Hydrogenation of dehydroamino acid derivatives

Hydrogenation of ct-dehydroamino acid derivatives has been a typical reaction to test the efficiency of new chiral phosphorus ligands. Indeed, a number of chiral phosphorus ligands with great structural diversity are found to be effective for the Rh-catalyzed hydrogenation of a-dehydroamino acid derivatives. Since (Z)-2-(acetamido)cinnamic 

Ligand Substrate SIC ratio Reaction conditions Percent ee of product (confign.) References 

Compared to the great advance achieved in the Rh-catalyzed asymmetric hydrogenation, the Ru-catalyzed asymmetric hydrogenation of ct-dehydroamino acid derivatives takes a different mechanistic pathway,215 and little success has been made. 

In contrast to the high enantioselectivity achieved for the Z-isomeric substrates, hydrogenation of the E-isomers usually proceeds with lower rates and afford products with diminished enantioselectivities [92]. The rhodium-catalyzed hydrogenation of the - and Z-isomers, with BINAP as a ligand in THE, affords products with opposite absolute configurations [16]. Remarkably, the DuPhos-Rh system provides excellent enantioselectivity for both isomeric substrates with the same absolute configuration, irrespective of the /Z-geometry (Eqs. 1 and 2). This result is particularly important for the construction of alkyl dehydroamino acid derivatives, which are difficult to prepare in enantiomericaUy pure form. 

Hydrogenation of/ ,/ -disubstituted a-dehydroamino acids remains a challenging problem. Remarkably, the less bulky DuPhos- or BPE-type ligands, such as Me-DuPhos and Me-BPE, provide excellent enantioselectivity for a variety of this type of substrate [93]. The rhodium complexes of chiral ligands such as BuTRAP [46 b], f-KetalPhos [55], Cy-BisP [57a], MiniPhos [61], and unsymmetrical BisP (L9) [63 b] have also shown high efficiencies for some / ,/ -disubstituted a-dehydroamino acid substrates, as outhned in Tab. 1.2. 

The asymmetric hydrogenation of yS,yS-disubstituted a-dehydroamino acids, in which the yS-substituents are nonequivalent, provides the opportunity to selectively construct two stereogenic centers. The Me-DuPhos or Me-BPE ligands facilitate the rhodium-catalyzed hydrogenation of the E- and Z-isomers of yS,yS-disubstituted a-dehydroamino acid 

The asymmetric hydrogenation of the E- or Z-isomer of y9-(acetylamino)-y9-methyl-a-dehydroamino acids with Me-DuPhos-Rh catalyst provides either diastereomer of the N,N-protected 2,3-diaminobutanoic acid derivatives with excellent enantioselectivity (Eqs. 3 and 4) [95]. 

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NMR evidence for intermediate dihydrides of cationic Rh catalysts remained elusive for a long time, ever since the first demonstrations [33] of effective enan-tioselective catalysis, for example in the homogeneous hydrogenation of dehydroamino acid derivatives for the synthesis of L-DOPA. 

Corma and coworkers tested a number of rhodium and other transition metal complexes with ligands based on proline (Fig. 29.23). These authors reported ee-values of 54—90% for the hydrogenation of dehydroamino acid derivatives with a catalyst prepared from ligand 38 [51]. With ligand 39, an ee-value of 34% was recorded for the hydrogenation of ethyl acetamidocinnamate 10 [52]. 

The polymer-supported chiral phosphine obtained (Fig. 42.15) was treated with an Rh precursor and used for the enantioselective hydrogenation of dehydroamino acid derivatives. The obtained catalyst gave up to 82% ee, albeit with still low activity. Stille has developed this immobilization technique further by even more careful tuning of the polarity of the support with that of the reaction medium. For example, he introduced DIOP to a monomer vinylbenzalde-hyde in reactions analogous to those shown for the polymer in Figure 42.11. 

Kang et al.6 reported a practical synthesis of an air-stable ferrocenyl bis-(phosphine) (p5, p5 )-l,l,-bis-(diphenylphosphino)-2,2 -di-3-pentyl ferrocene ([5, 5]-FerroPhos, 10a) and its application in the rhodium(I)-catalyzed enan-tioselective hydrogenation of dehydroamino acid derivatives. 

Catalytic Hydrogenation of Dehydroamino Acid Derivatives. Probably the most important reaction of dehydroamino acid derivatives obtained from 5(4//)-oxazo-lones is hydrogenation of the double bond. Typically, this reaction is performed... 

It is well known that hydrogenation of dehydroamino acid derivatives derived from ring opening of unsaturated 5(4H)-oxazolones affords new racemic amino acids and, in some cases, enantiomerically pure compounds. On the other hand, a number of attempts have been made to hydrogenate the double bond of the unsaturated oxazolone itself. For example, 4-benzyl-2-methyl-5(4//)-oxazolone was prepared from 4-benzylidene-2-methyl-5(4H)-oxazolone using Raney Ni as a catalyst. This process is reported to be a general procedure to prepare saturated oxazolones directly (Scheme 7.194). 

Chiral catalysis was introduced in industrial synthesis in the mid-1970 s. The standard example is the catalytic hydrogenation of dehydroamino acid derivatives such as (Z)-2-acetyl-amino-3-phenylpropenoic acid with chiral rhodium complexes to give /V-acetylphenylalanine in high optical purity1. 

Enantioselective hydrogenations of dehydroamino acid derivatives are also catalyzed by rhodium complexes of phosphinated glucopyranosides (97). [Rh(Me-a-glup-OH)(COD)]BF4 and [Rh(Ph-/3-glup-OH)(COD)]BF4... 

Based on the concept mentioned above, Brown realized the asymmetric deactivation of a racemic catalyst in asymmetric hydrogenation (Scheme 9.18) [35]. One enantiomer of (+)-CHIRAPHOS 28 was selectively converted into an inactive complex 30 with a chiral iridium complex 29, whereas the remaining enantiomer of CHIRAPHOS forms a chiral rhodium complex 31 that acts as the chiral catalyst for the enantioselective hydrogenation of dehydroamino acid derivative 32 to give an enantio-enriched phenylalanine derivative... 

In these 1968 papers, the substrates to be hydrogenated were a-ethylstyrene, a-methoxystyrene, a-phenylacrylic acid, itaconic acid, etc. The hydrogenation of dehydroamino acid derivatives entered the literature with the papers of Kagan and co-workers [59, 60] and Knowles et al. [61]. Actually, the hydrogenation of (Z)-c -acetamidocinnamic acid to give A-acetylphenylalanine (eq. (3)) became the most frequently studied test system for the evaluation of new catalysts. 

Amino-derived BDPP (2,4-bis[diphenylphosphino]pentane) has been used in asymmetric hydrogenation catalysis [15-17] (cf. Sections 6.2 and 6.9). NMR analysis showed that a ten-fold excess of HBF4 is sufficient to protonate reversibly all four amino groups in the [Rh(diene)(BDPP)]BF4 complex. Recycling of the catalyst after enantioselective hydrogenation of dehydroamino acid derivatives in methanol is achieved by acidification with aqueous FIBF4 followed by extraction of the product with Et20. Immobilization of the protonated BDPP rhodium complex on a Nafion support has been studied as well [18]. 

Hydrogenation. Phosphoramidite ligands to make up a Rh catalyst for enantioselec-tive hydrogenation of dehydroamino acid derivatives include 10, which is derived from 3,3 -bis(diphenylphosphino)-BINOL, and 11 that contains two binaphthyl groups. ... 

Hydrogenation Easily prepared monodentate phosphoramidite ligands containing a BINOL residue are employed in conjunction with (cod)2RhBp4 in asymmetric hydrogenation of dehydroamino acid derivatives and a-substituted acrylic esters (ee > 99% reachable). 

The asymmetric hydrogenation of dehydroamino acid derivatives is stiU a popular research area. For the synthesis of N-acetyl o-alanine methyl ester, the hydrogenation is carried out in supercritical carbon dioxide with catalyst 76. On the other hand, the preparation of protected L-valine and related compounds requires the hydrogenation of a tetrasubstituted double bond. An Rh catalyst with ligand 77 is well suited for this... 

General procedure for asymmetric hydrogenation of dehydroamino acid derivative ... 

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