Diphosphine ligands double bond hydrogenation

As enantioselective hydrogenations of prochiral substrates are undoubtedly the most common applications of chiral diphosphine ligands, a broad screening of our ligands was undertaken with some commonly used standard substrates. As substrates for the hydrogenation of C=C double bonds dimethyl itaconate (DlMl), methyl 2-acetamidoacrylate (MAA), methyl acetamidocinnamate (MAC) as an a-amino acid precursor, and ethyl (Z)-3-acetamidobutenoate ( 3-ENAM1DE) as a p-amino acid precursor were chosen (see Eig. 1.4.5). 

The reduction of lactam substrates containing proximal exo double bonds may be achieved in high e.e. as demonstrated by the reduction of 3-alkylidene-2-piperidones (Scheme 19)119. Cyclic amino acids may be prepared by, for example, asymmetric hydrogenation of 3 to 4 in up to 79% e.e.120 and the reduction of 5 to 6 in 99% e.e.121. In the latter case a number of chiral diphosphines were screened, and the best results were obtained using BINAP as a ligand with rhodium metal. Several other diphosphines, notably DuPHOS and DIOP, also performed well. The research group which produced... 

The carbon-carbon double bond of an enamine is also applicable for asymmetric hydrogenation leading to chiral amino acids. For example, hydrogenation of 13 by rhodium catalyst with ferrocenyl diphosphine 15 as a ligand was successful for the synthesis of methyl 3-amino-4-polyfluorophenylbutanoate 14 with excellent stereoselectivity (see Scheme 9.5) [15]. 

Asymmetric hydrogenation was boosted towards synthetic applications with the preparation of binap 15 by Noyori et al. [55] (Scheme 10). This diphosphine is a good ligand of rhodium, but it was some ruthenium/binap complexes which have found spectacular applications (from 1986 up to now) in asymmetric hydrogenation of many types of unsaturated substrates (C=C or C=0 double bonds). Some examples are listed in Scheme 10. Another important development generated by binap was the isomerization of allylamines into enamines catalyzed by cationic rhodium/binap complexes [57]. This reaction has been applied since 1985 in Japan at the Takasago Company for the synthesis of (-)-menthol (Scheme 10). 

When steric hindrance inhibits hydrogenation on one face of a double bond, addition will take place exclusively to the less hindered face. This principle has been used to develop enantioselective or so-called asymmetric hydrogenation. The process employs homogeneous (soluble) catalysts, consisting of a metal, such as rhodium, and an enantiopure chiral phosphine ligand, which binds to the metal. A typical example is the Rh complex of the diphosphine (R,R)-DIPAMP (margin). After coordination of the alkene double bond and a molecule of H2 to rhodium, hydrogenation occurs via syn addition, just as in the case of insoluble metal catalysts. 

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