Rose oxide synthesis

The anodic oxidation of olefins in the presence of nucleophiles, such as CH3OH or CHjCOOH, is in principle a reaction of very great industrial interest since it permits allyl oxidation as well as C—C coupling. Nevertheless, it is hardly used industrially today. This is essentially due to the fact that the selectivities are frequently poor. Over the past few years, the reaction principle has been used in synthesis problems in the area of fine chemicals. For example, the anodic methoxylation of citronellol is a key step in a new rose oxide synthesis by Sumitomo35). 

Review problem 34 Design a synthesis for rose oxide, TM 307, a perfiime occuring in rose and geranium oils which is made at present by the oxidation of another natural product, citronellol. 

This reaction was used for a convenient synthesis of Rose oxide (equation 11)... 

Figure 23. Synthesis of (—)-rose oxide by sensitized oxidation of (-)-citronellol [2, 3,81].

See Section 3 for a discussion of the photochemical synthesis of an endothelin receptor antagonist 199 using the Barton reaction and the synthesis of a precursor to (-)-rose oxide 200 which is of industrial interest to fragrance manufacturers. 

Scheme 77 Photooxygenation of (-)-p-citronellol (279) conducted in a glass microreactor and the subsequent use of hydroperoxide 278 in the synthesis of (-)-rose oxide (200).

Photo-oxidation of citronellol in polystyrene beads [120]. A sample of 3.0 g of polystyrene beads (commercial, cross-polymerized with 1% of divinylbenzene) was treated with a solution of 2 mg of tetraphenylporphyrin and 780 mg (5 mmol) of citronellol in 20 mL of ethyl acetate in a petri-dish (30 cm diameter). After 2h in a ventilated hood, the solvent has evaporated and the petri-dish was covered with a glass plate and irradiated for 5 h with a 150 W halogen lamp. The solid support was then washed with 3 x 20 mL of ethanol, the combined ethanol fractions were rota-evaporated and 900 mg of the hydroperoxide mixture (96%) was isolated as a slightly yellow oil. The hydroperoxides were quantitatively reduced to the corresponding allylic alcohols by treatment with sodium sulfite. One of these products is used in the industrial synthesis of rose oxide. 

Such allyloxylation reactions allow, for example, the formation of ( )-rose oxide from citronellol [161]. The synthesis of butenolides can be efficiently performed starting from )6-unsaturated acids [172] ... 

Certainly economical considerations are an important starting point for the development of a successful aroma chemical. The sensorial profile, impact and the absence of off notes is often underestimated. It is part of the knowledge and the professional skills of a flavourist to understand the relevance of effects like aging, isomerisation and oxidation. Over the years numerous strategies for the synthesis of fairly simple aroma chemicals, like straight-chain esters, and of complex structures, like the different isomers of rose oxide (2S, 4R rose oxide and 2R, 4R rose oxide), have been developed. 

Photooxidation rates of propan-2-ol in aqueous Ti02 suspensions are reported to be increased by ultrasound radiation, an observation which has been rationalised in terms of mass transport of the substrate and activation of the solid catalyst. The value of the newly described photochemical rearrangement of 2-phenylthio-l,3-cyclohexanediols such as (69) to deoxysugars (70) which are in equilibrium with the closed form (71) has been illustrated by its application to the synthesis of (+)-m-rose oxide (72), and the same authors have also described the regioselective photorearrangement of 2-phenylthio-3-aminocyclohexanols (73) to deoxyazasugars (74) this has proved to be useful in the synthesis of various piperidines (75), amino-sulfones, -sulfoxides and -acids. Hydroxy(alkoxy)methyl radicals have been generated by photo-induced electron transfer. ... 

In a third synthesis of rose oxide (909) from the lactone 919, addition of propynyllithium, followed by borohydride reduction, gave the diol 920, to which the additional methyl group was added with lithium dimethyl cuprate. Hydrolysis and treatment with silver nitrate yielded the rose oxides (909). This same paper describes a related synthesis of the naturally occurring 2,2,6-trimethyl-6-vinylpyran (921) (Vol. 2, p. 167). 

Yamamoto and Nakamura have reported a synthesis of rose oxide from the dimer 922 of isoprene. Prins reaction (formaldehyde) yielded the dihydropyran 923, which underwent specific ozonolysis and hydrogenation to the known (and naturally occurring) ketone 924. Conversion of the latter to rose oxide (909) is well known (Vol. 2, p. 168, Ref. 586). 

In a paper concerning the aluminum chloride-catalyzed Diels-Alder reaction between 4-methyl-1,3-pentadiene (piperylene) and the nitrile 930, rose oxide is mentioned, but the authors do not describe the synthesis. 

There are several cyclic ethers derived from acyclic monoterpenes which are of importance at lower levels in fragrances. Allylic oxidation of citronellol can be used to introduce a leaving group which allows cyclization to form the pyran, rose oxide. Chlorination was one of the first oxidation techniques employed various others, including electrochemical methods, have since been developed. An outline of the synthesis is given in Scheme 4.16. Rose oxide occurs in rose and geranium oils, to which it imparts a characteristic dry, green, rosy top-note. 

A variant of the ring-closure reactions for the synthesis of rose oxide (299) has been described by Eschinazi. It consists of oxidising the double bond of citronellyl acetate (296) with performic acid, then thermolysing the fully acetylated compound (297) to yield the diene acetate (298), the corresponding alcohol of... 

Matsuda, H. Yamamoto, T. Kanisawa, T. Synthesis and Odor Properties of Optical Isomers of Rose oxide and Dihydrorose oxide, in The 13th International Congress of Flavours, Fragrances and Essential Oils. 1995. Istanbul, Turkey, pp 85-91. 

This reaction was used in a synthesis of (- )-c/,s-rose oxide (5) from d-glucose (1). ... 

In this chapter, we first describe the peculiar electronic structure of 2 and its impact on its chemical reactivity that is opposite from that of ordinary oxygen 02-Then, we compare the respective advantages and limitations of photochemical and chemical methods to generate 2 in a context of industrial development. In particular, we detail the criteria for choosing a reaction medium compatible with both the organic substrate and water-soluble chemical sources of 02- Finally, the main reactions of 2 in organic chemistry are listed and illustrated with two industrially relevant examples recently developed in the fields of perfumery (synthesis of rose oxide) and pharmacy (synthesis of artemisinin). 

Scheme 22.7 Synthesis of rose oxide from p-citroneiioi.

Synthesis of rose oxide (5) by photooxygenation of citronellal as the first step Rose Bengal is used as a photosensitizer Ohioff et al. (1961)... 

A practical example of the use of singlet oxygen is provided by the synthesis of rose oxide (131) from /3-citronellol (129, equation 12.84). The sensitizer was rose bengal, a dye that can be used for singlet oxygen reactions induced by sunlight. The product of the ene reaction was reduced with Na2S03 to a diol (130), which then underwent spontaneous cyclization to 131 in a cold, acidic solution. ... 

The ene reaction of isovaleraldehyde with isoprene provides a 16% yield of ipsenol (7), a pheromone of the bark beetle ips confusus (see Figure 3). lo The major product formed in 60% yield is the Diels-Alder adduct 8 which is related to nerol oxide and rose oxide. Use of Me 2A1Q allows the isolation of acid-sensitive ipsenol, since protic acids are not present in the reaction mixture. The reaction of aldehydes with limonene occurs exclusively at the less substituted double bond as reported by Blomquist for the reaction with formaldehyde. 3a Isovaleraldehyde and limonene give a 70% yield of 9, an intermediate in Crawford s dihydro-ar-turmerone synthesis, n... 

The streptolidine lactam (1), a component of the streptothricin group of antibiotics, has been synthesized as outlined in Scheme 1 o-Glucose has been used as an optically active source material for the synthesis of a-multistriatin (2), a beetle hormone, which is summarized in Scheme 2, and of (- )-c/j-rose oxide (3), shown in Scheme 3. ... 

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