Citronellol, oxidation

Pulegone from Citronellol Oxidation with Pyridinium Chiorochromate... 

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. 

Further evidence of the difference between rhodinol and citronellol is forthcoming, in that the former yields on oxidation an aldehyde, rhodinal, whose oxime does not yield citronellic acid nitrile when treated with acetic anhydride, nor citronellic acid when the nitrile is treated with alkalis, wheras citronellal, the aldehyde of citronellol, does yield the nitrile and citronellic acid. 

No aldehyde or ketone has been obtained from it by oxidation. Its constitution is probably allied to those of citronellol and rhodinol, but, since it contains an asymmetric carbon atom, as shown by its optical activity, the three formulae given under bupleurol obviously cannot represent androl. 

Hdschle B, D Jendrossek (2005) Utilization of geraniol is dependent on molybdenum in Pseudomonas aeruginosa. evidence for different metabolic routes for oxidation of geraniol and citronellol. Microbiology (UK) 151 2277-2283. 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

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... 

The method of photosensitized oxygenation was successfully applied in the preparation of alcohols 265-270 from sylvestrene (264),207 and seems to be the most simple and successful method for the preparation of optically active rose oxides (272,273) from (+)- or (—)-citronellol C271).177 It may also be used for the preparation of certain organo-metallic hydroperoxides. Thus, the triphenyl-tin derivative of tri-methylethylene (274) undergoes a photosensitized oxygenation reaction with a rate similar to that of tetramethylethylene, giving rise to the hydroperoxides 275 and 276 219... 

Citronellol undergoes the typical reactions of primary alcohols. Compared with geraniol, which contains one more double bond, citronellol is relatively stable. Citronellol is converted into citronellal by dehydrogenation or oxidation hydrogenation yields 3,7-dimethyloctan-l-ol. Citronellyl esters are easily prepared by esterification with acid anhydrides. 

Preparation of (—)-Citronellol from Optically Active Pinenes. (+)-ci5-Pinane is readily synthesized by hydrogenation of (+)-0 -pinene or (+)-/3-pinene, and is then pyrolyzed to give (+)-3,7-dimethyl-l,6-octadiene. This compound is converted into (-)-citronellol (97% purity) by reaction with triisobutylalumi-num or diisobutylaluminum hydride, followed by air oxidation and hydrolysis of the resulting aluminum alcoholate [50]. 

Rose oxide is usually prepared from citronellol which can be converted into a mixture of two allyl hydroperoxides (e.g., by photosensitized oxidation with oxygen). Reduction of the hydroperoxides with sodium sulfite yields the corresponding diols [183]. Treatment with dilute sulfuric acid results in allylic rearrangement and spontaneous cyclization of one of the isomers a mixture of diastereoisomeric rose oxides is thus formed. The unreacted diol isomer is separated by distillation. (—)-Citronellol as the starting material yields approximately a 1 1 mixture of (—)-cis- and (—)-tra s-rose oxide. 

A study with houseflies (7) shows clearly that very small differences in the molecular structure can result in drastically different biological effects as exemplified in Table III by the optical Isomers (-)-limonene, a fly attractant, and (+)-limonene, a fly deterrent. A difference in oxidation state In the functional group as in citronellol, a fly attractant, and citronellal, a fly deterrent, also causes different responses. A difference in the length of the carbon chain as in farnesol (C15), a fly attractant, and geranlol (CIO), a fly deterrent, also confers different... 

Aluminum alkyls react by the Ziegler reaction with the least substituted double bond to give the tricitronellyl aluminum compound. Oxidation of the intermediate compound then produces the tricitronellyl aluminate, which is easily hydrolyzed with water to give citronellol (112,113). If the citronellene is optically active, optically active citronellol can be obtained (114). The (—)-citronellol is a more valuable fragrance compound than the ( )-citrondlol. 

Cyclodimerization of isoprene to 1,5-dimethylcycloocta-l,5-diene and disproportion with a rhenium oxide catalyst and isobutene produce 2,6-dimethylhepta-l,5-diene. The diene is hydroformylated to citronellal, which after hydrogenation produces citronellol (137). 

This allyloxylation was used to produce d,l-rose oxide from citronellol (Eq. 50) 1 -Similarly d, 1-dihydroactinidiolide was formed in one step by the intramolecular oxyselenation-deselenation sequence (Eq. (51))... 

In sensitized or photocatalyzed reactions, conditions of total or constant absorbance can easily be controlled by the concentration of the sensitizer or photocatalyst added. In addition, experience has shown that the concept of spatial separation between the light source and the reaction mixture is in general not required. Dragoco uses immersion-type annular reactor geometries [2, 3, 69, 70] for the production of ( —)-rose oxide by rose bengal sensitized oxidation of (— )-citronellol (Eqs. 45-48, Figure 23). 

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

In the same year the biotransformation of these monoterpenes by B. cinerea in model solutions was described by another group [41]. Although the major metabolites found were co-hydroxylation compounds, it is important to note that these authors only identified the -isomers in the extracts and that some new compounds were detected that were not described by the previous group, Fig. (9). Geraniol (20) was mainly transformed to (2 ,5 )-3,7-dimethyl-2,5-octadiene-l,7-diol (53), ( )-3,7-dimethyl-2,7-octadiene-l,6-diol (54) and (2 ,6 )-2,6-dimethyl-2,6-octadiene-1,8-diol (43), nerol (14) to (2Z,5 )-3,7-dimethyl-2,5-octadiene-1,7-diol (55), (Z)-3,7-dimethyl-2,7-octadiene-l,6-diol (56), and (2E,6Z) 2,6-dimethyl-2,6-octadiene-1,8-diol (47). Furthermore a cyclisation product (57) was formed which was not previously described. Finally citronellol (4) was converted to trans- (60) and cw-rose oxide (61) (a cyclisation product not identified by the other group), ( )-3,7-dimethyl-5-octene-l,7-diol (58), 3,7-dimethyl-7-octene-l,6-diol (59) and ( )-2,6-dimethyl-2-octene-1,8-diol (34). 

R,S)-Citronellal can be purchased from BASF, and (R)-citronellal from Dragoco, Fluka, or Takasgo Perfumery Co., Ltd., Japan. (R)-Citronellal can also be synthesized from pulegone with ee >99%.5 (S)-Citronellal may be obtained by oxidation of (S)-citronellol,6 which is accessible by different routes with ee 95%.7 The optical purity of citronellal can be determined by GLC after conversion to the acetal of (-)-(2R,4R)-pentanediol.8 For the reactions described, (R,S)-citronellal from BASF, (R)-citronellal from Dragoco, and (S)-citronellol from Fluka were used. (R,S)-Citronellal... 

Czs- and (-)-frans-rose oxide 6 are industrially produced perfume additives from citronellol. Several comparative studies have dealt with fruit and Gewiirtztraminer wine aroma (99JAFC665, 08JAFC1371). Guth... 

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 electrolysis of citronellol 54 in methanol provides 55 (89 % yield) and subsequent demethoxylative cyclization with BF3-etherate (or EG Acid) gives dl-rose oxide 5 (cis/trans = 9 1) in 84% yield from 54 (Scheme 3-19)67>. 

The EG acid-catalyzed demethoxylative cyclization of the olefin alcohol 55 prepared by electrochemical oxyselenation-deselenation of /-citronellol proceeds in a CH2C12— LiC104/Et4NC104 system to give l-rose oxide 5 in 82% yield (Scheme 3-27)... 

Alicyclic enol acetates can lead to the corresponding enones by anodic oxidation. The electrolysis of d-menthenyl acetate 74 in an AcOH—Et4NOTs—(C) system by passing 2.5 F/mol of electricity provides the d-menthenone 75, a precursor for d-menthone 76 and /-citronellol 54 syntheses, in 97% yield (Scheme 3-28)76a). 

However, the aldehyde cannot be citronellal as the stereochemistry would be wrong. In addition, both terminal alkenes must be oxidised away so that the rest of the molecule may be attached. So this is what they did the left-hand half of the molecule was assembled from citronellol 48 by oxidation to the aldehyde 50 and the remaining seven carbon atoms added by a Wittig reaction. The product is mainly Z-51 but this is irrelevant as the alkene will disappear. The phosphonium salt is ready for coupling to the right-hand half. 

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. 

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