Hydrogenation methylcinnamate

Brick et al. have studied this bromination in more detail and showed that the extent of the bromination can be controlled by changing the ratio of the reagents. The first substitution was found to be in the para position but subsequent intramolecular rearrangements allowed the formation of 2-5-dibrominated species. Brick et al. also reported the functionalization of such species using Pd-catalyzed reactions such as Heck and Suzuki couplings to give fully substituted p-stilbenes, p-biphenyls, diarylamines, and methylcinnamates. Hydrogenation of... 

Neither tritium or deuterium gas, with zero dipole moments, can be expected to interact positively with microwave radiation. Their low solubilities are seen as a further disadvantage. Our thoughts therefore turned towards an alternative procedure, of using solid tritium donors and the one that has found most favor with us is formate, usually as the potassium, sodium or ammonium salt. Catalytic hydrogen transfer of this kind is remarkably efficient as the results for a-methylcinnamic acid show [50]. The thermal reaction, when performed at a temperature of 50 °C, takes over 2 h to come to equilibrium whereas the microwave-enhanced reaction is complete within 5 min. A further advantage is that more sterically hindered al-kenes such as a-phenylcinnamic acid which are reduced with extreme difficulty when using H2 gas and Wilkinson s catalyst are easily reduced under microwave-enhanced conditions. 

The e.e.-values were moderate, an improved result of 79% e.e. being obtained with nmdpp (2f) which is not chiral on phosphorus. The use of the other, non P-chiral, ligand mdpp (2e) gave low enantioselectivity. Ligand 2f was also successfully used in the hydrogenation of 2-methylcinnamic and (l )-3-methylcinnamic acid [24]. 

Methylcinnamic acid, hydrogenation of, 25 89 2-Methyl-cis-byciclo [3.3.0] octane, 20 269 Methyl cyanide, catalytic hydrogenation, 35 145... 

More recent patents describe the following preparation from a-methylcinnam-aldehyde. a-Methylcinnamaldehyde (from benzaldehyde and propionaldehyde) is hydrogenated to a-methyldihydrocinnamic alcohol. The alcohol is alkylated with tert-butyl chloride or isobutene to 4-tert-butyl-o -methyldihydrocinnamic alcohol, which is subsequently dehydrogenated to the desired aldehyde [152, 153]. 

Methyl n-amyl carbinol. 247, 254 Methyl n-amyl ketone, 482 Methylaniline (mono), pure, from commercial methylaniline, 562, 570 P-Methylanthraquinone, 728, 740 Methyl benzoate, 780, 781 p-Methyl benzyl alcohol, 811,812 Methyl benzyl ketone, 727, 735 Methyl y-bromocrotonate, 926, 927 2-Methyl-2-butene, 239 Methyl n-butyl carbinol, 247,255 Methyl n-butyl ether, 314 Methyl n-butyl ketone, 475, 481 4-Methylcarbostyril, 855 p-Methylcinnamic acid, 719 4-Methylcoumarin, 853, 854 Methyl crotonate, 926, 927 Methylethylacetic acid, 354, 358 Methylethylethynyl carbinol, 468 Methyl ethyl ketone, 335, 336 purification of, 172 Methyl n-hexyl ether, 314 Methyl n-hexyl ketone, 335, 336 Methyl n-hexyl ketoxime, 348 Methyl hydrogen adipate, 938 Methyl hydrogen sebacate, 938,939 4-Methyl-7-hydroxycoumarin, 834 Methyl iodide, 287 Methyl isopropyl carbinol, 247,255 Methyl 4-keto-octanoate, 936... 

Only limited successful examples of asymmetric hydrogenation of acrylic acids derivatives have included the use of chiral Rh complexes (Scheme 1.17). The diamino phosphine (28) utilizes selective ligation of the amino unit to a Rh center and also exerts electrostatic interaction with a substrate. Its Rh complex catalyzes enantioselective hydrogenation of 2-methylcinnamic acid in 92% optical yield [116], Certain cationic Rh complexes can attain highly enantioselective hydrogenation of trisubstituted acrylic acids [ 1171. 2-(6 -Methoxynaphth-2 -yl)acrylic acid is hydrogenated by an (.S ..S )-BIPNOR- Rh complex in methanol at 4 atm to give (.S)-naproxen with 98% ee but only in 30% yield [26]. 

Hydrogenation of (Ej- and (Z)-Methyl-p-methylcinnamate with Rhodium (IIIj-Borohydride Complexes of Chiral Amides... 

In addition to this we have several examples of which the polymer conformation of the polymeric complex leads the asymmetrical selectivity Hydrogenation reactions of 1-methylcinnamic acid and 1-acetamidocinnamic acid by several poly(L-amino acid)-Pd complexes are observed (142-144). Poly(L-valine) (/3-form) and poly(/3-benzyl-L-aspartate) (a-helix, sinistral) give dextrorotative products, and poly(L-leucine) and poly( 3-benzyl-L-aspartate) (a-helix, dextral) do levo-rotatory products. Also, optical active poly-/3-hydroxyl esters-Raney Ni catalyst (145) and Ion-exchange resin modified by optical active amino acid-metal complex (146,147) are observed in asymmetrically selective hydrogenations. 

Grafted auxiliaries. Smith et al. [48] grafted chiral silyl ethers to a Pd surface through a Pd-Si bond. A borneoxysilyl-Pd catalyst was able to hydrogenate a-methylcinnamic acid with ee s up to 22%. Santini et al. [49] reported the preparation of a menthyl-Sn-Rh catalyst that hydrogenated ketopantolactone with 11% ee. 

The first report of enantioselective catalysis over metal catalysts was made in 1939 by Lipkin and Stewart who showed that hydrocinchonine / -methylcinnamate could be hydrogenated in ethanol over an Adams Pt catalyst to yield / -phenylbutyric acid which exhibited an optical rotation of 8%.89 Some 20 years later, Akabori and co-workers reported that Pd supported on silk-fibroin was enantioselective for compounds containing both C=N and C=C functionalities, yielding optical yields as high as 66%, although the origin of the enantioselectivity in these systems has never been clear.90 A further 20 years later, Orito and co-workers reported... 

Asymmetric hydrogenation. Morrison et al. have reported on asymmetric hydrogenations catalyzed by rhodium(I) complexes of the Wilkinson type containing chiral ligands. This type of asymmetric synthesis had been carried out previously with relatively inaccessible phosphine ligands that are asymmetric at phosphorus. Phosphines that are asymmetric at carbon are more readily available and appear to be more efficient. Thus reduction of (E)- 3-methylcinnamic acid with prereduced tris(neomenthyldiphenylphosphine)chlororhodium in the presence of triethylamine leads to 3-phenylbutanoic acid, +34.5°, which contains 61% enantiomeric excess of the S-isomer. Hydrogenations of olefins exhibit a lower degree of asymmetric bias. 

Variation of reactant structure was investigated in order to probe the interaction between NADPME and cinchonine (Figure 4). In a series of cinchonine-modified hydrogenations conducted under standard conditions, Z-a-methylcinnamic acid methyl ester (II) gave... 

Table 3.1. Asymmetric hydrogenation of 2-methylcinnamic acid on Pd catalysts supported on specifically modified silica gels (Sg) (modified data adapted from Beamer ).

Beamer et al. used Pd-polymer catalysts in the hydrogenation of the C=C bonds in 2-acetamidocinnamic acid to iV-acetylphenylalanine (Scheme 3.5.) and 2-methylcinnamic acid to 2-methyl-3-phenylpropanoic acid (Scheme 3.8.). The results are in Table 3.2. 

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