Ligand Josiphos

A number of candidates from our ligand library have been employed in this survey, bearing aliphatic as well as aromatic substituents on the phosphorus donor atoms, together with the benchmark ligands Josiphos and BINAP, which were included in this examination for comparison purposes. The results are collected in Table 1.4.3. 

Metallocenes have frequently been used as terminal moieties in dendrimer chemistry - as already demonstrated in previous sections. They are of interest primarily because of their potential application in catalysis [123]. An unusual metallodendrimer with peripheral ferrocene entities and optically active ferro-cenyldiphosphine ligands (josiphos ligands) was prepared by Togni et al. (Fig. 4.58) [124]. Adamantanetetracarboxlic acid was one of the core units employed. 

Many chiral ferrocene-based bisphosphane ligands with great structural variations have been developed recently. Togni and Spindler introduced non-Crsymmetric ferrocene-based Josiphos type ligands. Josiphos 38 has been found to be effective for Rh-catalyzed hydrogenation of a-acetamidocinnamate, dimethyl itaconate, and P-keto esters. A class of non-Cj-symmetrical ferrocene-based 1,5-diphosphane ligands (TaniaPhos 39) has also been... 

Another enantioselective retro-allylation is the desymmetrization of meso-tert-norbornenols by Cramer (Scheme 5.41) [29]. Ferrocene-based bidentate ligand Josiphos shows the best performance in regard to yield and selectivity while the use of the BINAP series also invokes high enantioselectivities. 

Other systems that prove successful in the highly enantioselective hydrogenation of a-acetamidoacrylates include the spirophosphinites 128 (94.2-97.2% ee)666 and the Josiphos ligands 129 with rhodium(I) (84-96% ee). Excellent... 

Intermolecular addition of activated methylenes to unsaturated systems has been investigated with silver,36 silver/ gold, and palladium catalysts. Thus, C-H addition of 2,4-pentandione to 1,3-cyclohexadiene occurs in THF at 0°C with 5mol% of palladium(ll) catalyst without base. Josiphos ligand 20 is used as a chirality source to induce... 

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. 

Nonetheless, among bidentate diphosphines and with the notable exception of BINAP 23, there have been only sporadic examples of ligands whose rhodium complexes give enantioselectivities above 85% in hydroboration Knochel s dicyclohexylphosphine 34,80 Togni s Josiphos 41,85 and TADDOL derivatives 48, 50-52.90 Even... 

Perhaps the first successful variation of the PPFA framework was the development of the JosiPhos family of ligands (33) [125, 131, 141, 142], Here, the two phosphorus groups are attached to the same cyclopentenyl ring rather than one to each of the rings. The C2-symmetry model is now a distant memory for these ligand families. 

The R,S-family 33, and of course its enantiomer, provide high enantioselectiv-ities and activities for the reductions of itaconic and dehydroamino acid derivatives as well as imines [141], The JosiPhos ligands have found industrial applications for reductions of the carbon-carbon unsaturation within a,/ -unsaturated carbonyl substrates [125, 127, 131, 143-149]. In contrast, the R,R-diastereoisomerof30 does not provide high stereoselection in enantioselective hydrogenations [125, 141]. 

The josiphos ligands arguably constitute the most versatile and successful ferro-cenyl ligand family. Because the two phosphine groups are introduced in consecutive steps with very high yields (as shown in Scheme 25.1), a variety of ligands is readily available with widely differing steric and electronic properties. 

A comprehensive review on the catalytic performance of josiphos ligands has recently been published [17]. Until now, only the (R, S)-family (and its enantiomers) but not the (R, R) diastereomers have led to high enantioselectivities (the first descriptor stands for the stereogenic center, the second for the planar chirality). The ligands are technically developed, and available in commercial quanti-... 

Fig. 25.9 I ndustrial applications of josiphos ligands for (for further information, see [19]).

Scheme 25.1 Preparation of josiphos ligands starting from the Ugi amine.

Table 25.4 Selected results for the Rh- and Cu-catalyzed hydrogenation using josiphos ligands (for structures, see Figs. 25.8 and 25.10).

The starting point for walphos was also the Ugi amine. Like josiphos, wal-phos ligands are modular but form eight-membered metallocycles due to the... 

Ferrocene-based complexes have some potential for the enantioselective reduction of ketones, but compared to other ligand classes this is relatively limited [3]. Rh complexes of bppfa, bophoz and josiphos are among the most selective catalysts for the hydrogenation of a-functionalized ketones (Table 25.9 Fig. 25.18, 30-32). Ru complexes of walphos and ferrotane are quite effective for... 

Some neutral rhodium catalysts with chiral ligands, such as MCCPM 9 (see Scheme 33.3) [20c], Cy,Cy-oxoProNOP 15, and Cp,Cp-IndoNOP 18, demonstrate excellent enantioselectivities and reactivities in the hydrogenation of a-ketoesters and ketoamides indeed, they compare well with ruthenium-based catalysts (Table 33.2). Togni et al. have successfully used the Josiphos 47 ligand for the hydrogenation of ethyl acetoacetate [27], while the use of MannOPs has led to somewhat high enantioselectivities [18]. 

Cyclic imines do not have the problem of syn/anti isomerism and therefore, in principle, higher enantioselectivities can be expected (Fig. 34.8). Several cyclic model substrates 6 were hydrogenated using the Ti-ebthi catalyst, with ee-val-ues up to 99% (Table 34.5 entry 5.1), whereas enantioselectivities for acyclic imines were <90% [20, 21]. Unfortunately, these very selective catalysts operate at low SCRs and exhibit TOFs <3 h-1. In this respect, iridium-diphosphine catalysts, in the presence of various additives, seem more promising because they show higher activities. With several different ligands such as josiphos, bicp, bi-... 

Rhodium diphosphine catalysts can be easily prepared from [Rh(nbd)Cl]2 and a chiral diphosphine, and are suitable for the hydrogenation of imines and N-acyl hydrazones. However, with most imine substrates they exhibit lower activities than the analogous Ir catalysts. The most selective diphosphine ligand is bdppsuif, which is not easily available. Rh-duphos is very selective for the hydrogenation of N-acyl hydrazones and with TOFs up to 1000 h-1 would be active enough for a technical application. Rh-josiphos complexes are the catalysts of choice for the hydrogenation of phosphinyl imines. Recently developed (penta-methylcyclopentyl) Rh-tosylated diamine or amino alcohol complexes are active for the transfer hydrogenation for a variety of C = N functions, and can be an attractive alternative for specific applications. 

A novel Ru precursor and a new reaction system had to be found because the classical Ru complexes and conditions for the hydrogenation of C=C bonds did not work. Besides the enantioselectivity, chemo- and cis-selectivity and activity problems (tetrasubstituted C=C) were solved on a very good level. A broad screening of Ru catalysts (partly in collaboration with Solvias) showed that selected Josiphos ligands and DuPhos satisfied the prerequisites (see Table 37.4). 

The search for a commercially viable process took many years [126], Several approaches with Rh or Ir complexes using commercially available diphosphine ligands were not successful. A critical breakthrough was achieved when Ir complexes with a new class of ferrocenyl-based ligands (now called Solvias Josiphos) were used. Extremely active and productive catalysts were obtained, especially in the presence of acid and iodide ions. Different Josiphos ligands were tested and a selection of the best results obtained is shown in Table 37.5. 

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