Asymmetric reduction, ruthenium

The first example of an asymmetric reduction of C=N bonds proceeding via DKR was reported in 2005 by Lassaletta et al. In this process, the transfer hydrogenation of 2-substituted bicyclic and monocyclic ketimines could be accomplished via DKR by using a HCO2H/TEA mixture as the hydrogen source and a chiral ruthenium complex including TsDPEN ligand,... 

Manufacture of ruthenium precatalysts for asymmetric hydrogenation. The technology in-licensed from the JST for the asymmetric reduction of ketones originally employed BINAP as the diphosphine and an expensive diamine, DAIPEN." Owing to the presence of several patents surrounding ruthenium complexes of BINAP and Xylyl-BINAP, [HexaPHEMP-RuCl2-diamine] and [PhanePHOS-RuCl2-diamine] were introduced as alternative catalyst systems in which a cheaper diamine is used. Compared to the BINAP-based systems both of these can offer superior performance in terms of activity and selectivity and have been used in commercial manufacture of chiral alcohols on multi-100 Kg scales. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

In order to show the versatility of the method Davis extended the concept to other hydrophilic liquids such as ethylene glycol and glycerol [70], The reactions then take place at the hydrophilic-hydrophobic liquid interface. In this specific example the supported-phase concept was used for asymmetric reduction using a ruthenium catalyst. 

Use of ruthenium(III) chloride with poly-L-methylethylenimine is said to give a homogeneous catalyst for asymmetric reduction of the keto... 

Asymmetric reduction of carbonyl via hydrogenation catalyzed by ruthenium(II) BINAP complex. 

Asymmetric reductive acetylation was also applicable to acetoxyphenyl ketones. In this case the substrate itself acts as an acyl donor. For example, m-acetoxyace-tophenone was transformed to (R)-l-(3-hydroxyphenyl)ethyl acetate under 1 atm H2 in 95% yield [16] (Scheme 1.12). The pathway of this reaction is rather complex. It was confirmed that nine catalytic steps are involved two steps for ruthenium-catalyzed reductions, two steps for ruthenium-catalyzed racemizations, two steps... 

Antimalarials Mefloquine is a major drug for malaria, in particular, for chloroquine-resistant malaria." However, some cases of neuropsychiatric adverse events and the apparition of resistance tend to limit its use. Metabolism into inactive and phototoxic 1 -7/-2-oxoquinoline is blocked by the presence of the CF3 group." Instead of performing the resolution of enantiomers at the end of the synthesis," the asymmetric reduction of the carbonyl group in the presence of ruthenium catalyst and a chiral diphosphine provided mefloquine with an excellent enantiomeric excess (Figure 8.25). °... 

The direct, in situ formation of highly efficient ruthenium catalysts for the asymmetric reduction of ketones was accomplished by combining chiral ligand... 

In order to reduce the time needed to perform a complete kinetic resolution Lindner et al53 reported the use of the allylic alcohol 30 in enantiomerically enriched form rather than a racemic mixture in kinetic resolution. Thus, the kinetic resolution of 30 was performed starting from the enantiomerically enriched alcohol (R) or (S)-30 (45%) ee obtained by the ruthenium-catalyzed asymmetric reduction of 32 with the aim to reach 100 % ee in a consecutive approach. Several lipases were screened in resolving the enantiomerically enriched 30 either in the enantioselective transesterification of (<5)-30 (45% ee) using isopropenyl acetate as an acyl donor in toluene in non-aqueous medium or in the enantioselective hydrolysis of the corresponding acetate (R)-31, (45% ee) using a phosphate buffer (pH = 6) in aqueous medium. An E value of 300 was observed and the reaction was terminated after 3 h yielding (<5)-30 > 99% ee and the ester (R)-31 was recovered with 86% ee determined by capillary GC after 50 % conversion. 

A number of methods have been developed for the asymmetric reduction of acetylpyridines. Asymmetric hydrogenation of 2- and 3-acetylpyridine occurs in high yield and >94% ee to give the (A)-alcohol product using 2.5 mol% chiral ruthenium complex 71 in 2-propanol in an autoclave pressurized with 50 atm of hydrogen gas <20000L1749>. 

Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

The newly developed ruthenium catalyst 184, having 2,2-bis(diphenyl-phosphanyl)-l, 1-binaphthyl (BINAP) and 2-picolylamine as ligands, effects asymmetric reduction of/-butyl (2-thienyl) ketone under mild conditions with very high enantioselectivity <2005JA8288>. The (6 )-enantiomer of the complex leads to the (/ )-alcohol with 98% ee (Equation 84). 

Asymmetric reduction The ruthenium(II)-BINAP catalysts developed by Noyori s group in 1980s were the most successful for the asymmetric hydrogenation of functionalized ketones such as a-ketoesters, a-hydroxyketones and a-aminoketones because the second... 

Asymmetric reduction with very high enantioselectivity has also been achieved with achiral reducing agents and optically active catalysts. Two approaches are represented by (1) homogeneous catalytic hydrogenation with the catalyst 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl-ruthenium acetate, BINAP Ru(OAc)2, which reduces... 

The asymmetric reduction of aryl ketone can be achieved with ruthenium catalysts (Scheme 24), prepared separately or in situ by formation of [RuCl2(arene)]2 and ligand, in z-PrOH [81]. The high enantioselectivities and rate are very dependent upon the functionality of the substrate, T -arene and A -substitution of the diamino or amino alcohol ligands on ruthenium [81]. The hydrogen transfer reaction in z-PrOH is reversible, necessitating low concentrations, while extensive... 

All effective catalysts for the asymmetric reduction of prochiral C=N groups are based on complexes of rhodium, iridium, ruthenium, and titanium. Whereas in early investigations (before 1984) emphasis was on Rh and Ru catalysts, most recent efforts were devoted to Ir and Ti catalysts. In contrast to the noble metal catalysts which are classical coordination complexes, Buchwald s a sa-titanocene catalyst for the enantioselective hydrogenation of ketimines represents a new type of hydrogenation catalyst [6]. In this chapter important results and characteristics of effective enantioselective catalysts and are summarized. 

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