Naphthamides cyclization

Recently, Clayden et al. reported a dearomatizing cyclization reaction of Uthi-ated 1 -naphthamides with a phenylglycinol-derived chiral auxiUary (Scheme 25) [74]. Amides 88 were dilithiated with t-BuLi which readily cyclized to afford 89 in moderate yields with diastereoselectivities up to 10 1. 

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. 

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. 

For the cyclization of naphthamide 9, design a crossover experiment to demonstrate that the proton transfer during the anion translocation is intramolecular. 

Scheme 1-133. Dearomatizing cyclization of lithiated TV -benzyl- or 7V-allyl-iV-tert-butyl-1 -naphthamides.

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