Lactone methylcyclohexanone

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. 

It has been reported that cyclohexanone monooxygenase displays a broad substrate specificity for cyclic ketones38. Moreover, the lactonization of 2-methylcyclohexanone (3), catalyzed by this enzyme, exhibits a regioselectivity comparable with that found for the chemical Baeyer Villiger oxidation oxygen insertion only takes place between the carbonyl group and the substituted carbon center393. 

Chiral lactones can be formed from ketones via the Bacyer-Villiger reaction. Such lactones are potentially useful synthons for a number of natural products (37). Many of the examples of enantioselective lactone formation have been demonstrated using cyclohexanone oxygenase isolated from various Acinetobacter spedes (37,38). Figure 14 shows the enzymatic lactonization of methylcyclohexanone, which gave an 80% yield with an enantiomeric excess greater than 98%. 

The highest enantiomeric excess of 58% was achieved with 2-( -pentyl)cy-clopentanone (11) as substrate and BINAP/2-vaniUin platinum complex 12 as catalyst (Eq. 5). As a comparison with the reaction of 2-methylcyclopentanone revealed, a shorter side chain in the substrate led to a sHghtly faster reaction but significantly decreased the enantioselectivity at the same time. Also, a six-mem-bered cyclic ketone, 2-methylcyclohexanone, was converted under identical conditions to the corresponding (S)-lactone with 45% ee. 

Similarly, 4-methylcyclohexanone can be converted into the corresponding lactone (Scheme 11) in 80% yield with > 98% ee with cyclohexanone oxygenase, obtained from Acineto bacter. 

The above mentioned formation of methylcyclohexanone carboxylic acid, the formation of phenol and the mechanistically unsecured formation of lactones from allyl carbonyl or butyne-l-ol-4 and carbon monoxide are the only known ring closure reactions which are catalyzed by nickel catalysts. 

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