Tiglic acid, asymmetric hydrogenation

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...

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

Table 5 Asymmetric hydrogenation of cinnamic and tiglic acid derivatives...

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... 

For the asymmetric reduction of tiglic acid (21) to 2-methyl-butanoic acid (22), isopropanol can also be used as the hydrogen source. In the presence of H4Ru4(CO)8(f ,R-DIOP)2 at 120°C, 42% of 21 was converted after 227 hr, giving R-22 (catalytic turnover 210) with 5.4% optical purity (cf. Scheme 4) 133). 

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). 

Application of subcritical gaseous CO2 to an organic liquid causes the liquid phase to expand noticeably, due to extensive dissolution of the CO2 into the liquid phase (131). This expansion is accompanied by a reduction in the liquid phase viscosity, an increase in the solubility of H2 in the liquid, and an increase in the mass transfer rates from the gas to liquid phase. There is evidence that this can affect the enantioselectivity of reactions in viscous liquids. The enantioselectivity of asymmetric hydrogenation of unsaturated carboxylic acids in a viscous ionic liquid was shown to be strongly affected by CO2 expansion of the liquid, the enantioselectively being improved for one substrate (atropic acid) and decreased for another (tiglic acid). The results were explained in terms of the solubility and rate of transfer of H2 gas into the expanded ionic liquid (23). The same effect was not observed in expanded methanol. 

Asymmetric hydrogenation was catalyzed by ruthenium clusters containing atropoisomeric diphosphines. Catalyst precursors were Ru4(/t-H)4(CO)]o (S)-(-)-BINAP (BINAP = 2,2 -bis(diphenylphosphino)-l,l -binaphthyl) and Ru4(/t-H)4(CO)io (S)-(-)-MOBIPH (MOBIPH = 2,2 -bis(diphenylphosphino)-6,6 -dimethoxy-l,l -diphenyl). Substrates included prochiral alkenes such as tiglic acid, (Z)- and ( )-2-methylbutendioic acids, ( )-2-methylbute-noic acid, and acetophenone. Optical purities up to 38% were obtained, but most results were low ee s. 

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. 

Heldebrant and Jessop have investigated several hydrogenations in liquid polymers. The asymmetric hydrogenation of tiglic acid [Eq. (6)] proceeded in reasonable conversion and enantioselectivity (88% ee) in PEG-2000 dimethyl ether, but gave poor enantioselectivity in PPG-3500, PMPS-710 and PTHE-2900 [54]. In each case, the C02-expanded solvent was used, although afterward the product was extracted with hexane. 

There are known to be some limitations to asymmetric hydrogenation of certain substrates. Asymmetric hydrogenation of tiglic acid requires alow H2 concentration, or low H2 pressure and mass transfer rates, which is obtained in viscous ionic liquids. On the other hand, the hydrogenation of atropic acid is more enantioselective when... 

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