Isoquinoline 3,4-quinodimethane

Polystyrene-bound o-quinodimethanes, which are formed upon thermolysis of ben-zocyclobutanes, can be converted into 1,2,3,4-tetrahydroisoquinoline derivatives by reaction with /V-sulfonylimines. Reaction of o-quinodimethanes with electron-poor nitriles leads to the formation of 1,4-dihydroisoquinolines, which undergo elimination with simultaneous release of isoquinolines into solution (Entry 7, Table 15.25). 

For fiirther reactions of this type see <95CC2025>. The synthesis of l,4-dihydrofurano[3,4-d]-3,2-oxathiine-2-oxides, precursors for nonclassical heteroaromatic o-quinodimethanes, and their application in the Diels-Alder reaction were reported <95CC2537>. The intramolecular Diels-Alder reaction with furans (e. g., 47) offers a rapid access to highly functionalized isoquinolines <95 JCS(P 1)2393>. 

In the presence of very reactive dienes, such as o-quinodimethanes, even electron-rich dienophiles, such as oxime ethers, can be reacted, as exemplified in Ae intramolecular cycloaddition of (143 Scheme 65), which is created in situ by an initial (2 + 2 -t- 2] cycloaddition reaction of (140) with (141) and subsequent electrocyclic ring opening of the resulting benzocyclobutene (142). This strategy has been applied recently to a novel isoquinoline synthesis. 

A few scattered examples of intramolecular Diels-Alder cycloadditions of nitriles have been documented. Oppolzer has synthesized some benzo-cyclobutene nitriles (Scheme 6-III) and found that on pyrolysis they were transformed into isoquinoline derivatives in excellent yields.10 o-Quinodimethanes are assumed to be transient dienes in all of these cycloadditions. 

Beyond RCM and CM strategies, Craig has reported cleavage using Diels-Alder reactions (Scheme 1.16). ° [4 + 2] Cycloaddition (with concomitant aromatization) of the o-quinodimethane precursor (52) with dimethylacetylene dicarboxylate (DMAD), trichlor-oacetonitrile, and benzoquinone provided dimethyl naphthalene-2,3-dicarboxylate (53), 3-(trichloromethyl)isoquinoline (54), and 2,3-naphthoquinone (55), respectively. The diverse products from a single polymer-supported intermediate, such as the bismuth linkers discussed previously, make Craig s multifunctional linker unit attractive for approaches toward diversity-oriented synthesis. 

The synthetic route developed by Craig et al. examines a traceless cleavage model for resin-bound o-quinodimethane (753) and the transformation into naphthalene-derivative 759,2,3-naphthoquinone (755) and 3-(trichloro-methyl)-isoquinoline (757) (Scheme 112). The linker unit synthesized via a three-step procedure contains no visible dien structure to undergo Diels-Alder reactions but can be seen as a precursor for a solid-supported dien. 

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