Chiral ferrocene diphosphine ligand

Until then, only heterogeneous catalyst had been successful. However, in the mid-1980s, the work of Ito et al. led to an outstanding discovery in a catalytic asymmetric aldol reaction. In this case, enantioselectivity was given by a chiral ferrocene diphosphine ligand, with a carbon nucleophile addition to a carbonyl... 

For our initial studies we chose to evaluate the hydrogenation of two unsaturated carbonyl model prochiral substrates with rhodium complexes of chiral ferrocene diphosphine and tetraphosphine ligands using a standard set of conditions. The substrates screened were methyl a-acetamido cinnamate (MAC) and dimethyl iticonate (DIMI). The substrates, catalysts, conditions, and experimental results are shown in Table 1. 

H.U. Blaser, M. Lotz, F. Spindler, "Asymmetric Catalytic Hydrogenation Reactions with Ferrocene Based Diphosphine Ligands" in Handbook of Chiral Chemicals, 2nd Edition, D. J. Ager (Ed.), CRC Press, Boca Raton 2005... 

Asymmetric hydroboration of prochiral alkenes has been achieved using transition metal catalysts and chiral phosphines as ligands to obtain enantiomerically pure alkyl boronates <1997CC173>. Catalysts such as Rh(COD)2+BF4 , Rh(COD)2+Cl, Rh+BF4 , etc., in combination with chiral phosphines like DIOP 71, BINAP 72, CHIRAPHOS 73, DIPAMP 74, BDPP 75, ferrocene-based diphosphines 76<1999TL4977>, etc., have been employed for the asymmetric hydroboration of prochiral alkenes with moderate to high ee (DIOP = 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane BINAP = 2,2-bis(diphenyl-phos-phanyl)-l,1-binaphthyl CHIRAPHOS = 2,3-bis(diphenylphosphino)butane DIPAMP = l,2-bis[(2-methoxyphe-nyl)phenylphosphino]ethane BDPP = 2,4-bis(diphenylphosphino)pentane). 

Azanorbornyl-3-methanol (93) shows its value as a chiral ligand in Ru-catalyzed transfer hydrogenation. On binding to Ru, C2-symmetric diphosphines (94, 95, etc.) and the ferrocene-based ligand 96 are able to exert their steric influences during hydrogenation of 1,3-diketones. 

Asymmetric hydroformylation of styrene has been studied with a range of bidentate phosphines, van Leeuwen reported phosphorus-chiral ferrocenyl-based diphosphines, the hydride complexes of which showed varying ee-ea ratios depending on ligand basicity, as determined by HP-IR and HP-NMR. This contrasted to the clear ea preference shown by complexes of the achiral l,l -bis(diphenylphosphino)ferrocene (dppf) ligand. Claver and van Leeuwen " " " investigated BDPP [(2A,4A)-bis(diphenylphosphino)pentane] and CHIRAPHOS [(2R,3R)-bis (diphenylphosphino)butane] for the same transformation. High pressure spectroscopic data for the catalytic species... 

The majority of the ferrocene ligands have both planar (Cp ring with two different substituents) and central (in the side chain) chirality. A matched combination is very convenient for achieving high levels of asymmetric induction. From a structural point of view, chiral ferrocenyl diphosphines can be divided in two classes depending on the relative position (1,1 or 1,2) of the phosphorus donor atoms, which, in turn, may be attached to one or both cyclopentadienyl rings directly or via a spacer. 

Josiphos Chiral diphosphine ligand derived from ferrocene... 

A) Planar Chiral Paracyclophane-Based Bidentate Ligands. As paracaclophane has to some extent similar characteristics as ferrocene, it allows the preparation of bidentate phosphines with planar chirality. First the paracyclophane-based diphosphine ligand, [2.2]Phane-Phos (83, R = Ph), was synthesized by Pye and coworkers.Both Rh- and Ru-complexes of PhanePhos... 

FIGURE 29.9. Selection of ferrocene-based chiral ligands (A) ferrocene-based diphosphines with planar chirality only (B) bidentate ferrocene-based ligands with ntixed planar and central chirality and (C) ligands with planar and axial chirality as well as planar, central, and axial chirahty. 

The ferrocene-derived Josiphos ligands (137) first reported by Togni and Spindler [99] are another class of chiral diphosphine ligands that are of immense importance both in asymmetric hydrogenations and in other asymmetric transformations. A variety of substrates can be reduced with high enantioselectivity in the presence of chiral metal complexes derived from these ligands. The reduction of dimethyl itaconate (136) furnishes 138 in quantitative yield and 98-99 % ee (Equation 39) [99]. 

While Josiphos 41 also possessed an element of atom-centered chirality in the side chain, Reetz reported a new class of ferrocene-derived diphosphines which had planar chirality only ligands 42 and 43, which have C2- and C -symmetry, respectively.87 Rhodium(i)-complexes of ligands (—)-42 and (—)-43 were used in situ as catalysts (0.75 mol%) for the hydroboration of styrene with catecholborane 1 for 12 h in toluene at — 50 °C. The rhodium/ i-symmetric (—)-43 catalyst system was the more enantioselective of the two - ( -l-phenylethanol was afforded with 52% and 77% ee with diphosphines (—)-42 and (—)-43, respectively. In both cases, the regioselectivity was excellent (>99 1). With the same reaction time but using DME as solvent at lower temperature (—60 °C), the rhodium complex of 43 afforded the alcohol product with an optimum 84% ee. 

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