Enantioselective α-Hydroxylation of β-Keto Esters Catalyzed by Cinchona Alkaloid Derivatives

Abstract

A highly efficient α-hydroxylation of β-keto esters catalyzed by cupreidine in the presence of cumyl hydroperoxide (CHP) was achieved. The reaction was applied to a wide variety of β-keto esters to give products in high yields (up to 95%) with excellent enantioselectivities (up to 97% ee). The reaction had been successfully scaled up to a gram quantity and (S)-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate -the important intermediate of Indoxacarb were obtained in 96% yield with 86% ee. The enantiomeric excess could be improved to 99% by crystallization, and this method has prospect of industrial application for its advantages of enantioselectivity, ease of catalyst preparation and reclamation of catalyst.

A Concise and Flexible Synthesis of C2′-Sulfonylated Quinine Derivatives

“…Our initial synthetic study toward C2′-sulfonylated cinchona alkaloid derivatives was carried out using quinine 1 as the starting material (Scheme 1 ). Accordingly, treatment of 1 with NaSEt in DMF, utilizing a known method, 10 11 12 proceeded smoothly to give the C6′-OH compound 2 in higher than 90% yield. Subsequent protection of the two hydroxy groups in 2 with Boc 2 O afforded product 3 in 82% yield.…”

“…Next, quaternization of the quinuclidinyl moiety of 10 with 1-(bromomethyl)-3-methylbenzene ( 11 ) proceeded uneventfully to give 12 in 90% yield. The attempted C6′-demethylation of 10 was examined initially according to the frequently reported methods using NaSEt 10 11 12 or BBr 3 13 14 as reagents. However, it was found that the reaction was less efficient, probably due to the presence of many heteroatom-containing functionalities in the substrate.…”

“…White solid; yield: 4.20 g (90%); [α] D 25 –153.9 ( c 0.2, MeOH); mp 148–150 °C (Lit. 11 182–185 °C).…”