DiPAMP ligand

The most effective catalysts for enantioselective amino acid synthesis are coordination complexes of rhodium(I) with 1,5-cyclooctadiene (COD) and a chiral diphosphine such as (JR,jR)-l,2-bis(o-anisylphenylphosphino)ethane, the so-called DiPAMP ligand. The complex owes its chirality to the presence of the trisubstituted phosphorus atoms (Section 9.12). 

If (R,R)-DiPAMP would produce the S enantiomer of l-DOPA, then the (S,S)-DiPAMP ligand would produce the opposite DOPA enantiomer, thus (R). 

N-acetylphenylalanine methyl ester during MAC hydrogenation in methanol solvent [C. R. Landis and J. Halpern, J. Am. Chem. Soc., 109 (1987) 1746]. The DI-PAMP coordinates to the rhodium through the phosphorus atoms and leaves plenty of space around the Rh cation for other molecules to bind and react. The unique feature of this system is that the chirality of the DIPAMP ligand induces the high stereoselectivity of the product molecules. An analogous nonchiral ligand on the Rh cation produces a catalyst that is not enantioselective. 

Figure 13.1 Structure of cytochrome P450 cam with its substrate (camphor, yellow), emphasizing the lock and key complementarity between the enzyme and its substrate (pdb ref. code 2CPP) (a) Structure of Knowles s Rh(dipamp) + bound to its substrate (yellow), emphasizing the limited space (hemisphere) occupied by the enantiopure dipamp ligand (CSD ref code VERY AS) (b)...

Rhodimn catalysts with the DIPAMP ligand (see Fig. 3-3) can hydrogenate amino acid precursors to give optically active amino acids with enantiomeric excesses up to 96 % (enantiomer ratio of 98 2). 

Similar trends have been observed in the hydrogenation of ACA (entries 23-36). With this substrate the best enantioseleetivities have been obtained with modified DiPAMP ligands (entry 24), Trichickenfootphos (entry 28), Tang-Phos (entry 30), BIPNOR (entry 34) and MeO-POP (entry 36). 

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