Hydrogenation of simple ketones

Some chiral amino phosphine-Ru catalysts are also effective for asymmetric hydrogenation of simple ketones. 

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The generally accepted mechanism of homogeneous hydrogenation of simple ketones seems to occur by a [7r2 + cr2] pathway as depicted in Scheme 16. 

The BINAP/l,2-diamine-RuCl2 complexes require the addition of alkaline base to form reactive RuH2 species for the hydrogenation of simple ketones to neutralize releasing HC1. trans-RuH( /1-BH4)(xylbinap)(dpen) (31G) produces the active species without an additional base, while an even higher rate is obtainable in the presence of an alkaline base (Fig. 32.31) [102]. The base-free procedure can be applied to the hydrogenation of several base-sensitive ketones. For example, the reaction of ethyl-4-acetylbenzoate catalyzed by (S,SS)-31G quantitatively yields ethyl (R)-4-(l-hydroxyethyl)benzoate in 99% ee [102]. No transesterification is observed. 

Fig. 32.32 Proposed catalytic cycle of hydrogenation of simple ketones with the TolBINAP/DPEN-Ru catalyst.

Enantioselective hydrogenation of simple ketones catalyzed by BINAP/chiral diamine-Ru complexes is applied to the synthesis of biologically active compounds and a chiral phosphine ligand. Some examples are shown in Figure 32.44 [85 a, 87, 102, 128, 130, 135],... 

Fig. 32.44 Examples of biologically active compounds and a chiral ligand obtainable through hydrogenation of simple ketones catalyzed by BINAP/chiral diamine-Ru complexes.

It is well accepted that the asymmetric reduction of simple dialkyl ketones generally proceeds with low enantioselectivity.68 Ohkuma et al.69 reported that hydrogenation of simple ketones can be achieved using Ru(II) catalysts in the presence of diamine and alcoholic KOH in 2-propanol. Promising results have been achieved in the asymmetric hydrogenation of alkyl aryl ketones with a mixture of an Ru-BINAP complex, chiral diamine, and KOH (Scheme 6-33). 

Jiang et al.4 have recently succeeded in hydrogenating both aryl alkyl and dialkyl ketones. High enantioselectivity was obtained using PennPhos (19)-coordinated Rh complex as the catalyst. This success is based on the finding that a weak base (such as 2,6-lutidine) can facilitate the Rh-catalyzed hydrogenation of simple ketones (Scheme 6 35). 

TABLE 6-8. Asymmetric Hydrogenation of Simple Ketones Catalyzed by Rh-PennPhos... 

In summary, the asymmetric hydrogenation of olefins or functionalized ketones catalysed by chiral transition metal complexes is one of the most practical methods for preparing optically active organic compounds. Ruthenium and rhodium-diphosphine complexes, using molecular hydrogen or hydrogen transfer, are the most common catalysts in this area. The hydrogenation of simple ketones has proved to be difficult with metallic catalysts. However,... 

Figure 1.18. Catalytic cycle of ToIBINAP/l,2-diamine-Ru-catalyzed hydrogenation of simple ketones.

A Rh complex with (/f.S. /f.S -Me-PennPhos efficiently catalyzes asymmetric hydrogenation of simple ketones (Figure 1.22). Addition of catalytic amounts of 2,6-lutidine is crucial to achieve high enantioselectivity. This catalyst is also... 

The asymmetric hydrogenation of ketones is one of the most powerful methods for the formation of enantiomerically pure alcohols.The use of the novel mono-dentate phosphorus ligand, BrXuPHOS (1), in a mthenium(II) complex S, S, SS)-BrXuPHOS-Ru-DPEN (4), furnishes a catalyst for the asymmetric hydrogenation of simple ketones, giving the corresponding alcohols at a substrate/catalyst ratio of up to 10000 with enantioselectivities of up to 99... 

T. Ohkuma, M. Koizumi, K. Muniz, G. Hilt, C. Kabuto, and R. Noyori, tmns-RuH(etal-BH4)(binap)(l,2-diamine) a catalyst for asymmetric hydrogenation of simple ketones under base-free conditions,... 

The discovery by the recent Nobel-laureate, Ryoji Noyori, of asymmetric hydrogenation of simple ketones to alcohols catalyzed by raras-RuCl2[(S)-binap][(S,S)-dpen] (binap = [l,l -binaphthalene-2,2/-diyl-bis(diphenylphosphane)] dpen = diphenylethylenediamine) is remarkable in several respects (91). The reaction is quantitative within hours, gives enantiomeric excesses (ee) up to 99%, shows high chemoselecti-vity for carbonyl over olefin reduction, and the substrate-to-catalyst ratio is >100,000. Moreover, the non-classical metal-ligand bifunctional catalytic cycle is mechanistically novel and involves heterolytic... 

Fig. 3.33 Bifunctional Ru-BINAP(diamine) complexes for enantioselective hydrogenation of simple ketones.

Whereas 5 only reacts with bifunctional substrates, a new modification enables the catalytic hydrogenation of simple ketones 13. The ternary catalyst consisting of [Ru(II)-BINAP] and a chiral 1,2-diamine in an alcoholic solution of KOH exhibits an activity more than 1000 times that of [Ru(II)-BINAP] alone. The products have been obtained with optical purities greater than 99 % ee by choosing a suitable chiral diamine... 

Table 1. Enantioselectivities for the hydrogenation of simple ketones RCOR .

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