Rhodium-DuPhos system

There have been many other independent reports of excellent S/C ratios using rhodium DuPHOS systems. For the synthesis of an (R)-metalaxyl intermediate 19 [21], a turnover number of 50000 has been demonstrated using Me-DuPHOS-Rh. Hoffmann la Roche have reported the Et-DuPHOS-Rh-catalyzed hydrogenation at S/C 10000-20000 of a cyclic enol acetate 21 to provide an intermediate 22 to Zeaxanthin in 98% ee [22] (Fig. 12). 

Work on the candoxatril precursor 11 [16] gave an insight into the importance of substrate purity for efficient hydrogenation using rhodium DuPHOS catalyst systems. The asymmetric hydrogenation of 11 with rhodium Me-DuPHOS furnished the desired intermediate 12 in excellent enantiomeric excess and yield (Fig. 9). 

The mechanism of the catalysis (Scheme 20.8) is quite unlike that of the rhodium-DuPhos catalysis of prochiral olefins described above, since the ketone substrate does not bind to the metal (ruthenium) atom. When a substrate binds the metal, as in the rho-dium-DuPhos systems, there are opportnnities for unwanted pathways that terminate the catalysis. On the other hand, a conseqnence of the metal being protected by its ligands in the Noyori-Ikariya catalysis in principle rednces the likelihood of catalyst deactivation and increases the expectation for achieving very high catalyst utilization (substrate/catalyst ratios). Thus, in the asymmetric hydrogenation of acetophenone to (i )-l-phenylethanol, Noyori et al. reported an astounding molar snbstrate/catalyst ratio of 2,400,000 1. ... 

Minnaard and coworkers [77], in 2005, reported that catalysts formed in situ from Pd(II) salts and (i ,i )-Me-DuPhos exhibited excellent activity and enantioselectivity in the 1,4-addition of arylboronic acids to cyclic enones (Scheme 5.25). Compared to rhodium-based systems, for linear substrates, the results are unsatisfactory as of now (see Scheme 5.25). Even so, the conditions are mild and the scope is broad, although further study is required in order to improve the performance with acyclic substrates. 

The Rh(I)/136 or Rh(I)/137 combination can be used in the asymmetric hydrogenation of 1-arylenamides in 90-99% ee, with Rh(I)/137 being the better of the two.676 Me-DuPHOS and related ligands with rhodium reduce 1-aryl-2-alkylenamides in >90% ee677 whereas the Rh(I)/DIOP combination carries this out in 97.3-99% ee selectivity.678 Finally, the Rh(I)/138 system reduces /3-substituted-a-arylenamides in 95-99% ee, and a-substituted acetamidoethylenes in 75.7-90% ee.674... 

The success in a simple model system encouraged Feldgus and Landis to study the fuller DUPHOS-based system for enantioselective hydrogenation (as defined in Fig. 31.9) [45]. ONIOM methods were required because of the level of complexity a core of the rhodium-complexed atoms was treated by DFT at B3LYP level, the core organic atoms at Hartree-Fock level, and the remainder by... 

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. 

A new family of chelating diphosphines, where phosphorus is part of a five-membered ring containing two asymmetric centers, was developed at Du Pont by Burk et al. in 1990 [58a]. These C2-symmetric Hgands (duphos and derivatives) gave excellent rhodium catalysts for asymmetric hydrogenation of many types of imsatuxated systems. 

Rhodium complexes of the type [(COD)Rh(DuPhos)]+X (X = weakly or noncoordinating anion) have been developed as one of the most general classes of catalyst precursors for efhcient, enantioselective low-pressure hydrogenation of enamides (21) (Scheme 9.22). ° The DuPhos approach overcomes some of the limitations of the DIPAMP system as the substrates may be present as mixtures of E- and Z-geometric isomers. For substrates that possess a single p-substituent (e.g., = H), the Me-DuPhos-Rh and Et-DuPhos-Rh catalysts were found to give enantioselec-... 

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