- Regio- and stereocontrolled palladium-catalyzed allylic substitution on n-acetylneuraminic acid derivatives
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A process for highly effective regio- and stereoselective palladium-catalyzed allylic substitution of 2,3-unsaturated derivatives of N-acetylneuraminic acid (Neu5Ac2en) has been developed. We show that the efficiency of the allylation reaction depends on suitable protecting groups on the starting material and that, with sodium malonate anion as a nucleophile, the regioselectivity can be fine-tuned by the nature of the ligands associated with the palladium complex. These results are explained by the stoichiometric preparation and study of the highly probable complexes involved in the catalytic reaction. Reactions of this type were also applied to other nucleophiles for the construction of C-C, C-N, and. C-O bonds, leading to the major formation of the C-4 regioisomers. The selective transformation of some of the substitution products provided easy access to a variety of modified sialic acid derivatives that might serve as useful, sialyl building blocks for biological research.
- Chang, Chih-Wei,Norsikian, Stephanie,Guillot, Regis,Beau, Jean-Marie
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experimental part
p. 2280 - 2294
(2010/07/10)
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- Useful sialic acid modifications catalyzed by palladium
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A stereo- and regioselective allylic substitution on simple N-acetylneuraminic acid (Neu5Ac2en) derivatives that ensures the control of the regio- and stereoselectivity and affords the C-2 or C-4 products with high efficiency, was studied. The Neu5Ac2en substrates were easily prepared from the peracetylated methyl ester 9 obtained by standard treatment overnight of the corresponding Neu5Ac methyl ester. Treatment of acetate 10 under Pd0-catalyzed allylic substitution conditions using sodium dimethylmalonate as a nucleophile failed to provide any alkylation product. The regioselectivity was largely improved to a synthetically useful level when using a more basic monophosphine ligand. A complete reversal of the regioselectivity occurred when the reaction was performed in the presence of bidentate phosphine. Selective transformations of these products provide easy entry to a variety of modified sialic acid derivatives, which can serve as useful sialyl building blocks for biological research.
- Chang, Chih-Wei,Norsikian, Stephanie,Beau, Jean-Marie
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body text
p. 5195 - 5199
(2009/12/22)
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