Asymmetric hydrogenation 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...

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],... 

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]. 

Extended X-ray absorption fine structure spectroscopy has been applied to obtain structural information on intermediates in solution in Rh(I)-catalyzed asymmetric hydrogenations. Further information comes from P nmr studies which have shown that the enamides PhCH= C(NHC0Ph)C02Me bind selectively to rhodium complexes of (4a) whereas itaconic acid derivatives CH2=C(C02R )CH2C02R bind weakly, the reverse being true for complexes of (4b). The kinetics of the... 

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. 

In addition, several S/S ligands were also investigated for the asymmetric hydrogenation of olefins. In 1977, James and McMillan reported the synthesis of various disulfoxide ligands, which were applied to the asymmetric ruthenium-catalysed hydrogenation of prochiral olefinic acid derivatives, such as itaconic acid. These ligands, depicted in Scheme 8.16, were active to provide... 

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... 

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]. 

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. 

Kollner et al. (29) prepared a Josiphos derivative containing an amine functionality that was reacted with benzene-1,3,5-tricarboxylic acid trichloride (11) and adamantane-l,3,5,7-tetracarboxylic acid tetrachloride (12). The second generation of these two types of dendrimers (13 and 14) were synthesized convergently through esterification of benzene-1,3,5-tricarboxylic acid trichloride and adamantane-1,3,5,7-tetracarboxylic acid with a phenol bearing the Josiphos derivative in the 1,3 positions. The rhodium complexes of the dendrimers were used as chiral dendritic catalysts in the asymmetric hydrogenation of dimethyl itaconate in methanol (1 mol% catalyst, 1 bar H2 partial pressure). The enantioselectivities were only... 

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). 

Because a comprehensive review on the catalytic performance of Josiphos ligands has been published,20 we restrict ourselves to a short overview on the most important fields of applications. Up to now, only the (7 )-(S)-family (and its enantiomers) but not the (R)-(R) diastereoisomers have led to high enantioselectivities (the first descriptor stands for the stereogenic center, and the second stands for the planar chirality). The most important application is undoubtedly the hydrogenation of C = N functions, where the effects of varying R and R1 have been extensively studied (for the most pertinent results see Table 15.5, Entries I—4). Outstanding performances are also observed for tetrasubstituted C = C bonds (Entry 5) and itaconic and dehydroamino acid derivatives (Entries 6 and 7). A rare example of an asymmetric hydrogenation of a heteroaromatic compound 36 with a respectable ee is depicted in Scheme 15.6.10b... 

Rhodium-Catalyzed Asymmetric Hydrogenation of Olefins. MiniPHOS (1) can be used in rhodium-catalyzed asymmetric hydrogenation of olefinic compounds. The complexation with rhodium is carried out by treatment of 1 with [Rh(nbd)2]BF4in THF (eq 2). The hydrogenation of a-(acylamino)acrylic derivatives proceeds at room temperature and an initial H2 pressure of 1 or 6 atm in the presence of the 0.2 mol% MiniPHOS-Rh complex 2. The reactions are complete within 24—48 h to afford almost enantiomerically pure a-amino acids (eq 3). Itaconic acids, enamides, and dehydro-3-ami no acids can also be hydrogenated with excellent enantioselectivity (eq 4—6). 

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