Chiral josiphos

Fig. 2 Fixation of chiral Josiphos ligands to a first-generation dendrimer containing a cyclotriphosphazene core...

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. 

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. 

Josiphos-rhodium systems have been also used to hydrogenate 2- or 3-substi-tuted pyridines and furans, yet both the activities (TOF = 1-2) and enantioselec-tivities were rather low (Scheme 16.22) [86, 87]. Comparable results were obtained with a number of chiral chelating diphosphines of various symmetries. 

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-... 

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]. 

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

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... 

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. 

In a further development of the norbornene/anihne OHA reaction, Salzer and coworkers used planar chiral arene-chromium-tricarbonyl-based diphosphines for the in situ formation of cis-trans mixtures of complexes 9 and 10 that gave enanti-oselectivities of 51% and 70%, respectively, at 333 K and with a 40-fold excess of naked fluoride , but activities were very low. In the same paper complex 6 was shown to be superior in both activity and enantioselectivity (64% ee) to the corresponding Josiphos compound 5 [15]. The activated N-H bond of benzamide was also stereoselectively added across the double bond of norbornene to afford N-benzoyl-e%o-aminonorbornane in up to 50% yield and 73% ee in the presence of 0.5mol% [IrCl((R)-MeO-bipheb)]2 at 373 K [16]. 

Whereas the simple bidentate nitrogen ligands proved to be rather limited, the frequent occurrence of a set of four P-phenyl or alkyl substituents, e. g., in coordinated Binap, MeO-Biphep, Josiphos or Duphos (shown, from left to right in Scheme 1.4), offered many more reporters . In this way, one can develop a more detailed NOE picture of how the complexed substrate interacts with the chiral pocket offered by these auxiliaries. From these NOE studies [97, 98] it can be shown that the atropisomeric bidentate ligands Binap and MeO-Biphep tend to have fairly classical axial and equatorial P-phenyl substituents. 

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. 

A highly enantioselective reduction of o /3-unsaturated nitriles has been conducted by using a Cu(OAc)2-josiphos complex as the catalyst under hydrosilylation conditions. This reaction provides access to valuable /3-aryl-substituted chiral nitriles in good yields and with excellent enantioselectivities by employing a stable catalytic pre- cursor and a readily available commercial bisphosphine ligand. The active reducing species is believed to be copper hydride.315... 

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 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. 

Only very low catalyst concentrations down to 5 x 10-5 kmol/m3 are consumed that keeps also the catalyst inventory very small [266], Only 0.08 mg of Rh and about 0.2 mg-13 pg of the very expensive chiral ligands (about 300-1000 /g), depending on their molecular weight, are consumed. Finally, a performance comparison for three different reactors was made for the substrate methylacetamidocinnamate and the two rhodium diphosphine complexes Rh/Josiphos and Rh/Diop (see Figure 4.57). The first reactor was a commercial Caroussel reactor (Radleys... 

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. 

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