Hydrogen transfer reduction of ketones

Table 9.3 Hydrogen transfer reduction of ketones using Ru (II)-(/5, 3R, 4R J-i-hydroxymethyl-2-azabicyclo [2.2.1]heptane as catalyst.

Asymmetric alkylation of benzaldehyde can be performed in a toluene/FC-72 biphasic system with Ti(0-iPr)4 and the fluorous BINOL ligand 7 (Figure 2) with reasonable yield and enantioselectivity [24]. The asymmetric hydrogen-transfer reduction of ketones works fairly... 

One place to look for good alcohol racemization catalysts is in the pool of catalysts that are used for hydrogen transfer reduction of ketones. One class of complexes that are excellent catalysts for the asymmetric transfer hydrogenation comprises the ruthenium complexes of mono sulfonamides of chiral diamines developed by Noyori and coworkers [20, 21]. These catalysts have been used for the asymmetric transfer hydrogenation of ketones [20] and imines [21] (Fig. 9.9). 

Scheme S.S Hydrogen-transfer reduction of ketones under FBS conditions.

Asymmetric transfer hydrogenation of ketones in the presence of soluble transition metal catalysts has been developed [8-10], enantioselectivities up to 99% ee being obtained using a ruthenium catalyst bearing mono-N-tosylated diphenyl-ethylenediamine as a ligand. Iridium complexes associated with fluorous chiral diimines 3a-3c or diamines 4a—4b have also been shown to be effective catalysts in hydrogen-transfer reduction of ketones [11,12]. 

Pincer organometallic compounds are reported mainly with regard to two types of compounds, PCP and NCN transition metal complexes [28, 34]. However, ruthenium pincer CNN compounds have also been applied to hydrogen-transfer reductions of ketones. 

Another very recent development in the field of enzymatic domino reactions is a biocatalytic hydrogen-transfer reduction of halo ketones into enantiopure epoxides, which has been developed by Faber, Bornscheuer and Kroutil. Interestingly, the reaction was carried out with whole lyophilized microbial cells at pH ca. 13. Investigations using isolated enzymes were not successful, as they lost their activity under these conditions [26]. 

Poessl, T.M., Kosjek, B., Ellmer, U. et al. (2005) Non-racemic halohydrins via biocatalytic hydrogen-transfer reduction of halo-ketones and one-pot cascade reaction to enantiopure epoxides. Advanced Synthesis and Catalysis, 347 (14), 1827-1834. 

Sinou and coworkers evaluated a range of enantiopure amino alcohols derived from tartaric acid for the ATH reduction of prochiral ketones. Various (2R,iR)-i-amino- and (alkylamino)-l,4-bis(benzyloxy)butan-2-ol were obtained from readily available (-I-)-diethyl tartrate. These enantiopure amino alcohols have been used with Ru(p-cymene)Cl2 or Ir(l) precursors as ligands in the hydrogen transfer reduction of various aryl alkyl ketones ee-values of up to 80% have been obtained using the ruthenium complex [93]. Using (2R,3R)-3-amino-l,4-bis(benzyloxy)butan-2-ol and (2R,3R)-3-(benzylamino)-l,4-bis(benzyloxy)butan-2-ol with [lr(cod)Cl]2 as precursor, the ATH of acetophenone resulted in a maximum yield of 72%, 30% ee, 3h, 25 °C in PrOH/KOH with the former, and 88% yield, 28% ee, 120 h with the latter. 

Leautey, M. Jubault, P. Pannecoucke, X. Quirion, J.-C. Synthesis and evaluation of a broad range of new chiral (aminoalkyl)phos-phane ligands for asymmetric hydrogen-transfer reduction of prochiral ketones. Eur. J. Org. Chem. 2003, 3761-3768. 

The catalytic performance of these hybrid materials has been evaluated in the hydrogen-transfer reduction of prochiral ketones (Scheme 5). 

TABLE 5.7 Hydrogen Transfer Reduction of Unsaturated Ketones over MgOai>... 

Aluminium alkoxides were anchored in the pores of siliceous MCM-41 type materials. The resulting catalysts were used in the hydrogen transfer reduction of a,p-unsaturated ketones to the corresponding allylic alcohols. The most active material is obtained by exposure of MCM-41 to a toluene solution of Al(OPr )3. With benzalacetone as a model substrate, optimum reaction conditions are cyclopentanol (hydride donor), toluene (solvent), and addition of 5A molecular sieve (water trapping). 

While, transition metal complexes (mostly of Ru, Rh and Ir) have been widely studied in homogenous TH of ketones, much less attention has been devoted to the hydrogen transfer reduction of carbonyl compounds under heterogeneous conditions. Generally, homogeneous catalysts are far more active and selective than... 

A clean hydrogen-transfer reduction of aldehydes and ketones to the corresponding alcohols has been reported. In a typical experiment, propan-2-ol is employed as reductant and solvent in an autoclave at 220-230°C and 4-5MPa. Although formally similar to Meerwein-Ponndorf-Verley reduction, the reaction requires no catalyst, which tends to cut down on side-products. 

Although metals have been supplanted for synthetic purposes by hydride donors in reactions involving addition of hydrogen, the reduction of ketones to alcohols in ammonia or alcohols provides some mechanistic insight into this group of reactions. The overall course of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl formed by a single-electron transfer. The intermediate, depending on its structure and the medium, maybe protonated, may disproportionate, or may dimerize. In hydroxylic solvents such as liquid ammonia or in the presence of alcohols, the protonation process dominates over dimerization. 

The advantages of hydrogen transfer over other methods of hydrogenation comprise the use of readily available hydrogen donors such as 2-propanol, the very mild reaction conditions, and the high selectivity. High concentrations of the reductant can be applied and the hydrogen donor is often used as the solvent, which means that mass transfer limitations cannot occur in these reactions. The uncatalyzed reduction of ketones requires temperatures of 300 °C [29]. 

Transition-metal catalysts are, in general, more active than the MPVO catalysts in the reduction of ketones via hydrogen transfer. Especially, upon the introduction of a small amount of base into the reaction mixture, TOFs of transition-metal catalysts are typically five- to 10-fold higher than those of MPVO catalysts (see Table 20.7, MPVO catalysts entries 1-20, transition-metal catalysts entries 21-53). The transition-metal catalysts are less sensitive to moisture than MPVO catalysts. Transition metal-catalyzed reactions are frequently carried out in 2-propanol/water mixtures. Successful transition-metal catalysts for transfer hydrogenations are based not only on iridium, rhodium or ruthenium ions but also on nickel [93], rhenium [94] and osmium [95]. It has been reported that... 

Alcohols will serve as hydrogen donors for the reduction of ketones and imi-nium salts, but not imines. Isopropanol is frequently used, and during the process is oxidized into acetone. The reaction is reversible and the products are in equilibrium with the starting materials. To enhance formation of the product, isopropanol is used in large excess and conveniently becomes the solvent. Initially, the reaction is controlled kinetically and the selectivity is high. As the concentration of the product and acetone increase, the rate of the reverse reaction also increases, and the ratio of enantiomers comes under thermodynamic control, with the result that the optical purity of the product falls. The rhodium and iridium CATHy catalysts are more active than the ruthenium arenes not only in the forward transfer hydrogenation but also in the reverse dehydrogenation. As a consequence, the optical purity of the product can fall faster with the... 

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