Dehydroamino acid derivatives

In 2006, Berens et al. reported the synthesis of novel benzothiophene-based DuPHOS analogues, which gave excellent levels of enantioselectivity when applied as the ligands to the asymmetric rhodium-catalysed hydrogenation of various olefins, such as dehydroamino acid derivatives, enamides and itaco-nates (Scheme 8.10). ... 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

Enantioselectivities of up to 47% ee were reported by Ruiz et al. in 1997 for the asymmetric hydrogenation of various prochiral dehydroamino acid derivatives and itaconic acid by using iridium cationic complexes of the novel chiral... 

A C2-symmetric bisphosphane FerroPhos has been developed by Kang and is found to be efficient for the Rh-catalyzed hydrogenation of a-dehydroamino acid derivatives.86,863 Knochel has independently reported a class of FERRIPHOS (MandyPhos) with similar structural features. All these ligands have provided excellent... 

Fu has reported a planar-chiral bisphosphorus ligand 45 with a phosphaferrocene backbone. The ligand has provided enantioselectivity up to 96% ee in the hydrogenation of a-dehydroamino acid derivatives.99 Another planar-chiral ferrocene-based bisphosphorus ligand 46 has been reported by Kagan recently and enantioselectivity up to 95% ee has been obtained in the reduction of dimethyl itaconate.100... 

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... 

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. 

Under isobaric conditions (k2 = k2 H2 J. many hydrogenations exactly follow this model. The classical example is the asymmetric hydrogenation of prochiral dehydroamino acid derivatives with Rh or Ru catalysts [21]. 

Blackmond et al. investigated the influence of gas-liquid mass transfer on the selectivity of various hydrogenations [39]. It could be shown - somewhat impressively - that even the pressure-dependence of enantioselectivity of the asymmetric hydrogenation of a-dehydroamino acid derivatives with Rh-catalysts (as described elsewhere [21b]) can be simulated under conditions of varying influence of diffusion These results demonstrate the importance of knowing the role of transport phenomena while monitoring hydrogenations. 

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. 

The low ee-values obtained with simple unsaturated acids as compared to the enamides of dehydroamino acid derivatives show that the oxygen atoms of the amide is a key to complex formation with the metal center. Knowles also proposed a quadrant model that has been adapted for many reactions [5, 22]. The mechanism of the reaction has been investigated, and it is known that the addition of the substrate to the metal is regioselective and that competing catalytic cycles can occur [5, 10, 22, 25, 27, 30-46]. 

The R,S-family 33, and of course its enantiomer, provide high enantioselectiv-ities and activities for the reductions of itaconic and dehydroamino acid derivatives as well as imines [141], The JosiPhos ligands have found industrial applications for reductions of the carbon-carbon unsaturation within a,/ -unsaturated carbonyl substrates [125, 127, 131, 143-149]. In contrast, the R,R-diastereoisomerof30 does not provide high stereoselection in enantioselective hydrogenations [125, 141]. 

The recent introduction of the TaniaPhos ligands (34) provides another excellent catalyst system for the reduction of dehydroamino acid derivatives and enol... 

The rhodium complexes of the ferrocene derivatives 39 have shown useful characteristics for the reduction of itaconates as well as dehydroamino acid derivatives [15, 167-170]. These compounds are hybrids between ferrocene-based ligands and the various other types. The P-chiral compounds, which in some ways are DIPAMP hybrids, showed tolerance for the reduction of N-methyl en-amides to produce N-methyl-a-amino acid derivatives [169-171]. 

BINAP (40a) was first reported as a ligand in an enantioselective hydrogenation in 1980 [172], and provides good selectivity for the reductions of dehydroamino acid derivatives [173], enamides, allylic alcohols and amines, and a,p-unsaturated acids [4, 9, 11, 12, 174, 175]. The fame of the ligand system really came with the reduction of carbonyl groups with ruthenium as the metal [11, 176]. The Rh-BINAP systems is best known for the enantioselective isomerizations... 

In general, the choice of counteranion has a minor effect on catalyst performance, with typical examples being selected from BF4, OTD, PFg, or BARF-. In one example, however, it was noted that [(R.R)-Et-DuPhos Rh CODJOTf gave superior selectivity for the reduction of / -/ disubstituted a-dehydroamino acid derivatives than the corresponding BARF complex when performed in a range of solvents, including supercritical carbon dioxide [39]. 

Table 24.1 Phospholanes reported to hydrogenate model a-dehydroamino acid derivatives in >95% ee.

Scheme 24.7 Non-standard a-dehydroamino acid derivatives reduced by Rh-phospholane-based catalysts.

Several accounts have described (Z)-dehydroamino acid esters as being less active than the corresponding (F)-isomer [59c, 143-145]. In fact, Bruneau and Demonchaux reported that when reduction of an (E/Z)-mixture of 73 with Rh-Et-DuPhos in THF was not complete, only unreacted (Z)-73 was detected. These findings conflict, however, with results obtained in MeOH [56 d], where the ligand structure was also found to be significant to the relative reactivity of each stereoisomer. As for a-dehydroamino acid derivatives, preformed metal-diphosphine complexes generally perform in superior fashion to those prepared in situ [56d]. 

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