O-xylylene intermediates

Although 1, -elimination of o xylene polyhalides with sodium iodide, zinc, copper, or iron metal is a fundamental method for the formation of o-xylylene intermediates, it is difficult to carry out the reaction under mild conditions such as at room temperature. o Trimethylsilylmethyl)-benzyltrimethylammonium halides were devised for this purpose and were shown to generate the o-xylylene at room temperature. However, we have successfully generated o-xylylene at room temperature by the reaction of a, 0,-dibromo o-xylene with metallic nickel(51). The Diels-Alder reaction of... 

Magnus and co-workers7 have used a related desilylation for a novel synthesis of I la-hydroxyestrone methyl ether (8) from the epoxide (7) via an o-xylylene intermediate,... 

Nickel-Assisted Room Temperature Generation and Diels-Alder Chemistry of o-Xylylene Intermediates... 

A variety of methods have been employed to generate the o-xylylene intermediate ... 

One of the more fundamental methods for generation of the o-xylylene intermediate is 1,4-elimination from o-xylene derivatives. o-Xylene di-, tri-, or tetrabromides undergo intramolecular 1,4-dehalogenation by means of sodium iodide [102], lithium [103], zinc [104], copper [105], iron [106], and chromium [107]. Hoffman degradation of (o-methylbenzyl)trimethylammonium hydroxides [108], as well as the more recently developed fluoride ion-induced elimination from [o-[a-(trimethylsilyl)alkyl]benzyl]trimethylammonium halides [109], have also been effectively utilized in the generation of 2. 

In addition to the o-xylylene intermediate 2, isoindene 14 and 2,3-dihy-dronaphthalene 15 were generated by the 1,4-eliminations from 1,3-dibromoin-dan and 1,4-dibromotetralin, respectively, using activated nickel (Figure 7.4). 

The substituted o-xylylene intermediates 18 and 19 demonstrate that electron-deficient substituents can be tolerated. The use of intermediates 17, 18, and 19 provide a convenient entry into the synthesis of 1,4-naphthoquinones with electron-withdrawing groups in the 2,3,6,7-positions as well as just in the 6,7-positions (Figure 7.5). 

In summary, the nickel-assisted generation of o-xylylene and substituted o-xylylenes represents a mild and convenient method for generation of this useful synthetic intermediate. While not all dienophiles are effective in trapping this intermediate, an extensive list has been shown to provide modest to good yields of the Diels-Alder products (Table 7.10). Finally, it has been demonstrated that the o-xylylene intermediates can tolerate electron-withdrawing groups such as nitriles and halogens. 

Intramolecular Diels-Alder Routes. In recent years the intramolecular variant of the Diels-Alder reaction has proved an extremely powerful tool for ring construction. There is usually a considerable rate acceleration over the inter-molecular variant and in addition two or more rings are generated in a single step. In the past few years this strategy has proved particularly useful in the synthesis of steroids through intramolecular Diels-Alder reaction of o-xylylene intermediates [e.g. (23) - (24)] and this work has now been reviewed by one of the pioneers of... 

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