Rhodium-catalyzed hydrogenation enamides

Rhodium-catalyzed hydrogenation of enamides has been successfully performed using monodentate phosphites 17, with enantioselectivities of up to 95% being obtained [53]. The rate of hydrogenation is low in order to reach full conversion with a SCR of 500, hydrogenation is performed at a pressure of 60 bar for 20 h. The use of ligand 17 am in the rhodium-catalyzed hydrogenation of aromatic enamides resulted in ee-values of up to 95%. 

A broad screening of ligands and ionic liquids was carried out by Feng et al. [104]. For rhodium-catalyzed hydrogenation of enamides the best catalysts were found to be the rhodium-ferrocenyl-diphosphine complexes with taniaphos, josiphos, walphos and mandyphos as ligands (Fig. 41.9). 

Recently, high enantioselectivity was obtained in the rhodium-catalyzed hydrogenation of a-aryl enamides and E/Z-isomeric mixtures of y9-substituted enamides. Tab. 1.3 lists some examples for the hydrogenation of a-phenylenamide and the /Z-isomeric mixture of yS-methyl-a-phenylenamide. A P-chiral ligand, TangPhos, proved to be particularly efficient for the rhodium-catalyzed hydrogenation of enamides, given the excellent enantioselectivity and reactivity, with up to 10000 turnovers. 

Rhodium-Catalyzed Hydrogenation of Aromatic Enamides Using Monodentate Phosphoramidite Ligands... 

Rhodium catalyzed hydrogenation of enamides has attracted much attention recently. With the development of more efficient chiral phosphorus ligands, extremely high ee s can be obtained. Hydrogenation of tetra-substituted enamides, such as p,p-dimethyl-a-phenyl enamide derivative 56, has been reported with f-Bu-BisP and f-Bu-MiniPhos providing amide 57 with excellent ee.45... 

The asymmetric hydrogenation of enamides is a useful reaction in the production of chiral amino acids. The rhodium-catalyzed hydrogenation of enamides frequently employs bisphosphines to induce chirality. Although the hydrogenation has proven to give excellent stereoselectivity in a number of cases (Scheme 3) [28, 31 -34], some substrate-Ugand combinations result in poor stereoinduction [35,36]. 

Fig. 2 Proposed mechanism for the rhodium-catalyzed hydrogenation of enamides...

Rhodium-catalyzed enantioselective hydrogenation of N-acyl enamides provides access to enantioenriched amides which can be hydrolyzed to the free amines. The synthesis of the substtates is considerably less sttaightforward than that of N-acyl dehydroamino acids, which explains the smaller number of reports devoted to N-acyl enamides. 

Modification of the electronic and steric properties of BINAP, BIPHEMP, and MeO-BI-PHEP led to the development of new efficient atropisomeric ligands. Although most of them are efficient for ruthenium-catalyzed asymmetric hydrogenation [3], Zhang et al. have recently reported an ortho-substituted BIPHEP ligand, o-Ph-HexaMeO-BIPHEP, for the rhodium-catalyzed asymmetric hydrogenation of cyclic enamides (Scheme 1.2) [31]. 

The reaction pathway for rhodium-catalyzed asymmetric hydrogenation of enamides is described and intermediates are defined in solution by P-31, C-13, and H-l NMR. The stereochemical relationship of bound enamide to rhodium alkyl and to the product of hydrogenation is demonstrated. Experiments involving the addition of HD to a variety of olefins in the presence of rhodium biphosphine catalysts suggest that a concerted addition of hydrogen to olefin and metal may occur in appropriate cases. 

Many other reports of ligand libraries for specific catalytic applications have been reported. Among them, Gilbertson and co-workers reported a chiral phosphine library, tested in the rhodium-catalyzed asymmetric hydrogenation of an enamide (158,159), and a similar library for the palladium-catalyzed allylation of malonates (160, 161) Hoveyda and co-workers (162, 163) reported a chiral Schiff base library, screened in the titanium-catalyzed opening of epoxides with (TMSCN) (trimethyl silyl cyanide) ... 

Rhodium-Catalyzed Asymmetric Hydrogenation of Olefins. MiniPHOS (1) can be used in rhodium-catalyzed asymmetric hydrogenation of olefinic compounds. The complexation with rhodium is carried out by treatment of 1 with [Rh(nbd)2]BF4in THF (eq 2). The hydrogenation of a-(acylamino)acrylic derivatives proceeds at room temperature and an initial H2 pressure of 1 or 6 atm in the presence of the 0.2 mol% MiniPHOS-Rh complex 2. The reactions are complete within 24—48 h to afford almost enantiomerically pure a-amino acids (eq 3). Itaconic acids, enamides, and dehydro-3-ami no acids can also be hydrogenated with excellent enantioselectivity (eq 4—6). 

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