Enantioselective hydrogenation Josiphos

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... 

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 Rh complex of the chiral Cj symmetry Josiphos 47 is also effective for the enantioselective hydrogenation of ethyl 3-oxobutanoate [27]. 

Rh(cod)Cl]2 is the complex of choice for the in situ preparation of very versatile catalyst precursors for a number of quite challenging transformations. In the course of the development of a new technical synthesis at Lonza [38] for biotin, a water-soluble vitamin, the Rh/Josiphos-catalyzed diastereoselective hydrogenation of a tetrasubstituted C=C bond was the key step (Scheme 13). The enantioselective hydrogenation (N-benzyl instead of N-(/ )-phenethyl)) afforded the desired... 

Highly Enantioselective Hydrogenation of Unprotected P-Enamino Amides and the Use of Josiphos-Ligands... 

Nowadays enantioselective synthesis of the herbicide (5)-metolachlor (Dual Magnum) is, to our knowledge, one of the most successful commercial applications of asymmetric C=N bond hydrogenation. Developed by Blaser and Spindler as a key step in the technical synthesis of (5)-metolachlor, the enantioselective hydrogenation of an imine intermediate 193 proceeds in the presence of an iridium ferrocenyl-diphosphine catalyst bearing a Solvias Josiphos-type chiral ligand (/ )-Xyliphos to give... 

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-... 

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). 

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). 

Kollner et al. (29) prepared a Josiphos derivative containing an amine functionality that was reacted with benzene-1,3,5-tricarboxylic acid trichloride (11) and adamantane-l,3,5,7-tetracarboxylic acid tetrachloride (12). The second generation of these two types of dendrimers (13 and 14) were synthesized convergently through esterification of benzene-1,3,5-tricarboxylic acid trichloride and adamantane-1,3,5,7-tetracarboxylic acid with a phenol bearing the Josiphos derivative in the 1,3 positions. The rhodium complexes of the dendrimers were used as chiral dendritic catalysts in the asymmetric hydrogenation of dimethyl itaconate in methanol (1 mol% catalyst, 1 bar H2 partial pressure). The enantioselectivities were only... 

As seen in Table 1, the mono- and bis-rhodium complexes of tetraphosphine 2 provide similar enantioselectivities in the chiral hydrogenation of both substrates as the rhodium complex of the diphosphine (Josiphos) ligand 1 does. The bis-rhodium complex of 6 provides higher conversion but similar enantioselectivity as the rhodium complex of the diphosphine (Bophoz) ligand 5 in the chiral hydrogenation of MAC. 

By using Josiphos ligands, palladium-catalysed hydrophosphorylation of norbomen-es with hydrogen phosphonates proceeds efficiently to give the corresponding phos-phonates in high enantioselectivities.90... 

Ir-f-binaphane complexes show good to excellent enantioselectivities but modest TONs and low TOFs for the hydrogenation of A -aryl imines with the general structure 27 (Table 15.3).14 The reaction has to be performed in poorly coordinating solvents such as dichloromethane and at a relatively high hydrogen pressure. As with the Ir-Josiphos catalysts, the best ee s are obtained with 2,6-disubstituted /V-aryl imines (Entries 1 and 2), whereas alkyl ketimines give low enantioselectivities (Entry 3). In some cases, the addition of I2 has a beneficial effect on enantioselectivity (Entries 4 and 5). 

Because a comprehensive review on the catalytic performance of Josiphos ligands has been published,20 we restrict ourselves to a short overview on the most important fields of applications. Up to now, only the (7 )-(S)-family (and its enantiomers) but not the (R)-(R) diastereoisomers have led to high enantioselectivities (the first descriptor stands for the stereogenic center, and the second stands for the planar chirality). The most important application is undoubtedly the hydrogenation of C = N functions, where the effects of varying R and R1 have been extensively studied (for the most pertinent results see Table 15.5, Entries I—4). Outstanding performances are also observed for tetrasubstituted C = C bonds (Entry 5) and itaconic and dehydroamino acid derivatives (Entries 6 and 7). A rare example of an asymmetric hydrogenation of a heteroaromatic compound 36 with a respectable ee is depicted in Scheme 15.6.10b... 

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. 

A second strategy is to place mnltiple chiral Josiphos-type (329) units along the exterior of dendrimers, and snccessful apphcations for rhodium-catalyzed asynunetric hydrogenation ntUize cores composed of benzene-l,3,5-tricarboxyhc acid esters (381), adamantane-l,3,5,7-tetracarboxylic acid esters (382), and cyclophosphazenes see Phosphazenes) (383)." Enantioselectivities are excellent and these dendrimeric materials can be recovered by filtration throngh a nanofiltration membrane. 

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