Enantioselective Syntheses of Muscone

Enzymatic resolution of the mixture of 3-methylcyclopentadecanol diastereo-mers gives selectively the acetates of the (3R)-diastereomers. After chromatographic separation from the unreacted (3S)-alcohols, followed by hydrolysis and oxidation, R-(-)-muscone is obtained with an enantiomeric excess of 90%. [194] 

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

If exaltenone, generated for example via the Stoll-Hansley-Prelog procedure cf. section 3.6.5), is treated, not with Cu2Cl2/methylmagnesium bromide, but with dimethyMnc in the presence of an enantiomerically pure copper complex, then, starting from the ( )-enone, the desired product is obtained in excellent yields and high optical purity. [ 199,200] 

Takasago Perfumery Ltd. manufactures optically pure (Jl)-muscone from the racemic compound by way of its silyl enol ether which is dehydrosUylated with palladium acetate to the pure (Z)-enone. [202] The enantioselective hydrogenation with ruthenium-BINAP catalysts finally gives the enantiomericaUy pure product. [203] 

The above example shows one of the hitherto very few successful enantioselective hydrogenations of enones. The enantiomeric excess lies in the range of 94-98 %. The direction of induction, just as in the synthesis of menthol cf. section 3.4.2), is strongly dependent on the configuration of the double bond and that ofthe catalyst. [204] 

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