Citronellol, synthesis

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. 

The synthesis of the natural product citronellol (1) (used in perfumery) shows guidelines 1 and 4 in action. Disconnection at the branchpoint is possible (la) and the required alcohol (2) comes from available ketone (3) (p Tl) by reduction. 

The procedure for the synthesis of the title compound is a representative example of asymmetric hydrogenation in the presence of BINAP-Ru(ll) diacetate.5 The method is based on the synthesis of BINAP-Ru(ll) dicarboxylate complexes and enantioselective hydrogenation of geraniol.7 The present method provides the first practical means for asymmetric synthesis of (S)- and (R)-citronellol. (S)-(-)-Citronellol of optical purity up to 92% can be obtained in a limited quantity from rose oil. A microbiological reduction of geraniol was reported to give enantiomerically pure (R)-(+)-citronellol. ... 

A second nonselective synthesis involved chain extension of the tosylate of ( )-citronellol (82) with 2-methylpentyl magnesium bromide and lithium tetrachlorocuprate catalysis to give the carbon skeleton 83 (Scheme 12A) [92]. Allylic oxidation with Se02 and ferf-butylhydroperoxide, hydrogenation of the... 

Stereospecific syntheses of the eight stereoisomers [94] used a variation of the methodology developed in Mori s previous synthesis of the stereoisomers of 6,10,13-trimethyltetradecanol (see Scheme 5) [91], using chiral synthons derived from commercially available enantiomers of citronellol and methyl 3-hydroxy-2-methylpropanoate, and the iterative series of steps outlined in Scheme 13A for one of the stereoisomers [94]. A key step involved moving the... 

Therefore, (S)-3-hydroxy-2-methylpropanoic acid (1) is preferred over the structurally similar citronellol derivatives which have more, but often superfluous, carbon atoms and which are optically impure (ee values of 80%). Application of ent-2 in ex-chiral-pool synthesis is demonstrated in the preparation of ac-tocopherol (vitamin E)14. 

Production. (—)-Citronellol is still obtained mainly from geranium oil by saponification followed by fractional distillation. Although of high odor quality, it does not possess the true (—)-citronellol odor due to impurities. Much larger quantities of (+)- and (zb)-citronellol are used and are prepared by partial or total synthesis. 

Synthesis of (+)- and ( )-Citronellol from the Citronellal Fraction of Essential Oils. (+)-Citronellal is obtained by distillation of Java citronella oil and is hydrogenated to (+)-citronellol in the presence of a catalyst (e.g., Raney nickel). Similarly, (zb)-citronellol is prepared from the ( )-citronellal fraction of Eucalyptus citriodora oil. 

Synthesis from Citronellol. ( )-Citronellal can also be obtained by dehydrogenation of citronellol under reduced pressure with a copper chromite catalyst [64]. 

Synthesis from Citronellol. Citronellol is hydrated to 3,7-dimethyloctan-l,7-diol, for example, by reaction with 60% sulfuric acid. The diol is dehydrogenated catalytically in the vapor phase at low pressure to highly pure hydroxydihydrocitronellal in excellent yield. The process is carried out in the presence of, for example, a copper-zinc catalyst [68] at atmospheric pressure noble metal catalysts can also be used [69]. 

Terpenes important for both fragrances and flavours can be prepared from citral, such as citronellol, linalool, nerolidol, geraniol, farnesol and bisabolol. Citral is also an important starting material for the synthesis of vitamins A and E, carotenoids and other flavour and fragrance compounds like ionones. Most of the /3-ionone synthesised is probably used for vitamin A synthesis. 

The most important and frequently used terpene esters in flavours are the acetates of nerol, geraniol, citronellol, linalool and isoborneol [12], As discussed before, all these terpene alcohols are available both from renewable resources and from petrochemical origin. Acetic acid can be obtained from renewable resources by pyrolysis of wood as wood vinegar, and also by synthesis from petrochemical origin. 

The production of myrcene (7) from p-pinene is important commercially for the synthesis of a wide variety of flavor and fragrance materials. Some of those include nerol and geraniol, citronellol (27) and citral (5). 

Uses and Reactions. The main use for citronellol is for use in soaps, deteigents, and other household products. It is also important as an intermediate in the synthesis of other important fragrance compounds, such as citronellyl acetate and other esters, citronellal, hydroxycitronellal, and menthol. 

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

The Rh(I)-catalyzed isomerization of prochiral allylic amines to optically active enamines is used for the giant-scale synthesis of citronellal, citronellol, menthol, and other fragrances (18)(Chapter 3). 7-Meth-oxydihydrocitronellal, thus prepared, is an insect growth regulator. All of these processes can be carried out economically and with extremely high optical yields. 

Since the conversion of (-)-citronellol to (S)-pulegone is reported, the enantiomeric (+)-8-phenylmenthol likewise may be synthesized. The latter should also be obtainable in a seven-step synthesis starting from (R)-pulegone (48% overall yield) as Corey and co-workers claimed.3 ... 

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). 

The point of this synthesis is that the workers recognised that oxidative cleavage of citronellal and citronellol would give two-ended fragments that could be used to make the core of the pheromone with the right stereochemistry. We shall see in the next chapter that this reconnection strategy is vital for the synthesis of one important group of compounds 1,6-diCOs. 

Conjugate addition of RMnCl to alkylidenemalonic esters proceeds in generally good yields (80-87%, equation I), which are generally higher than those obtained by use of RLi or RMgCl. A new synthesis of citronellol (1) is based on this reaction.3... 

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).

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