A,3-Dehydroamino acids

In 2004, a series of other chiral thioether-phosphine ligands based on a cyclopropane backbone were evaluated in the rhodium-catalysed hydrogenation of a dehydroamino acid by Molander el al As shown in Scheme 8.2, even if these ligands were generally active, only moderate enantioselectivities of up to 47% ee were obtained. 

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... 

Table 2 Asymmetric hydrogenation of / ,/3-dimethyl a-dehydroamino acid esters...

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. 

In the case of the a-dehydroamino acid (Fig. 10.23, right), it could be shown by using low-temperature NMR spectroscopy that the isolated crystals correspond to the major substrate complex in solution. However, according to the major-minor concept (see Scheme 10.2), it does not lead to the main enantiomer [63]. On the contrary, it could be proven unequivocally for various substrate complexes with yS-dehydroamino acids that the isolated substrate complexes are major-substrate complexes. Surprisingly, they also gave the main enantiomer of the asymmetric hydrogenation, which would not be expected on the basis of... 

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]. 

The parent DuPhos and BPE ligands exhibit excellent enantioselectivities routinely in excess of 95% with the majority of model a-dehydroamino acid substrates (Table 24.1) [4a, 8, 12, 13, 20, 90]. High molar SCRs (in the order of >1000 1), as well as TOFs in excess of 1000 h 1, are indicative of the high catalyst activity and productivity typically found with DuPhos and BPE systems with these simple substrates. Burk reported that in the enantiomeric hydrogenation... 

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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