Itaconic Acid Derivatives

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]. 

Scheme 23. Rh-catalyzed asymmetric hydrogenation reactions of itaconic acid derivatives...

In contrast to the many successful examples for hydrogenation of the parent itaconic acid or its dimethyl ester, only a few ligands have been reported to be efficient for the hydrogenation of / -substituted itaconic acid derivatives. Rh complexes with chiral ligands such as MOD-DIOP,69,69a 69h BPPM,246 Et-DuPhos,247 and TangPhos116 are... 

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]. 

With ferrocenes, an alternative approach has been to attach the phosphorus moieties only to side chains. The WalPhos family (36) forms an eight-mem-bered chelate with the metal. Members of this family provide good selectivity and reactivity for the reductions of dehydroamino and itaconic acid derivatives as well as a,/ -unsaturated carboxylic acids [145, 156],... 

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

Breakthroughs that took place around the year 2000 have shown, in contrast to the common view, that indeed chiral monodentate phosphorus ligands can also lead to high enantioselectivities in a number of asymmetric hydrogenations. In the years following, monophosphines, monophos-phonites, monophosphoramidites, and monophosphites have been successfully used in the enantioselective hydrogenation of a-dehydroamino acids and itaconic acid derivatives [25],... 

Since the formation of Complex 11 from 10b is a second-order process and the formation of product from Complex 11 is a first-order process, their entropies of activation will be very different. A value of AS f = -121 J mol 1deg 1 has been reported for hydrogen addition to Yaska s compound, carbonylchloro bis-triphenylphosphineiridium(I) (12). As pointed out by Halpern (II), formation of the alkyl will be favored at low temperatures and it is observed to decay rapidly above -40°C. The observation and characterization of Complex 11 proved to be both fortunate and fortuitous, since we were unsuccessful in all of our attempts to form alkyls from chiraphos or DIOP, or from DiPAMP with itaconic acid derivatives. 

Rh complexes of ferrocene-based ligands are very effective for the hydrogenation of several types of dehydroamino (2,3,29,41,42,44) and itaconic acid derivatives (4,5,28) as well as for enamide 45, enol acetate 26, and a tetrasubstituted C = C-COOH 21. Of particular interest are substrates that have unusual substituents (41,42,44) at the C = C moiety or are more sterically hindered than the usual model compounds (21,42). Table 15.10 lists typical examples with very high ee s and often respectable TONs and TOFs. Several industrial applications have already been reported using Rh-Josiphos and Ru-Josiphos (see Figure 15.7) as well as Rh-Walphos (Scheme 15.8). 

Finally, several examples of the enantioselective hydrogenation of unsaturated substrates without any heteroatom attached to the olefinic double bond are noteworthy. Of particular relevance to the production of pharmaceutics, agrochemicals, flavors and aroma stuffs is the formation of the chiral 2-substituted succinates based on relevant itaconic acid derivatives. Burk et al. demonstrated that a rhodium(I) catalyst derived from (5,5)-ethyl-DuPHOS is able to hydrogenate aryl- or alkyl-substituted itaconic... 

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

Itaconic acid was isolated in 1836 from the pyrolysis products of citric acid (7) and the pol3mierization of the ethyl ester was observed by SwAETS in 1873 (2). While many patents relating to the acid and its esters as monomers have issued since that time, only recently have reports begun to appear in the scientific journals. The voluminous patent literature describes the use of polymeric itaconic acid derivatives in such applications as protective and decorative coatings, synthetic fibers, oil additives and rigid plastics as well as many others. Several summaries of the patent art and present commercial applications are available (3). Such information has been omitted from this review, which is directed primarily toward chemical behavior of the itaconic monomers and polymers. 

The reduction of itaconic acid derivatives was found to be selective and was used to access compounds under investigation as HIV protease inhibitors (Fig. 9) [26-28],... 

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]. 

Itaconic acid derivatives are hydrogenated in high enantioselectivity, if a free carboxyl group is present . 

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