A stereoconvergent strategy for the synthesis of enantiomerically pure (R)-(−) and (S)-(+)-2-(6-methoxy-2-naphthyl)-propanoic acid (naproxen)

Pharmaceuticals

“…[196] An interesting solution was provided by a process developed by the Zambon company. [197] Friedel-Crafts acylation of 2-methoxynaphthalene is followed by a ketalisation with diethyl (R,R)-tartrate and a double bromination, at C-1 and in the side-chain, yielding a 92 : 8 mixture of diastereomers. After hydro lysis of the tartrate, the reaction mixture is heated to 90 °C in water.…”

α-Haloketal (1′R,4S,5S)-dimethyl 2-(1′-bromoethyl)-2-(3,4-dimethoxyphenyl)-1,3-dioxolane-4,5-dicarboxylate

“…The absolute con®gurations of the other asymmetric centres at C12 and C13 were already known. These ®ndings are important in understanding the mechanism of diastereofacial selectivity induced by a chiral auxiliary in the halogenation of aryl enol ethers (Castaldi et al, 1986(Castaldi et al, , 1987Giordano et al, 1990), which is the key step in the industrial asymmetric synthesis ofarylpropionic acid derivatives (Giordano et al, 1989;Elks & Gamellin, 1990), the non-steroidal anti-in¯ammatory drugs widely prescribed as analgesics and in the treatment of rheumatoid arthritis (Reuben & Wittcoff, 1989), and also in the enantiomeric synthesis of the sulfur analogue of an 8,4 Hoxyneolignan derivative showing selective antagonistic activity in Platelet Activating Factor-induced platelet aggregation (Lariucci et al, 1995).…”

Synthetic half-reactions

“…10e). Lastly, the presence of a leaving group at the alpha position gives rise to a semipinacol-like reactivity 15 (Fig. 10f).…”