Enantioselective hydrogenation catalyst precursor

Early transition-metal complexes have been some of the first well-defined catalyst precursors used in the homogeneous hydrogenation of alkenes. Of the various systems developed, the biscyclopentadienyl Group IV metal complexes are probably the most effective, especially those based on Ti. The most recent development in this field has shown that enantiomerically pure ansa zirconene and titanocene derivatives are highly effective enantioselective hydrogenation catalysts for alkenes, imines, and enamines (up to 99% ee in all cases), whilst in some cases TON of up to 1000 have been achieved. 

Highly mesoporous carbon supported Pd catalysts were prepared using sodium formate and hydrogen for the reduction of the catalyst precursors. These catalysts were tested in the enantioselective hydrogenation of isophorone and of 2-benzylidene-l-benzosuberone. The support and the catalysts were characterized by different methods such as nitrogen adsorption, hydrogen chemisorption, SEM, XPS and TPD. 

The reduction of the catalyst precursor with sodium formate resulted in a lower Pd dispersion than the catalyst prepared by hydrogen reduction, the particle size is much larger in the former catalyst. The mesoporous carbon supported Pd catalysts are near to those of Pd on titania with respect to their enantiodifferentiating ability. Besides the metal dispersion, the availability of the Pd surface in the pores for the large modifier molecules seems to be the determining factor of the enantioselectivity. 

When a chiral ansa-type zirconocene/MAO system was used as the catalyst precursor for polymerization of 1,5-hexadiene, an main-chain optically active polymer (68% trans rings) was obtained84-86. The enantioselectivity for this cyclopolymerization can be explained by the fact that the same prochiral face of the olefins was selected by the chiral zirconium center (Eq. 12) [209-211]. Asymmetric hydrogenation, as well as C-C bond formation catalyzed by chiral ansa-metallocene 144, has recently been developed to achieve high enantioselectivity88-90. This parallels to the high stereoselectivity in the polymerization. 

During the late 1960s, Homer et al. [13] and Knowles and Sabacky [14] independently found that a chiral monodentate tertiary phosphine, in the presence of a rhodium complex, could provide enantioselective induction for a hydrogenation, although the amount of induction was small [15-20]. The chiral phosphine ligand replaced the triphenylphosphine in a Wilkinson-type catalyst [10, 21, 22]. At about this time, it was also found that [Rh(COD)2]+ or [Rh(NBD)2]+ could be used as catalyst precursors, without the need to perform ligand exchange reactions [23]. 

Despite the remarkable enantioselectivities observed with the Ti-ebthi catalyst for the imine and enamine hydrogenation, we consider its technical potential rather low. The ligand is difficult to prepare, the activation of the catalyst precursor is tricky, for the moment the catalytic activity is far too low for preparative purposes, and last - but not least - its tolerance for other functional groups is low. 

PfefFer, de Vries and coworkers developed the use of ruthenacycles, based on chiral aromatic amines as enantioselective transfer hydrogenation catalysts. These authors were able to develop an automated protocol to produce these catalysts by reacting ligand and metal precursor in the presence of base, KPFS in CH3CN. After removal of the solvent, isopropanol was added followed by the substrate, acetophenone, and KOtBu. In this way, a library of eight chiral... 

When the peptide synthesis was complete, the phosphines were deprotected by sequential treatment with MeOTf and HMPT (Scheme 36.9). Addition of the rhodium precursor then created the catalyst library, which was screened, on the pin in the enantioselective hydrogenation of methyl-2-acetamidoacrylate (see Scheme 36.10). Unfortunately, this beautiful concept was poorly rewarded with rather low enantioselectivities. 

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. 

Takaya and co-workers46 found that BINAP-based Ru(II) dicarboxylate complexes 31 can serve as efficient catalyst precursors for enantioselective hydrogenation of geraniol (2E)-32 and nerol (2Z)-32. (R)- or (iS )-citroncllal 33 is obtained in nearly quantitative yield with 96-99% ee. The nonallylic double bonds in geraniol and nerol were intact. Neither double bond migration nor (fi)-/(Z)-isomerization occurred during the catalytic process. Furthermore, the S/C ratio was extremely high, and the catalyst could easily be recovered (Scheme 6-18). This process can be applied to the asymmetric synthesis of a key intermediate for vitamin E. 

Furanoside diphosphinite ligands 10 and 11 (Fig. 11) were applied in the Ir-catalyzed asymmetric hydrogenation of several dehydroaminoacid derivatives [25]. The best enantioselectivities (ee s up to 78%) were obtained in the reduction of methyl W-acetamidoacrylate with ligand 10. These results using the lr/10-11 catalysts precursor show that enantiomeric excesses are strongly dependent on the absolute configuration of the C-3 stereocenter of the carbohydrate backbone. The best enantioselectivity were therefore obtained with ligand 10 with an... 

Remarkable activity and enantioselectivity in asymmetric hydrogenation of aromatic ketones were reported when ionic liquids were used as solvents for a rhodacarborane catalyst precursor having an alkene ligand, [closo-l,3 p-(ri -3-CH2= CHCH2CH2) -3-H-3-PPh3-3,l,2-RhC2B9Hio] 215). In ionic liquids... 

Table 3.1 Enantioselective hydrogenations of benchmark substrates and /1-amino acid precursors using Rh(I)-[(R,R)-bis(diphenylphosphino)-l,3-diphenylpropane] as a catalyst. ...

The C2-symmetric diphosphinite and CVsymmetric phosphinite-phosphate ligands, based on a carbohydrate scaffold, and iridium complexes give catalyst precursors that are active in the hydrogenation of imines. Cationic iridium complexes gave rise to catalytic systems that were more active than the neutral iridium complexes. Enantioselectivities up to 76% were obtained.347... 

A class of chiral bisphosphines based on 3,4-bis(diphenylphosphino)pyrrolidines (9) has been developed by Degussa and the University of Munich. Rhodium-bisphosphine catalysts of this class can reduce a variety of enamides to chiral amino acid precursors with high enantioselectivities. These catalysts are extremely rapid and can operate with high S/C ratios (10,000-50,000) under moderately high hydrogen pressure (150-750 psig). Contrary to other rhodium catalysts that contain... 

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