R - -Citronellal

BINAP is a versatile ligand the S-enantiomer, complexed with rhodium, is used in the commercial production of 1-menthol (Scheme 4.23). In this case the reaction involves isomerization of diethylgeranylamine to R)-citronellal enamine, which proceeds to approximately 99% ee. 

Oxidation of the o-QM complex 13 (formed by treating the phenol complex with (R)-citronellal and pyridine) with CAN resulted in an intramolecular Diels-Alder reaction to form the benzo[c]chromene 15 (Scheme 3.8). 

R)-Citronellal purchased from Aldrich Chemical Company, Inc., Dragoco, Holzmlnden, or Takasago, Perfumery Co., Ltd., Tokyo was used as received. (R)-Citronellal can also be synthesized from pulegone with ee > 99%.3 The optical purity... 

Isomerization of allylic amines is another example of the application of the BINAP complex. Rh BINAP complex catalyzes the isomerization of N,N-diethylnerylamine 40 generated from myrcene 39 with 76-96% optical yield. Compound (R)-citronellal (R)-42. prepared through hydrolysis of (R)-41, is then cyclized by zinc bromide treatment.49 Catalytic hydrogenation then completes the synthesis of (—)-menthol. This enantioselective catalysis allows the annual production of about 1500 tons of menthol and other terpenic substances by Takasago International Corporation.50... 

Separation of catalysts from high-value products such as fine chemicals or pharmaceuticals is often accomplished by precipitating the catalyst from the product solution. Recycling of these catalysts is feasible, provided that they do not decompose. In industry, catalyst recovery by means of catalyst precipitation is applied only in relatively small batch processes. An example of such a process is the production of (—)-menthol (id) in which an Rh-BINAP isomerization catalyst converts the allylic amine substrate into (R)-citronellal (after hydrolysis of the enamine) in high yield (99%) and with high enantioselectivity (98.5% ee). After distillation of the solvent (THF) and product, the catalyst is recovered from the residue by precipitation with -heptane. 

R = vinyl or ethynyl) predominates (c/. Vol. 1, p. 36 Vol. 2, p. 35). Base treatment of a 2-alkoxypyridinium tosylate of nerol gives expected e.g. limonene 82%) cyclic hydrocarbons whereas the corresponding geraniol salt yields similar amounts of cyclic and acyclic hydrocarbons. SnCU-catalysed cyclization of the N-benzylimine derived from R-(+)-citronellal yields the expected menthylamines after catalytic hydrogenation. ... 

Enantiomerically pure citronellal in both of its antipodal forms has outstanding importance as a key intermediate for the production of fine chemicals, especially for the production of fragrances and flavors. In this respect the isomerization of diethylgeranylamine to R) -citronellal enamine in the presence of Rh /(S) -BINAP is an exceptional industrial process, for instance as one of the key steps of the Takasago process for the production of (-) -menthol [22]. In the search for alternatives for this process, both Josiphos and Daniphos derivatives were evaluated (Scheme 1.4.5) [23]. 

LXXIX (R)-Citronellal- diathylacetal CuPuP 228,4 Chloro- form 0,1168 25 589 +4,91 ... 

Stereoselective intramolecular Diels-Alder reactions The reaction of Meldrum s acid (1) with (R)-citronellal (2) in the presence of ethylenediammonium acetate (EDDA)2 at 15-20° results in the tricyclic dihydropyran 3 as the major product with an optical purity of >98%. The product evidently results from an intramolecular hetero-Diels-Alder addition. It can be converted by acid into the optically pure a-methoxycarbonyllactone 4. 

Intramolecular ene reaction of 1,7-dienes.1 The ZnBr2-catalyzed reaction of the activated 1,7-diene 1 gives the frans-disubstituted cyclohexane 2 (>98% selectivity.) Under the same conditions, the chiral 1,7-diene 3 [from (R)-citronellal] is converted into two diastereomeric frww-disubstituted cyclohexanes, 4 and 5 in the ratio 96.5 3.5. Slightly higher diastereoselectivity obtains with (C2H5)2A1C1 (96% de), but the thermal ene reaction gives 4 and 5 in the ratio 86 14. 

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... 

Dimethyl-1,3-Dioxane-4,6-dione (Meldrum s Acid) Malonic acid, cyclic isopropylidene ester (8) 1,3-Dioxane-4,6-dione, 2,2-dimethyl- (9) (2033-24-1) Ethylenediammonium diacetate 1,2-Ethanediamine diacetate (9) (38734-69-9) (R)-Citronellal 6-Octenal, 3,7-dimethyl-, (R)-(+)- (8,9) (2385-77-5)... 

Noyori s BINAP catalysts deserve special attention because their chirality is based on the bulkiness of the naphthalene groups, rather than on carbon or phosphorus asymmetric centers (Figure 3.28, inset) [77]. One of the many examples of asymmetric catalysis using BINAP is the synthesis of (—)-menthol, an important additive for flavors, fragrances, and pharmaceuticals. Starting from myrcene, the process is carried out by Takasago International on a multi-ton scale. The key step is the isomerization of geranyldiethylamine to (R)-citronellal enamine [78], which is then hydrolyzed to (R)-citronellal with nearly 99% ee. 

S)-4 and/or its enantiomer (R)-4 have been prepared via resolution of an intermediate, starting from (R)-citronellic acid, by stoichiometric asymmetric synthesis1 -18 (76-88% ee), and by a microbiological method.17... 

Optically active polyaldehydes possessing optically active side chains, such as poly-(R)(+)-citronellal, poly-(R)(+)-6-methoxy-4-methylhexanal, and poly-(S)(+)-2-methylbutanal, have been prepared by Goodman (1, 22). The optical activity of the polymers was enhanced as compared with their model compounds. It was concluded that the enhancements of the optical activity arose from a conformational rigidity around the asymmetric center in the side chain of the polymer. From degradation studies of the polymers it was concluded that the optical activity of the monomer was unchanged, and no racemization had occurred during polymerization and degradation. 

Otsuka and coworkers277 278 have described the isomerization of prochiral allylamines into chiral enamines with a [Rh(BINAP)COD] + BF4 catalyst (COD = cyclooctadiene). The isomerization of 66 gave R-citronellal enamine (68) and... 

R-citronellal (69). This isomerization is a crucial step in the synthesis of ( — )-menthol. Enantioselectivity in this isomerization exceeds 96%. 

Details are also available for isomerization of prochiral N,N-dialkylamines to the optically pure corresponding (E)-enamine (11, 53- 54) using BINAP as the chiral catalyst. This novel chemistry permits a short synthesis of optically pure (R)-( + )-citronellal (4) from isoprene utilizing the isomerization of N,N-diethylneiylamine (2) to R( — )-3. ... 

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