Citronellal reduction

Triethylammonium formate is another reducing agent for q, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

I The three optical varieties of rhodinol have thus been obtained, namely, laevo-rhodinol, the natural constituent of rose and geranium oils dextro-rhodinol by conversion of dextro-citroneUol obtained by reduction of citronellal, and inactive rhodinol by the reduction of synthetic ethyl rhodinate. 

According to Skita, the reaction proceeds in a different manner if the reduction be effected with palladium chloride and hydrogen. In this case the citral in alcoholic solution is mixed with an aqueous solution of palladium chloride and the whole thickened with gum-arabic. Hydrogen gas is then forced into this solution under pressure. The products of the reduction include citronellal and citronellol and a di-molecular aldehyde, C Hj O, which probably has the following constitution —... 

Another example from Liu s team in this field concerns the selective hydrogenation of citronellal to citronellol by using a Ru/PVP colloid obtained by NaBH4 reduction method [112]. This colloid contains relatively small particles with a narrow size distribution (1.3 to 1.8 nm by TEM), whereas the metallic state of Ru was confirmed by XPS investigation. This colloid exhibited a selectivity to citronellol of 95.2% with a yield of 84.2% (total conversion 88.4%), which represented a good result for a monometallic catalyst. 

Chapter 2 to 6 have introduced a variety of reactions such as asymmetric C-C bond formations (Chapters 2, 3, and 5), asymmetric oxidation reactions (Chapter 4), and asymmetric reduction reactions (Chapter 6). Such asymmetric reactions have been applied in several industrial processes, such as the asymmetric synthesis of l-DOPA, a drug for the treatment of Parkinson s disease, via Rh(DIPAMP)-catalyzed hydrogenation (Monsanto) the asymmetric synthesis of the cyclopropane component of cilastatin using a copper complex-catalyzed asymmetric cyclopropanation reaction (Sumitomo) and the industrial synthesis of menthol and citronellal through asymmetric isomerization of enamines and asymmetric hydrogenation reactions (Takasago). Now, the side chain of taxol can also be synthesized by several asymmetric approaches. 

Selective catalytic hydrogenation with chromium-promoted Raney nickel is reported (e.g. citral and citronellal to citronellol) NaHCr2(CO)io and KHFe(CO)4 reduction of a/3-unsaturated ketones (e.g. citral to citronellal) has been described (cf. Vol. 7, p. 7). The full paper on selective carbonyl reductions on alumina (Vol. 7, p. 7) has been published." Dehydrogenation of monoterpenoid alcohols over liquid-metal catalysts gives aldehydes and ketones in useful yields. ... 

The 1-pro-7 -hydrogen is lost on oxidizing geraniol with a cell-free extract from Cannabis sativa (Vol. 7, p. 9, ref. 96), asymmetric microbial reduction of ( )-citronellal to (-)-citronelloI is reported, and callus cultures of Nicotiana tabacum selectively hydroxylate linalool, dihydrolinalool, and the derived acetates at the -methyl group [e.g. to give (59)]. ... 

In a similar approach, Shishido et al. (241) used oxime 215 [derived from the monoterpene (+)-citronellal (214)] for the synthesis of (—)-mintlactone (218) and (+)-isomintlactone (219), sweet compounds isolated from some Mentha species (Scheme 6.89). Bicyclic isoxazoline 216 was obtained in good yield from the cycloaddition. As expected, the product possessing tra i-l,4-substimtion prevailed. Reductive hydrolysis of the major isomer of 216 using hydrogen-Raney Ni-trimethyl borate provided p-hydroxyketone 217. This compound was dehydrated to give an enone and this was followed by carbonyl reduction-lactonization to complete the synthesis of both lactones 218 and 219 (241). 

Addition of dihydrosilane to a, /j-unsaturated carbonyl compounds such as citral (49), followed by hydrolysis, affords saturated citronellal (50) directly. The reaction is used for the selective reduction of conjugated double bonds[45,46]. In addition to Pd catalyst, the use of a catalytic amount of... 

Chemoselective reduction of the conjugated double bond of a, /f-unsaturated aldehydes such as citral (556) to give citronellal (577) is possible by Pd-catalysed hydrostannation in the presence of AcOH [213],... 

Menthol is used in many consumer products, such as toothpaste, chewing gum, cigarettes, and pharmaceutical products, with an estimated worldwide consumption estimated at 4500 tons per year (Chapter 31)4143 (-(-Menthol (22) is manufactured by Takasago Co. from myrcene (23), which is available from the cracking of inexpensive P-pinene (Scheme 12.6)4244 The key step in the process is the asymmetric isomerization of /V,/V-diethylgcranylarninc (24) catalyzed by either [Rh(L2)(5 -BINAP)]+BF f (where L is diene or solvent) or Rh(.S -BINAP)2]+BF f to the diethyl enamine intermediate 25 in 96-99% ee.3645 Citronellal (26) is obtained in 100% ee after hydrolysis of the enamine intermediate natural citronellal has an optical purity of 80%.35 A stereospecific acid-catalyzed cyclization followed by reduction produces 22.42... 

Citronellal, an aldehyde with a trisubstituted double bond, was hydrogenated to citronellol over a ruthenium catalyst poisoned with lead acetate in 90-100% yields (eq. 5.22)46 or over chromium-promoted Raney Ni in 94% yield in methanol at 75°C and about 0.31 MPa H2.47 Court et al. studied the selective hydrogenation of citral (1, eq. 5.24) to citronellol over unsupported Nij. o catalysts, prepared by reduction of mixtures of metal iodides with naphthalene-sodium as reducing agent, in cyclohexane and in 2-propanol at 80°C and 1.0 MPa H2.48 Higher yields of citronellol were obtained in 2-propanol than in cyclohexane, primarily via citronellal as the predominant intermediate. The yields of citronellol for the overall hydrogenation in 2-propanol over Mo-promoted catalysts were Mo0 03 96%, Mo0 06 98%, and Mo012 96%. 

Scheme 18. Selective reduction of citronellal to isopulegol over Li or NaX or to citronellol over CsX.

HPLC on an octadecyl column can be applied to the analysis of caffeine from tea or cola syrup (Chapter 8—use 20% methanol, 0.8% acetic acid, and 79.2% water as eluant), the acetylation of cholesterol (Chapter 10) pulegone and citronellal from citronellol (Chapter 25), cholesterol from gallstones (Chapter 22), the isolation of eugenol from cloves (Chapter 28— use 10% methanol, 5.4% acetic acid, and 84.6% water as eluant), isolation of lycopene and /3-carotene (Chapter 9), and the product obtained from enzymatic reduction of ethyl acetoacetate (Chapter 59). 

For the synthesis of (+)-citronellol (6), the mixed pinenes were catalytically hydrogenated to give (-)-cis-pinane (7) which was pyrolysed to (-)-citronellene. Application of the Ziegler reaction with aluminium hydride proceeded selectively at the more reactive disubstituted double bond and following atmospheric oxidation and aqueous work-up, (+)-citronellol was isolated identical with that derived by the reduction of natural citronellal by the Ponndorf-Meerwein-Verley method (ref.9) as shown. 

Construction of the acyclic segment 395 was initiated by conversion of (-)-citronellal (392) into bromo aldehyde 393. Formation of the unsaturated aldehyde via the intermediate enamine was followed by reduction to the allylic alcohol 394. Elimination of the vinyl bromide in 394 to the acetylene was followed by the addition of trimethylaluminum to give the terminal vinyl alane. The intermediate alane was then quenched with iodine to furnish the corresponding iodo-vinyl alcohol, which was protected as the THP ether to afford 395. 

Oppolzer has developed a method of asymmetric synthesis based on the use of the chiral auxiliaries 39A and 39B derived respectively from (+ )-camphor [(+ )-40] and (- )-camphor [(- )-40]. Crotonylation of 39A gave the ester that was attacked by 4-methyl-3-pentenyllithium in the presence of copper iodide tributylphosphine and boron trifluoride from only one side of the molecule, the product 41 having the (S)-configuration (enantioselectivity 98.5%). The ester 42—similarly obtainable from 39B—was methylated under similar conditions, also yielding 41 with 92% enantioselectivity. (S)-Citronellic acid [(S)-36] or (S)-citronellol [(S)-33] were then obtained from 41 by the action of sodium hydroxide or lithium aluminum hydride (Scheme 6). Reduction of potassium... 

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