Dearomatizing anionic cyclizations

TOTAL SYNTHESIS OF KAINOIDS BY DEAROMATIZING ANIONIC CYCLIZATION... 

The dearomatizing anionic cyclization of r-naphthamides bearing chiral fV-substitu-ents occurs with >99% retention of configuration. Apparently anion translocation following ortho lithiation occurs for only one of the two atropisomers at —78 °C the resulting a-lithiated species can cyclize to only one diastereoisomer of the product. 

Many alkylative dearomatizations proceed with complete stereoselectivity due to conformational rigidity of the cyclization substrates. Diastereoselective dearomatization of more flexible substrates is possible provided nonbonding interactions encountered in the Sj.j2-like transition states are sufficient to differentiate prochiral faces of the phenolate anions. For example, benzoate... 

Treatment of 3-allyloxyphenyl oxazolines with organolithium gives allyllithiums that undergo dearomatizing cyclization. The resulting anions react with electrophiles to form benzopyrans (Scheme 188). ... 

Aromatic amides like 1 (both benzamides and naphthamides) can be dearomatized to yield bi- and polycyclic amides 2 in a stereoselective cyclization reaction triggered by a benzylic lithiation a to the amide nitrogen to form organolithium intermediate 3. The proposed mechanism of the reaction consists of the intramolecular conjugate addition of the benzylic anionic center in 3 into the electron-deficient ortho position of the aromatic ring (Scheme 28.1). In most cases, the addition of l,3-dimethyltetrahydro-2(l//)-pyrimidinone (DMPU) to the reaction medium is required to promote the cyclization step. Considering the proposed mechanism, the high stereoselectivity observed in the cyclization is truly remarkable. 

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