Chiral monodentate phosphoramidite

The enantioselective conjugate addition of dialkylzinc to nitroalkenes using other phosphoramidite,79,79a 83a sulfonamide,84 and binaphthol-based thioether ligands65 has also been studied in the past few years. Particularly noteworthy are the efficient chiral monodentate phosphoramidite ligands (S,R,R)-29 and (A,A)-55 developed by Feringa et al. and Alexakis et al., respectively, for this reaction. (S,R,R)-29 provided excellent enantioselectivities (up to 98% ee) for acyclic nitroalkenes (Scheme 25).80 It also worked well for other nitroolefin substrates such as 3-nitrocoumarin 7068 and methyl 3-nitropropenoate 7185. 

Ojima and co-workers found that chiral monodentate phosphoramidite (S,R,R)-35 was highly effective for the enantioselective conjugate addition of diethylzinc to acyclic nitroalkenes (up to 99% ee).86... 

Recently, Reek et al. published the synthesis of a 9H,9 H- [4,4 ]bicarbazole-3,3r-diol (BICOL)-based chiral monodentate phosphoramidite ligand, which was functionalized with two different third-generation carbosilane dendritic wedges (Fig. 26) [57]. As reference reaction in the catalytic study, the rhodium-catalyzed asymmetric hydrogenation of Z-methyl-a-acetamido-cinnamate was chosen. Using a ligand-to-rhodium ratio of 2.2 led to enantio-selectivities which were comparable to the results obtained using the parent BINOL-derived monodentate phosphoramidite MonoPhos. 

Reek et al.73 developed a new bicarbazolediol-74 (BICOL)-based, chiral monodentate phosphoramidite ligand, in which the Ai-sites in the bicarbazole skeleton permitted the easy introduction of metal centers. As a model reaction, the Rh-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate was evaluated. Using a ligand to rhodium ratio of 2.2, the enantioselectivity induced by the rhodium complex (Figure 10.7) was 93% at full conversion,... 

In the search for new ligands for asymmetric catalysis Ben L. Feringa and coworkers developed the synthesis of chiral monodentate phosphoramidites (PipPhos) (Figure 3.20) which were excellent ligands for asymmetric hydrogenation of aromatic enol acetates, and enol carbamates with high ee values up to 98%. 

Figure 2.39 Chiral monodentate phosphoramidite ligands with chiral amine residues.

Chiral monodentate phosphoramidite DpenPhos Kgand (696), bearing a primary amine moiety, has been found to be highly efficient in the Rh(I) catalysed asymmetric hydrogenation of a- and p-enamido phosphonates... 

Figure 4.22 Modular chiral dendritic chiral monodentate phosphoramidite ligands for the Rh-catalyzed asymmetric hydrogenation of a-dehydroamino acid esters.

Chiral monodentate phosphites and phosphoramidites are also effective ligands for Rh-catalyzed asymmetric hydrogenation of enamide substrates. As seen in the structure of MonoPhos illustrated in Figure 1.2, combination of the mod-ihed BINOF backbone and the amine part gives a structural variety to this type of ligand. Combinatorial methods are effective for optimization of the chiral structures.Elucidation of the hydrogenation mechanism catalyzed by the MonoPhos-Rh complex is in progress." ... 

Fig. 2.10 The ligand universe A stunning breadth of structural variation with members representing various motifs, e.g. atropisomeric biaryls, ferrocene-based bisphosphanes, P-chiral bisphosphanes, bisphosphites, monodentate phosphoramidites, AJ,P-ligands.

Highly diastereo- and enantio-selective catalytic capture of chiral zinc enolates using nitroolefins as electrophiles has been described. The tandem y-nitro ketone products were obtained in the presence of a monodentate phosphoramidite ligand, in good yields with high diastereo- and enantio-selectivities (up to 96% ee). 

A real breakthrough of the application of monodentate ligands has taken place recently. A family of BINOL-based monodentate phosphoramidites (11) is synthesized and is used in various homogeneous catal3d ic reactions. The amine moiety of the phosphoramidate was varied from 2-methyl-benzylamine, possessing another chiral center, to simple secondary amines such as piperidine and morpholine (12). 

In spite of the prevailing application of homo- and heterobidentate chiral ligands, BINOL-derived monodentate phosphoramidites have been used in highly enantioselective rhodium-catalyzed hydrogenations (14,233). 

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