Ketones. hydrogen transfer reduction

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. 

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.

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. 

The competition between insertion and hydrogen transfer is also crucial to the selectivity of the reaction of aluminium alkyls with carbonyl compounds. Aluminium alkyls, like organolithium compounds and Grignard reagents, can add to aldehydes and ketones to form secondary or tertiary alcohols, respectively. If the aluminium alkyl has a j -hydrogen, however, reduction of the carbonyl compound is a common side reaction, and can even become the main reaction [16]. Most authors seem to accept that reduction involves direct j5-hydrogen transfer to ketone. 

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. 

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... 

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>... 

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.

Hydrogen transfer to ketones from 2-propanol was developed into an extremely efficient method of obtaining secondary alcohols [256,257] and the use of chiral N-(p-tolylsulfonyl)diamines allow the reduction of prochiral ketones with extraordinary stereoselectivity [257-259], In general, water is not well tolerated in such processes, and several studies showed that both the rate and the enantioselectivity of transfer hydrogenations from 2-propanol decrease substantially in increasingly aqueous mixtures even in the presence of water soluble catalysts [260,261], However, in a recent study the opposite effect was found. Using the water soluble Rh- and Ir-complexes... 

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). 

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]. 

Enantioselectivities up to 56% ee were obtained using [Ir(COD)Cl]2 associated with fluorous diimines 3a-3c at 70 °C in the reduction of acetophenone with isopropanol as the hydride source in the presence of Galden D-lOO (mainly n-perfluorooctane, b.p. 102 °C) as the fluorous solvent. The hydrogen-transfer reduction was extended to other ketones, enantioselectivity of 60% ee being obtained... 

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. 

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. 

Kejrwords Dynamic kinetic asymmetric transformation (DYKAT) Dynamic kinetic resolution (DKR) Hydrogenation Imine reduction Ketone reduction Mechanism of carbonyl reduction Mechanism of imine reduction Mechanism of dUiydrogen activation Ruthenium catalysis Shvo s catalyst Transfer hydrogenation... 

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