Ketopantolactone hydrogenation

Asymmetric hydrogenation of ketopantolactone (19) in the presence of chiral dirhodium complexes gave (R)-pantolactone (9) in high yield and excellent selectivity (36) (Table 2). 

Recently, Vayner and coworkers [239] have revisited the model proposed by Augustine et al. [34] which is based on the assumption that the QN can make a nucleophilic attack to an activated carbonyl. According to this model the two possible zwitterionic intermediates that can thus be formed have different energies, which leads to the selective formation of one of the two intermediates, and, therefore, to e.s. after hydrogenolysis by surface hydrogen. This model nevertheless does not explain the e.d. of nonbasic modifiers, such as the one reported by Marinas and coworkers [240], which have no quinuclidine moiety and no nitrogen atom, and thus no possibility to form zwitterionic intermediates. Furthermore, in situ spectroscopic evidence for hydrogen bond formation between the quinuclidine moiety of cinchonidine and the ketopantolactone has been provided recently [241], which supports the hypothesis of the role of weak bond formation rather than the formation of intermediates such as those proposed by Vayner and coworkers. 

Most of the studies of Pt catalysts with cinchona alkaloids have focused on the hydrogenation of a-keto esters, especially ethyl pyruvate, as shown above, However, enantioselective hydrogenation of ketopantolactone and l-ethyl-4,4-dimethylpyrrolidine-2,3,5-trione is attainable with a Pt catalyst modified by cinchonidine, giving the corresponding R alcohols with 92% ee and 91% ee, respectively (Scheme 1.40) [213]. These reactions can be performed with an S/C of up to 237,000 [213a],... 

Asymmetric hydrogenation of > C—O. This bisphosphine is the most effective ligand for asymmetric hydrogenation of ketopantolactone (2) to provide R-(- )-pantolactone (3). ... 

On the other hand, rhodium complexes with fully alkylated phosphine ligands were used for the hydrogenation of carbonyl compounds, a-ketoamides " and ketopantolactone (66% ee). When a rhodium complex with CyDlOP (23) was used, a slightly higher asymmetric yield (71% ee) was observed in the hydrogenation of a-ketoamides. Hydrogenation of A(-(a-ketoacyl)amino acid esters was... 

The pivotal role of the conformational behavior of a cinchona alkaloid (e.g., cinchonidine) in its enantioselectivity was nicely illustrated in the platinum-catalyzed enantioselective hydrogenation of ketopantolactone in different solvents [18]. The achieved enantiomeric excess shows the same solvent dependence as the fraction of anti-open conformer in solution, suggesting that this conformer plays a crucial role in the enantiodifferentiation. As a more dramatic example, the solvent affects the absolute chirality of the product in the 1,3-hydron transfer reaction catalyzed by dihydroquinidine [20]. An NMR study revealed that the changes in the ratio between the two conformers of dihydroquinidine can explain the observed reversal of the sense of the enantioselectivity for this reaction when the solvent is changed from o-dichlorobenzene (open/closed 60 40) to DMSO (open/dosed 20 80). 

Grafted auxiliaries. Smith et al. [48] grafted chiral silyl ethers to a Pd surface through a Pd-Si bond. A borneoxysilyl-Pd catalyst was able to hydrogenate a-methylcinnamic acid with ee s up to 22%. Santini et al. [49] reported the preparation of a menthyl-Sn-Rh catalyst that hydrogenated ketopantolactone with 11% ee. 

Dimethyloxolane-2,3-dione (ketopantolactone), which contains an activated keto group, is one of the standard substrates for the enantioselective hydrogenation of carbonyl groups. Its hydrogenation product, 3-hydroxy-4.4-dimethyloxolan-2-one (pantolactone). is a precursor of pantothenic acid, a vitamin B block constituent. 

On chiral modified metal catalysts very important results were obtained from the hydrogenation of ketopantolactone to pantolactone (see also. Chapter 7) with ee s up to 79% (Baiker A very important role has... 

This process is used in the industrially important reaction, the hydrogenation of ketopantolactone (KPL) (4,4-dimethyltetrahydrofuran-2,3-dione) into pantolactone (PL) [(7 )-(-)-3-hydroxy-4,4-dimethyltetrahydofuran-2-one] (Scheme 5.19.). 

Effect of reaction temperature. Increasing Ihe temperature of the hydrogenation of ketopantolactone in the range of 7-27 C leads to a maximum ee of 78%, while increasing the temperature of the hydrogenation of pyruvates results in decreasing enantioselectivity. 

Scheme 5.27. Transition complex formed between cinchonidine and the half-hydrogenated state of ketopantolactone resulting ( )-pantolactone...

Schuerch, M., Schwalm, 0., Mallat, T., Baiker, A. (1996) Enantioselective hydrogenation of ketopantolactone on Pt/alumina, 4 Int Symp. Heterogen. Catal. Fine Chem., Basel, Book of Abstracts, pp. 132-133. 

This chapter summarizes some of the most characteristic results obtained with the use of mainly homogeneous metal complex eatalysts either in the industry or in processes recommended for practical use. These are large seale processes of asymmetric synthesis of the herbicide metolachlor, synthesis of optically pure menthol with the use of chiral iridium and rhodium phosphine complexes, consideration of the synthesis of ethyl 2-hydroxybutyrate as a monomer for the preparation of biodegradable polyesters with use of heterogeneous ehiral modified nickel catalyst, the manufacturing of (fJ)-pantolactone by means of a possible eata-IjTic systems for enantioselective hydrogenation of ketopantolactone, and catalytic systems for the preparation of other pharmaceuticals. 

The methods of preparation of pantolactone via as5mmetric hydrogenation of ketopantolactone are of great interest Here practical aspects of... 

In the case of the Rh complexes with ligands 1 and 2 (Scheme 7.28.) was found that a neutral Rh-complexes of these ligands in THF gave pantolactone with an ee s of 41% S and 60% S, respectively, while both cationic complexes gave an ee of 10% and R-configuration. Thus it was found that the above Rh complexes are more effective catalysts than [Rh(Alk)(D10P)] complexes in the asymmetric hydrogenation of ketopantolactone. 

A new Rh(I)-complex catalyst bearing two chiral ligands, the (R,R)-DIOP and an A,A -co-ligand based on (R)- or ( S)-phenylethylamines, pyr-roleimines, or pyrroleoxazolines proved to be enantioselective in the hydrogenation of ketopantolactone into (R)-pantolactone at 50 and 50 bar in toluene solution at a relationship of substrate to Rh 200... 

Morimoto, T., Takahashi, H., Fujii, K., Chiba, M. and Achiwa, K. (1986) S5mthesis of a new chiral p5nTolidine ligand bearing two different types of phosphino groups and their effects on the asymmetric hydrogenation of ketopantolactone, Chem. Lett., 2061-2064. 

Brunner, H., and Tracht, T. (1998) Asymmetric catalysis. 128. Diastereo-meric Rh(l) complexes in the enantioselective hydrogenation of ketopantolactone, Tetrahedron Asymm. 9,3773-3780. 

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