Anhydrides enantioselective opening

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. 

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. 

Asymmetric ring opening of achiral monocyclic, bicyclic and tricyclic anhydrides under formation of the corresponding chiral monoesters can be accomplished in high yield with modest enantioselectivity with methanol in the presence of less than stoichiometric amounts of cinchona alkaloids in toluene or diethyl ether (Table 9)91 94. As expected the use of cinchonine A or quinidine C, and of cinchonidine B or quinine D gives opposite enantiomers. Recrystallization of the monoesters and lactones affords material of considerably higher enantiomeric purity (Table 9, entries 15, 16, 21, and 23). 

Table 9. Enantioselective Ring Opening of Anhydrides with Methanol Catalyzed by Cinchona Alkaloids...

Catalytic enantioselective reductive desymmetrisation of achiral and meso-compounds, in particular, transformations of imides to lactams or lactones, anhydrides to lactones, and ring-opening of oxacycfic rings 13CC10666. 

Seheme 15.16 First, efficient large-scale process for enantioselective anhydride opening using a stoichiometric quantity of quinine. 

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. 

Scheme 6.11 Enantioselective ling opening of meso anhydrides affords chiral monoesters of valuable dicarboxylic acids in excellent enantioselectivity using the sulfoneunide catalyst 77...

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