Quinodimethane, o-

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). 

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-... 

The Diels-Alder reaction of o-quinodimethanes (from benzocyclobutenes) with nitrogen-ubstituted enes has also been applied to alkaloids synthesis (see p. 280f. T. Kametani, 1972, 1973, 1974 W. Oppolzer, 1978 A). 

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

A highly efficient construction of the steroidal skeleton 166 is reported by Kametani and coworkers111 in the intramolecular Diels-Alder reaction of the a, jS-unsaturated sulfone moiety of 165 (equation 117). Thus, when the sulfone 165 is heated in 1,2-dichlorobenzene for 6h, the steroidal compound 166 can be obtained in 62% yield. The compound 166 produces estrone (167) by elimination of benzenesulfinic acid and subsequent hydrogenation of the formed double bond. The stereoselectivity of the addition reflects a transition state in which the p-tosyl group occupies the exo position to minimize the steric repulsion between methyl and t-butoxy groups and the o-quinodimethane group as shown in equation 117. 

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). 

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). 

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. 

Keywords Lewis acids, asymmetric reactions, tandem, tethered. Intramolecular reactions, o-quinodimethanes, o-quinone methides, befera-Dlels-Alder reactions... 

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... 

Sulfolene dioxide thermolysis has also been applied to formation of o-quinodimethanes. 

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). 

Table 5.1. Synthesis of tetralines by intermolecular trapping of hydroxy-o-quinodimethanes.

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). 

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.

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],... 

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