Meso-cyclic anhydrides reaction

There has been considerable interest in the stereoselective ring opening of meso-cyclic anhydrides. The stereoselective alcoholysis of these anhydrides is particularly attractive as the resulting hemiesters are used as versatile intermediates in the construction of many bioactive compounds [1], Much effort has, therefore, been devoted to the development of efficient enzymatic and nonenzymatic catalytic systems for this reaction [2], Among the stereoselective catalysts developed to date,... 

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. 

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. 

This chapter covers the kinetic resolution of racemic alcohols by formation of esters and the kinetic resolution of racemic amines by formation of amides [1]. The desymmetrization of meso diols is discussed in Section 13.3. The acyl donors employed are usually either acid chlorides or acid anhydrides. In principle, acylation reactions of this type are equally suitable for resolving or desymmetrizing the acyl donor (e.g. a meso-anhydride or a prochiral ketene). Transformations of the latter type are discussed in Section 13.1, Desymmetrization and Kinetic Resolution of Cyclic Anhydrides, and Section 13.2, Additions to Prochiral Ketenes. 

Cw-Disubstituted butyrolactones (50) have been investigated less extensively than their /ra/i -counterparts. One attractive route to such compounds involves the diastereoselective opening of a cyclic meso-anhydride (49) (scheme 15) [67]. The required anhydride was prepared by a route involving two consecutive Stobbe condensations, leading to the doubly unsaturated anhydride (48). Differentiation of the two acyl groups of (49) was achieved by reaction with an enantiomerically pure primary amine. The monoacid monoamide was then converted into the required lactone (50). 

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