Cinnamyl derivatives reduction

It is well known that copper salts can catalyze the photocycloaddition of dienes [56]. The reaction can be very diastereoselective and useful as an access to polycyclic molecules, especially 1 - vinyl-2-allylcyclanes [57]. The reaction of vinylglycine, cinnamyl derivatives 76, and analogs is also catalyzed by Cu(I) produced in situ by the reduction of cupric triflate. The coordination of the double bonds to the copper ion during the [2 4- 2]-photocycloaddition process increase ... 

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...

The results of this investigation suggested that to promote 1,2-regioselectivity in the CuH-catalyzed asynunetric reduction of enones, a-substitution in the substrates appears to be a necessary condition however, it is certainly not a sufficient one. Thus, with a chiral o-bis-(diphenylphosphino)benzene as a ligand, reduction of a-methyl cinnamyl derivative 14 (R =Ph R, R =Me) proceeded predominantly along the 1,4-manifold [13]. Clearly, the ligands with their specific electronic and steric properties have an important role to play in the regioselectivity of the process. 

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... 

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... 

The ready formation of esters of P amino acids by reduction of the correspond ing imines/enamines (Table 4.6, entries 12 14), which in turn can be prepared from the readily available P keto esters, allowed an expedient synthesis of SCH48461 (56), a potent, orally active inhibitor of cholesterol absorption [22]. Enamine 36n (Scheme 4.6) was reduced (via imine lOn) with ChSiH in the presence of Sigamide (35) to afford the P amino ester ISn (80% isolated yield, 88% ee), whose treatment with methylmagnesium bromide (acting as a base) produced p lactam 55 (92%). Enolization of the latter derivative with LDA followed by alkylation with cinnamyl bromide and catalytic hydrogenation afforded 56 in 77% overall yield for the last two steps (S. Stoncius, A.V. Malkov, and P. Kocovsky, unpublished results). 

The cinnamyl ester, which is somewhat more stable to nucleophiles, can be prepared from an activated carboxylic acid derivative and cinnamyl alcohol or by transesterification with cinnamyl alcohol in the presence of the H-Beta zeolite (toluene, reflux, 8h, 59-96% yield) or DMAP (CH3CN, heat). It is cleaved under nearly neutral conditions [Hg(OAc)2, MeOH, 23°C, 2-4 h KSCN, HjO, 23°C, 12-16 h, 90% yield] by treatment with sulfated Sn02, toluene, anisole, reflux or with K-10 clay and microwave heating. The latter conditions will also cleave crotyl and prenyl esters. Pd catalysis may also be used to induce cleavage either with a nucleophile or reductively with TEA/HC02H. ... 

Figure 9.11 Analysis of P-O-4 structures in lignin according to the DFRC method (derivatization followed by reductive cleavage) resulting in the formation of cinnamyl alcohol derivatives suitable for quantification. AcBr = acetyl bromide, Ac20/Py = acetic anhydride/pyridine [59].

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