O-Quinodimethanes generation

The synthetic utility of o-quinodimethane generated by cheletropic elimination of S02 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide122. When 1,3-dihydro-l-(4-pentenyl)benzo[c]thiophene 2,2-dioxide (201) prepared from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide and 4-pentenyl bromide is heated in di-n-butyl... 

Various o-quinodimethanes, generated in situ from o-alkenylbenzyltributyl-stannane precursors, have been used to synthesize functionalized polycycles by Diels Alder reaction with maleic anhydride, methylacrylate, dimethylfumarate and N-phenyl maleimide in the presence of electrophiles [37] (Scheme 2.16). 

The synthetic utility of o-quinodimethane generated by cheletropic elimination of SO2 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation... 

An efficient method for the generation of oquinodimethanes via desilylation reaction involves treatment of a 2-[(trimethylsilylmethyl)benzyl]trimethylarmnonium iodide with fluoride ion (equation 31)64. This reaction was applied by Saegusa and coworkers for the synthesis of estrone in which an intramolecular Diels-Alder reaction of an o-quinodimethane, generated in situ, served as the key reaction (equation 32)65. 

Alternatively, the o-benzoquinodimethane may be generated by fluoride-induced 1,4-elimination from trimethyl[2-(trimethylsilylmethyl)benzyl]ammonium iodide (13a). Interception with l-bromo-2-chlorocyclopropene gave the adduct 15a in 38% yield.Tetrahalocy-clopropenes were, however, unreactive. This method of o-quinodimethane generation has also been applied to pyridine derivatives, and provided a short route to l//-cyclopropa[g]quino-linc (16b).The interception was unsuccessful when the approach was applied to cyclo-propaisoquinoline. ... 

In an analogous system, it was found that a phenanthrene o-quinodimethane, generated by a reductive process, acted as a diene in [4 + 2] cycloadditions with two neutral imines to give pentacyclic adducts, although yields were rather low [Eq. (17)].68... 

Langa et al. [16] described the microwave-induced Diels-Alder reaction of o-quinodimethane, generated in situ from 4,5-benzo-3,6-dihydro-l,2-oxathiin-2-oxide (2) (sultine) [17], which led to cycloadduct 3 (Scheme 21.3). This reaction was the first application of microwave irradiation in the preparation of a functionalized Ceo [16]. 

Reductive Dehalogenation This was the first method used to produce an o-quinodimethane and has been widely applied to the formation of both 5- and 6-membered heterocyclic analogues as can be seen from the Table and from the examples in Scheme 3. The nonnal procedure uses Nal in DMF at temperatures ranging from ambient to 150 C. Activated zinc has been used extensively for non-heterocyclic o-quinodimethanes but has found little application with heterocyclic systems <91SC1055>. Yields of Diels-Alder adducts from 5-membered heterocyclic o-quinodimethanes generated by this method tend to be low to moderate and are accompanied by polymers. However, use of molecular sieves has been shown to give improved yields <92TL4499>. The elimination is most commonly carried out on the dibromo compounds but the dichloro compounds can also be used both most likely proceed via the diiodo derivative. 

Scheme 8. First example of cheletropic elimination of SO2 for o-quinodimethane generation (a), and application of the strategy as the key step in Nicolaou s total synthesis of estra-1,3,5(10)-trien-17-one (b).

Steroids.—Intramolecular Diels-Alder reactions of o-quinodimethanes, generated by thermolysis of the corresponding benzocyclobutanes, continue to form the basis of many steroid syntheses, " including estradiol derivatives, 18-hydroxyestrone, (+)-chenodeoxycholic acid, and des-A-ring steroids. Two alternative ways to obtain o-quinodimethanes, by photoenolization of o-methylphenyl ketones or by a fluoride-ion-induced elimination reaction [(191)- (192)1, have been utilized in syntheses of 19-nor-steroids and O-methyl estrone (193), respectively. 

Next, we investigated an asymmetric Diels-Alder reaction of o-quinodimethanes generated in situ from benzocyclobutenols utilizing a tartaric acid ester as a chiral auxiliary. The Diels-Alder reaction of o-quinodimethane with olefins is a useful method to construct tetrahydronaph-thalene frameworks bearing up to four stereocenters, which are key intermediates for the synthesis of polycyclic... 

During investigation of the synthesis of benzocyclobutane 193, Cava and coworkers118 found that o-quinodimethane 192, generated in the pyrolysis of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide (191), can be trapped by Af-phenylmaleimide to give N-phenyl-1,2,3,4-tetrahydronaphthalene 2,3-dicarboimide (194) (equation 125). 

Dimethylene-2,3-dihydrothiophene (37, Figure 2.3) is the thiophene analog [38] of o-quinodimethanes and has been used to develop a Diels-Alder-based synthetic approach to benzothiophene derivatives. Generated in situ by treating the trimethylsylyl ammonium derivatives 38 or 39 with Bu4N F , it... 

Thieno-o-quinodimethanes 46 and 48, generated in situ by iodide-induced 1,4-elimination from the respective 2,3-bis(chloromethyl)thiophene 45 and 2,3-bis(bromomethyl)benzo[b]thiophene 47 precursors, undergo Diels Alder... 

Bis-o-quinodimethanes have also been used to functionalize [60]-fullerene by Diels Alder reaction. An example is the preparation of main-chain polymers with incorporated [60]-fullerene units [48] illustrated in Scheme 2.20. Cycloaddition of bis-diene 50 generated in situ from bis-sulfone 49 with [60]-fullerene leads to an oligomer mixture 51. Another type of functionalization is based on the... 

The o-quinodimethanes are very reactive, unstable dienes, which are usually prepared in situ. The cycloaddition under high pressure of the dibromo-o-quinodimethane 91, generated in situ from a,a,a, a -tetrabromo-o-xylene. 

Utley et al. were able to perform Diels-Alder reactions in aqueous solution via electrogenerated or//zo-quinodimcthancs.34 They cathod-ically generated the or// o-quinodimethanes in aqueous electrolyte in the presence of /V-mcthylmaleimide, which is both the redox mediator and the dienophile. Competition from the electrohydrodimerization of /V-mcthy Irrialci midc is suppressed, allowing for the efficient formation of the endo-adduct (Scheme 12.1). 

Retro-Diels-Alder reactions can be used to regenerate dienes or alkenes from Diels-Alder protected cyclohexene derivatives under pyrolytic conditions144. Most of the synthetic utility of this reaction comes from releasing the alkene by diene-deprotection. However, tetralin undergoes cycloreversion via the retro-Diels-Alder pathway to generate o-quinodimethane under laser photolysis (equation 89)145. A precursor of lysergic acid has been obtained by deprotection of the conjugated double bond and intramolecular Diels Alder reaction (equation 90)146. 

The Parylene family has very attractive properties for use as dielectric materials as was noted above, but their thermal stability at the temperatures used in the fabrication of electronic devices is less than optimum. When considering alternatives as possible precursors for VDP, the isomeric ortho-xylylene (o-quinodimethane) is a likely candidate (Scheme 4). This approach involves the thermolysis ofbenzocyclobutene derivatives to generate a reactive dieneoid intermediate (o-quinodimethane),... 

Copolymers of [60] fullerene and in situ generated bis-o-quinodimethanes were prepared by Gtigel and colleagues114. In order to get soluble polymers, it proved necessary to introduce flexible groups on the bis-o-quinodimethanes. A maximum of 10 [60]fullerene units were incorporated into oligomers when [60]fullerene was reacted with a 7 3 mixture of 157 and 158 (i.e. with o-quinodimethanes 159 and 160). Monosulfone 158 was added to induce the formation of triple cycloadducts of [60]fullerene. This prevented polymerization of the oligomer (quadruple cycloadditions to [60]fullerene are hard to accomplish) and enhanced its solubility. 

In practice, the equivalent synthon of 2 was l-cyano-4,5-dimethoxybenzocyclobutene 22 (Scheme 3.7) which on heating generates a reactive o-quinodimethane by a conrotatory electrocyclic ring opening process (Cf. Scheme 3.7) and reacts, at 150-160 °C, with the 3,4-dihydroisoquinoleine 23 to give 80-88%yield of 13-cyanoprotoberberine 24. A simple reductive decyanation with lithium in liquid ammonia in the presence of isopropyl alcohol afforded xylopinine (19) in 84.6% yield [19]. 

The o-quinodimethane (40) may also be generated by fluoride-induced 1/4/elimination of trimethyl(2-[(trimethylsilyl)methyl]-benzyl) ammonium iodide (43). When this elimination is carried out at low temperature, the reaction conditions are ecjually compatible with the presence of 27, and this provides an additional route to 42. ... 

The thermal [4 + 2] cycloaddition of 3-acetyl-2(3F/)-oxazolone 84 to the reactive dienes, o-quinodimethane 224 and isobenzofuran 226, generated from benzocyclobutane and 1-ethoxydihydroisobenzofuran, respectively, proceeds... 

The thermolysis of benzocyclobutene either in the condensed or vapor phase has been shown by a variety of techniques to initially yield an o-quinodimethane (Fig. 9). The fate of the o-quinodimethane in the absence of other coreactive species appears to depend to a large extent upon the conditions under which it is generated. Thus for example, the thermolysis of benzocyclobutene hydrocarbon itself in a sealed flask at 200 °C gave a 24% yield of 1,2,5,6-dibenzocycloocta-diene 20 along with a mixture of unidentified oligomeric materials (Fig. 12) [70]. 

Very interesting Diels Alder comonomers for BMI are the bis(benzocyclobutenes). Under appropriate thermal conditions, the strained four-membered ring of benzocyclobutene undergoes electrocylic ring opening to generate, in situ, o-quinodimethane, which, in the presence of BMI, reacts via a Diels-Alder reaction (83). The chemical structure of a bis(benzocyclobutene-imide) is provided in Fig. 28. The synthesis and properties of BCB and BMI/BCB blend systems is described in detail in chapter I of this book. 

O-Quinodimethanes. A recent simple synthesis of Al") 5(lu)-estratriene-l 7-one (5)2 is based on the fact that on pyrolysis substances such as 1 lose sulfur dioxide with generation of o-quinodimethanes.1 The anion of 1 is generated most satisfactorily with KH (1.1 equivalent) in DMF. at 0°. It can be converted predominately to monoalkylated products, particularly if an excess of the anion is used. Thus reaction of the anion of 1 with 2 results in the diastereoisomers 3 and 4. After deketalization, the corresponding ketones are heated at 210" for 8 hours. The o-quinodimethane (a) is formed and undergoes intramolecular cycloaddition to form 5. 

The annulated ring in type C carbonyl ylides 152, generated from oxi-ranes 151, can be heteroaromatic (furo- or thieno-), and the products 153 have good Diels-Alder reactivity, functioning as o-quinodimethane heteroanalogs (Scheme 46) [88AG(E)568 93CB975],... 

The synthetic strategies used for the preparation of pyrans on insoluble supports have mainly been hetero-Diels-Alder reactions of enones with enol ethers and ringclosing olefin metathesis (Table 15.33). Benzopyrans have been prepared by hetero-Diels-Alder reactions of polystyrene-bound o-quinodimethanes with aldehydes. The required quinodimethanes were generated by thermolysis of benzocyclobutanes, which were prepared in solution [308]. Other solid-phase procedures for the preparation of benzopyrans are the palladium-mediated reaction of support-bound 2-iodo-phenols with 1,4-dienes (Entry 5, Table 15.33) and the intramolecular Knoevenagel... 

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