Enantioselective 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]. 

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]. 

Table 26.7 Enantioselective hydrogenation of itaconic acid derivatives.

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],... 

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

MAC), methyl 2-acetamidoacrylate (MAA), and methyl 2-acetamidobutenoate (MAB) (Figure 15.7) as well as two itaconic acid derivatives, namely dimethyl ita-conate (DMI) and ( )-dimethyl-2-phenyl itaconate (DMPI). In general, good to excellent enantioselectivities (of up to >99% ee) were observed. Ligand backbone modification by coordination of bulky Au-X substituents to the free phospholane unit of the tripodal DPP Hgand led to a remarkable enhancement of the catalyst... 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

Enantioselectivities of up to 47% ee were reported by Ruiz et al. in 1997 for the asymmetric hydrogenation of various prochiral dehydroamino acid derivatives and itaconic acid by using iridium cationic complexes of the novel chiral... 

Fu has reported a planar-chiral bisphosphorus ligand 45 with a phosphaferrocene backbone. The ligand has provided enantioselectivity up to 96% ee in the hydrogenation of a-dehydroamino acid derivatives.99 Another planar-chiral ferrocene-based bisphosphorus ligand 46 has been reported by Kagan recently and enantioselectivity up to 95% ee has been obtained in the reduction of dimethyl itaconate.100... 

The R,S-family 33, and of course its enantiomer, provide high enantioselectiv-ities and activities for the reductions of itaconic and dehydroamino acid derivatives as well as imines [141], The JosiPhos ligands have found industrial applications for reductions of the carbon-carbon unsaturation within a,/ -unsaturated carbonyl substrates [125, 127, 131, 143-149]. In contrast, the R,R-diastereoisomerof30 does not provide high stereoselection in enantioselective hydrogenations [125, 141]. 

The enantioselective hydrogenation of a,fj- or / ,y-unsaturated acid derivatives and ester substrates including itaconic acids, acrylic acid derivatives, buteno-lides, and dehydrojasmonates, is a practical and efficient methodology for accessing, amongst others, chiral acids, chiral a-hydroxy acids, chiral lactones and chiral amides. These are of particular importance across the pharmaceutical and the flavors and fragrances industries. 

Marinetti [53] and Burk [54] reported the preparation of chiral l,l -bis(phos-phetano)ferrocenes (FerroTANE) independently, in which Et-FerroTANE demonstrated excellent enantioselectivity in the rhodium-catalyzed hydrogenation of itaconates. Zhang has reported a l,T-bis(phospholanyl)ferrocene hgand (f-KetalPhos) with ketal substituents at 3,4-positions [55], which proved an excellent ligand for the enantioselective hydrogenation of a-dehydroamino acid derivatives [56]. 

Some excellent bisphosphonite ligands have also been developed. For example, Re-etzfs binaphthol-derived ferrocene-based bisphosphonite hgand L12 has demonstrated to have excellent reactivity and enantioselectivity in the rhodium-catalyzed hydrogenation of itaconates and a-dehydroamino acid derivatives [76]. Zanotti-Gerosa s bisphosphonite ligand L13 has also been successfully apphed to the asymmetric hydrogenation of a-dehydroamino acid derivatives with up to 99% ee [77]. 

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