Cinnamyl cinnamate reduction

The order of reactivity of this Ru/silane combination to various functional groups differs greatly from that of its Pd/silane/ZnCh analog. While the latter is very useful for allylic reductions and essentially useless for unsaturated esters, the Ru-based system exhibits opposite reactivity. This complementary che-moselectivity is illustrated by the reduction of cinnamyl cinnamate (Scheme 59), a substrate containing both an allylic carboxylate and an a, -unsaturated ester.Each of these can be reduced separately by silicon hydride and the appropriate transition metal catalyst. 

One of the first practical methods for the manufacture of cinnamyl alcohol involved reduction of cinnamic aldehyde diacetate with iron filings in acetic acid. This approach suffered from low yields and Hberation of a significant amount of the starting aldehyde. 

Phenyl-propyl alcohol, CgH. CHj. CH.2. CHj. OH, is the next highest homologue of phenyl-ethyl alcohol, and is also known as hydro-cinnamyl alcohol. Like the last described bodies it has been known for many years, its first preparation being described in the Aivnalen (188, 202). It occurs as a cinnamic acid ester in storax, and as an acetic ester in cassia oil. It is prepared synthetically by the reduction of cinnamyl alcohol with sodium amalgam and water, or by the reduction of cinnamic or benzyl acetic esters with sodium and absolute alcohol. It has the following characters —... 

Much more conveniently, even a,)S-unsaturated esters can he transformed into a,)S-unsaturated alcohols by very careful treatment with lithium aluminum hydride [1073], sodium bis(2-methoxyethoxy)aluminum hydride [544] or diiso-butylalane [1151] (Procedure 18, p. 208). An excess of the reducing agent must be avoided. Therefore the inverse technique (addition of the hydride to the ester) is used and the reaction is usually carried out at low temperature. In hydrocarbons as solvents the reduction does not proceed further even at elevated temperatures. Methyl cinnamate was converted to cinnamyl alcohol in 73% yield when an equimolar amount of the ester was added to a suspension of lithium aluminum hydride in benzene and the mixture was heated at 59-60° for 14.5 hours [1073]. Ethyl cinnamate gave 75.5% yield of cinnamyl alcohol on inverse treatment with 1.1 mol of sodium bis(2-methoxy-ethoxy)aluminum hydride at 15-20° for 45 minutes [544]. 

Cinnamyl alcohols.1 These alcohols can be prepared by oxidation of 3-arylpropenes with selenium dioxide in dioxane. The yield compares favourably with that oblained by LiAlH4 reduction of esters of cinnamic acids. 

The reductive sequence from an appropriate cinnamic acid to the corresponding cinnamyl alcohol is not restricted to lignin and lignan biosynthesis, and is utilized for the production of various phenylpropene derivatives. Thus cinnamaldehyde (Figure 4.23) is the principal component in the... 

Cinnamic acid, starch ester, I, 303 Cinnamaldehyde, phytochemical reduction of, IV, 79, 91 Cinnamyl alcohol, IV, 91 phytochemical reduction of, IV, 92 Citraconic acid, IV, 327 Citral, phytochemical reduction of, IV, 79... 

The product of a lithium aluminum hydride reduction of a cinnamic acid or ester 1 is highly dependent on the solvent. The product of exclusive carbonyl reduction, cinnamyl alcohol 2, was obtained in hydrocarbon solvents (pentane, hexane or benzene) even under prolonged reflux. 3-Phenylpropanol 3, resulting from carbonyl and C-C double bond reduction was produced in diethyl ether. However, phenylcyclopropane 4 was obtained in tetrahy-drofuran or 1,2-dimethoxyethane, notably after prolonged reflux. 

L-Phenylalanine,which is derived via the shikimic acid pathway,is an important precursor for aromatic aroma components. This amino acid can be transformed into phe-nylpyruvate by transamination and by subsequent decarboxylation to 2-phenylacetyl-CoA in an analogous reaction as discussed for leucine and valine. 2-Phenylacetyl-CoA is converted into esters of a variety of alcohols or reduced to 2-phenylethanol and transformed into 2-phenyl-ethyl esters. The end products of phenylalanine catabolism are fumaric acid and acetoacetate which are further metabolized by the TCA-cycle. Phenylalanine ammonia lyase converts the amino acid into cinnamic acid, the key intermediate of phenylpropanoid metabolism. By a series of enzymes (cinnamate-4-hydroxylase, p-coumarate 3-hydroxylase, catechol O-methyltransferase and ferulate 5-hydroxylase) cinnamic acid is transformed into p-couma-ric-, caffeic-, ferulic-, 5-hydroxyferulic- and sinapic acids,which act as precursors for flavor components and are important intermediates in the biosynthesis of fla-vonoides, lignins, etc. Reduction of cinnamic acids to aldehydes and alcohols by cinnamoyl-CoA NADPH-oxido-reductase and cinnamoyl-alcohol-dehydrogenase form important flavor compounds such as cinnamic aldehyde, cin-namyl alcohol and esters. Further reduction of cinnamyl alcohols lead to propenyl- and allylphenols such as... 

Cinnamic (1), p-coumaric (2), and related acids may be activated by conversion to CoA esters by CoA ligases [e.g., 4-coumarate CoA ligase (EC 6.2.1.12)] in much the same way that fatty acids are activated. The reduction of the CoA esters of cinnamic acids to cinnamyl alcohols involves two enz)mies cinnamoyl-CoA oxidoreductase (which forms the aldehydes) and cinnamyl alcohol dehydrogenase (Grisebach, 1981). Phenylpropanoids appear to be synthesized from the CoA esters of this series of acids by conversion to the corresponding aldehydes, then to the alcohols, and finally, by elimination of a phosphate group, to allyl and propenyl compounds. In many plants, mixtures of all t3q>es co-occur (Fig. 8.7) (Gross, 1981 Mann, 1987). Reduction of the side chain to produce dihydrocinnamic acids and related compounds is also known to occur in nature. 

Fig. 3.8. Derivation of some classes of natural products from the final metabolites of the shikimate pathway. In the cases of cinnamic acid and aldehyde derivatives X = H or X = OR. In the case of the cinnamyl alcohol derivatives, reduction occurs only if X = OR. The two phenolic units represent triketide precursors...

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