Imine hydrogenation, asymmetric

Asymmetric catalytic hydrogenation is unquestionably one of the most significant transformations for academic and industrial-scale synthesis. The development of tunable chiral phosphorous ligands, and of their ability to control enantioselectivity and reactivity, has allowed asymmetric catalytic hydrogenation to become a reaction of unparalleled versatility and synthetic utility. This is exemplified in the ability to prepare en-antiomerically enriched intermediates from prochiral olefins, ketones, and imines through asymmetric hydrogenation, which has been exploited in industry for the synthesis of enantiomerically enriched drugs and fine chemicals. 

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 ... 

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. 

Other aminophosphines have also been sought and applied in different enantio-selective transformations, e. g., allylic substitution [56] (up to 95 % ee), and Ir-based imine hydrogenation (88% ee) [57]. Chiral aminophosphines have also been investigated in the asymmetric transfer hydrogenation of ketones (up to 84 % ee for the reduction of aryl ketones) [58],... 

Chiral Amines with a Disubstituted Nitrogen Atom, HNR R 183 Table 6.1 Metals used in catalysts for direct asymmetric imine hydrogenation. 

A Representative Synthesis It would be inappropriate, and near impossi ble, to review asymmetric imine hydrogenation without discussing (S) metolachlor. A great deal of progress in the iridium catalyzed asymmetric hydrogenation of imines has been inspired by the industrial synthesis of (S) metolachlor and by the extremely well documented development of this synthesis [28 30]. The key step in the commercial synthesis of (S) metolachlor is the hydrogenation of MEA imine, E (Scheme 6.2) [67]. 

Scheme 6.9 Asymmetric imine hydrogenation to produce the sultams 35.

Imine hydrogenation produces an N H bond, so the chiral amines produced by this method will necessarily have mono or disubstituted N atoms. Chiral NR-R R amines can, however, be produced by asymmetric hydrogenation, using N,N disubstituted iminium ions or enamines as substrates. Neither of these substrate classes has been studied to the same extent that imines have, but both can be hydrogenated enantioselectively. 

Hydrogen transfer. Using Hantzsch ester as hydrogen source imines undergo asymmetric reduction that is catalyzed by BINOL phosphates. The 3,3 -bis(9-anthracenyl)-binaphthyl phosphate ent-lA mediates the saturation of C=N bond and semihydrogenation of a conjugated triple bond. ... 

In recent years an amazing number and variety of chiral ferrocene ligands have been used in asymmetric catalysis. A quite remarkable example of the great utility of chiral ferrocene hgands is the synthesis of a precursor of the herbicide (IX)-metolachlor by an Ir-Xyliphos-catalysed asymmetric imine hydrogenation reaction (Scheme 3.19). 

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