Imines, hydrogenations

Pr(H2)CPPh3)2(solv)2]+ catalysts for imine hydrogenation have been kinetically explored. This area is notably less developed than the reduction of C=0 bonds.88,110... 

Although imine hydrogenation is discussed in greater detail in Chapter 34, it seems appropriate at this point to describe one-pot reductive amination of aldehydes and ketones. The reductive amination of aldehydes and ketones using so-... 

The first example of this type of transformation was reported in 1974 [76]. Three catalysts were investigated, namely [Co2(CO)8], [Co(CO)g/PBu ], and [Rh6(CO)i6]. The [Co OJg/PBu ] catalyst showed activity for reductive animation using ammonia and aromatic amines. The [Rh6(CO)16] catalyst could be used for reductive animation using the more basic aliphatic amines that were found to poison the cobalt catalyst. This early report pointed out that the successful reductive animation of iso-butanal (Me2CCHO) with piperidine involves selective enamine hydrogenation, that reductive animation of cyclohexanone with isopropylamine probably involves imine hydrogenation, and that reductive amination of benzaldehyde with piperidine would presumably involve the reduction of a carbinolamine. 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

For Rh and Ir diphosphine-based catalysts there exist some indications on reactive species and also on hydrogen activation. James and coworkers [43, 85] investigated the Rh-catalyzed DMA-imine hydrogenation and concluded that the imine is -coordinated to the Rh center via the nitrogen lone pair, and not via the 7i-system of the C = N bond. They also suggested that the hydrogen activation occurs after the imine is coordinated. 

The formation of dimers and trimers is a major issue in hydrogenations with iridium catalysts. In the context of developing an industrial process to produce (S)-metolachlor via an enantioselective imine hydrogenation (see Chapters 34 and 37), Blaser et al. investigated the causes of catalyst deactivation in the iri-dium/bisphosphine-catalyzed hydrogenation of DMA imine (Scheme 44.11) [84]. 

Scheme 44.11 Iridium-catalyzed enantioselective imine hydrogenation.

Fig. 44.12 Dependence of rate of imine hydrogenation on catalyst loading on the support.

Dihydrido iridium Triisopropylphosphine Complexes as Imine Hydrogenation Catalysts... 

H-NMR spectroscopic features of SAMP/RAMP-hydrazones include a singlet for the methoxy group at 3.2 3.3 ppm and, in the case of aldehyde hydrazones, a triplet for the imine hydrogen at 6.4 6.5 ppm. 

Reviews on asymmetric imine hydrogenations a) F. Spindler, H.-U. Blaser, in Transition Metals for Organic Synthesis, 2nd ed. (Eds. M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004 ... 

Despite its apparent noble character, gold catalysts have been recently found to be active in many homogeneous and heterogeneous catalytic processes such as oxidation reactions, nucleophilic additions, cross-coupling reactions, and alkene and imine hydrogenations (69—71). Corma and co-workers showed that Au... 

The use of an acidic medium, in general, is favorable for the hydrogenation with any of the above catalysts. This is presumably connected with the elimination of the inhibitory effect of the amines formed during the hydrogenation. In imine hydrogenation reactions on Rh, five- to eightfold rate increases are observed when tartaric, phthalic, mandelic, salicylic or formic acids are added to the alcoholic reaction mixture (in a 95 5 mixture of EtOH-MeOH)447. 

Figure 3.35 a Chemical structures of the four stereoisomers of metolachlor b 3D representation ofthe (aR, l S) isomer, showing the chiral axis and c the asymmetric imine hydrogenation step. 

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