Chiral DIPAMP

In contrast to CAMP, DIPAMP is a stable solid that melts at 102 °C. Heated at 100 °C, it has a half-life of 3-5 h. This racemization was somewhat faster than Mislow s phosphanes, which did not invert appreciably until 10-15 °C higher. The rate was reasonable, if one considers that inversion at either end destroys chirality. DIPAMP complexed to rhodium must invert much more slowly because efficient, asymmetric hydrogenations have been obtained at 95-100°C. For the sake of convenience, particularly on a large scale, a solid complex was made by reacting two equivalents of phosphane with one equivalent of [Rh(cod)Cl]2 in alcohol. This air-stable orange solid [Rh(bisligand)(cod)]+BF4 made a most suitable catalyst precursor. 

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). 

The numerous chiral phosphine ligands which are available to date [21] can be subclassified into three major categories depending on the location of the chiral center ligands presenting axial chirality (e.g., BINAP 1 and MOP 2), those bearing a chiral carbon-backbone (e.g., DIOP 3, DuPHOS 4), and those bearing the chiral center at the phosphorus atom (e. g., DIPAMP 5, BisP 6), as depicted in Fig. 1. 

An especially important case is the enantioselective hydrogenation of a-amidoacrylic acids, which leads to a-aminoacids.29 A particularly detailed study has been carried out on the mechanism of reduction of methyl Z-a-acetamidocinnamate by a rhodium catalyst with a chiral diphosphine ligand DIPAMP.30 It has been concluded that the reactant can bind reversibly to the catalyst to give either of two complexes. Addition of hydrogen at rhodium then leads to a reactive rhodium hydride and eventually to product. Interestingly, the addition of hydrogen occurs most rapidly in the minor isomeric complex, and the enantioselectivity is due to this kinetic preference. 

Early work in the field of asymmetric hydroboration employed norbornene as a simple unsaturated substrate. A range of chiral-chelating phosphine ligands were probed (DIOP (5), 2,2 -bis(diphenyl-phosphino)-l,l -binaphthyl (BINAP) (6), 2,3-bis(diphenylphosphino)butane (CHIRAPHOS) (7), 2,4-bis(diphenylphosphino)pentane (BDPP) (8), and l,2-(bis(o-methoxyphenyl)(phenyl)phos-phino)ethane) (DIPAMP) (9)) in combination with [Rh(COD)Cl]2 and catecholborane at room temperature (Scheme 8).45 General observations were that enantioselectivities increased as the temperature was lowered below ambient, but that variations of solvent (THF, benzene, or toluene) had little impact. 

Subsequently, Burgess79 prepared a series of hybrid ligands (27a-c) (Figure 3) which were chiral not only in the carbon backbone like (R, R)-DIOP 25 but also at phosphorus, like DIPAMP. 

The rhodium complexes of the ferrocene derivatives 39 have shown useful characteristics for the reduction of itaconates as well as dehydroamino acid derivatives [15, 167-170]. These compounds are hybrids between ferrocene-based ligands and the various other types. The P-chiral compounds, which in some ways are DIPAMP hybrids, showed tolerance for the reduction of N-methyl en-amides to produce N-methyl-a-amino acid derivatives [169-171]. 

DIPAMP-Rh complex to give the corresponding chiral a-amino acid derivative in over 98% ee. The chiral product has been used for the synthesis of (S)-(-)-ac-romelobic acid [88]. Hydrogenation of a tetrahydropyrazine derivative catalyzed by a PHANEPHOS-Rh complex at -40"C gives an intermediate for the synthesis of Crixivan in 86% ee [82a]. Hydrogenation of another tetrahydropyrazine carboxamide derivative catalyzed by an (R)-BINAP-Rh catalyst leads to the chiral product in 99% ee [89]. 

The preparation of this type of catalyst is quite simple. HPAs such as phos-photungstic acid were adsorbed onto inorganic supports such as clays, alumina, and active carbon. Subsequently, the metal complex was added to form the immobilized catalyst. If necessary, the catalyst can be pre-reduced. These types of catalysts were developed mainly for enantioselective hydrogenations. For instance, a supported chiral catalyst that was based on a cationic Rh(DIPAMP) complex, phosphotungstic acid and alumina showed an ee-value of 93% with a TOF of about 100 IT1 in the hydrogenation of 2-acetamidoacrylic acid methyl ester (Fig. 42.4 Table 42.2). 

The related chiral rhodium catalyst 4 has been used to effect kinetic resolution of these substrates.2 In this catalyst the achiral phosphine ligand of 1 is replaced by (R,R)-l,2-bis(o-anisylphenylphosphino)ethane (DIPAMP). Hydrogenation cat-... 

The hydrogenation reaction is carried out with a substituted cinnamic acid. The acetamido group is of particular importance because it functions as a secondary complexation function in addition to the alkene functionality. In the first step the alkene co-ordinates to the cationic rhodium species (containing an enantiopure phosphine DIPAMP in Figures 4.4 and 4.5 with the chirality at phosphorus carrying three different substituents, Ph, o-An, CH2) for which there are several diasteromeric structures due to ... 

Although enol esters have a similar structure to enamides, they have proven more difficult substrates for asymmetric hydrogenation, which is evident from the significantly fewer number of examples. One possible explanation is the weaker coordinating ability of the enol ester to the metal center, as compared to the corresponding enamide. Some rhodium complexes associated with chiral phosphorous ligands such as DIPAMP [100, 101] and DuPhos [102] are effective for asymmetric hydrogenation of a-(acyloxy)acrylates. 

---