JosiPhos

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- 

Ru - josiphos or duphos ee 90% Rh - josiphos de 99% TON 2,000 TOF 200 h 1 TON 2,000 TOF n.a. medium scale production medium scale production Firmenich Lonza 

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Catalyst screen at 90 psi hydrogen at r.t. and 60 °C for 20 h - No product detected Pfaltz-lr-BARF-cat, (Et-Duphos)Rh(COD)BF4,(BINAP)Ru(ll)CI2, Phanephos/(COD)2RhBF4, Josiphos SL-J009-1/(COD)RhCI,... 

The electron-poor biphenyl diphosphine (15) displays poorer regioselectivity for hydroboration of styrene (78% chemical yield) but higher enantioselectivity (78%).51 The [l,2-(diphenylphos-phino)ferrocenyl]ethyldicyclohexylphosphine (JOSIPHOS) ligand52 (16) in combination with... 

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... 

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. 

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. 

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).

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]. 

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... 

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