Nerol synthesis

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, citroneUol (27) and citral (5). 

Takaya and co-workers46 found that BINAP-based Ru(II) dicarboxylate complexes 31 can serve as efficient catalyst precursors for enantioselective hydrogenation of geraniol (2E)-32 and nerol (2Z)-32. (R)- or (iS )-citroncllal 33 is obtained in nearly quantitative yield with 96-99% ee. The nonallylic double bonds in geraniol and nerol were intact. Neither double bond migration nor (fi)-/(Z)-isomerization occurred during the catalytic process. Furthermore, the S/C ratio was extremely high, and the catalyst could easily be recovered (Scheme 6-18). This process can be applied to the asymmetric synthesis of a key intermediate for vitamin E. 

We have reported one of the shortest total syntheses of epothilone D so far. A large moiety of the 16-membered macrocycle is derived from the easily available isoprenoid nerol. Only four C-C bond formations and three protective groups are required. Only one step requires the use of a (recoverable) chiral auxiliary. The other stereocenters are constructed by catalytic hydrogenation (C8), resolution (C15), and induction (C6, C7). In particular the northern half synthesis is well suited for large-scale preparation because of the combination of cheap reagents and catalytic processes. Using essentially the same method, a number of epothilone D5 analogues were synthesized. 

Synthesis from Linalool. A 96% pure synthetic geraniol prepared by isomerization of linalool has become commercially available. Orthovanadates are used as catalysts, to give a >90% yield of a geraniol nerol mixture [31]. Geraniol of high purity is finally obtained by fractional distillation. 

Synthesis from Geraniol. Currently, the most important synthetic procedures are vapor-phase dehydrogenation and oxidation of geraniol or geraniol-nerol mixtures. Catalytic dehydrogenation under reduced pressure using copper catalysts is preferred [54]. 

Synthesis from Geraniol or Nerol. ( )-Citronellal can be obtained by vapor-phase rearrangement of geraniol or nerol in the presence of, e.g., a barium-containing copper-chromium oxide catalyst [63]. 

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 reaction of Gilman reagents with ,)8 -epoxy-oximes yields -hydroxy-ketones [e.g. (17 X=OH)].56 Vinyl copper compounds are converted stereo-specifically into /3,/3-disubstituted a-ethylenic acids by carbonation nerol (18) was synthesized (Scheme 3).57 Further papers on /3-ketosulphoxide synthesis [e.g. of... 

Methyl-3-propiolactone is useful as a four-carbon building block for terpenoid synthesis (eq 4). Citronellic acid (9) isprepared by reaction with the homoprenyl Grignard reagent pulegone (10), citronellol (11), geraniol, and nerol (12) can be obtained by further functional group manipulations. ... 

Treatment of lV-methanesulfonyl-l,4-dihydFopyridine with n-butyllithium, followed by benzyl bromide, leads to the corresponding lV-l-(2-phenylethyl)sulfonyl-l,4-dihydropyridine in low yield. The sulfonamide shown in Scheme 131 (entry c) has proved a valuable c -isoprenoid synthon which allows the two-step C -homologation of allyl halides. This synthon was used for the remarkable two-step stereoselective synthesis of nerol from 3-methyl-2-butenyl chloride (Scheme 131, entry c). Finally, the a-chloro dicarbanion of 4-(a-chlon>methanesulfonyl)morpholine is readily availabl on reaction with 2 equiv. of n-butyllithium in THF, and it leads to the corresponding dimethyl derivative with no detectable monoalkylated product or starting sulfonamide on methylation. Intramolecular versions of these reactions allow the low yield synthesis of neopentyl cyclopropanesulfonate (scheme 131, entry d) and the efficient preparation of cyclopropanesulfomorpholine (scheme 131, entry e). ... 

Composition The European Pharmacopoeia lists linalyl acetate (56-78%), linalool (6.5-24%) and germacrene D (1.0-12%). a-Terpineol is limited to 5.0%, a- and P-thujone to 0.2%. Sclareol (0.4-2.6%) is found mainly in the concrete and is used for the synthesis of ambra fragrance materials. Further constituents are linalool oxide, geraniol, nerol, neryl and terpinyl acetate, citronellol, 1,8-cineole, benzaldehyde and n-nonanal. For further literature see [64, 65]. 

A word about the synthesis of the a-series, a-geraniol (73) and a-nerol (74), is warranted because they are often intermediates in the synthesis of 1-hydroxylated compounds (e.g., some diols described below). Weiler has continued his exploitation of the dianion of methyl acetoacetate to this end. Instead of prenylation (Vol. 4, p. 461, Ref. 73) he carried out a similar series of operations by alkylating the dianion with 4-bromo-2-methyl-l-butene, thus arriving at compounds of the a-series via the keto ester 75, methylating the enol phosphate to 76. He also prepared the double methylene isomer 77 (R = COEt) of geranyl propionate from the intermediate 75. The purpose of synthesizing this propionate was to prepare the pheromone of the San Jose scale, Quadraspidiotus pernicious, which is a mixture of the propionates of 73, 74,... 

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