Chiral Ru complexes

Several chiral Ru complexes have been applied successfully for the asymmetric hydrogenation of a-, (3-, and y-diketones. Hydrogenation of an a-diketone, 2,3-butandione, catalyzed by an (i )-BINAP-Ru complex gives optically pure (R,R)-2,3-butanediol and the meso-diol in a ratio of 26 74 (Equation (73)).12a... 

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. 

Figure 1.34. Asymmetric transfer hydrogenation of imines catalyzed by chiral Ru complexes.

When the substrate is readily epimerizable, as with 3, the problem is even easier. Xumu Zhang of Pennsylvania State University reports (J. Am. Chem. Soc. 2004,126, 1626) the development of a chiral Ru complex (derived from C,-Tunephos) that selectively hydrogenates one of the two interconverting enantiomers of 3, delivering 4 with high enantioselectivity and diastereoselectivity. 

The highly enantioselective reduction of benzils was achieved by the use of the chiral Ru complex (S,S)-28 with an S/C of 1,000 in a formic acid-triethylamine mixture to give the R,R diol in >99% ee (Scheme 34) [108]. The sense of enan-tioselection was the same as that of the reduction of simple aromatic ketones, suggesting that the adjacent oxygen atom does not participate in the stereoregulation. Introduction of electron-accepting functions at the 4 and 4 positions increased the reaction rate, while the enantioselectivity was not affected by the electronic properties of the substituents. Use of 2-propanol as a hydride source caused both the rate and enantioselectivity to decrease. An unsymmetrical 1,2-... 

Cationic chiral Rh and Ru complexes were prepared by reaction of [(T -C5H5)RhCl2]2 and [RuCl2(T 6-mes)]2 with chiral bidentate or monodentate oxazoline ligands, respectively. Treatment of these monocationic metal complexes, with AgSbF produced dicationic complexes, which were also found to be highly effective for the enantioselective Diels-Alder reaction of methacrolein [12,13] (Eq. 8A.6). On the basis of spectroscopic and structural studies, a full catalytic cycle of a chiral Ru complex was proposed for the Diels-Alder reaction of cyclopen-tadiene with methacrolein [14]. 

Ketones are reduced by asymmetric hydrogen transfer from either HCO2H or 2-propanol as hydrogen sources, catalysed by chiral Ru complexes [66]. HCO2H is used... 

Asymmetric hydrogen transfer from 2-propanol to aromatic ketones such as acetophenone (99) has been achieved by using the same chiral Ru complex in 2-propanol containing KOH at room temperature, and (S)-1 -phenylethanol (100) with 98% ee was obtained [68,69]. Similarly, efficient Ru-catalysed transfer hydrogenation of aromatic ketones using the cyclic amino alcohol [(I. S, 3R,4i )-2-azanorbomylmetha-nol] (110) [70] and bis(oxazolinylmethyl) amine (111) [71] was reported. 

Another fact is the quite impressive functional group selectivity of this method. Because of their greater reactivity imines can be reduced in the presence of ketones, although chiral Ru-complex 9 catalyzes the transfer hydrogenation of ketones. Besides this catalytic enantioselective reduction of imines others are known.8... 

Asymmetric hydrogenation of cyclic imine 8 using two mol % of chiral Ru-complex 9 in a formic acid-triethylamine mixture, as developed by Noyori and co-workers, results in the desired stereoisomer 10 with an excellent optical purity of 97 %... 

By using chiral Ru complexes such as BINAP-Ru(II) or DIOP-Ru(II), 3-substituted glutaric anhydrides are enantioselectively hydrogenated to give 3-substituted d-valerolactone in up to 60% e.e. [201]. 

The Noyori asymmetric transfer hydrogenation was utilized in the synthesis of the chiral 1,2,3,4-tetrahydroisoquinolines by R.A. Sheldon et al. These compounds are important intermediates in the Rice and Beyerman routes to morphine. The "Rice imine" was exposed to a series of chiral Ru " complexes, which was prepared from r -arene-Ru " chloride dimeric complexes and A/-sulfonated 1,2-diphenylethylenediamines along with the azeotropic mixture of HCOOH/NEts. With the best catalyst the desired tetrahydroisoquinoline was isolated in 73% yield and the enantiomeric excess was 99%. 

An alternative approach is the use of a PS support bearing sulfonate pendant groups. For this, a quaternary ammonium salt of styrenesulfonic acid was copolymerized with a N-(p-styrenesulfonyl)-l,2-diphenylethylenediamine monomer. The polymeric chiral Ru complex was prepared from 177 and [RuCl2(p-cymene)]2 and applied to the asymmetric transfer hydrogenation of aromatic ketones in water (Scheme 3.55) [114]. The polymeric chiral complex was evenly suspended in water and the reaction proceeded smoothly to produce the alcohol in quantitative yield and with high enantioselectivity. For several of the aromatic ketones tested, higher... 

In contrast to air-sensitive chiral Rh-phosphine complexes, the chiral Ru complexes of BINAP or BINAP analogues were known to be more effectively... 

Ruthenium is cheaper than Rh and chiral Ru complexes have been well investigated in asymmetric work. Usually, lower induction occurs than with the corresponding Rh complexes . However, Ru complexes involving atropisomeric phosphine ligands prove superior to their Rh counterpart in many cases, and become more frequently used . 

Chiral Ru complexes are successful in reducing even y-ketoesters, producing... 

Table 7.1. presents the main characteristics of the process involving the reduction of beta-keio butyrate, i) acted upon by Baker s yeast, ii) using a Raney Ni catalyst modified by (2R,3R)-tartaric acid + NaBr, and iii) in the presence of a chiral Ru complex containing chiral diphosphine BINAP. 

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