132353-67-4

Upstream product

• 52779-90-5 4-(thien-2-ylcarbonyl)phenylacetic acid 
• 107-21-1 ethylene glycol 
• 98-03-3 thiophene-2-carbaldehyde 
• 4654-39-1 4-bromophenethanol 
• 173593-53-8 {4-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-phenyl}-thiophen-2-yl-methanol 
• 73899-15-7 1-(t-butyldimethylsilyloxy)-2-(4-bromophenyl)ethane 

Downstream Products

• 132353-69-6 (S)-2-[4-(2-Thiophen-2-yl-[1,3]dioxolan-2-yl)-phenyl]-propionic acid 2'-hydroxy-[1,1']binaphthalenyl-2-yl ester 
• 52780-13-9 (R)-Suprofen 
• 52780-12-8 (S)-Suprofen 
• 132353-68-5 [4-(2-Thiophen-2-yl-[1,3]dioxolan-2-yl)-phenyl]-acetic acid 2'-hydroxy-[1,1']binaphthalenyl-2-yl ester 

Relevant academic research and scientific papers

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

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.

Complex-induced proximity effects in enolate formation. Highly diastereoselective α-methylation of binaphthyl esters of arylacetic acids

Highly diastereoselective methylation of binaphthyl esters of arylacetic acids and its application to the syntheses of antiinflammatory drugs, (S)-suprofen and (S)-naproxen.