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Bierenstiel, Matthias (2005): Transition Metal Catalyzed Selective Oxidation of Sugars and Polyols. Dissertation, LMU München: Faculty of Chemistry and Pharmacy
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Abstract

Oxidation reactions of sugars to their corresponding lactones and the selective oxidation of a secondary alcohol of sugar substrates to keto-sugars using transition metal catalysis were investigated. Research results demonstrate that Shvo’s hydrogen-transfer catalyst, [(η4-C4Ph4CO)(CO)2Ru]2, selectively oxidized unprotected sugars to δ-lactones under very mild conditions. This is the first method to synthesize δ-D-galactonolactone, the first oxidation product of the 3rd most abundant sugar. δ-D-Galactonolactone was fully characterized by conformational analysis through NMR experiments and computational methods. We propose that in aprotic, anhydrous solvents the δ→γ lactone rearrangement mechanism proceeds via a bicyclic transition state. The oxidation of alicyclic vicinal diols to α-hydroxy ketones was investigated as a model system for the selective oxidation of a secondary hydroxyl group in sugar substrates to keto-sugars. The challenge was to develop a method that allows selective oxidation, yet prevents over-oxidation to the dione or dicarboxylic acids products. Based on a mathematical model of consecutive bimolecular reactions, the rate constants for the initial oxidation step k1(diol→α-OH ketone) and second oxidation step k2(α-OH ketone→dione) must be k1 > 10 k2 in order to obtain a synthetically useful method for α-hydroxy ketone synthesis. The metal-ligand bifunctional hydrogen transfer reactions of Shvo’s catalyst and Noyori’s η6-arene N-tosyl-1,2-diaminoethane ruthenium(II) complexes were investigated with alcohol model systems and it was concluded that hydrogen transfer reactions are insufficient in the oxidation of vicinal diols due to a unfavourable position of the equilibrium. Under oxidizing conditions, the 16-electron ruthenium complexes of the Noyori systems compete with a β-elimination process and thus new degradation resistant ligands were synthesized. The apparent slower oxidation of Noyori’s η6-arene N-tosyl-1,2-diaminoethane ruthenium(II) complexes under oxidizing conditions, i.e. in acetone or cyclohexanone solvent, was investigated through NMR and IR experiments finding no evidence of a kinetic inhibition by the solvent. We propose that the slower reactions depend on a relatively high energy barrier for the reaction of the 16-electron complex with a hydrogen donor and that a kinetic model must account for two effectively different oxidation and reduction catalysts. In an alcohol/ketone equal-concentration experiment with Noyori-type ruthenium(II) complexes a linear relationship was found between the initial rate of alcohol consumption/production and ∆G°. Reactions involving peroxides as the oxidant were investigated in order to avoid equilibrium processes. The oxidation of alcohol model systems with several Mo and W catalysts and peroxide sources indicated a deactivation of the Mo and W catalysts by formation of water or hydroxide complexes. The product distribution of the oxidation of trans-1,2-cyclohexanediol with the MoO2(acac)2/Na2CO3 x 1.5 H2O2 method was in agreement with the theoretical model, yet only had a k1 = 1.5 k2 rate ratio resulting in a maximum α-hydroxy cyclohexanone content of 45 %. The NiBr2 mediated oxidation of alcohols and benzoylperoxide was investigated. The selective oxidation of vicinal diols was unsuccessful with this method. However, the oxidation reaction of mono-alcohol substrates was greatly improved using water in the reaction. The reaction mechanism was investigated and we propose that the actual oxidant in the NiBr2 mediated benzoylperoxide method is [Br+], which is generated by the hydrolysis product of benzoylhypobromite, hypobromic acid (HOBr). Ishii’s stoichiometric NaHSO3/NaBrO3 reagent selectively oxidized vicinal diols to α-OH ketone without overoxidation. This oxidation reaction was investigated with regards to substrate, concentration and pH. The reactivity and selectivity were studied and it was found that the oxidation mechanism is based on a multitude of comproportionation and disproportionation equilibria at low pH. A small but steadily replenished HOBr concentration is the source of the actual oxidant and effectively acts as a redox buffer. While the NaHSO3/NaBrO3 reagent demonstrated excellent selectivities with the alcohol model systems, the oxidation of sugar substrates failed due to side-reactions occurring at the required low pH.