Reduction 2,6-dimethylcyclohexanones

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

A convenient synthesis of 3,3-dimethylcyclohexanone, a compound obtained otherwise with difficulty, involves hydrogenolysis of 5,5-dimethyl-l,3-cydohexanedione (55). The reduction is believed to go through 3,3-dimelhyl-cyclohexenone (24). Hydrogenation virtually ceases after absorption of 2 mol of hydrogen. 

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). 

The stereochemistry of the photocycloadducts can be predicted from the result of a dissolving metal reduction of the same ,/)-unsaturated ketone. For example, sodium/ammonia reduction of 3,4-dimethylcydohexenone yielded trans- and cis-dimethylcyclohexanone 37 in a ratio of 84 16, which was similar to the ratio of the two photocycloadducts 38 (80 20) [33b, 42],... 

The two-phase reduction of cyclohexanones by sodium dithionite in the presence of a stoichiometric amount of Adogen gave higher yields of the cyclohexanols than those obtained by the standard procedure using sodium dithionite in a water dioxane system (Table 11.9). A marked improvement in yield was also observed with the reduction of sterically hindered 2,6-dimethylcyclohexanone and there was a greater degree of stereoselectivity, which was comparable to that noted for the corresponding reduction with the borohydride ion [4]. 

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. 

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). 

While the condensation of enamine 37 with methyl OY7 s-2-butenoate, followed by acid hydrolysis and sodium borohydride reduction affords lactone 38 with reasonable efficiency, the cyclodehydrative ring contraction of this intermediate with PPA gives a mixture of bicyclo[3.3.0]octenones in abysmal (< 5 %) yield.66 To circumvent this difficulty and enable the large scale production of 39,2-carbo-methoxy-4,4-dimethylcyclohexanone was initially transformed to tram diacid 40 under Favoiskii conditions (Scheme 14). Conversion to the diacid chloride and condensation with lithium dimethylcuprate resulted in formation of the diacetyl derivative. In basic solution, the latter is reported to experience epimerization and aldol cyclization with dehydration in 82 % yield. With hydrogen and palladium on charcoal, the essentially quantitative production of 39 was achieved.66 ... 

Ultramicroscale Reduction of 2,6-Dimethylcyclohexanones with Sodium Borohydride... 

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

Many of the naturally occurring ochtodanes have a double bond in the ring, and the most direct way to 5,5-dimethyl-2-cyclohexenone (728) is from the enol ether of dimedone by lithium aluminum hydride reduction. " The cyclohexenone can then be used directly to introduce a C2 unit it was also reduced catalytically to the previously mentioned 3,3-dimethylcyclohexanone. Treatment of the ozonolysis product from 3-carene (277) with sodium ethoxide also led to a ketone, 729, that might be a useful starting material. ... 

A selective reduction of keto groups is possible in the presence of epoxides using triisobutyl-aluminum at low7 temperatures153. Thus, 2,3-epoxy-4,4-dimethylcyclohexanone is reduced with good stereoselectivity [d.r. (cis/trans) 5 95] to fr[Pg.822]

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)-)... 

Condensation of p-O-methoxyphenylhydrazine (74S) with 2,5-dimethylcyclohexanone (746) gave mainly the tetrahydrocarbazole 747, which was dehydrogenated with chloranil in refluxing THF. The resulting carbazole 746 was formylated under Vilsmeier-Haack conditions to afford 744. Formation of the pyridine ring can then be achieved by condensation with the diethylacetal of aminoacetaldehyde followed by reduction of the imine, N-tosylation, and cyclization to give 743 as described previously (Scheme 57). When the 4-methyl group is not present in the carbazole 748,... 

The dknethylcyclohexane compounds are obtained in a Horner-Wadsworth-Emmons reaction from dimethylcyclohexanone with subsequent reduction. As possible starting materials, m-cresol [210], Just like acetone and methyl vinyl ketone [211], can be considered. The second methyl group may be inserted advantageously using trimethylaluminium. [212]... 

The product stereochemistry and rates of reduction by sodium borohydride in propan-2-ol at various temperatures have been investigated for a number of 2-sub-stituted cyclohexanones. Reduction of 2,6-dimethylcyclohexanone gave rise to... 

The unexpected finding that reduction of c -2,6-dimethylcyclohexanone with sodium borohydride in methanol gave predominantly the axial alcohol prompted a detailed investigation of the reaction. Rates of epimerization versus reduction are compared, and the discrepancies arising are probed by molecular modelling. The study was also extended to the fran -reactant, and to lithium aluminium hydride as an alternative reductant. 

The [RuCl2(PPh3)3]- or [RhCl(PPh3)3]- catalysed reduction of 3,4-, 3,5-, and 2,5-dimethylcyclohexanone by propan-2-ol is retarded by axial methyl groups, Carbonylation of RC(Me)=CH2 with Co2(CO)g in CH3OD gives RCD(Me)-... 

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