Ferrocenyl diphosphines

Platinum complexes [PtCl2(diphosphine)] and [PtCl(SnCl3)(diphosphine)] of the ferrocenyl diphosphine ligands (35a), (35b), and (36) have been synthesized. Complexes [PtCl2(35)] and [PtCl2(36)] have been structurally characterized by XRD. Both the preformed and the in situ catalysts have been used in the hydroformylation of styrene.112... 

Among the various catalyst types investigated in recent years for the hydrogenation of imines, Ir-diphosphine complexes have proved to be most versatile catalysts. The first catalyst of this type generated in situ from [Ir(cod)Cl]2, a chiral diphosphine and iodide was developed by the Ciba-Geigy catalysis group in 1985. Ir ferrocenyl diphosphines (josiphos) complexes in presence of iodide and acid... 

A broad screening of ligands and ionic liquids was carried out by Feng et al. [104]. For rhodium-catalyzed hydrogenation of enamides the best catalysts were found to be the rhodium-ferrocenyl-diphosphine complexes with taniaphos, josiphos, walphos and mandyphos as ligands (Fig. 41.9). 

The research group of Van Leeuwen has focused on catalysis at the core of a carbosilane dendrimer in an effort to be able to control stereoselectivity [10]. To this end, a ferrocenyl diphosphine backbone was functionalized with different generations of carbosilane dendrons producing a series of dendrimer phosphine ligands with an increasing steric demand (see 7 for an example, Scheme 6). In situ... 

Recently Togni et al. [19] focussed on the preparation of asymmetric dendrimer catalysts derived from ferrocenyl diphosphine ligands anchored to dendritic backbones constructed from benzene-1,3,5-tricarboxylic acid trichloride and adamantane-l,3,5,7-tetracarboxylic acid tetrachloride (e.g. 11, Scheme 11). In situ catalyst preparation by treatment of the dendritic ligands with [Rh(COD)2]BF4 afforded the cationic Rh-dendrimer, which was then used as a homogeneous catalyst in the hydrogenation reaction of, for example, dimethyl itaconate in MeOH. In all cases the measured enantioselectivity (98.0-98.7%) was nearly the same as observed for the ferrocenyl diphosphine (Josiphos) model compound (see Scheme 11). 

When the catalyst is located in the core of a dendrimer, its stability can also be increased by site-isolation effects. Core-functionalized dendritic catalysts supported on a carbosilane backbone were reported by Oosterom et al. 19). A novel route was developed to synthesize dendritic wedges with arylbromide as the focal point. These wedges were divergently coupled to a ferrocenyl diphosphine core to form dppf-like ligands (5). Other core-functionalized phosphine dendritic ligands have also been prepared by the same strategy 20). 

FIGURE 3. Representative examples of conjugate addition products using Cu/ferrocenyl diphosphine catalysts. Adapted with permission from Acc. Chem. Res., 40, 179-188 (2007). Copyright 2007 American Chemical Society... 

Table 7 Rh-catalyzed hydrogenation of the N-acetyl dehydrophenylalanine derivative 146 with ferrocenyl diphosphines 51-53... 

The mechanism of the enantioselective 1,4-addition of Grignard reagents to a,j3-unsaturated carbonyl compounds promoted by copper complexes of chiral ferrocenyl diphosphines has been explored through kinetic, spectroscopic, and electrochemical analysis.86 On the basis of these studies, a structure of the active catalyst is proposed. The roles of the solvent, copper halide, and the Grignard reagent have been examined. 

Ferrocenyl diphosphine core-functionalized carbosilane dendrimers have been prepared as ligands for homogeneous catalytic reactions applied in a CFMR by Van Leeuwen et al. [20,21,67,68]. The syntheses of these dppf-like ligands (Go-G2)-17 were performed using carbosilane dendritic wedges with an aryl bromide as focal point. These wedges were coupled to the core via quenching of the lithiated species with ferrocenyl phosphonites (Scheme 11). 

The first example of asymmetric rhodium-catalyzed hydrogenation of prochi-ral olefins in dendrimer catalysis was reported by Togni et al., who immobilized the chiral ferrocenyl diphosphine Josiphos at the end groups of dendrimers, thus obtaining systems of up to 24 chiral metal centres in the periphery (Fig. 2) [12-14]. The fact that the catalytic properties of the dendrimer catalysts were almost identical to those of the mononuclear catalysts was interpreted as a manifestation of the independence of the individual catalytic sites in the macromolecular systems. 

The Rh/Diop catalytic system is one of the fastest catalyzed gas-liquid asymmetric hydrogenations. A (R,S)-Cy-Cy-Josiphos ligand behaves almost as good as the Diop ligand and provides abetter enantioselectivity of 75% (Josiphos family of ferrocenyl diphosphine ligands cy cyclohexyl). The latter is the most active of the Josiphos family (88% conversion). The reproducibility of the data obtained has been checked with the Rh/Diop catalytic system. For more than five tests, the mean deviation was 2% for conversions and less than 1% for the enantiomeric excess that proved the reliability of this new microdevice. 

Valuable intermediates 78 for a novel synthesis for (+)-biotin (79), which is referred to as vitamin H, are obtained effectively by use of a rhodium catalyst with the ferrocenyl diphosphine 70 (Scheme 24) [80]. The optimized process is suitable for industrial production. 

Hydrogenation of the enamide 86 with a Ru catalyst and MeOBIPHEP 31 gives a feasible approach to the antitussive agent dextromethorphan (89) (Scheme 26). The readily available imine substrate 87 is hydrogenated using an Ir catalyst with the ferrocenyl diphosphine 88, albeit with a relatively low substrate/catalyst molar ratio of 1500 and an ee of 89% [20]. 

The carbon-carbon double bond of an enamine is also applicable for asymmetric hydrogenation leading to chiral amino acids. For example, hydrogenation of 13 by rhodium catalyst with ferrocenyl diphosphine 15 as a ligand was successful for the synthesis of methyl 3-amino-4-polyfluorophenylbutanoate 14 with excellent stereoselectivity (see Scheme 9.5) [15]. 

Figure 2.55 reports the preparation and structure of ferrocenyl diphosphine ligands and the dependence of the performances on the substituents in the ligand. 

Tab. 2 MEA imine hydrogenation with selected Ir-ferrocenyl diphosphine complexes (formulas see Fig. 8)...

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