Cyclic anhydrides enantioselective opening

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

Our final example is that of cyclic anhydrides, namely prochiral 3-sub-stituted glutaric anhydrides (7.101, R = Me, Et, or Pr). When incubated with lipase in an inert solvent in the presence of an alcohol (methanol, butan-l-ol, etc.), these compounds underwent nucleophilic ring opening with formation of a hemiester (7.102) of (/ -configuration (60-90% ee) [180]. This product enantioselectivity and, of course, the lack of reactivity in the absence of lipase show the enzymatic nature of the reaction. 

When an anhydride such as succinic anhydride is reacted with a racemic alcohol in organic solvent with a lipase, an enantioselective resolution can be achieved [89]. The enantioselective opening of racemic or meso cyclic anhydrides can constitute a good method for the preparation of nearly optically pure esters [90-93]. Examples of these reactions are depicted in Scheme 13. 

C. Bolm, I. Schiffers, C.L Dinter, A. Gerlach, Practical and highly enantioselective ring opening of cyclic meso-anhydrides mediated by cinchona alkaloids, J. Org. Chem. 65 (21) (2000) 6984-6991. 

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