Hydrogenation of tiglic acid

Jessop and co-workers studied asymmetric hydrogenation reactions with the catalyst complex Ru(OAc)2(tolBINAP) dissolved in [BMIM][PFg]. In both reactions under investigation - the hydrogenation of tiglic acid (Scheme 5.2.10) and the hydrogenation of the precursor of the anti-inflammatory dmg ibuprofen (Scheme 5.2.11) - no CO2 was present during the catalytic transformation. However, SCCO2 was used in both cases to extract the reaction products from the reaction mixture when the reaction was complete. 

Scheme 5.2-10 Ru-catalyzed asymmetric hydrogenation of tiglic acid, followed by product...

The first application involving a catalytic reaction in an ionic liquid and a subsequent extraction step with SCCO2 was reported by Jessop et al. in 2001 [9]. These authors described two different asymmetric hydrogenation reactions using [Ru(OAc)2(tolBINAP)] as catalyst dissolved in the ionic liquid [BMIM][PFg]. In the asymmetric hydrogenation of tiglic acid (Scheme 5.4-1), the reaction was carried out in a [BMIM][PF6]/water biphasic mixture with excellent yield and selectivity. When the reaction was complete, the product was isolated by SCCO2 extraction without contamination either by catalyst or by ionic liquid. 

Scheme 5.4-1 Asymmetric, Ru-catalyzed hydrogenation of tiglic acid in [BMIM][PFg] followed by...

Racemic and enantioselective hydrogenations of tiglic acid each exhibited an apparent activation energy of 17 kJ mol (268 to 308 K). Enantiomeric excess was constant at 20 to 23% over the range 273 to 308 K but lower, 13%, at 268 K. Enantioselective hydrogenation of trifluorotiglic acid exhibited an activation energy of 23 kJ mol" (253 to 323 K) and a temperature-independent enantiomeric excess of 13 2%. 

Figure 2 Enantiomeric excess (%) as a function of the solvent polarity in the hydrogenation of tiglic acid using a CD-doped Pd/y-Al203 catalyst.

Hydrogenation of tiglic acid in scC02 catalyzed by a chiral complex such as (136) (Scheme 68) proceeds cleanly with cis stereochemistry to afford 2-methylbutanoic acid in up to 89% ee and over 99% yield.367 These studies revealed a different influence of H2 pressure on the selectivity between liquid solvents and scC02. 

Scheme 3.9 A possible mechanism of the hydrogenation of tiglic acid catalyzed by Ru((S)-binap)(OAc)2 (as adapted from [84]). The stereochemistry of the metal center and coordination geometries are speculative at this stage.

Figure 11. Asymmetric hydrogenation of tiglic acid with 4.4-47 nmol, S/C = 150-160, Pchf, = 170-180 atm, Pchf, =...

Rhodium Mandyphos catalysts have been used to reduce enamide esters and acids with enan-tioselectivities that range from 95% to 99%.175 183 185 Other applications reported are the asymmetric hydrogenation of tiglic acid and ethyl 3,3-dimethyl-2-oxobutyrate in 97% ee and >97% ee, respectively.175... 

Recently, Halpem et al. (76) and Noyori et al. (77) independently reported the deuterium labelling effect on the Ru(BINAP)(OAc)2-catalyzed hydrogenation of tiglic acid. Two important conclusions were drawn regarding the mechanism of the reaction ... 

Noyori also observed that under high pressure of H2, the solvolysis of the ruthenium-alkyl species was less important for the product formation. In our study of the Ru(H)-catalyzed hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid in CH3OD, we found the deuterium labelling in the naproxen product to be similar to those reported on the hydrogenation of tiglic acid ... 

Asymmetric hydrogenation of tiglic acid CO2 Ruthenium catalyst... 

Jessop and coworkers investigated the asymmetric hydrogenation of tiglic acid using Ru-tolBINAP as a catalyst in wet [bmim][PFs] [115, 116]. Extraction of the product with SCCO2 from the ionic liquid containing the catalysts provided the extremely pure product from the CO2 effluent, in which neither the ionic liquid nor catalyst was contaminated at all. In this way a conversion of up to 99% and an ee-value of 90% were obtained. The recovered ionic liquid catalytic solution was reused up to four times without any reduction of the conversion and enantioselectivity (Scheme 7.44). 

Substrates that give the greatest enantioseleetivity at low H2 concentrations were first tested in SCCO2 by Xiao et al. (103), who investigated the hydrogenation of tiglic acid [Eq. (18)] ... 

Scheme 4.7-2 Asymmetric hydrogenation of tiglic acid in scCOa- lypical results are listed in Table 4.7-1.

Table 4.7-1 Effect of pressure and solvent on the asymmetric hydrogenation of tiglic acid with [Ru(OAc)2(6)J catalyst [20, 36].

Rotation was +0.046° on Ni-/-quartz and -0.046° on Ni-c/-quartz. Besides the asymmetric resolution of racemates, metal-quartz catalysts were used to accomplish pure as5mimetric syntheses. The first attempt was reahzed by Schwab (1934) in the hydrogenation of tiglic acid [( )-2-methylbut-2-enoic acid] over Ni-quartz catalysts. 

Then it was shown that catalysts modified with Cnd were effective in the hydrogenation of tiglic acid (( )-2-methylbut-2-enoic) acid on Pd-silica with an ee of 22% (Bartok et al. ). The detailed studies of Nitta et al. 120,124,125 shown that enantioselective hydrogenations of E)-2-... 

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