Ru-TsDPEN catalyst

Preparation of polymer-supported ru-tsdpen catalysts and their use... 

PREPARATION OF POLYMER-SUPPORTED RU-TSDPEN CATALYSTS AND THEIR USE FOR ENANTIOSELECTIVE SYNTHESIS OF (5)-FLUOXETlNE... 

As the transfer hydrogenation reactions using Ru-TsDPEN catalyst could take place in aqueous solution [108-111], the next stage was to develop a polymeric catalyst suitable for the aqueous conditions. One such example was the use of PEG as a polymer support, as reported by Xiao [112]. The PEG-supported TsDPEN 176 (Scheme 3.54) was highly effective in the Ru(II)-catalyzed transfer hydrogenation of simple ketones by sodium formate in water. The same polymeric catalyst was also effective for the same reaction by using a formic acid-triethylamine azeotrope [113]. 

The above catalytic systems for the asymmetric hydrogenation of quinolines are mainly iridium catalysts. In 2008, Fan and coworkers developed recyclable phos phine free chiral cationic ruthenium catalyzed asymmetric hydrogenation of qui nolines [23]. They found that the phosphine free cationic Ru/TsDPEN catalyst exhibited unprecedented reactivity and high enantioselectivity in the hydrogenation of quinolines in neat ionic liquid. The results were very excellent and enantioselec... 

PNU-142721, a potent anft-HIV medicine. Wills reported that his tethered version of the Ru(TsDPEN) catalyst is also highly effective for asymmetric reduction of 2,6-diacetylpyridine with a mixture of HC02H/N(C2H5)3 to a chiral diol with 99.6% ee in 91% yield [36]. 

Ionic liquids have also been applied in transfer hydrogenation. Ohta et al. [110] examined the transfer hydrogenation of acetophenone derivatives with a formic acid-triethylamine azeotropic mixture in the ionic liquids [BMIM][PF6] and [BMIM][BF4]. These authors compared the TsDPEN-coordinated Ru(II) complexes (9, Fig. 41.11) with the ionic catalyst synthesized with the task-specific ionic liquid (10, Fig. 41.11) as ligand in the presence of [RuCl2(benzene)]2. The enantioselectivities of the catalyst immobilized by the task-specific ionic liquid 10 in [BMIM][PF6] were comparable with those of the TsDPEN-coordinated Ru(II) catalyst 9, and the loss of activities occurred one cycle later than with catalyst 9. 

The enantioselectivities obtained with the catalyst immobilized by the task specific ionic liquid 2 in [BMIM][PF6] were found to be comparable with those of the TsDPEN-coordinated Ru(il) catalyst 1 and reached 93%. Both systems could be recycled five times with only a slight decrease in conversion in cycles 4 and 5 for the TsDPEN-coordinated Ru(ii) catalyst 1. The recycling results are displayed in Table 5.3-6. 

The high enantioselectivity in the hydrogenation of ketones to chiral secondary alcohols, achieved by using chiral diphosphines and amine-based Ru complexes under neutral to slightly basic conditions, was reviewed. The high reactivity was attributed to a concerted six-membered transition state. The j -arene/TsDPEN-Ru (TsDPEN = A -(p-toluenesulfonyl)-l,2-diphenylethylenediamine) and MsDPEN-Cp Ir catalysts affected the asymmetric reaction under slightly acidic conditions. ... 

As already mentioned, Ru-tethered complexes (like 24) usually exhibited higher efficiency in ATH than the original Noyori s Ru(ll)-TsDPEN catalysts (like 26). Rhodium versions of tethered complexes were also prepared and extensively studied in TH of ketones by Wills and co-workers. They reported the use of the first tethered amino alcohol-Rh(III) catalyst 123 in ATH which, however, did not remain stable under reduction conditions (basic i-PrOH) [99]. Replacing the amino alcohol with TsDPEN linked to an arene ring resulted in complex 124 which proved to be a very effective catalyst in ATH and demonstrated improved activity over its untethered version [100]. It is noteworthy that, using the catalyst 124, a-tetralone was reduced with 99.9 % ee which was the highest enantioselectivity reported for this substrate. Even though Ru(II) catalysts are more economical and more versatile... 

Another magnetically recoverable catalytic silica microreactors 156 were prepared and tested in the ATH of ketones in aqueous medium [135]. Magnetite nanoparticles were coated with shells synthesised via co-polymerisation of Si(OEt)4 and the Ru-TsDPEN complex 157 functionalised with a trimethoxysilane group. The transport of the hydrophobic reactants from the water medium to an entrapped catalyst in a sol-gel matrix was ensured by the surfactant CTAC. Under these conditions, ring-substituted acetophenones were almost quantitatively reduced with HC02Na giving the corresponding alcohols in over 90 % ees within 24 h (Fig. 49). 

In addition to the more established TsDPEN ligand derivatives, proline-derived water-soluble arene Ru(ll) catalysts containing sulfonylated ligands have been used for ATH of Qt-aryl ketones and imines in aqueous solution [80]. The ligands in Fig. 17 were prepared and incorporated into Ru(II) aqua complexes (i.e. cationic) ... 

A mesoporous silica-supported TsDPEN/Ru(II) catalyst was also productively applied to this transformation [76]. 

Soni, R. Hall, T. H. Mitchell, B. P. Owen, M. R. Wills, M. Asymmetric reduction of electron-rich ketones with tethered Ru(II)/TsDPEN catalysts using formic acid/triethylamine or aqueous sodium formate. /. Org. Chem. 2015,80,6784-6793. 

The asymmetric synthesis of allenes via enantioselective hydrogenation of ketones with ruthenium(II) catalyst was reported by Malacria and co-workers (Scheme 4.11) [15, 16]. The ketone 46 was hydrogenated in the presence of iPrOH, KOH and 5 mol% of a chiral ruthenium catalyst, prepared from [(p-cymene) RuC12]2 and (S,S)-TsDPEN (2 equiv./Ru), to afford 47 in 75% yield with 95% ee. The alcohol 47 was converted into the corresponding chiral allene 48 (>95% ee) by the reaction of the corresponding mesylate with MeCu(CN)MgBr. A phosphine oxide derivative of the allenediyne 48 was proved to be a substrate for a cobalt-mediated [2 + 2+ 2] cycloaddition. 

Ikariya and Noyori et al. also reported the synthesis of new chiral Cp Rh and Cp Ir complexes (13 and 14) bearing chiral diamine ligands [(R,R)-TsCYDN and (R,R)-TsDPEN] (Scheme 5.10) these are isoelectronic with the chiral Ru complex mentioned above, and may be used as effective catalysts in the asymmetric transfer hydrogenation of aromatic ketones [42], The Cp Ir hydride complex [Cp IrH(R,R)-Tscydn] (14c) and 5-coordinated amide complex (14d), both of which would have an important role as catalytic intermediates, were also successfully prepared. 

In conclusion, we have found a convenient and practical method for the selective reduction of C=0 bond of a wide spectrum of a-keto-)S, -unsaturated esters with Ru(p-cymene)(TsDPEN) as catalyst. The transition metal catalyzed transfer hydrogenation reaction with good selectivity and high efficiency offers possibilities to provide the optically active a-hydroxy-/l, y-unsaturated esters with chiral catalysts. Table 3.8 gives different substrates that can be reduced with Ru(p-cymene) (TsDPEN) complex in isopropyl alcohol. 

---