Desymmetrizations methanolytic

The non-alkaloid derived organocatalysts 13a-e - readily accessible from proline and hydroxyproline, respectively - were reported by Uozomi et al. (Scheme 13.7) [17]. Of the five compounds, 13b and 13e performed best. In the presence of 100 mol% 13e, the methanolytic desymmetrization of cyclic meso anhydrides was found to proceed with up to 89% ee. 

Shortly thereafter, Aiken and coworkers also reported that quinine (4) could be used as a catalyst (50mol%) to promote the methanolytic desymmetrization of the meso-epoxy anhydride 8a to give the lactone 9a in 57% yield and 76% ee (Scheme 11.6) [4]. Lowering the reaction temperature to 0 or —30 °C did not result in any increase in selectivity. meso-Aziridine anhydride 8b was also tested under similar reaction conditions, but a lower enantioselectivity (40% ee) was obtained (Scheme 11.6). 

However, highly interestingly, unusual concentration and temperature effects on the enantioselectivity were observed by Song and coworkers [11a]. As shown in Figure 11.2, the enantioselectivity in the methanolytic desymmetrization reaction of the meso-cyclic anhydride IS increases with increasing dilution of the reaction mixture and on raising the reaction temperature from —20 to 20 °C. 

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