O-Quinodimethane, cycloaddition

Scheme 6. Vollhardt s tandem alkyne cyclotrimerization/o-quinodimethane cycloaddition strategy for polycycle synthesis.

Following earlier application of o-quinodimethane cycloaddition methodology to the alkaloid field, Oppolzer s initially described approach to steroids involved the reaction 93 94, which apparently has not been described in detail. ... 

Finally, both Oppolzer and Kametani and their respective collaborators have adapted their steroidal syntheses based upon intramolecular o -quinodimethane cycloaddition to achieve asymmetric induction by incorporation of an optically active cyclopentane moiety in the cyclization precursor. 

Malpass, 1977). Diels-Alder type [2 + 4]-cycloadditions are possible with certain hetero-"ene components (J.R. Malpass, 1977 S.F. Martin, 1980) or with highly reactive o-quinodimethanes as diene components (W. Oppoizer, I978A). 

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... 

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. 

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... 

The forerunner in the Co-catalyzed [2+2+2] cycloaddition domino processes was that identified by Vollhardt and colleagues [273], with their excellent synthesis of steroids. Reaction of 6/4-1 with [CpCo(CO)2] gave compound 6/4-3 with an aromatic ring B via the intermediate 6/4-2. In this process, trimerization of the three alkyne moieties first takes place, and this is followed by an electrocyclic ring opening of the formed cyclobutene to give o-quinodimethane. This then undergoes a Diels-Alder reaction to provide the steroid 6/4-3 (Scheme 6/4.1). 

Cycloadditions selectively afford the adducts on the 6,6-ring junctions [65], and the products occasionally undergo a facile retro-Diels-Alder reaction as a consequence of the low thermodynamic stability of the adduct. Very stable Diels-Alder cycloadducts have, however, been prepared by use of different substituted o-quinodimethanes, probably because of stabilization by aromatization of the resulting adducts [66],... 

The thiophene ring system can be utilized as a synthetic scaffold for the preparation of nonthiophene materials as the sulfur moiety can be removed by reduction (desulfurization) or extrusion (loss of SO2). The extrusion of sulfur dioxide from 3-sulfolenes (2,5-dihydrothiophene 1,1-dioxides) give dienes (butadienes or o-quinodimethanes) that can be utilized to prepare six-membered rings by cycloaddition chemistry. For example, thermolysis of 3-sulfolene 120 provided tricyclic pyrazole 122 via an intramolecular cycloaddition of the o-quinodimethane 121 that results by extrusion of sulfur dioxide <00JOC5760>. Syntheses of 3-sulfolenes 123 and 124 <00S507> have recently been reported. 

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. 

These cycloadditions with o-quinodimethanes provide a broad variety of useful fullerene functionalizations, since o-quinodimethanes can be prepared using several routes and the resulting cycloadducts are thermally stable [42], There exist several alternatives to the iodide-induced bromine 1,4-elimination of 1,2-bis (bromomethyl)-benzenes [44-47]. o-Quinodimethanes have been prepared by thermolysis of 3-isochromanone (42) [43], benzocyclobutenes (43) [48-50], isobenzothiophene 2,2-dioxides (44) [42] and sultines [51,52] or by photolysis of o-alkylphenones such as 45 [53-55] and could be added to Cjq in good yields (Scheme 4.7). Indene, thermally rearranged to isoindene, also adds to Cjq in similar fashion to quinodimethanes [56]. 

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

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... 

Replacing the hydrogen in 68 with a phenyl group leads to the secondary acetylenic monomer 70. It was believed that this disubstituted acetylene would suppress the reaction of acetylene with itself and insure that there was an acetylene functionality available for reaction with the o-quinodimethane at 200 °G The DSC of 68 showed the presence of a single exothermic peak at 263 °C which the authors felt was adequate evidence for the occurrence of a Diels-Alder reaction between the acetylene and benzocyclobutene. Unfortunately they did not report on any control experiments such as that between diphenylacetylene and simple benzocyclobutene hydrocarbon or a monofunctional benzocyclobutene in order to isolate the low molecular weight cycloaddition product for subsequent characterization. The resulting homopolymer of 68 had a Tg of 274 °C and also had the best thermooxidative stability of all of the acetylenic benzocyclobutenes studied (84% weight retention after 200 h at 343 °C in air). 

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. 

MI1), which can formally be derived from the isoconjugated indenyl anion 1. As they are compounds with an o-quinodimethane structural element 3, they are especially suited for inter- and intramolecular cycloadditions. 

Several additional Diels-Alder cycloaddition strategies have been applied to the total synthesis of the steroid skeleton. For example, the first enanlio-selective synthesis of (+)-conisone was accomplished by the intramolecular [4 + 21 cycloaddition of an otefinic o quinodimethane that contained an optically active stereodirecting group as the key chemical step. 

In a recent re-examination of the thermolysis of benzocyclobutenes for the in situ generation of o-quinodimethanes, the resultant IMDA diastereoselectivity was highly dependent on the nature of the hydroxyl protective group.90 The intramolecular 4 + 2-cycloaddition of o-quinodimethanes (83), derived from ene-bis(sulfinylallenes) (82), with electron-deficient and electron-rich alkenes produced the corresponding polycyclic aromatic compounds (84) (Scheme 22).91 The enantioselective Diels-Alder... 

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