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ABSTRACT: The remarkable stability of glycals under oxidative conditions becomes apparent by their redox data in solution, computed HOMO energies, and behavior on the addition of electrophilic radicals generated in the presence of cerium(IV) ammonium nitrate. Oxidation potentials up to 2.03 V vs ferrocene were obtained, which are exceptionally high for cyclic enol ethers but correlate nicely with the reaction times of the radical reactions. Protecting groups have a strong influence on the oxidation stability and HOMO energies of glycals as E(ox) is shifted from O-silyl over O-benzyl to O-acetyl by more than 500 mV. Interestingly, this effect must be transmitted through sigma-bonds, even up to the para-position of a benzoate group, as verified by a wide variation of remote substituents in the carbohydrate. Favorable interactions of the sigma*-orbital of the adjacent C-O bond with the HOMO of the double bond are proposed as a mechanistic rationale, which might be important for the redox behavior of other allylic systems. Finally, donors and acceptors in the 1-position exert the strongest influence on the oxidation stability, shifting the potentials by almost 1 V and resulting in different follow-up reactions of the cerium(IV)-mediated additions of malonates. It is the remarkable oxidation stability of glycals that makes them valuable building blocks in carbohydrate chemistry.
Journal of the American Chemical Society 11/2008; 130(47):16003-10. · 9.91 Impact Factor
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ABSTRACT: 2-C-malonyl carbohydrates were synthesized in only few steps and high yields by radical additions of malonates to glycals. For the first time, the undesired formation of nitrates was completely suppressed with anhydrous cerium ammonium nitrate (CAN) as oxidizing agent. A coherent explanation for the high stereoselectivities of the additions to gluco-configured glycals was provided by variation of the substituents in the 3-position. We established steric effects for the face selectivity, and electronic effects strongly influence the reactivity of the double bonds. The scope and limitation of transition-metal-mediated radical reactions in the synthesis of 2-C-branched carbohydrates was thoroughly investigated. Thus, unsaturated disaccharides and benzyl-protected glycals were used as substrates for the first time. Finally, the 2-C-malonyl carbohydrates were transformed into various products by decarboxylation, saponification and reduction, which afforded interesting precursors for C-disaccharides. In this paper we describe the syntheses of more than 40 new 2-C-analogues of carbohydrates, which were isolated in high yields in analytically pure form. Therefore, the transition-metal-mediated radical addition of malonates to glycals offers a simple and convenient entry to such important carbohydrate derivatives.
Chemistry 02/2007; 13(36):10152-67. · 5.93 Impact Factor
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ABSTRACT: Only three steps are required for the convenient synthesis of 2-C-branched glyco-amino acids from glycals with good yields and stereoselectivities.
Chemical Communications 12/2004; · 6.17 Impact Factor
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ABSTRACT: A general and convenient synthesis of carbohydrate 2-C-analogs by addition of malonates to glycals is described. The method is applicable to glycals derived from hexoses and pentoses and is characterized by easily available precursors. The reactions are mediated by manganese(III) or cerium(IV) and proceed via intermediarily generated malonyl radicals. All additions exhibit a very high degree of regioselectivity, since only 2-C-branched sugars were obtained. This result can be best rationalized by favorable orbital interactions between the SOMO of the malonyl radical and the HOMO of the double bond. Variation of the steric demand of the malonate or the glycal allows the stereoselectivities to be increased up to >98%. Highest selectivities were obtained with tri-O-acetyl-d-galactal and di-O-acetyl-d-arabinal, where the attack occurs exclusively from one face of the carbohydrate. For all cerium(IV)-mediated reactions, methyl glycosides are formed as main products in 73−89% yield, which can be isolated in analytically pure form on a gram scale. Strong evidence was found for a ligand transfer rather than electron transfer during the formation of carbohydrate 1-nitrates, which sheds light on the mechanism of transition-metal-mediated radical reactions. In terms of starting materials, stereoselectivities, and yields, the herein described method for the synthesis of carbohydrate 2-C-analogs is superior to literature known procedures.
10/1997;
