Hydrogenation 3, 3-disubstituted enamides

Table 12.1 Hydrogenation of (3, p-disubstituted enamides by [(COD)Rh (.S,.S)-Me-BPE] and [(COD)Rh (R,R)-Me-DuPHOS] catalysts121 (results according to the literature).

The AHF of 1,1-disubstituted enamides gives access to precursors of -amino acids. Stahl and Landis [43] generated aldehyde precursors, for example, by the AHF of Af-phthaloyl 3-(benzyloxy)prop-l-en-2-amine (Scheme 4.74). Under the applied conditions, the undesired isomerization of the terminal into the nonre-active internal enamide could be suppressed. After oxidation of the formyl group, P -amino acids are obtained, which are usually prepared by an asymmetric hydrogenation route. 

A DuPHOS-Rh catalyst reduces both E and Z enamides with a high enantioselectivity even in an alcoholic solvent without E/Z isomerization [57], Notably, (3,(3-disubstituted oc-enamides are also smoothly hydrogenated to (3-branched a-amino acids [58], Sterically less-hindered Me-DuPHOS- and Me-BPE-Rh catalysts provide a high enantioselectivity. The cationic Rh complexes of TRAP [24], BisP [30], and [2.2]PHANEPHOS [27] are also active for hydro-... 

We recently have shown that this concept may be realized. A key feature of the cationic DuPHOS-Rh and BPE-Rh catalysts is their great tolerance to a broad range of solvents and organic functional groups. We have found that under the proper conditions, a wide array of both simple and p,p-disubstituted a-enamides 12 can be hydrogenated efficiently with these catalysts in SC-CO2 (Scheme 6) [35]. 

The synthesis of p,p-disubstituted a-amino acids still remains a challenge and there are few examples in which high enantioselectivities (> 95%) have been reported in the literature. The Rh-complexes of Me-BPE and Me-DuPhos were found to show excellent enantioselectivies for p,p-disubstituted a-enamide substrates (157). Good chemoselectivity was observed in the hydrogenation of substrates that contained other olefin flinctionalities. ... 

Table 3 Enantioselectivities for the Hydrogenation of P,P-Disubstituted a-Enamides Catalyzed by the Cationic Et-DuPHOS-Rh Complexes of Scheme 9 (184)...

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