Monodentate chiral amines

With olefins other than ethene two isomeric chlorohydrins can be obtained, one of them being chiral. When pyridine was replaced by monodentate chiral amines in [PdCl3(pyridine)], the enantioselectivities were low (8-12%) (Scheme 8.3) [14]. The mononuclear [PdCl2(L2)] complexes (L2 = sulfonated p-tolyl-BINAP) performed better providing the chird chlorohydrin in 46-76% e.e. Even better activities and... 

Monodentate phosphites are another type of prominent monodentate phosphorus ligands applied in asymmetric hydrogenation of enamides for the synthesis of chiral amines. Chiral monodentate phosphites can be easily prepared from a chiral diol and an alcohol. Generally, the chiral diol was first reacted with a phosphorus trichloride to form a phosphorochloridite, followed by the reaction with an appropriate alcohol to yield a chiral monodentate phosphite [35[. The reaction of an alcohol with phos phorus trichoride to yield a phosphorodichloridite, which was then treated with a chiral diol, is also a good procedure for the synthesis of chiral monodentate phosphites [36]. 

The diversity requirement of chiral amines in the synthesis of natural products and chiral drugs is everlasting and the most studies about the catalytic asymmetric hydrogenation of enamines have dealt with simple substrates to date. Hence, it is necessary to explore highly efficient enantioselective protocol to provide more complex and also industrially useful chiral amines. We are confident that the easily accessible and changeable monodentate phosphorus hgands will find a wide appli cation in this field. 

In a recent review on predetermined chirality at metal centers, Khof and von Zelewsky described the chiral quadruply bonded species A and A-[Mo2Cl4(5,5-dppb)2] (where dppb = 2,3-bis(diphenylphosphino)butane) as M-configurational double helices. Such twisted multiply bonded complexes are paradigm examples of intrinsically chiral chromophores where the chiral center is not located at the metal atom but embraces the whole twisted M02X4P4 unit. The CD spectra of a range of chiral quadruply bonded compounds, with a variety of bidentate and monodentate chiral ligands (phosphines and amines) have been reported and can be explained by a simple metal localized theory. ... 

Figure 2.39 Chiral monodentate phosphoramidite ligands with chiral amine residues.

It thus came as a surprise that in the year 2000, three groups independently reported the use of three new classes of monodentate ligands (Scheme 28.2) [12], The ligands induced remarkably high enantioselectivities, comparable to those obtained using the best bidentate phosphines, in the rhodium-catalyzed enantioselective alkene hydrogenation. All three being based on a BINOL backbone, and devoid of chirality on phosphorus, these monophosphonites [13], monophosphites [14] and monophosphoramidites [15] are very easy to prepare and are equipped with a variable alkyl, alkoxy, or amine functionality, respectively. 

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." ... 

Malhotra introduced monodentate amines derived from a-pinene as chiral lithium amide precursors118. Using 20 mol% of the base 105 with excess LDA resulted in 95% ee of the corresponding (R)-allylic alcohol (Scheme 76). 

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). 

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... 

---