Ruthenium -catalyzed asymmetric reduction

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... 

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. 

The enantio- and diastereoselective synthesis of the nitrogen-containing heterocyclic compounds 612 was achieved by a one-pot reaction via the ruthenium-catalyzed enyne coupling of 608 with 609 followed by the palladium-catalyzed asymmetric C—N bond formation (Scheme 186).264a The enyne coupling reaction proceeds through formation of the ruthenacycle 611 followed by -elimination—reductive elimination. 

We developed two highly efficient approaches toward the 5HT2b receptor antagonist LY414197. The first route utilized a Pictet-Spengler reaction to construct the racemic TH(3C derivative. Access to the most active (5)-enantiomer was then achieved in up to 70% yield through a one-pot resolu-tion-racemization process. The second approach is based on the chiral A-arenesulfonylated-1,2-diamine/ruthenium(II)-catalyzed asymmetric reduction of a 3,4-dihydro- 3-carboline precursor, obtained from a Bischler-Napieralski or related Friedel-Crafts methodology. 

Scheme 7.7. Ul relative topicity (e.g., P-BINAP/Re face) is uniformly observed for ruthenium BINAP catalyzed asymmetric reduction of functionalized ketones [70],...

Ruthenium-catalyzed asymmetric reductions of aromatic ketones 180 can be performed under microwave irradiation. Moberg [98] described this reaction using a monomode microwave reactor and ruthenium complexes 182 with enan-tiomerically pure chiral diamines 181 (Scheme 5.51). The reaction is very fast and efficient even sterically hindered tert-butylphenylketone, which is normally quite umeactive, was reduced in almost quantitative yield in 3 minutes. The enantio-selectivity was, however, lower than that obtained under standard conditions similarly to that described by Larhed [77] in the enantioselective Heck reaction between cydopentene 115 and phenyl triflate 116 (Scheme 5.33). 

Having demonstrated the potential of artificial metalloenzymes for the reduction of V-protected dehydroaminoacids, we turned our attention towards organometallic-catalyzed reactions where the enantiodiscrimination step occurs without coordination of one of the reactants to the metal centre. We anticipated that incorporation of the metal complex within a protein enviromnent may steer the enantioselection without requiring transient coordination to the metal. In this context, we selected the palladium-catalyzed asymmetric allylic alkylation, the ruthenium-catalyzed transfer hydrogenation as well as the vanadyl-catalyzed sulfoxidation reaction. Indeed, these reactions are believed to proceed without prior coordination of the soft nucleophile, the prochiral ketone or the prochiral sulfide respectively. Figure 13.5. 

Bied, C., J. J. E. Moreau, and M. Chi Man Wong, 2001. Chiral amino-urea derivatives of (lR,2R)-l,2-diaminocyclohexaneas hgands in the ruthenium catalyzed asymmetric reduction of aromatic ketones by hydride transfer. Tetrahedron Asymmetry 12 329-36. 

Strotman NA, Baxter CA, Brands KMJ, Cleator E, Krska SW, Reamer RA, Wallace DJ, Wright TJ. Reaction development and mechanistic study of a ruthenium catalyzed intramolecular asymmetric reductive amination en route to the dual orexin inhibitor suvorexant (MK-4305). J. Am. Chem. Soc. 2011 133(21) 8362-8371. 

The use of chiral ruthenium catalysts can hydrogenate ketones asymmetrically in water. The introduction of surfactants into a water-soluble Ru(II)-catalyzed asymmetric transfer hydrogenation of ketones led to an increase of the catalytic activity and reusability compared to the catalytic systems without surfactants.8 Water-soluble chiral ruthenium complexes with a (i-cyclodextrin unit can catalyze the reduction of aliphatic ketones with high enantiomeric excess and in good-to-excellent yields in the presence of sodium formate (Eq. 8.3).9 The high level of enantioselectivity observed was attributed to the preorganization of the substrates in the hydrophobic cavity of (t-cyclodextrin. 

Scheme 4.11 Asymmetric synthesis of allene via a ruthenium (I l)-catalyzed reduction.

Although the chiral ketoiminatomanganese(lll) complexes were reported to catalyze the asymmetric aerobic alkene epoxidations, an aldehyde such as pivalaldehyde is required as a sacrihcial reducing agent. Groves reported that the dioxo(porphyrinato)ruthenium complexes 31, prepared with m-chloroperoxyben-zoic acid, catalyzed the aerobic epoxidation without any reductant. " On the basis of these reports, Che synthesized the optically active D4-porphyrin 35 and applied it to the truly aerobic enantioselective epoxidation of alkenes catalyzed by the chiral frani-dioxo (D4-porphyrinato)ruthenium(Vl) complex. The dioxoruthenium complex catalyzed the enantioselective aerobic epoxidation of alkenes with moderate to good enantiomeric excess without any reductant. In the toluene solvent, the turnovers for the epoxidation of T-(3-methylstyrene reached 20 and the ee of the epoxide was increased to 73% ee. 

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