Et-DuPHOS

It was assumed that pyridine derivative 181 yielded pyrido[l,2-c]pyrimidine betaine 182 under catalytic hydrogenation conditions over (5,S)-Et-DuPHoS-Ph catalyst (99TL1211). 6,7-Dehydro derivative 184 of trequinsin (3) was obtained from pyrimidinone 183 by heating in an 1 1 mixture of MeOH and cone. HCl under reflux (97IJC(B)349). 

The pharmaceutical industry has been giving increased attention to homogeneous asymmetric hydrogenation for the synthesis of chiral molecules due to significant improvements in this technology (1). We recendy synthesized a chiral a-amino acid intermediate using Et-DuPhos-Rh catalyst, obtaining enantiomeric pmities (EP) of... 

The eonversion as a function of time for Et-DuPhos-Rh eatalyst determined in a Buehi reaetor is presented in Figure 3.3. It takes more than 700 minutes to get eomplete eonversion. It should be noted that the relationship between the reaction conversion and time is not linear exeept at the beginning of the reaetion as shown in this figure. 

It should be noted that the reaetion using Et-DuPhos-Rh catalyst is not limited by hydrogen mass transfer sinee the hydrogen mass transfer rate is at least 5 times as fast as the initial reaction rate. Furthermore, the overall reaction time, 700 minutes, remained the same regardless of the size of the reactor. 

Figure 3.3 Conversion of SM vs. Reaction Figure 3.4 Comparison between Time Using Et-DuPhos-Rh Experimental Data and...

Catalyst Decay. Asymmetric hydrogenation of the SM using the Et-DuPhos-Rh catalyst exhibits a catalyst threshold behavior. When the initial charge of the catalyst is below this threshold value, the reaction is not completed. This indicates that the catalyst may become deactivated. 

The results from the kinetic study using Et-DuPhos-Rh catalyst lead to the following snggestions for reactivity improvement ... 

Figure 3.8 Impact of MSA Addition on Figure 3.9 Reactivity of Et-FerroTane-Rh Induction Time and Reactivity. Catalyst vs. Et-DuPhos-Rh Catalyst.

Table 3.n Criteria for Commercially Viable Process Et-DuPhos-Rh Catalyst... 

Search for More Active Catalyst. An extensive screening effort was undertaken to find a catalyst more active than Et-DuPhos-Rh. As a result of this effort, Et-FerroTane-Rh and some other competitive catalysts were found. The reactivity of Et-FerroTane-Rh and Et-DuPhos-Rh, is presented in Figure 3.9. The reaction rate with Et-FerroTane-Rh catalyst is very high with a small induction period, and the total time for reaction completion is drastically less than with Et-DuPhos-Rh. 

Catalyst screen at 90 psi hydrogen at r.t. and 60 °C for 20 h - No product detected Pfaltz-lr-BARF-cat, (Et-Duphos)Rh(COD)BF4,(BINAP)Ru(ll)CI2, Phanephos/(COD)2RhBF4, Josiphos SL-J009-1/(COD)RhCI,... 

Using unmodified Ru-BINAP and Rh-Et-DUPHOS catalysts Jacobs et al. performed hydrogenation reactions of dimethylitaconate (DMI) and methyl-2-acetamidoacrylate (MAA), respectively. [11,47] The continuous hydrogenation reaction was performed in a 100 mL stirred autoclave containing an MPF-60 membrane at the bottom, which also acts as a dead-end membrane reactor. The hydrogenation reactions will be discussed in paragraph 4.6.1. 

In contrast to the many successful examples for hydrogenation of the parent itaconic acid or its dimethyl ester, only a few ligands have been reported to be efficient for the hydrogenation of / -substituted itaconic acid derivatives. Rh complexes with chiral ligands such as MOD-DIOP,69,69a 69h BPPM,246 Et-DuPhos,247 and TangPhos116 are... 

NMR spectroscopy provides analogue results. Inspection of hydrogen consumption curves following the hydrogenation of X- or E-methyl 3-acetamidobu-tenoate with [Rh(Et-DuPHOS)(MeOH)2]BF4 (Et-DuPHOS = l,2-bis(2,5-diethyl-phospholanyl)benzene)) showed the reaction to exhibit first-order kinetics (Fig. 10.19). 

Fig. 10.21 Hydrogen consumption for the hydrogenation of (Z)-3-N-acetylamino-3-(phe-nyl)-methyl propenoate with [Rh((R,R)-Et-DuPHOS)(MeOH)2]BF4 in 7-PrOH (59% ee) and (Z)-2-benzoylamino-3-(3,4-dimethoxy...

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