Josiphos derivative

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... 

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... 

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]. 

Recently, Merck chemists reported the Rh-josiphos-catalyzed hydrogenation of unprotected dehydro / -amino acids with ee-values up to 97%, but relatively low activity [23]. It was also shown that not only simple derivatives but also the complex intermediate for MK-0431 depicted in Scheme 25.2 can be hydrogenated successfully, and this has been produced on a > 50 kg scale with ee-values up to 98%, albeit with low to medium TONs and TOFs [24]. 

Besides Ir-diphosphines, two more catalyst systems have shown promise for industrial application. As mentioned in Section 37.5.2, the Rh-Josiphos-cata-lyzed hydrogenation of unprotected /1-dehydro amino acid derivatives by Merck actually involves the hydrogenation of a C=N and not a C=C bond (see Fig. 37.10) [3, 51]. Noyori s Ru-PP-NN catalyst system seems also suitable for C=N hydrogenation [129], and was successfully applied in a feasibility study by Dow/Chirotech for the hydrogenation of a sulfonyl amidine [130]. Avecia also showed the viability of its CATHy catalyst for the transfer hydrogenation of phosphinyl imines [115] (see Fig. 37.34). 

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). 

Enantiomerically pure citronellal in both of its antipodal forms has outstanding importance as a key intermediate for the production of fine chemicals, especially for the production of fragrances and flavors. In this respect the isomerization of diethylgeranylamine to R) -citronellal enamine in the presence of Rh /(S) -BINAP is an exceptional industrial process, for instance as one of the key steps of the Takasago process for the production of (-) -menthol [22]. In the search for alternatives for this process, both Josiphos and Daniphos derivatives were evaluated (Scheme 1.4.5) [23]. 

Ferrocene-derived ligand (l ,S)-Josiphos, which is widely used for catalytic asymmetric hydrogenation reactions, is also a good catalyst for the asymmetric copper-catalyzed 1,4-addition. Reaction in f-BuOMe in the presence of 6 mol% of this ligand gives products with up to 98%. ... 

Wittig reaction to give the desired Michael acceptor. A second catalytic conjugate addition using Josiphos or its enantiomer affords with excellent diastereoselectivities the syn- or awf/-l,3-dimethyl derivative. 

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... 

Rh complexes of ferrocene-based ligands are very effective for the hydrogenation of several types of dehydroamino (2,3,29,41,42,44) and itaconic acid derivatives (4,5,28) as well as for enamide 45, enol acetate 26, and a tetrasubstituted C = C-COOH 21. Of particular interest are substrates that have unusual substituents (41,42,44) at the C = C moiety or are more sterically hindered than the usual model compounds (21,42). Table 15.10 lists typical examples with very high ee s and often respectable TONs and TOFs. Several industrial applications have already been reported using Rh-Josiphos and Ru-Josiphos (see Figure 15.7) as well as Rh-Walphos (Scheme 15.8). 

The introduction of chirafity into NHCs will therefore follow different strategies than those that have proved to be successful in phosphine-based asymmetric catalysis. For example, N-heterocydic carbene units will not create an edge-to-face arrangement of their aryl substituents, a structural feature common to many chiral diphosphines, such as the derivatives of Diop, Binap, Josiphos, Chiraphos and others. Results obtained in asymmetric catalysis, using chiral phosphine ligands, are therefore not directly transferable to the respective NHC-analogues. 

BINAPHOS L3 and its derivative L4, which has not been tested experimentally so far, possess two and one chiral axes, respectively, whereas JOSIPHOS L5 and its constitutional isomer L6 combine planar chirality with a carbon stereocenter. In the case of L3, the relative configuration of the two chiral axes decides the total stereoselectivity. Synergistic/antagonistic backbone-substrate interactions are the main reason for the good/bad performance of L3-(/f,S)/L3-(/f,R) and their enantiomers L3-(S,R)/L3-(S,5). This is reminiscent of the matched/ mismatched concept [38]. Furthermore, one chiral axis, as in L4, seems to be insufficient for a high ee. 

The synthesis and application of chiral ferrocene derivatives has attracted much interest.358 Hence the ferrocenyldiphosphine (163) (Josiphos) can be prepared by direct HPR2 substitution of the dimethylamino group (Equation (40)).359 Various other ferrocene-based chiral ligands are known (e.g., the TRAP ligands (164)).360-364... 

For an article on the discovery and development of Josiphos ligands, eponymously derived from the first name of the chemist who first synthesized them, see H.-U. Blaser, W. Brieden, B. Pugin, F. Spindler, M. Studer, and A. Togni, Top. Catal., 2002,19, 3. 

The general reaction mechanism has been shown to involve typical steps for cross-coupling [98, 113]. Oxidative addition of an aryl halide generates a Pd(II) species that undergoes transmetalation to form a Pd(II)-thiolate. C-S reductive elimination provides the aryl sulfide and regenerates the Pd(0) catalyst. More recently, Hartwig reported a detailed mechanistic analysis of the Pd/Josiphos system derived from different Pd precursors. The dominant Pd species were found to be off the catalytic cycle, which accounted for differences in rates between stoichiometric and catalytic reactions [114]. Thioketones are also effective thiolate nucleophiles for C-S bond formation. The reaction involves tandem Pd-catalyzed thioenolate alkylation, followed by 5-arylation (8) [102]. Presumably, the arylation process proceeds by a similar mechanism to related Pd-catalyzed transformations. 

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