DIP AMP ligand

Table 3.12 surveys current industrial applications of enantioselective homogeneous catalysis in fine chemicals production. Most chiral catalyst in Table 3.12 have chiral phosphine ligands (see Fig. 3.54). The DIP AMP ligand, which is used in the production of L-Dopa, one of the first chiral syntheses, possesses phosphorus chirality, (see also Section 4.5.8.1) A number of commercial processes use the BINAP ligand, which has axial chirality. The PNNP ligand, on the other hand, has its chirality centred on the a-phenethyl groups two atoms removed from the phosphorus atoms, which bind to the rhodium ion. Nevertheless, good enantio.selectivity is obtained with this catalyst in the synthesis of L-phenylalanine. 

Revision. This phosphine oxide is used in the synthesis of DIP AMP, the chiral ligand for asymmetric catalytic hydrogenation mentioned in the chapter. What are the various reagents doing in the conversion into DIP AMP ... 

When coordinated to the metal, the chiral ligand plays an important role in the control of enantioselectivity during the course of the catalysis reaction. These ligands can contain chirality in the backbone (e.g.. CHIRAPHOS, 1), at the phosphorus atom (e.g., DIP AMP, 2), or atropisomerically from C2 symmetric axial configurations (e.g., BINAP, 3). Typically, most chiral ligands possess di-phenylphosphine moieties (Figure 1). 

Scheme 7.15. Possible orientations for oxidative addition of dihydrogen to the major (left) and minor (right) diastereomers of the catalyst-substrate complex (for simplicity, the linkages connecting the atoms bonded to the metal are indicated with a curved line). The boxed structures are the only octahedral structures that are not encumbered by severe non-bonded interactions they are redrawn at the bottom with the bisphosphine to the rear and in the horizontal plane. The topicity illustrated is for ligands having the structure of Figure 7.8, such as R,R DIP AMP, R.R-DIOP, or R,R CHIRAPHOS (see Figure 7.8).

Although DIP AMP is a suitable ligand for this reaction as well, the industrial process uses the diphosphine DNNP. Unfortunately, the product is initially obtained in rather modest enantiomeric excess (83%), but recrystallization improves this to 97%. In the manufacture of aspartame, coupling with natural (and therefore 100% ee) aspartic acid turns the 1.5% of the minor enantiomer into a diastereoisomeric impurity that can be removed by crystallization (essentially a resolution). 

The usage of more complex ligands, e.g., DIOP [33], led to the improvement of these reactions and allowed the higher ee s to be obtained. One important application of this methodology was the industrial synthesis of l-DOPA, developed in the group of Knowles, employing the bidentate ligand DIP AMP. 

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