Asymmetric hydrogenation of itaconate

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... 

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...

A few efficient bisphosphite ligands have been used for asymmetric hydrogenation of itaconates or a-dehydroamino acid derivatives. Reetz has developed a series of C2-symmetric bisphosphite ligands such as L14, which are based on the structure of 1,4 3,6-dianhydro-D-mannite [78]. The ligands exhibit excellent reactivity and enantioselectivity for the asymmetric hydrogenation of itaconates. 

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. 

Table 2 Asymmetric Hydrogenation of Itaconates 24 Using Et-DuPHOS-Rh Catalyst...

As well as impurities being deleterious we have also found the judicious introduction of additives can be critical for developing economic catalytic processes. This is demonstrated in the asymmetric hydrogenation of itaconic acid derivatives to give chiral succinates 17 (Fig. 11) [3]. 

Figure 5.12 Reaction scheme for catalysed asymmetric hydrogenation of itaconic acid.

Asymmetric hydrogenation of itaconic add 7.7 (R = H) with trimethylam-monium or (S)-1 -phenethylammonium formate in the presence ofRh(I)-bppm 3.36 (R = Ar = Ph, R = O-few-Bu) complex has been carried out [873]. This reaction takes place near room temperature, and it is highly enantioselective [1324], With other ligands or other substrates, the results are less useful. 

Polyhydroxyphospholanes of the RoPHOS type [24] were prepared by Zhang and co-workers [23, 25]. With the ethyl-substituted ligand 15b in the Rh(I)-cata-lyzed asymmetric hydrogenation of itaconic acid in a water/methanol mixture as solvent 100% conversion and > 99% ee were achieved. 

Hydrogenation. For an effective asymmetric hydrogenation of itaconic esters, the heterocomplex with Rh(I) center associated with two BINOL-derived phosphites of opposite electron-richness (lA, IB) emerges as a more active and selective catalyst. Also having been examined are 2 and the one bearing a carboranyl residue. ... 

Linear polystyrene has also been used to support asymmetric hydrogenation catalysts containing chiral diphosphine rhodium(I) complexes (50). Asymmetric hydrogenations of itaconic acid were carried out, forming (R)-2-raethylbutanedioic acid with e.e. s ranging from 20-37%. None of the polymer-bound catalysts were more effective than (-)-DIOP-RhCl and the observed e.e. s were found to be dependent on the molecular weight of the polymer chain, its raicrostructure and solubility. 

Tang W, Liu D, Zhang X (2003) Asymmetric hydrogenation of itaconic acid and enol acetate derivatives with the Rh-TangPhos catalyst. Org Lett 5 205-207... 

The immobilization of homogeneous catalysts is still a challenge in catalysis. This field is not discussed in detail in this article, but a promising result is worth to mention. A PYRPHOS-rhodium(I) complex was embedded at a specific site in a protein (biotin) and used for asymmetric hydrogenation of itaconic acid (243). 

Morimoto T, Chiba M, Achiwa K. Highly efficient asymmetric hydrogenation of itaconic acid derivatives catalyzed by a modified DIOP-rhodium complex. Teterahedron Lett. 1989 30(6) 735-738. 

---