Imines homogeneous hydrogenation

Early transition-metal complexes have been some of the first well-defined catalyst precursors used in the homogeneous hydrogenation of alkenes. Of the various systems developed, the biscyclopentadienyl Group IV metal complexes are probably the most effective, especially those based on Ti. The most recent development in this field has shown that enantiomerically pure ansa zirconene and titanocene derivatives are highly effective enantioselective hydrogenation catalysts for alkenes, imines, and enamines (up to 99% ee in all cases), whilst in some cases TON of up to 1000 have been achieved. 

Until now, most studies on homogeneous hydrogenation by clusters have concentrated on alkenes and alkynes, though hopefully other substrates such as aldehydes, ketones, imines, and others will be further investigated, particularly using those systems that are now known to be genuine cluster catalysts. 

I 75 Homogeneous Hydrogenation of Aldehydes, Ketones, Imines, and Carboxylic Acid Derivatives... 

Only a few detailed studies of the reaction mechanism of the homogeneous hydrogenation of imines have been published until now. A generalization seems to be very difficult for two reasons. First, rather different catalyst types are effective and probably act by different mechanisms. Second, the effect of certain additives (especially iodide or iodine and acid/base) is often decisive for ee and rate, but a promoter in one case can be a deactivator in another case. 

Two alternatives to the homogeneous hydrogenation of the isolated MEA imine have been investigated (see Figure 1.4). The first method involved the direct ami-nation of MEA with methoxyacetone in order to avoid isolation of the MEA imine [27] the second method involved the use of immobihzed josiphos Hgands in order to avoid product distillation [28], While both variants led to the desired product with similar ee-values as the homogeneous process, both the TON and TOF were insufficient for a technical application. 

As an aside, decades of work have gone into the study of enantioselective homogeneous hydrogenation processes in both organic and aqueous systems. There is increasing commercial interest in this field spurred by the spectacular, time-encrusted development of a complex catalyst for the enantioselective hydrogenation of an imine to a chiral amine needed for manufacture of the important herbicide, (,S )-Metolaclor. The technical success of this program (Scheme l)25 owed much to the perserverance... 

The reaction mechanism of the homogeneous hydrogenation of imines has scarcely been investigated. From the available data, the catalytic cycle depicted in Figure 18, applied to the imine precursor of metolachlor, can be postulated. 

In contrast to the generally accepted mechanism for the homogeneous hydrogenation of C=C double bonds catalysed by rhodium or iridium complexes, which is assumed to occur through M(III)/M(I) species, the postulated cycle for the hydrogenation of imines involves only Ir(III) species. Many aspects remain unclear for example the simple cycle neither explains the origin of the enantioselectivity nor the effect of acids and iodide used as promoters. 

There are some reports on the asymmetric catalytic hydrogenation of C=N double bonds. Rhodium phosphine complexes do not have high activity, and the stereoselectivity is low. - Homogeneous hydrogenation of oximes, Schiff s bases and cyclic imines " have been reported. A cyano cobalt complex has been used for the homogeneous catalytic hydrogenation of oximes and Schiff s bases but the degree of asymmetric induction is unknown. 

Catalyst activity many of the classical homogeneous hydrogenation catalysts have a low activity for the hydrogenation of imines. Some of the reactions require high pressures and temperatures (which may lead to lower selectivities). 

Full details have been published on the reduction of imines to optically active amines with chiral borohydride reagents. The homogeneous hydrogenation of azo-, imino-, and nitro-groups to amine derivatives is reported a rhodium salt-sodium borohydride system is used. 

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