Uronic derivatives, radicals

Figure 7.16 Potential captodative stabilisation of radicals at position 5 of uronic derivatives.

Electron donating a-substituents favour the non-Kolbe reaction but the radical intermediates in these anodic processes can be trapped during co-electrolysis with an alkanoic acid. Anodic decarboxylation of sugar uronic acids leads to formation of the radical which is very rapidly oxidised to a carbonium ion, stabilised by the adjacent ether group. However, in the presence of a tenfold excess of an alkanoic acid, the radical intermediate is trapped as the unsymmetrical coupling product [101]. Highly functionalised nucleotide derivatives such as 20 will couple successfully in the mixed Kolbe reaction [102], Other examples include the co-electrolysis of 3-oxa-alkanoic acids with an alkanoic acid [103] and the formation of 3-alkylindoles from indole-3-propanoic acid [104], Anodic oxidation of indole-3-propanoic acid alone gives no Kolbe dimer [105],... 

Photobromination of methyl (tri-0-acetyl-/ -D-glucopyranosyl fluoride)uronate, followed by radical reduction of the derived 5-bromide, gave access to the corresponding glycosyl fluoride of the 0-L-ido series.102... 

Many important natural products are (formerly) derived by chain elongation at position 5 of pentoses, or at position 6 of hexoses. Uronic acids, which are easily prepared, can be converted into the 4 radical 90 by chemistry based on the thiohydroxamate 6.77 We postulated that, if the hindrance on the a-side of the molecule was great enough, the carbon-carbon bond formed by reaction of 90 with a suitable radicophilic olefin would be the natural / -bond. In fact, even a dimethyl-ketal as in 90 (B = natural base or protected derivative thereof) was sufficient to direct the bond formation very largely to the desired face.77 The diacetone ketal of glucuronic acid 91 upon conversion to its iV-hydroxy-2-thiopyridone derivative 92 and then photolysis in the usual way in the presence of methyl acrylate gave the expected derivative 93 as a mixture of... 

Only 2-pyridyl reverse C-nucleosides are known. Coupling saccharide free radicals 831 and 834 with protonated pyridine derivatives gave the 2-pyridyl reverse C-nucleosides 832 and 835, respectively. Free radical 831 was obtained by decarboxylative photolysis of the uronic acid derivative 830 in the presence of hypervalent iodine compounds (92TL7575 (Scheme 232), whereas free radical 834 was obtained by thermal homolysis of the carbon-iodine bond in the 6-iodo-6-deoxy-o-galactopyranose derivative 833 in the presence of benzoyl peroxide (93JOC959) (Scheme 233). 

The reaction of carboxylic acids with the PhI(OAc)2-iodine system may result in a decarboxylation ieading to the intermediate formation of a carbon-centered radical, which can be further oxidized to a carbocation and trapped by a nucleophile. This process has been utilized in several syntheses [97, 615,616, 617]. In a typical example, the oxidative decarboxylation of uronic acid derivatives 568 in acetonitrile under mild conditions affords acetates 569 in good yields (Scheme 3.225) [615]. A similar oxidative decarboxylation has been be used for the synthesis of 2-substituted pyrrolidines 571 from the cyclic amino acid derivatives 570 [616,617]. 

C-6-Allylated pyranoses and C-S-allylated fliranoses were prepared from the corresponding iodides by Keck radical coupling with allyltributyltin (e.g. 44->4S). The selective formation of product 47 in the chain-extension of the acetal-protected uronic acid derivative 46 by radical addition of methyl acrylate using Barton s method was ascribed to addition from the less hindered side to a conformationally stable radical intermediate the peracetate 48 furnished a 1 1 mixture of 49 and 50. ... 

Photochemical cleavage of the glycosidic linkage of uronic acid-containing compounds was studied using methyl (methyl D-glucopyranosid)uronate, and compounds (12)—(16) were identified amongst the products. The first three are believed to be derived from a radical produced at C-5 by C-5—C-6 fission. 

---