Fragranol

Cyclobutane.—Grandisol syntheses have been re viewed,and Trost s full paper on grandisol and fragranol synthesis (Vol. 6, pp. 21, 22) has been published. 

Both fragranol and grandisol skeletons were obtained by treatment of racemic butyl 6,7-epoxygeranyl sulfide with butyllithium in 7V,7V,Ar, 7V -tetramethylethylenediamine (TMEDA). In addition to the trans-product trans-16 (fragranol skeleton) and the ra-product m-16 (grandisol skeleton), a cyclopentane derivative was also isolated.16... 

This method was successfully applied to the total synthesis of the monoterpene ( )-fragranol 85 [158]. 

Cydobutane.—Four syntheses of grandisol (73) have been reported,163 166 one of which also led to fragranol (74) (Vol. 4, p. 23).166 Ozonolysis of compound (75),... 

D1 (+)-fra/7s-Chrysanthemic acid D2 (+)-frans-Pyrethric acid D3 (1S,2S)-Fragranol D4Junionone... 

The final step involves peracid oxidation and sulfoxide elimination to obtain the desired isopropenyl group. Fortunately, this elimination occurs without isomerization of the double bond and is therefore a useful method for introduction of an isopropenyl unit. Although the synthesis is lengthy, only the compounds formulated are purified, and yields in all steps are >80%. However, the NMR spectrum of the saturated methyl region of the final product indicates that it consists of grandisol and the isomeric fragranol (9) in the ratio 4 1. 

Fragranol [2-(frans-2-isopropenyl-1 -methy l-cyclo-butyl)ethanol]. 

Fragranol (85), a cyclobutane derivative, has been obtained from root of Artemisia fragrans, where several of its esters are also present (54). Eucarvone (86), which was isolated in 1905 (379) occurs in the essential oil from rhizomes of Asarum sieboldii. Two related compounds are the carboxylic acids, shonanic acid (87) from the wood of Libocedrus formosana and thujic acid (88) present in the heartwood of Thuja plicata, which also contains its methyl ester (140). 

Rautenstrauch has shown that the cyclobutane ring system found in the monoterpenes fragranol and grandisol can be produced by intramolecular cyclization from an epoxy-sulphide of the type (43), and Corbel et al have demonstrated the use of epoxy-sulphones [viz. (44)] in the elaboration of cyclobutanols. 

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