Enantioselective Ring Opening of Meso- and Racemic Epoxides with Phenyl Lithium Catalyzed by Chiral γ-Amino Alcohols Derived from α-D-Xylose

Abstract

Enantioselective desymmetrization of symmetrical epoxides is one of the most attractive and useful methods to obtain optically active compounds, since the reaction can generate two contiguous stereogenic centers from an achiral starting material. A number of the asymmetric desymmetrization reaction by the ring opening of the epoxides with a wide variety of nitrogen, sulfur, oxygen, halogen, and cyano nucleophiles have been reported. However, only two examples have been reported for the ring opening reactions with carbon nucleophile, such as chiral schiff bases and salens-catalyzed reaction and stoichiometric chiral ligandmediated reaction by organolithiums. During the course of study on developing new chiral catalysts for the reaction, we found that chiral 1,2-O-isopropylidene-5-deoxy-5-dialkylamino-α-D-xylofuranones (1) (Figure 1) derived from α-Dxylose played a role as effective catalysts for such reaction. Herein we wish to report the results of the desymmetrization reaction using these catalysts. As a model system, the enantioselective ring opening reaction of cyclohexene oxide with phenyllithium was chosen. We initially investigated the efficacy of catalysts 1aj possessing different kinds of amine substituents at the 5position of the xylofuranose ring. The reaction was carried out by adding the epoxide to a mixture of 1.6 equiv. of phenyllithium and 0.05 equiv of 1 in hexane at room temperature, which provided (1R,2S)-2-phenylcyclohexanol with moderate to good chemical yields and enantioselectivities (Table 1). The enantioselectivity of product alcohol was determined by HPLC analysis using Chiralcel OD-H column. Of the catalysts examined, 1j afforded the best result to be found as 71% ee (entry 10, Table 1). Next, we examined the loading effect of the catalyst on enantioselectivity by varying only the amount of catalyst 1j for the same reaction. As shown in Table 2, the use of 5 mol% of 1j provided to be the best. Increasing the amount of 1j from 5 to 25 mol% did not significantly affect the enantioselectivity, which was 71% ee with 5 mol%, 71% ee with 10 mol% and 25 mol% (entries 1-4). The desymmetrization reactions for cyclpentene oxide and cis-2,3-epoxybutane, with PhLi using 5 mol% of 1j as the catalyst gave (1R,2S)-2-phenylcyclopentanol with 79% ee and (2R,3S)-3-phenyl-2-butanol with 54% ee (entries 5-6). Other symmetrical oxides, such as cis3,4-epoxy-1,4-dibenzyloxybutane and 3-phenyloxetane, did not undergo the ring opening reaction with PhLi under the