Vulcanolide

The variety of uses of (-)-isopropylephedrine as a chiral auxiliary in enantiose- Another important tetra-lective protonation was demonstrated by Charles Fehr, not only for damascene lin-musk scent is tonalide. Its but also for tetralin-musk-scented compounds (e.g. Vulcanolide ). Deprotonation of 2,2,4,5-tetramethylhex-4-en-3-one with LDA gives the dienolate in an ( /Z)-ratio of 1 9. This can be protonated very selectively with iso-... 

In contrast to the initial results involving a chiral mixed aggregate, the asymmetric protonation of enolate promoted by (—)-H-E as the sole reagent was successfully applied in the course of the multistep synthesis of (/ )-muscone (i )-25) and (5,5)-vulcanolide (5,5)-26), two fragrances with a strong musky smell. In both cases, the lithium enolate was quenched with chiral proton source... 

A similar strategy was used by Fehr and co-workers to achieve the enantioselective (5,5)-vulcanolide (5, 5)-26 synthesis (Scheme 31.12). Li-enolate of ketone 33 was protonated by ( )-//-E affording the enantioenrichied ketone 34. Then, Friedel-Craft alkylation of o-xylene followed by reduction provides the secondary alcohol 35. The trans cyclohexyl derivative 36 was easily obtained under acidic conditions in 44% over three steps. Then, a monooxidation affords the (5,5)-vulcanolide (S,5)-26) in ca. 29% yield over five steps with 83% ee. 

Fehr C, Chaptal-Gradoz N, Galindo J. Synthesis of ( )-vulcanolide by enantioselective protonation. Chem. Eur. J. 2002 8 853-858. 

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