0-Hydroxy ketones, chiral building blocks

Reduction of symmetrical and prochiral 1,3-diketones with yeast gives optically active 3 hydroxy ketones, which are useful chiral building blocks in organic synthesis. 

S)-3-Hydroxy-2,2-dimethylcyclohexanone as a Building Block. Reduction of 2,2-dimethylcyclohexane-l,3-dione (24) with baker s yeast gives (S)-3-hydroxy-2,2-dimethylcyclohexanone (25) of 98-99% e.e. 21). This hydroxy ketone 25 was proved to be a versatile chiral building block in terpene synthesis (3). 

The selective catalytic hydrogenation of exocyclic a,/3-unsaturated ketones was successfully utilized in the assymetric synthesis process of the chiral building blocks, a-hydroxy acids. The influence of the catalyst support, solvent and additives in the selective 1,4-reduction was studied in a series of exocyclic enone systems (Scheme The best conditions for the selective reduction of the exocyclic double bond were obtained in an apolar solvent like toluene over a range of Pd-supported catalysts (Pd black, Pd/Ti02, Pd/Al203, Pd/SiOa, Pd/C). The usage of polar solvents like methanol and DMF decreased the selectivity dramatically but addition of triethyl amine, pyridine or potassium acetate to the reaction mixtures revert this result successfully. 

Hydroxynitrile lyases (HNLs or oxynitrilases) catalyze C—C bond-forming reactions between an aldehyde or ketone and cyanide to form enantiopure cyanohydrins (Figure 1.15), which are versatile building blocks for the chiral synthesis of amino acids, hydroxy ketones, hydroxy acids, amines and so on [68], Screening of natural sources has led to the discovery of both... 

Microbial reduction of prochiral cyclopentane- and cyclohexane-1,3-diones was extensively studied during the 1960 s in connection with steroid total synthesis. Kieslich, Djerassi, and their coworkers reported the reduction of 2,2-dimethylcyclohexane-l,3-dione with Kloeokera magna ATCC 20109, and obtained (S)-3-hydroxy-2,2-dimethylcyclohexanone. We found that the reduction of the 1,3-diketone can also be effected with conventional baker s yeast, and secured the hydroxy ketone of 98-99% ee as determined by an HPLC analysis of the corresponding (S)-a-methoxy-a-trifluoromethylphenylacetate (MTPA ester).(S)-3-Hydroxy-2,2-dimethy1cyc1ohexanone has been proved to be a versatile chiral non-racemic building block in terpene synthesis as shown in Figure 1. 

The Evans aldol reaction using chiral p-keto imide 23 as a dipropionate building block is also very effective for the construction of polypropionate segments in polyoxomacrolides (Scheme 2) [8]. The diastereoselective aldol reaction of 23 via different metal enolates (Ti, Sn, and B enolates) afforded three kind of aldols, syn-syn-24, anti-syn-25, and anti-anti-26, with high diastereoselectivity, respectively. The subsequent stereoselective reduction of the resulting p-hydroxy ketones 24-26 provides various types of dipropionate units. Based on this strategy, the... 

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