Hydroxy-3,5-dimethylcyclohexanone

Enzymatic Baeyer-Villiger oxidations have been studied for a long time some very useful applications in natural product synthesis date back more than two decades. For example, prochiral (3A, 5,S )-4-hydroxy-3,5-dimethylcyclohexanone was successfully oxidized using a CHMO from Acinetobacter sp. NCIMB 9871. In this case the seven-membered ring formed rearranges spontaneously into the thermodynamically more stable y-lactone. The rearranged lactone has been used in the synthesis of natural products such as tirandamycin or calyculin A (Fig. 25) [157-159],... 

Representative procedure for conjugate reduction-aldol 3-CC 2- Hydroxy-[l-[tolue sulfonyl)- H-indol-3-yl]-methyl -4,4-dimethylcyclohexanone [35]... 

Examples of palladium-catalyzed reduction are 4-chloro-2,6-di-r-butyl-phenol to 2,6-di-t-butylcyclohexanone (750 psig, 25 C) with loss of halogen 24), 1,8-dihydroxynaphthalene to 8-hydroxy-1-tetralone 30), and 2,4-dimethylphenol to 2,4-dimethylcyclohexanone (27). 

Catalytic hydrogenation transforms keto esters to hydroxy esters under very gentle conditions. In cyclic ketones products of different configuration may result. Ethyl 3,3-dimethylcyclohexanone-2-carboxylatC on hydrogenation over platinum oxide in acetic acid gave 96.3% yield of cis, and over Raney nickel in methanol gave 97% yield of trans ethyl 3,3-dimethyl-cyclohexanol-2-carboxylate, both at room temperature and atmospheric pressure [847]. 

Elution with hexane-ethyl acetate (10 1-5 1) gives 5-6 g of recovered starting material. Further elution with hexane-ethyl acetate (5 1-1 Z) gives 7.7-7.9 g (47-52X) of (S)-3-hydroxy-2,2-dimethylcyclohexanone. An analytical sample can be obtained by distillation, bp 85-87°C/3.7 mm, [a] +23.0° (CHC13, o 2.0) (Notes 13, 14, and 15). 

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. 

HYDROXY-1-CYCLOHEXENE-1-CARBOXALDEHYDE 1-CYCLOHEXENE-1 -CARBOXALDEHYDE, 3-HYDROXY- (67252-14-6), 67, 205 (S)-(+)-3-HYDROXY-2,2-DIMETHYLCYCLOHEXANONE Cyclohexanone, 3-hydroxy-2,2-dimethyl-, (S)- (87655-21-8), 68, 56 Hydroxylamine, N-phenyl-, 67, 187 a-Hydroxylation of ketones, 66, 138... 

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). 

Yeast Reduction of 2,2-Dimethylcyclohexane-l,3-dione (S)-(+)-3-Hydroxy-2,2-dimethylcyclohexanone... 

The preparation of optically active (-)-cis- and (-)- r ms-2,4-dimethylcyclohexanones by enantioselective double-bond reduction with B. sulfurescens and the application of these products to the synthesis of cycloheximides has recently been reported93. The same reaction was explored later using Geotrichum candidum for the reduction of 3-carboxy-2-cyclohexenone ester leading to a single optically pure (15,35 )-hydroxy ester. The product of this bioconversion was used in a synthesis of chiral glutamic acid analogs99. 

YUST REDUCTION OF 2,2-DIMETHYLCYCLOHEXANE-l,3-OIONE (S)-(+)-3-HYDROXY-2,2-DIMETHYLCYCLOHEXANONE (Cyclohexanone, 3-hydroxy-2,2-dimethyl-, (S)-)... 

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