Hydrogenation of C-N bonds

The enantioselective hydrogenation of C=N bonds is the least-developed hydrogenation reaction, even though many active ingredients contain chiral amine moieties. The main reason for this situation is that effective catalysts - mainly Ir-diphosphine complexes - have been developed only during the past 10 years [124]. A major incentive for the development of more active catalysts was the chiral switch of metolachlor made in 1997 by Ciba-Geigy [125, 126]. 

Many of the comments related to C=0 reduction in this section also apply to the homogeneous reductions of C=N bonds, a process for which heterogeneous methods predominate192. This section will therefore concentrate on recent developments and, in particular, on asymmetric transformations. Transfer hydrogenations of C=N bonds by homogeneous catalysts have been reported264. 

Zhou explored the asymmetric hydrogenation of 2,3 disubstituted quinolines. They thought that the hydrogenation mechanism of 2,3 disubstituted quinolines was somewhat different from that of 2 substituted quinolines (Scheme 10.20) [3]. For the hydrogenation of 2 substituted quinoline, the hydrogenation of C=N bond is the enantioselectivity controlled step (Scheme 10.19, H-I), while the enantioselectivity controlled step of 2,3 disubstituted quinolines is the isomerization of enamine to imine and the hydrogenation of C=N bond, which is in fact a dynamic kinetic... 

A similar mechanism of action was found in the case of a Pd catalyst supported on silk fibroin in the asymmetric hydrogenation of C=N bonds in prochiral compounds. The mechanism of action consists of the formation of the chiral complexes on the silk fibres of the Pd-fibroin which act as chiral catalysts. This principle was later developed for a number chirally modified catalysts that are very effective in the asymmetric hydrogenation of Acta-keto esters... 

Rhodium and ruthenium complexes with chiral diphosphine ligands (L) are mainly active in hydrogenation of functionalized alkenes or ketones. In the hydrogenation of C=N bonds these complexes were less effective. And the first attempts to hydrogenate the imine precursor of the important herbicide Metolachlor (trade name DUAL) was not very successful (Scheme 7.6.). 

In recent years, a significant amount of research has been carried out on the transfer hydrogenation of C=N bonds using complexes based on a range of metals, but most frequently on the use of mthenium, iridium and rhodium. Many of the advances have... 

Fig. 37 A nickel-based catalyst for asymmetric transfer hydrogenation of C=N bonds...

SCHEME 30 J7. Enantioselective hydrogenation of C=N bond in the synthesis of (5 -metolachlor. 

Sertraline hydrochloride (known under the trade names Zoloft and Lustral, both from Pfizer) is an antidepressant chiral drug acting as a selective serotonin reuptake inhibitor (SSRI). It is primarily used in major depression treatment and as obsessive/compulsive, panic, and social anxiety disorders. Ir-Catalyzed enantioselective hydrogenation of C=N bond can be employed to install a second stereogenic... 

In addition to the example discussed in section 1.2.3, the complementary character of iminium and enamine mechanisms was also exploited for the transfer hydrogenation of C=N bonds. Reaction of 8-diketones with aromatic amines in the presence of a Hantzsch ester and an acid catalyst yields prevalently tra 5-disubstitued cyclohexylamines [74] (Scheme 2.16). In this transformation, the initially formed enamine undergoes cyclization yielding an a, 3-unsaturated iminium ion which in turn reacts with two molecules of Hantzsch ester to liberate the final product. The acid catalyst is crucial to maintain a high concentration of the iminium ion in the reaction mixture. 

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