Sandalwood synthesis

Another opportunity to combine two reaction steps towards a one pot synthesis is the epoxidation of a-pinene and the isomerization of the epoxide to campho-lenic aldehyde (Scheme 5.6). Zeolite Ti-Beta seems adequate to deal with both steps as a catalyst [24]. Campholenic aldehyde is the starting material for several sandalwood fragrances. 

Campholenic Aldehyde Manufacture. Campholenic aldehyde is readily obtained by the Lewis-acid-catalyzed rearrangement of a-pinene oxide. It has become an important intermediate for the synthesis of a wide range of sandalwood fragrance compounds. Epoxidation of (+)- Ct-pinene (8) also gives the (+)-o -a-pinene epoxide [1686-14-2] (80) and rearrangement with zinc bromide is highly stereospecific and gives (-)-campholenic aldehyde... 

Otherwise, in general construction the perfume follows closely that of a classical oriental, with citrus oils (making up some 25%), lavender, sandalwood, patchouli, vanillin, coumarin, castoreum, and rose. The general sweetness of the perfume is further enhanced by the choice of musk materials, Galaxolide (5%), Tonalid, ethylene brassylate, and musk ketone, as well as by the use of Cashmeran, an intensely sweet fruity musk material associated with the synthesis of Galaxolide. 

Alpha-Pinene oxide 9 (Eq. 15.2.5) is known as a reactive molecule which rearranges easily under the influence of an acid catalyst (6, 7). Thereby many products can be formed. For example compounds such as the isomeric campholenic aldehyde 11, trans-carveol 12, trans-sobrerol 13, p-cymene 14 or isopinocamphone 15 are observed as main by-products. At temperatures higher than 200°C more than 200 products can be formed. The industrially most desired compound among these is campholenic aldehyde 10. It is the key molecule for the synthesis of various highly intense sandalwood-like fragrance chemicals (7, 8). 

This reaction has been used or h synthesis of tricyclo-efca-santalol (3), a minor constituent of sandalwood oil (equation I). 

Endo-exo selectivity typically ranges from 20 1 to 45 1 with a maximum of 97.5 2.5 diastereoselection. Prepara-tively convenient reaction conditions are employed (CH2CI2, CH2Cl2/cyclohexane temp, approx. 0°C ca. 0.3 M concentration and 0.1-1.0 molar equiv of Lewis acid). Products are typically crystalline and brought to high optical purity by recrystallization. Epimerization-free hydrolysis is effected with LiOH in THF/water. This procedure has been successfully applied in a nine-step synthesis of cyclosarkomycin in 17% overall yield (eq 2), and to syntheses of the sandalwood fragrances. ... 

Witteveen JG, van der Weerdt AJA. Structure-odor relationships of some new synthetic sandalwood aroma chemicals. Synthesis and olfactive properties in a series of bicyclo(4.4.0.decan-3-ols. Rec. Trav. Chim. Pays Bas. 1987 106 29-34. 

Bajgrowicz JA,Frank 1, Prater G, Plennig M. Synthesis and structure elucidation of a new potent sandalwood-oil substitute. Plelv. Chim. Acta 1998 81 1349-1358. 

Heissler, D., and Riehl, J.-J., Synthesis with benzenesulfenyl chloride. On the structure of a ( 12IIis hydrocarbon from East Indian sandalwood oil. Tetrahedron Lett., 21, 4711, 1980. 

This stereoselectivity was also useful for synthesis of material reputed to possess sandalwood-like odors [equation (g)] , and for the preparation of the axial alcohol frans-9,10,c/s-8,9-f/-8-hy oxy-2-methyldecahydroisoquinoline °. 

Diels-Alder reaction of l,l-dimethylcyclopenta-2,4-diene and 2-acetoxy-acrylic acid ester gives two esters (290), which can be converted by conventional reductive steps into the two a-fenchene hydrates (291) and (292). Cyclopen-tadiene and ethyl but-2-ynoate also undergo a Diels-Alder reaction, this time to a norbornadiene ester (293), which was the start of a synthesis of a Cu aldehyde (294) found in East Indian sandalwood oil. ... 

Epoxy-a-pinene, produced by epoxidation of (+)-a-pinene, rearranges in the presence of Lewis acids to (-)-campholenealdehyde which is not only one of the constituents of various juniper species, but also the starting reagent for the synthesis of fragrances with the odor of sandalwood. Sandalore, for example, is produced by Knoevenagel aUcenylation of campholenealdehyde with propanal followed by reduction of the aldehyde function with sodium borohydride... 

Fencholene aldehyde (7), an interesting starting material for the synthesis of sandalwood fragrance compounds, has been prepared by AgNOa-assisted fragmentation of biomoisofenchol (6). The acetals (8) of fencholene aldehyde (7) are directly available in a one-pot reaction under anhydrous conditions. Also, these acetals are useful as fragrances (Scheme 7). 

Camphene is the starting material for the synthesis of camphor and of isobornyl acetate (Fig. 10.1.10). Condensation of camphene with phenolic compounds followed by hydrogenation gives a mixture of isobornyl cyclohexanol isomers, which have the odor of (costly) sandalwood. Methoxyeugenol, another com-... 

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