Hydrogenation of itaconic acid

Although the asymmetric hydrogenation of itaconic acid derivatives is a potential synthetic approach to many useful product [105], lower enantioselectivities are often reported. In contrast with other catalysts, f-Bu-BisP, Ad-BisP, t-Bu-MiniPHOS, BIPNOR 27, and Brown s ligand 25 gave high to almost perfect ees in the hydrogenation of these substrates (Scheme 23) [101]. 

Bidentate chiral bis(aminophosphanes) such as 55-57 (Scheme 44) have been used for the Rh(I)-cataIyzed asymmetric hydrogenation of itaconic acid... 

Scheme 8.16 Hydrogenation of itaconic acid with disulfoxide ligands.

On the other hand, James reported, in 1976, the use of a chiral sulfoxide as a ligand of ruthenium for the asymmetric hydrogenation of itaconic acid, providing a low enantioselectivity of 12% ee (Scheme 8.23). ... 

Table 7 Asymmetric hydrogenation of itaconic acid or dimethyl ester...

During the 1980s, Achiwa and colleagues examined a number of derivatives of DIOP, and found that MOD-DIOP (12c) allowed for the enantioselective hydrogenation of itaconic acid derivatives with >96% ee [68-75]. 

Several methods have been described to liberate the hydroxyl groups from 24 to produce the water-soluble, tetrahydroxyl bidentate ligand 25 [52, 53b]. Water-soluble ligands are of interest due to the prospect of recycling the catalyst into an aqueous phase, ideally without loss of performance. The enantiomeric hydrogenation of itaconic acid was performed in aqueous methanol over a range of solvent compositions (MeOH H20, 9 1 to 3 97), with consistently excellent levels of performance (100% conversion, 99% ee, SCR 100, 12 h) [52 b]. Interest-... 

Many chiral phosphorus ligands have shown excellent reactivities and enantio-selectivities in the Rh-catalyzed hydrogenation of itaconic acids or esters. Some successful (>95% ee) hydrogenations of itaconic acid or its dimethyl ester with different chiral phosphorus ligands are listed in Table 26.7. High reactivity is observed with electron-rich phosphane ligands such as BICHEP [7c[. 

Table 26.7 Enantioselective hydrogenation of itaconic acid derivatives.

Fig. 37.12 Hydrogenation of itaconic acid derivatives substrate and ligand structures.

Table 42.4 Enantioselective hydrogenation of itaconic acid using sol-gel-entrapped Rh complexes [51].

Scheme 5 Rhodium-catalysed hydrogenation of itaconic acid (16) in an inverted biphasic system SCCO2/H2O...

The sol-gel entrapment of the metal complexes [Ru(p-cymene)(BINAP)Cl]Cl and the rhodium complexes formed in situ from the reaction of [Rh(COD)Cl]2 with DlOP and BPPM has been reported by Avnir and coworkers [198]. The metal complexes were entrapped by two different methods the first involved addition of tetramethoxysilane to a THF solution of the metal complex and triethylamine, while the second method was a two-step process in which aqueous NH4OH was added to a solution of HCl, tetramethoxysilane and methanol at pH 1.96 followed by a THF solution of the appropriate metal complex. The gel obtained by each method was then dried, crushed, washed with boiling CH2CI2, sonicated in the same solvent and dried in vacuo at room temperature until constant weight was achieved. Hydrogenation of itaconic acid by these entrapped catalysts afforded near-quantitative yields of methylsuccinic acid with up to 78% e.e. In addition, the catalysts were found to be leach-proof in ethanol and other polar solvents, and could be recycled. 

The asymmetric hydrogenation of itaconic acid (Scheme 21) and its derivatives132 has become adopted as something of a standard by which catalysts are compared. A selection of results is given in Table 2 (e.e.s only)133,76. Further applications of related reductions include the synthesis of the Renin inhibitor subunit 12 by reduction of 13 in 95% e.e.132 and the protease inhibitor 14 by reduction of 15 in this case in up to 84% e.e.134. For these processes the ligands of choice were either BINAP (in conjunction with Ru) or a derivative of BPPM (P7). 

Excellent results have been obtained in the asymmetric hydrogenation of itaconic acid (97% ee) and dimethyl ester (94% ee) using Rh/MonoPhos.31 The latter substrate could be hydrogenated in 99% ee using the piperidine ligand 24d.40 These hydrogenations are relatively fast and have been carried out on a 100-g scale with an S/C of 10,000. Preliminary results with some alkylidene and benzylidene succinates were also very promising. 

Asymmetric hydrogenation of itaconic acids.1 Japanese chemists have prepared a new bisphosphine ligand (2), which is more efficient than DIOP for asymmetric hydrogenation of itaconic acids when complexed with rhodium. It is available in four steps from 4-bromo-2,6-dimethylphenol. 

The approach of Wilson and Whitesides was not further developed for 20 years, until, in 1999, Chan and coworkers (99) extended the work by linking a chiral diphosphine to biotin. The resulting complex was tested for the hydrogenation of itaconic acid. Using this strategy, the authors were able to prepare methylsuccinic acids with moderate enantioseiectivity. 

Table 4 Enantioselective hydrogenation of itaconic acid derivatives with Rh[(S,S)-ethyl-DuPHOS](cod) +BF4 (MeOH, 25 °C, 0.56 MPa Hz)...

Hydrogenation of Itaconic Acid. Compared to the hydrogenation of amidoacylic acids, enols, and enamides, the Rh(/ -SpirOP)+ catalyzed hydrogenation of itaconic acid was less successful. After optimizing the hydrogenation conditions, 76.8% ee of the corresponding product was obtained in isopropanol at ambient temperature under 100 psi H2 for 2 h (eq 3). 

Lin C-C, Lin C-W, Chan ASC. Catalytic hydrogenation of itaconic acid in a biotinylated Pyrphos-rhodium(l) system in a protein cavity. Tetrahedron Asymmetry 1999 10 1887-1893. 

Hydrogenation of itaconic acid (14) with Rh(COD)Cl2 catalyst and commercially available triethylammonium formate as hydrogen source delivers (5)-(15) in good enantiomeric excess (equation 14) with hydrogen as reductant instead of ammonium formate a 94% ee is obtained. ... 

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