Racemic seven-membered lactones

CHMO is known to catalyze a number of enantioselective BV reactions, including the kinetic resolution of certain racemic ketones and desymmetrization of prochiral substrates [84—87]. An example is the desymmetrization of 4-methylcyclohexanone, which affords the (S)-configurated seven-membered lactone with 98% ee [84,87]. Of course, many ketones fail to react with acceptable levels of enantioselectivity, or are not even accepted by the enzyme. 

A large number of mono- and bicyclic lactones (73-91) have been obtained by using pig liver esterase in combination with horse liver esterase for the enantiomer-differentiating hydrolysis of the corresponding racemic lactones. Interestingly, in the series of methyl-substituted lactones (85-89), both enzymes show toward the seven-membered lactone (86) the opposite enantiomer selectivity as compared to the other lactones. 

The ketal 215 was hydrolysed with pyridinium tosylate and the ketoalcohol reduced stereoselectively to the anti 1,3-diol 216 (antbsyn = 96 4) using Evans s method (58). The C-6 and C-8 hydroxyl groups were differentiated by formation of the seven-membered lactone 217 using Mukaiyama s method (59). The minor enantiomer of the lactone 217 was largely removed because the racemate crystallised, thereby improving the e.e. from 92% to >99%. The 8-hydroxy group was... 

Lipase catalysis is often used for the enantioselective production of chiral compounds indeed, lipase has been known to induce an enantioselective ROP of racemic lactones. In the lipase-catalyzed polymerization of racemic j8-butyrolactone (/3-BL), the enantioselectivity was low rather, an enantioselective polymerization of /3-BL occurred by employing a thermophilic lipase to yield the (R)-enriched polymer with 20-37% enantiomeric excess (e.e.) [101]. The enantioselectivity was greatly improved by copolymerization with seven- or 13-membered nonsubstituted lactones, using the lipase CA catalyst, whereby the e.e.-value reached almost 70% for the copolymerization of /3-BL with DDL [102]. It should be noted that, in the case of the lipase CA catalyst, the (S)-isomer was reacted preferentially to produce the (S)-enriched, optically active copolymer. The lipase CA-catalyzed copolymerization of i5-CL (six-membered) with DDL proceeded enantioselectively, to yield the (R)-enriched optically active polyester with an e.e.-value of 76%. 

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