Hydrogenation of Ketones and Imines

This is an expedient synthetic route to 1,2- and 1,3-amino alcohols 22, which are important building blocks for the preparation of many natural and pharmaceutical products. Good results have been obtained with the electron-rich diphosphines DuanPhos and BINAPINE (Table 7.6). 

Good yields and enantioselectivities could be obtained for both types of substrates. DuanPhos led to better enantioselectivities with primary a-amino ketones (entries 2-4) and secondary p-amino ketones (entries 7-10) whereas BINAPINE was better suited to hydrogenate secondary a-amino ketones (entries 1, 5 and 6). 

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Noyori and coworkers reported well-defined ruthenium(II) catalyst systems of the type RuH( 76-arene)(NH2CHPhCHPhNTs) for the asymmetric transfer hydrogenation of ketones and imines [94]. These also act via an outer-sphere hydride transfer mechanism shown in Scheme 3.12. The hydride transfer from ruthenium and proton transfer from the amino group to the C=0 bond of a ketone or C=N bond of an imine produces the alcohol or amine product, respectively. The amido complex that is produced is unreactive to H2 (except at high pressures), but readily reacts with iPrOH or formate to regenerate the hydride catalyst. 

Palmer and Wills in 1999 reviewed other ruthenium catalysts for the asymmetric transfer hydrogenation of ketones and imines [101]. Gladiali and Mestro-ni reviewed the use of such catalysts in organic synthesis up to 1998 [102]. Review articles that include the use of ruthenium asymmetric hydrogenation catalysts cover the literature from 1981 to 1994 [103, 104], the major contributions... 

I 5 Catalytic Activity of Cp Iridium Complexes in Hydrogen Transfer Reactions Table 5.3 Transfer hydrogenation of ketones and imines catalyzed by ll. "... 

Chan et al. synthesized first- and second-generation dendrimers containing up to 12 chiral diamines at the periphery (Fig. 8) [29]. Their ruthe-nium(II) complexes displayed high catalytic activity and enantioselectivity in the asymmetric transfer hydrogenation of ketones and imines. Quantitative yields, and in some cases a slightly higher enantioselectivity compared to those of the monomeric systems (up to 98.7% ee), were obtained. 

The use of the Rh complex 29 bearing a tridentate carbene ligand has also been described for the transfer hydrogenation of ketones and imines [74], The catalyst was found to be highly active, needing only 0.001 mol% (up to 68 000 TON) to completely reduce to substrates. 

These spacer-free Janus bis-carbene complexes were successfully employed in the intramolecular cyclisation of acetylenic carboxylic acids (4-pentynoic acid and 5-hexynoic acid) as well as the transfer hydrogenation of ketones and imines. 

Precursor of Useful Chiral Ligands. OPEN is widely used for the preparation of chiral ligands. Organometallic compounds with these ligands act as useful reagents or catalysts in asymmetric induction reactions such as dihydroxylation of olefins, transfer hydrogenation of ketones and imines, Diels-Alder and aldol reactions, desymmetrization of meso-diols to produce chiral oxazolidinones, epoxidation of simple olefins, benzylic hydroxylation, and borohydride reduction of ketones, imines, and a,p-unsaturated carboxylates. ... 

Ligands for Iron-based Homogeneous Catalysts for the Asymmetric Hydrogenation of Ketones and Imines... 

Following the development of successful catalytic hydrogenation of olefins, recent attention is directed to catalytic hydrogenation and transfer hydrogenation of ketones and imines [77]. Because of requirement of production of various pharmaceutical compounds of importance, further development is expected in asymmetric catalytic hydrogenation. 

Since the discovery of the Wilkinson catalyst, most of the work on hydrogenation has been carried out with functionalised alkenes as substrates and Rh(I) complexes as catalytic precursors. These hydrogenations are discussed in the next sections. There are also a few results on hydrogenation of ketones and imines, described in Section 7.2.3. 

Complexes of primary and secondary amines can serve as reactive ligands. For example, 1,2-diamines have acted in a hybrid fashion on catalysts for enantioselective hydrogenation of ketones and imines, serving a role in both controlling structure and delivering the hydrogen to the ketone or imine, as shown schematically in Figure 2.38. " ... 

A classic reduction of ketones is the Meerwein-Pondorf-Verlay reaction, in which a ketone is reduced by an alcohol in an equilibrium process catalyzed by aluminum oxides. A modern version of this overall transformation that occurs by a different mechanism is the "transfer hydrogenation" of ketones and imines using alcohols as reagent. For years, little progress on this reaction had been made with transition metal complexes. However, a breakthrough was made when Noyori discovered that ruthenium complexes of amino sulfonamides (Figure 15.15) and amino alcohols catalyze... 

Vaclavik, J. Kacer, R Kuzma, M. Cerveny, L. Opjxjrtimities offered by chiral n6-arene/N-arylsulfonyl-diamine-RuII catalysts in the asymmetric transfer hydrogenation of ketones and imines. Molecules 2011,16,5460-5495. 

Shvo s catalyst 1 is a cyclopentadienone-ligated dimthenium complex, [Ru2(CO)4 (/t-H)(C4Ph4COHOCC4Ph4)]. It was first synthesized in 1984 by Shvo et al. [1, 2], Since then it has been widely applied in various hydrogen transfer reactions, including hydrogenation of carbonyl compounds [2, 3], transfer hydrogenation of ketones and imines [4,5], disproportion of aldehydes to esters [6], and Oppenauer-type oxidations of alcohols [7-9] and amines [10-12]. Shvo s complex 1 has also been found to be effective as a racemization catalyst for secondary alcohols and amines, and complex 1 has therefore been used together with enzymes in several dynamic kinetic resolution (DKR) protocols [13-18]. 

The particular features of phosphonium salts were exploited for a number of synthetic applications in 2014. Phosphonium chloride salts found applications as chlorine source and as modifiers for homogeneous catalyst systems. As an example, Muller, Rosenthal and co-workers reported the study of a chromium-based catalyst for the selective tri-merization of ethylene. A phosphonium precursor of the type i cyclo-(PR2CH2CH(OH) )2][Br]2) was used for the preparation of iron(n) complexes containing unsymmetrical P-N-P pincer ligands (Scheme 5). The group of Prof. Morris tested these compounds as catalysts for the asymmetric hydrogenation of ketones and imines. ... 

Noyori Asymmetric Transfer Hydrogenation Noyori s well-designed chiral Ru -arene complexes catalyze the asymmetric transfer hydrogenation of ketones and imines (not shown) with stable organic hydrogen donors such as 2-propanol [69]. The reaction is reversible, and the involved chiral ruthenium species and the proposed transition state are depicted in Scheme 2.140. 

Li L, Wu J, Wang F, Liao J, Zhang H, Lian C, Zhu J, Deng J. Asyimnetric transfer hydrogenation of ketones and imines with novel water-soluble chiral diamine as ligand in neat water. Green Chem. 2007 9 23-25. 

Bifunctional rhenium complexes [Re(H)(N0)(PR3)(C5H40H)] (R = Cy, j-Pr) have effected the transfer hydrogenation of ketones and imines DFT calculations suggest a secondary-coordination-sphere mechanism for the former. ... 

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