesting to note that this method has led to the formation of Diels-Alder adducts in the difficult ca.se of quinoxaline o-quinodimethane where other routes have failed. However, the isolation of products incorporating both halogen and trap in the case of A/-phenylmaleimide raises the question of whether "free" o-quinodimethane is involved (Scheme 16) <95TL6777>. 

Many examples of Diels-Alder reactions have been carried out on quinodimethanes derived in a variety of ways from pyrrole and indole precursors. This area continues to be widely investigated because of its generality and its synthetic utility. In the case of pyrrole derivatives, this methodology leads to the synthesis of indoles, and particularly those substituted in the benzene ring. 

The purple orf/io-quinodimethane-derived seco-isomer rac- 10 can only cyclize in conrotatory manner, on grounds of strain ). It, therefore, reacts photochemically as a triene, via [rac-10 ], with ring closure to give the yellowish cyclohexadiene derivative rac-12, and thermally under the mildest conditions at which reaction takes place at all, as a diene, with ring closure to give the colorless cyclobutene derivative 11 ). 

Cases exist, such as the natural or commercial preparation of provitamin D from provitamin D (Sect. 1) or the ring opening of cycIohexa-2,4-dienones to their dieneketene seco-isomers (Sect. 2), in which the photoreaction has the advantage. There are other instances such as the preparation of reactive or//(o-quinodimethane derivatives as intermediates in steroid synthesis ) (Sect. 3), in which either pliotoenoKzation or thermal seco-isomeriza-tions of appropriate benzocyclobutene derivatives may be used equally weU. 

Finally, an intramolecular Diels-Alder reaction with an indolo-2,3-quinodimethane derivative prepared from a gramme precursor was investigated. In this manner, gramine 348 was heated at reflux in toluene (2 h) to produce the tetracyclic product 350 (34% yield) (Scheme 75), thus demonstrating the excellent stereocontrol inherent... 

The extrusion of SO2 from heteroaromatic-fused 3-sulfolenes has been successfully used as a general strategy for the synthesis of a variety of o-quinodimethane derivatives [137]. This synthetic approach is quite attractive due to the relative ease with which the sulfolenes are prepared, as well as the stability of these versatile precursors. Under thermal conditions (150°C), indolo-3-sulfolenes 417a-b readily produce the quinodimethane intermediates 418a-b, which then undergo Diels-Alder cycloaddition reactions with A-phenylmaleimide (220) to produce the [4-1-21-cycloadducts 419a-b in good yields (Scheme 95) [138]. 

Startg. diol allowed to react with HI in benzene-methanol -> p-quinodimethane derivative. Y 82%. R. R. Hill and G. H. Mitchell, Chem. Commun. 1968, 1243. 

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