- 1,1′-binaphthalene-2,2′-diol as a chiral auxiliary. Diastereoselective alkylation of binaphthyl esters, complex-induced proximity effects in enolate formation, and one-step synthesis of an optically active β-substituted ketone
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Diastereoselective alkylation of enolates derived from (S)-naphthyl phenylacetate 1 with LDA in THF gave the S,S-isomer as a major product. The diastereoselectivity increased as the bulkiness of the alkylating agent was increased. The low diastereomeric excess (~70%) of methylation was markedly raised to 92% by the use of n-BuLi as a base due to the complex-induced proximity effect (CIPE) in enolate formation. This highly diastereoselective methylation was used to synthesize the clinically important anti-inflammatory drugs (S)-naproxen (60) and (S)-suprofen (68). The stereochemistry of ketene trimethylsilyl acetals generated from several phenylacetates was investigated to understand the origin of the diastereoselectivity in this alkylation. Methyl phenylacetate (46) predominantly gave a (Z)-enolate by kinetic deprotonation, while the (E)-enolate was predominantly obtained from phenyl phenylacetate (47). An optically active ketone (88) was synthesized from binaphthyl ester 84 by a one-pot procedure involving the 1,4-addition, followed by the 1,2-addition, of organometallics. The CIPE again played a crucial role in the high enantiomeric excess in this case.
- Tanaka, Fujie,Node, Manabu,Tanaka, Kiyoshi,Mizuchi, Maki,Hosoi, Shinzo,Nakayama, Masayo,Taga, Tooru,Fuji, Kaoru
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p. 12159 - 12171
(2007/10/03)
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- Complex-induced proximity effects in enolate formation. Highly diastereoselective α-methylation of binaphthyl esters of arylacetic acids
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Highly diastereoselective methylation of binaphthyl esters of arylacetic acids and its application to the syntheses of antiinflammatory drugs, (S)-suprofen and (S)-naproxen.
- Fuji,Node,Tanaka
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p. 6553 - 6556
(2007/10/02)
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- BINAPHTHOL AS A CHIRAL AUXILIARY. ASYMMETRIC ALKYLATION OF ARYLACETIC ACID
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Binaphthyl esters of substituted and unsubstituted phenylacetic acids were alkylated with a high diastereoselectivity.
- Fuji, Kaoru,Node, Manabu,Tanaka, Fujie,Hosoi, Shinzo
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p. 2825 - 2828
(2007/10/02)
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