Asymmetric ruthenium-catalysed

In addition, several S/S ligands were also investigated for the asymmetric hydrogenation of olefins. In 1977, James and McMillan reported the synthesis of various disulfoxide ligands, which were applied to the asymmetric ruthenium-catalysed hydrogenation of prochiral olefinic acid derivatives, such as itaconic acid. These ligands, depicted in Scheme 8.16, were active to provide... 

As an alternative to the use of hydrogen gas, asymmetric ruthenium-catalysed hydrogen transfer reactions have been explored with significant success [381. 

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

In another context, chiral thioimidazolidine ligands have been successfully applied to the ruthenium-catalysed asymmetric hydrogen transfer of several aryl ketones by Kim et al., furnishing the corresponding chiral alcohols with high yields and enantioselectivities of up to 77% ee (Scheme 9.12). ... 

Figure 6.4. (Rj-BINAP ligands used in ruthenium catalysed asymmetric hydrogenation of dimethyl...

Ruthenium-catalysed asymmetric transfer hydrogenation of acetophenone 133... 

R, 4/ )-2-AZANORBORNYLMETHANOL, AN EFFICIENT LIGAND FOR RUTHENIUM CATALYSED ASYMMETRIC TRANSFER HYDROGENATION OF AROMATIC KETONES... 

Lutsenko, S. and Moberg, C., Microwave mediated ruthenium-catalysed asymmetric hydrogen transfer, Tetrahedron Asymmetry, 2001, 12, 2529-2532. 

In practice in the literature of the past 20 years the important results with ruthenium in epoxidation are those where ruthenium was demonstrated to afford epoxides with molecular oxygen as the terminal oxidant. Some examples are presented (see later). Also ruthenium complexes, because of their rich chemistry, are promising candidates for the asymmetric epoxidation of alkenes. The state of the art in the epoxidation of nonfunctionalized alkenes is namely still governed by the Jacobsen-Katsuki Mn-based system, which requires oxidants such as NaOCl and PhIO [43,44]. Most examples in ruthenium-catalysed asymmetric epoxidation known until now still require the use of expensive oxidants, such as bulky amine oxides (see later). 

Fig. 6.32. Asymmetric BINAP-ruthenium catalysed hydrogenation of enamide with cis-phenyl...

The ruthenium catalysed olefin metathesis reaction is one of the most important catalytic reactions [77-79] and one that is distinctly underdeveloped for asymmetric applications [80]. Only a few concepts have been brought forward [80,81], of which the combination of a NHC ligand with a 1,1-binaphlhyl scaffold carrying a hydroxyl anchor group is the most promising to date. 

An asymmetric route to the fused azepine derivatives 44 has been reported by Pedrosa et al. <05EJO2449>. The power of ruthenium-catalysed ring closing metathesis is further demonstrated in this synthesis, involving conversion of 43 to 44 (e.g. with R = H, R = CH3 82% yield, 92% de). Compounds of type 44 could then be readily converted into the reduced azepin-3-ol derivatives 47 via 45 and 46. 

The sertraline precursor is a chiral alcohol with the stereogenic centre adjacent to an aromatic ring. An obvious approach is to make the hydroxyl group by asymmetric reduction of the corresponding ketone. CBS reduction is a possibility, as is a ruthenium-catalysed hydrogenation using the ligand TsDPEN (p. 1115 of the textbook). 

The scope of the ruthenium-catalysed asymmetric hydrogenation is relatively wide and a diverse array of alkenes has been reduced with high enan-tioselectivity. For example, diketene (2.94), and unsaturated lactone (2.96) imdergo highly enantioselective hydrogenation using BINAP as ligand. The... 

As well as rhodium-catalysed hydrosilylation, asymmetric ruthenium and titanium-catalysed hydrosilylation have also been reported. Amongst these, Buchwald s report of the hydrosilylation of ketones using titanocene catalysts and inexpensive polymethyUiydrosiloxane (PMHS) appear to be the most general. 

As an extension of this work, a total synthesis of sulfobacin A, a von Willebrand factor receptor antagonist, was reported by the same group, in 2004. The key steps of this short route to sulfobacin A involved ruthenium-catalysed asymmetric hydrogenation reactions of a /i-ketoester and a /J-keto-a-amino ester hydrochloride to afford, respectively, the corresponding enantiomerically pure S-hydroxy ester and the enantio-enriched anti -hydroxy-a-amino ester hydrochloride through DKRs (Scheme 2.15). 

The application of dynamic kinetic discrimination to the ruthenium-catalysed hydrogenation of cyclic ketones such as 2-arylated cycloalkanones was reported by Noyori s group in 2004. Hence, the asymmetric hydrogenation of various 2-arylcycloalkanones with tra s -RuCl2(BINAP)(l, 2-diamine) and t-BuOK in ijo-propyl alcohol selectively gave the corresponding cis-2-arylcycloalkanols in excellent enantiomeric purity and quantitative yield, as shown in Scheme 2.25. 

The scope of the ruthenium-catalysed asymmetric transfer hydrogenation methodology was very recently extended to a-alkyl-substituted )S-ketoamides by Limanto et Indeed, the first enantio- and diastereoselective synthesis of various syn a-alkyl-substituted jS-hydroxyamides via highly efficient Ru-cata-lysed hydrogenation through DKR of the corresponding ) -ketoamides has been successfully demonstrated. As shown in Scheme 2.31, excellent diastereo-and enantioselectivities of up to 98% de and > 99% ee, respectively, were observed when the process was performed in CH2CI2 or toluene as the solvent. 

On the other hand, several groups have also recently developed asymmetric domino reactions through relay catalysis with combinations of organocatalysts with ruthenium catalysts. For example. You et al. demonstrated in 2009 that ruthenium catalyst could be compatible with Bronsted acid catalyst. They reported a practical and economical synthesis of chiral tetrahydropyrano[3,4-b]indols and tetrahydro-p-carbolines by the combination of ruthenium-catalysed olefin cross-metathesis and a chiral phosphoric acid-catalysed Friedel-Crafts alleviation reaction, as shown in Scheme 7.41. This domino reaction allowed the use of readily available materials to highly enantioselectively construct synthetically valuable polycyclic indole frameworks in enantioselectivity of up to 94% ee. 

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