Of R -muscone

This reaction has been used for a synthesis of (R)-muscone (1) from cyclopen-tadecanone in 60% overall yield (equation I).3... 

The enantioselective addition of dialkylzincs to aromatic ketones is especially difficult. Yus and co-workers have developed a new chiral ligand 59, allowing the addition of dialkylzincs to various aromatic ketones in good yields. The enantioselective addition is promoted by Ti(0(-Pr)4, and tolerates the presence of several functional groups (Equation (120)).205 An elegant synthesis of (R)-(—)-muscone has been reported by Oppolzer and co-workers (Equation (121)).80b 206... 

In 2001, the Grubbs group reported the use oftheirseeondgeneration ruthenium complex [(SIMes)RuCl2(=CHPh)(PCyj)] 57 in tandem metathesis/TH reactions leading to the formation of a series of unsaturated heteroeyclic alcohols in <56% overall yield. This strategy was notably used for the preparation of (R)-(-)-muscone, a natural product with a pleasant fragranee. 

Tanaka reported the synthesis of (/ )-muscone (10) by an enantioselective conjugate addition of chiral alkoxydimethylcuprate, which was prepared from chiral ercdo-3-[(l-methylpyrrol-2-yl)methylamino]-l,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (9), methyllithium, and copper iodide (Scheme 9.7) [16]. In this reaction, convex deviation from a linear correlation was observed when the chiral ligand had a higher enantiopurity. This positive NLE was probably induced by the formation of a reactive homochiral dinuclear copper complex to give (R)-muscone. Rossitter also observed asymmetric amplification in a copper-catalyzed conjugate addition of methyl-... 

Alexakis et al,231 reported copper-catalyzed enantioselective Michael additions in the presence of various 2-arylcyclohexyl-substituted phosphites. Ligand 279 turned out to be particularly efficient for the 1,4-addition of organozinc reagents to cyclopentadec-2-enone. Whereas Et2Zn gave the addition product with 87% ee, the corresponding reaction of dimethylzinc furnished (R)-(—)-muscone with an enantiomeric excess of 79% ee (Scheme 74). 

A Wagner-Meerwein-type rearrangement of the cation has been often observed in the oxidation of carboxylic acids (equation 59). The relative migratory aptitude of R and R has been studied, and this type of rearrangement has been applied to the synthesis of )-muscone (equation 60). ... 

One step in a synthesis of dl-muscone (4) from exaltone (1) involved dehydrobromina-tion of (2). This was effected with l,5-diazabicyclo[4.3.0]nonene-5 in 70% yield. Treatment with potassium r-butoxide in 7-butanol or DMSO afforded only the dioxine (5).2... 

Asymmetric conjugate addition of CHjLi.2 The cuprate 2, prepared by reaction of the chiral bornane 1, (2R,2S,3S,4S)-3[( l-methylpyrrolyl)mcthylamino)-1,7,7-trimethylbicyclo[2.2.1 ]-hcptanol-2, with Cul and then ClljLi, undergoes 1,4-addition to (E)-cyclopcntadeccnone-2 (3) to form (R)-muscone 4 in 80% yield and 91% cc. If CHjLi is replaced by CHjMgCl, only the 1,2-adduct of 3 is formed. 

Grubbs reported tandem olefin metathesis/hydrogenation as a means to make saturated cyclic products and a one-pot RCM/transfer dehydrogenation/hydrogenation route to (R)-(—)-Muscone utilizing (4a) (Scheme 19). Snapper and coworkers took advantage of the isomerization side reaction... 

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]... 

The dichlorocyclopropanes (391 R R, R = H, alkyl), readily obtained from the corresponding allylic alcohols by the Makosza procedure, rearrange on heating with hydrobromic acid to the cyclopentenones (392). This sequence has been applied (Scheme 34) to the preparation of the bicyclic ketone (393), a versatile intermediate in the synthesis of pyridomuscone, muscone, and [10]metacyclophane. ... 

Due to their unique olfactive characteristics, the macrocyclic ketones (R)-muscone and (R,Z)-5-muscenone are highly prestigious musk odorants. A short and practical synthesis of these exceptional musk odorants has been recently developed by Knoplf and Kuhne starting from a readily available... 

Whereas the examples above used substrate control for stereoselective transannular aldol or related reactions, reagent control has also been reported for the transannular aldol reactions. One example is synthesis of the musk ordorants (R)-muscone and (R,Z)-5-muscenone by Knopff and co-workers. It involved enantioselective formation of 73 by the transannular aldol condensation of the symmetrical macrocyclic 1,5-diketone 72 using sodium ephedrate for desymmetrization (Scheme 20.19). The reaction was assumed to proceed by a reversible transannular aldol reaction followed by an enantioselective dehydration reaction. 

SCHEME 20.19. The transannular aldol reaction in the synthesis of (A)-muscone and R,Z)-5-muscenone. 

SCHEME 31.11. As3fmmetric s3fnthesis of (7 )-muscone (R)-2S) using as3fmmetric protonation as key step. 

Nickel(O) forms a n-complex with three butadiene molecules at low temperature. This complex rearranges spontaneously at 0 °C to afford a bisallylic system, from which a large number of interesting olefins can be obtained. The scheme given below and the example of the synthesis of the odorous compound muscone (R. Baker, 1972, 1974 A.P. Kozikowski, 1976) indicate the variability of such rearrangements (P. Heimbach, 1970). Nowadays many rather complicated cycloolefins are synthesized on a large scale by such reactions and should be kept in mind as possible starting materials, e.g. after ozonolysis. 

Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 10 or the 1,4-keto aldehyde 12 can be prepared by the allylation of a ketone[24] or aldehyde[61,62], followed by oxidation. The reaction is a good annulation method for cyclopentenones (11 and 13). Syntheses of pentalenene[78], laurenene[67], descarboxyquadrone[79], muscone (14 R = Me)[80]) and the coriolin intermediate 15[71] have been carried out by using allyl group as the masked methyl ketone (facing page). 

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