Cinnamate derivatives

The widespread use of cinnamic derivatives has led to the pursuit of reUable methods for thek dkect synthesis. Commercial processes have focused on condensation reactions between ben2aldehyde and a number of active methylene compounds for assembly of the requisite carbon skeleton. The presence of a disubstituted carbon—carbon double bond in the sidechain of these chemicals also gives rise to the existence of two distinct stereoisomers, the cis or (Z)- and trans or (E)- isomers ... 

Bartoli recently discovered that by switching from azide to p-anisidine as nucleophile, the ARO of racemic trans- 3-substituted styrene oxides could be catalyzed by the (salen)Cr-Cl complex 2 with complete regioselectivity and moderate selectivity factors (Scheme 7.36) [14]. The ability to access anti-P-amino alcohols nicely complements the existing methods for the preparation of syn-aryl isoserines and related compounds [67] by asymmetric oxidation of trans-cinnamate derivatives [68]. 

The arylation of alkenes by treatment with a diazonium chloride (or bromide) solution and cupric chloride (or bromide) is called the Meerwein arylation reaction, after its discoverer (Meerwein et al., 1939). Originally, it was discovered using a,P-unsaturated carbonyl compounds, namely coumarin (Scheme 10-43) and cinnamic derivatives (Schemes 10-44 and 10-45). As Scheme 10-45 shows, the Meerwein reac-... 

If a target aminodicarboxyl units bears an aryl group in one of its side chains, retrosynthetic analysis indicates that a bromoamide synthon 12, bearing an aliphatic side-chain, should react with a nucleophilic partner carrying the aromatic side chain. In the alternative bromoamide 21, HBr elimination to cinnamic derivatives competes with the desired bromine substitution. 

While asymmetric approaches are certainly important, other synthetically significant epoxidation protocols have also been reported. For example, buffered two-phase MCPBA systems are useful for epoxidations in which the alkenes and/or resultant epoxides are acid-sensitive. Bicarbonate works quite well for cinnamate derivatives (e.g., 55) <96SC2235> however, 2,6-di-t-butyl-pyridine was shown to give superior results in the case of certain allyl acetals (e.g., 57) <96SC2875>. 

The crystal of 2 OPr recrystallized from EtOH/H20 solution, and the mixed crystal of the same ethyl and propyl cinnamate derivatives (2 OEt and 2 OPr), on photoirradiation for 2h at room temperature with a 500 W super-high-pressure Hg lamp, afforded the highly strained tricyclic [2.2] paracyclophane (2 OEt-2 OPr-cyclo) crystal quantitatively (Maekawa et ai, 1991b). A crystal structure analysis was carried out of a single crystal of the complex of 2 OEt-2 OPr-cyclo with HFIP (recrystallization solvent) in a 1 2 molar ratio. Fig. 13 shows the molecular structure of 2 OEt-2 OPr-cyclo viewed along the phenylene planes. The short non-bonded distances and deformation of the benzene rings, as seen in Fig. 13, are common to those of [2.2] paracyclophanes, as previously reported (Hope et ai, 1972a,b). 

The use of chiral amide ligands has been restricted to rhodium, where the catalyst precursor is [Rh(BH4)(amide)py2Cl2]. The work has been reviewed (10, 35) cinnamate derivatives were reduced to up to 57% ee, and hydrogenation of a carbon- nitrogen double bond in folic acid leads to tetrahydrofolic acid with high biological activity (308). 

The arylation of alkenes was discovered by Meerwein146 in 1939 using ,/)-unsaturated carbonyl compounds, namely coumarin and cinnamic derivatives. Diazotizations for Meerwein reactions are made in aqueous HC1. The substitution proper may be combined with addition of HC1 to the double bond. As catalyst, CuCl2 is used. Various observations (see elsewhere7k) demonstrate that in typical Meerwein systems, part of Cu11 is reduced to Cu1. 

Finally, osmium tetroxide-loaded, immobihzed DHQ-hgand system (28) disperses activity in the asymmetric aminohydroxylations of trans-cinnamate derivatives (Scheme 4.14) [95]. Here, the reagent system AcNHBr/LiOH was employed as nitrogen source. The immobihzed catalyst could entirely be removed by filtra-... 

Some of the acidic and basic polymers of the cell wall bear phenolic side-chains. The acidic polysaccharides carry ferulic and p-coumaric acid and related cinnamate-derivatives, esterified to specific hydroxy groups... 

For white wines (85), a similar HPLC condition to that of Betes-Saura et al. (79) was employed with a Nucleosil C)8 column (250 X 4.0-mm ID, 5 /zm) with binary gradient using eluent (A) acidified water (pH 2.65) and eluent (B) 20% A with 80% acetonitrile applied for hydroxy-cinnamate derivatives esters (caffeoyl tartaric, p-coumaroyl tartaric, and feruloyl tartaric acid esters) and free hydroxycinnamic acids (caffeic, ferulic, and p-coumaric acids). 

Most recently, silica gel-supported bis-cinchona alkaloid 20 was successfully employed in the A A of fraws-cinnamate derivatives [62b]. The resulting products had excellent enantiopuri-ties (>99% ee). Recovered samples of 20 contained osmium and could be used in the AA again, though with a slight loss of activity. Therefore, recovered catalyst was regenerated upon addition of osmium salts. 

Hz) at 4.81 ppm present in the spectrum of lyaloside and which disappears after addition of heavy water. In addition, the two hydrogen atoms at the 6 carbon atom are deshielded by 0.4 to 0.6 ppm in the spectrum of the mixture 37 + 38, as compared with their chemical shift in the spectrum of lyaloside. A similar effect is observed by Sticher et al. for glucoiridoids (62). Furthermore, the chemical shift of the carbon atoms of the sugar moiety undergo the effect expected as a result of alkoylation, e.g., the shielding of the a carbon (C-6 ), and the deshielding of the p carbon (C-5 ) (Table V). For comparison, the data published for catalpol (41) and its 6 -/rani-cinnamate derivative, picroside (42) (62,63), are also listed in Table V. 

Scheme 2 shows Rapoport s synthesis [15]. The cinnamic acid derivative 3 prepared from m-methoxy benzaldehyde [20] was ethylated by diethyl sulfate to give ethyl cinnamate derivative 4, followed by Michael addition with ethyl cyanoacetate to afford compound 5. Compound 5 was converted to lactam 6 by the reduction of the cyano group and subsequent cyclization. Selective reduction of the lactam moiety of 6 was achieved by treatment with trimethy-loxonium fluorob orate followed by sodium borohydride reduction. Amine 8 was obtained by the reductive methylation of amine 7. Amine 8 was converted to compound 9 by methylene lactam rearrangement [21], followed by selenium dioxide oxidation to provide compound 10. Allylic rearrangement of compound 10 and subsequent hydrolysis gave compound 12. The construction of the decahydroisoquinoline structure began with compound 12,... 

Green notes Floral cinnamic derivatives Eugenol cA-3-Hexenyl acetate Violet leaf absolute c/.s-3-Hexenyl benzoate Isoeugenol... 

Floral cinnamic derivatives 6 /.s-3-Hexanol and esters Hivertal Phenylacetaldehyde glyceroacetal Acetaldehyde diphenylethyl acetal... 

Flavone glycosides often occur as acylated derivatives either with aliphatic or aromatic acids. Hydroxy-cinnamic acid derivatives are the most frequent in nature and MS fragmentations of these types of compounds show ions produced by the loss of 146,162,176, or 206 m.u., corresponding to the losses of the acyl residues />-coumaroyl, caffeoyl, femloyl, or sinapoyl, respectively. Brassicaceae species are rich in flavonoid glycosides acylated with hydroxyl-cinnamic derivatives, and most of them... 

In general, 4//-thiochromen-4-ones are synthesized either by condensation of p-keto esters and thiophenols with pol3q)hosphoric acid [213-215] or by cyclization of p-substituted cinnamates derived from thiophenols and appropriate propiolates [211, 216, 217]. 

The first, reported in 1986 (46) utilizes Sharpless oxyamination of the C-13 cinnamate derivative (25), leading in one step to both the correct substitutions at C-2 and C-3 and to the threo configuration present in taxol. This reaction yields 10-deacetyl taxol (23f), after deprotection and benzoylation of the oxyamination product, in five steps starting from 13a with an overall yield of about 10% and to taxol (1) itself starting from 13b. When the standard conditions described for oxyamination are used, the reaction is nonspecific and leads to two regioisomers and their associated diastereoisomers (27a-d). Use of asymmetric catalysts (50) in the reaction leads to an improvement in the yield of the desired isomer 27a, the precursor of natural deacetyltaxol. 

For the compounds obeying the Hammett equation, the distribution pattern for the OH attack can be estimated by assuming that the position on the ring with the maximum C7 value has the least probability, while the one with the minimum has the greatest probability. In our recent work > on cinnamate derivatives where the addition of the OH radical to the olefmic double bond is an additional pathway, a value of-0.3 was estimated from the Hammett plot (Fig. 5). This value is in agreement with those reported earlier for several substituted benzenes (p" = -0.52 to -0.4). However, the Hammett treatment for reactions with rate constants close to diffusion-controlled ones may not be satisfactory due to limited variation in kinetic data and large experimental uncertainty. In contrast, better correlation is expected in the corresponding gas phase reactions. 

Fig. 5. Hammett plot for the reaction of "OH radical with cinnamate derivatives (1) OT-hydroxycinnamate, (2) -hydroxycinnamate, (3) w-methoxycinnamate, (4) p-methoxycinnamate, (5) w-chlorocinnamate, (6) p-chlorocinnamate, (7) OT-nitrocinnamate, and (8) p-nitrocinnamate pH 7, Dose/pulse 15 Gy. [Taken from P. Yadav, Ph.D. Thesis, University of Pune, 2006.]...

Asymmetric Epoxidation of Electron-deficient trans-Olefins. (f )-l can also catalyze epoxidation of electron-deficient trans -olefins, especially ( )-cinnamate derivatives (eq 4). With 5 mol % of (f )-l, epoxidation of acrylate (5) is completed in 27 h with 74% yield and 85% ee. The crude product can be purified using a continuous dissolution and crystallization process to afford enantiomerically pure product and recover the ketone catalyst simultaneously. A similar practical method has been employed for large-scale synthesis of a key intermediate for diltiazem hydrochloride (a potent calcium antagonist for treatment of cardiovascular disease). 

The thiazolidine-2-thione analogs of (7b) and (7c) are more reactive dienophiles and, therefore, the cycloaddition can be carried out at lower temperature. However, the selectivities and yields are similar as with (7b) and (7c). The corresponding cinnamate derivative (7) (R = Ph), on the other hand, reacts with substantially lower enantioselectivity than the corresponding thiazolidine-2-thione analog (90% vs. 97% ee). 

TABLE I, . Synthesis and caracteristies of 4-vinyl cinnamic derivatives. ... 

The Sharpless regioreversed asymmetric aminohydroxylation protocol was used as a key step in the total synthesis of ustiloxin D by M.M. Joullie and co-workers.The ( )-ethyl cinnamate derivative was subjected to in situ generated sodium salt of the N-Cbz chloroamine in the presence of catalytic amounts of the anthraquinone-based chiral ligand to afford the desired A/-Cbz protected (2S,3R)-(3-hydroxy amino ester in good yield and with good diastereoselectivity. 

The Horner-Wadsworth-Emmons reaction between bis(benzyloxy)benzalde-hydes and an ester-substituted benzylphosphonate or triethylphosphonoacetate, yield the correponding stilbene or cinnamate derivatives, respectively. These are crucial steps in the synthesis of chiral AB2 monomers which are themselves valuable dendrimer precursors. Standard Horner-Wadsworth-Emmons reactions between P-ketophosphonates and aldehydes have been used in the synthesis... 

Figure 36 Gymnocin-B 80 and the lowest-energy conformation of its 10,37-bis(TPP-cinnamate) derivative 81 obtained by Monte Carlo/MMFF94s with Spartan 02. Experimental CD (in MeOFI, c —3.0 x 10 6) 419nm (Ae+11), 414 nm (Ae-15) Boltzmann weighted (at 298 K) average CD calculated by De Voe s method 420 nm (Ae +25), 414 nm (Ae -25). Redrawn from K. Tanaka Y. Itagaki M. Satake H. Naoki T. Yasumoto K. Nakanishi N. Berova, J. Am. Chem. Soc. 2005, 127, 9561-9570.

Trichoderina sp. Coconut, anise, cinnamon 6-pentyl-a-pyrone Sesquiterpenes, cinnamate derivatives... 

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