Linalool oxide epoxides

There are many compounds closely related to natural products that are associated with novel syntheses. Dehydrated linalool oxide 891, for example, is conveniently made by chlorination of linalool acetate (28 acetate) with calcium hypochlorite, then cyclization of the allyl chloride 892 with sodium hydroxide and Aliquat 336 in methanol. Once obtained 891 was converted to the dehydrogenated lilac alcohols 893 (R = H). The monoepoxides (on the isopropenyl group) were transformed in a mixture of diacetates that were pyrolyzed to the acetates 893 (R = Ac). Linalool oxide epoxides (894) have... 

Linalool, 3 231, 232, 233 24 477, 495, 496, 500-503, 546 acid treatment of, 24 502 epoxidation of, 24 502 main producers of, 24 501 Linalool oxide, 24 502 Linalyl, 24 479 Linalyl acetate, 24 501 Linalyl alcohol, 24 500 Linalyl esters, 3 231 Linalyl oxide, 24 503 Lincomycin, registered for use in aquaculture in Japan, 3 221t Lincosamide, bacterial resistance mechanisms, 3 32t Lindane, 13 145-147... 

The interdigital secretion of the red hartebeest, A. b. caama, consists of fewer compound classes. It contains a few alkanes and short-chain, branched alcohols, fatty acids, including a few of the higher fatty acids up to octadecanoic acid, an epoxide and the cyclic ethers, rans-(2 ,5.R)-furanoid linalool oxide 23, as-(2JR,5S)-furanoid linalool oxide 24 and ds-(2S,5i )-furanoid linalool oxide 25 (Fig. 5) in a ratio of 2.5 1 1.5 respectively [138]. From the point of view that many of the constituents of the interdigital secretion of this animal are probably of microbial origin, it is interesting that cis- and trans- furanoid linalool oxides have also been found in castoreum [77]. 

Optically pure trans- and czs-linalool oxides, constituents of several plants and fruits, are among the main aroma components of oolong and black tea. These compounds were prepared from 2,3-epoxylinalyl acetate (9) (Scheme 17) [102]. The key step consist of a separation of the diastereomeric mixture of 9 by employing an epoxide hydrolase preparation derived from Rhodococcus sp. NCIMB 11216, yielding the product diol and remaining epoxide in excellent diastereomeric excess (de>98%). Further follow-up chemistry gave both linalool... 

Scheme 17. Synthesis of cis- and frans-linalool oxide using bacterial epoxide hydrolase...

The synthesis of tetrahydrofurans through cyclization via epoxide ring opening has been well investigated and has been applied to the preparation of a-bisabolol oxides (69IJC1060) and linalool oxides (77H(6)1365) and by Kishi et al. in the synthesis of lasalocid A (195), where the epoxide pathway resulted in a stereospecific construction of six out of the ten chiral centers (Scheme 93) (78JA2933). 

Attention is drawn to the synthesis the oxygenated linalool oxide 896. This compound (and other stereoisomers) is not a naturally occurring monoterpenoid, but a fragment required in the synthesis of a calcium ion-selective ionophore, ionomycin, and was made from hydroxygeranyl acetate (113, R = Ac), then Sharpless conditions for introducing a chiral epoxide were used. The vital step is the cyclization of 897 by epoxidizing again under Sharpless conditions (titanium tetraisopropoxide and diethyl tartrate) when the product 896 is obtained. ... 

FIGURE 19.22 Four stereoisomers of furanoid linalool oxides. (Modi ed from Noma, Y. et al.. Reduction of terpene aldehydes and epoxidation of terpene alcohols by S. ikutamanensis, Ya-2-1, Proceedings of 30th TEAC, 1986, pp. 204-206.)... 

Epoxidation of linalool occurs at the more substituted double bond. Ring closure of this epoxide gives a mixture of the cis [5989-33-3] and trans [34995-77-2] isomers of the furan (131), and also the cis and trans isomers of the pyran (133) [14049-11-7] as shown in Fig. 8.27. This mixture is known as linalool oxide, and sometimes erroneously as epox-ylinalool or epoxydihydrolinalool. Linalool oxide has a sweet woody, floral powerful, sweet, and penetrating odor with earthy undertones. It is used in perfumes and in essential oil reconstitutions in which it adds a natural note to linalool. 

Mischitz, M. and Faber, K. (1996) Chemo-enzymatic s5mthesis of (2R,5S)- and (2R,5R)-5-(1-hydroxy-1-methylethyl)-2-vinyl-tetrahydrofuran ("linalool oxide") preparative application of a highly selective bacterial epoxide hydrolase. Synlett, 978-980. 

The Ti,Al-Beta shows both acidic and oxidative properties which is reflected in unwanted side-reaction. The group of Corma used the bifunctionality in the epoxidation/rearrangement of cx-terpineol to cineol alcohol and in the formation of furans from linalool.81,82 Similarly van Klaveren et al. applied Ti,Al-Beta in the one-pot conversion of styrene to phenyl acetaldehyde.83 Sato et alM solved the unwanted acid-catalyzed side reaction by neutralizing the acid site by ion exchange with alkali metals. Nevertheless the bifunctionality restricts the use of this catalyst to a limited number of reactions. 

The reaction was carried out in acetonitrile at 353 K using TBHP as oxidant. Conversions as high as 80 % were obtained. As shown in Scheme 6, it was postulated that the reaction takes place via epoxidation over Ti sites foUowed by acid catalyzed intramolecular opening of the epoxide ring by the 3-hydroxy group. Ti-6 zeolite gave somewhat lower conversions in addition to the preferential formation of furans over pyrans (ratio of ca. 1.5) due to shape selectivity. Ti-MCM-41 and gave furan to pyran ratios of ca. 0.9, comparable to those obtained by the epoxidase conversion of linalool. 

Many hydroxylated linalools [including compounds 105, 106, 108, and 110, both (Z)- and ( )-isomers], as well as the epoxides of both furanoid (109) and pyranoid (see section on pyrans) linalyl oxides, have been identified in papaya fruit (Carica papaya). At the same time, the first reported occurrence of die two linalool epoxides (112) in nature was made. These epoxides are well known to be unstable and easily cyclized (see Vol. 2, p. 165) and have been made by careful peracid oxidation of linalool. An interesting new method has now been described. While the vanadium- or titanium-catalyzed epoxidation of geraniol (25) gave the 2,3-epoxide (see above), as does molybdenum-catalyzed epoxidation with hydrogen peroxide, the epoxidation of linalool (28) with molybdenum or tungsten peroxo complexes and hydrogen peroxide led, by reaction on the 6,7-double bond, to 112. ... 

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