Methyl cinnamate, reduction

Scheme 49 Reductive thioalkylation of methyl cinnamate with disulfide.

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]. 

Reduction of 4-methylcoumarin in aqueous buffers employed for the asymmetric reduction resembles the reactions of methyl cinnamate (p. 67) The process leads... 

Intramolecular cyclisation of a 4-arylbutanoic acid system is also an important step in a convenient synthesis of the polycyclic system, chrysene, which is formulated and described in Expt 6.12. Here, methyl cinnamate is first subjected to reductive dimerisation to give methyl meso-ft,y-diphenyladipate, which is accompanied by some of the ( + )-form. The meso isomer (16) is the most easily isolable and cyclisation occurs smoothly in sulphuric acid to yield the diketone 2,1 l-dioxo-l,2,9,10,ll,18-hexahydrochrysene, which is obtained as the trans form (17) as shown in the following formulation. Clemmensen reduction of this ketone followed by dehydrogenation (in this case using selenium) completes the synthesis of chrysene. 

This method is highly selective for unsaturated ketones and aldehydes, whereas reduction of a,p-un-saturated carboxylic acid derivatives, such as esters, amides and nitriles, is very sluggish. Thus, benz-ylideneacetone was selectively and cleanly reduced in the presence of methyl cinnamate, cinnamonitrile or cinnamamide. ... 

In the reductive dimerization of methyl cinnamate to a cyclopentanone [Eq. (5)], similar yields are found at the cathode [42] and with metals (sodium, THE, and TBAI, —78°C) [40]. Because of the potential selective conversion at the electrode, halides can be reduced at the cathode to carbanions in the presence of carbonyl compounds, which are reduced at more cathodic potentials. This way labile carbanions can be obtained and reacted under conditions in which the same species generated by a metalorganic route would decompose. Eor example, trichlorobromoalkane can be cathodically converted in the presence of aldehydes to a dichloromethyl anion 0°C [route a, Eq. (6)] and be trapped to form a dichlorotetrahydrofuran, but for the metallorganic route [route b, Eq. (6)] a reaction temperature of — 110°C is necessary [43]. 

Scheme 7.13. (a) Morrison s asymmetric reduction of P-methyl cinnamic acid [116]. (b) Kagan s asymmetric reduction of Al-acetyl dehydrophenylalanine and the debut of the DIOP ligand [117]. 

When the ligand (5,5)-70 was used, methyl cinnamate (71) was converted to the corresponding aziridine (S,S)-72 in 63% yield with an ee of 94% , but the optimal conditions for the aziridination of the cinnamate esters cannot be reliably extrapolated to other acyclic olefins . Reductive ring opening of (S,S)-72 by transfer hydrogenation afforded the corresponding (/f)-methyl iV-(p-toluenesulphonyl)phenylalaninate [(R)-73] and established the absolute configuration of (S,5 )-72 . This latter reaction and other reactions of the... 

The study of the involvement of hydridopalladium complexes under basic conditions is far more elusive. The involvement of these species in the /S-hydrogen elimination step has never been observed directly and their involvement is only implied based on mechanistic considerations. A good example was provided by studies of the reductive elimination step of the Heck arylation reaction. An alkylpalladium(II) intermediate releases the product methyl cinnamate, while simultaneously capturing a... 

In conjugate reduction of enones with other transition metals such as chromium, the rates of reduction were shown to be dependent on the conformation of the substrate, with faster reactions being observed with the cisoid forms as compared with the transoid onesJ However, with the Pd/Si/Zn system, the rigid transoid enone of cyclohexenone and the flexible enone of acetylcyclohexene are both reduced in comparable rates. This indicates that palladium interacts exclusively with the olefinic part of the enone without significant participation of the carbonyl. Interestingly, this method is highly selective for unsaturated ketones and aldehydes, as the reduction of corresponding o,jS-unsaturated carboxylic acid derivatives, such as esters, amides, and nitriles, is very slow under the conditions used. Thus, ben-zylideneacetone is selectively and cleanly reduced in the presence of methyl cinnamate, dnnamonitrile, or dnnamamide.t" ... 

The reaction of benzyl chloride with metallic nickel in the presence of methyl acrylate was carried out at 85°C, and the expected addition product methyl 4-phenylbutanoate was formed in 17% yield (Equation 7.12). The reaction with acrylonitrile gave 4-phenylbutanenitrile in 14% yield together with cis- and tra 5-4-phenyl-2-butenenitriles, 4-cyano-6-phenylhexanenitrile, and 2-ben-zyl-4-phenylbutanenitrile (Equation 7.13). The results suggest the presence of a benzylnickel(II) chloride complex (1), which could have been formed by the oxidative addition of benzyl chloride to the metallic nickel (Scheme 7.7). The complex (I) would then be expected to add to the electron-deficient olefins, affording the addition product (111) via intermediate complex (IV). The formation of cis- and tra s-4-phenyl-2-butenenitrile (V) is reasonably explained by the reductive elimination of nickel hydride from intermediate (IV), which is analogous to the substitution reaction of olefins with alkylpalladium compound [158] and to the addition-elimination reaction of bis(triphenylphosphine) phenylnickel(II) bromide with methyl acrylate to yield methyl cinnamate [130]. Furthermore, intermediate (IV) seems to add another molecule of acrylonitrile to give the 1 2 adduct 4-cyano-6-phenylhexanenitrile (VI). 2-Benzyl-4-phenylbutanenitrile (VIII) would be formed by the metathesis of complex IV and the benzylnickel chloride (I). 

Porco et al. reported the synthesis of ( ) methyl rocaglate using [3 + 2] dipolar photocycloaddition reaction of an oxidopyrylium betaine derived from excited state intramolecular proton transfer reaction of 3-hydroxyflavin and methyl cinnamate [144]. Methyl rocaglate was obtained by a base-mediated a-ketol rearrangement followed by hydroxy-directed reduction sequence. They subsequently succeeded in the asymmetric synthesis of methyl rocaglate using functionalized TADDOL derivative (34) (Figure 2.30) as a chiral Bronsted acid (Scheme 2.77) [145]. 

The add is obtained by the reduction of cinnamic acid by means of sodium amalgam. The acid is then esterified by the condensing action of a mineral acid in methyl alcohol solution. The ester is an oil of very sweet odour, and is very useful for flower bouquets. 

The same authors also reported the dispersion of palladium nanoparticles in a water/AOT/n-hexane microemulsion by hydrogen gas reduction of PdClJ and its efficiency for hydrogenation of alkenes in organic solvents [79]. UV-visible spectroscopy and TEM analysis revealed the formation of Pd nanoparticles with diameters in the range of 4 to 10 nm. Three olefins (1-phenyl-l-cyclohexene, methyl trans-cinnamate, and trans-stilbene) were used as substrates for the catalytic hydrogenation experiments under 1 atm of H2 (Table 9.12). All of the Start-... 

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,... 

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