C-glycosides synthesis

Deslongschamps P (1993) In Thatcher GJ (ed), The Anomeric Effect and Associated Stereoelectronic Effects. American Chemical Society, Washington, DC, p 26 Recent reviews on C-glycoside synthesis (a) Du Y, Linhardt RJ, Vlahov IR (1998) Tetrahedron 54 9913 (b) Levy DE, Tang C (1995) The Chemistry of C-Glycosides. Elsevier Science, Oxford... 

Enolates represent a special class of sp -hybridized C(l) nucleophiles. This is an important and developing aspect of carbohydrate reactivity and the carbonyl function can either be located at C(2), or be external to the sugar ring (as in sialic acid derivatives). Although the latter are not strictly C(l) nucleophiles, both their value in C-glycoside synthesis and relationship to other topics covered in this chapter merit inclusion of these systems. 

Carbon-based radicals stabilized by oxygen, though electronically neutral, can exhibit nucleophilic reactivity. C-Glycoside synthesis based on anomeric... 

It is also appropriate to recognize the role of enolates stabilized by an exocyclic carbonyl function in C-glycoside synthesis. The use of LN to achieve reductive cleavage of anomeric sulfones to provide access to an ester-stabilized enolate and, ultimately, 2-deoxy- -C-glycosides has already been illustrated in Scheme 11 (Sect. 2.1.1). 

The enolate reactivity associated with this approach to C-glycoside synthesis was, however, first developed with octulosonic acid derivatives, such as 283 [114], 284 [115], and 285 [116], and a series of examples involving aldehyde and halide-based electrophiles are shown in Scheme 74. Related studies involving stereoselective protonation of this class of exocyclic enolate have also been described [13] and Scheme 75 illustrates this with an example of reductive samariation (using ethane-1,2-diol, but no HMPA) of an anomeric acetate 286 [117]. 

C-Glycoside synthesis may be achieved in twro ways. Intermolecular radical addition reactions are observed with (i) polarized, electron-deficient alkenes, (ii) alkenes that provide a high level of stabilization to the initial radical adduct and (in) substrates that undergo a facile fragmentation (e.g. allyl stannanes). Additions to less reactive substrates, though not favored for intermolecular processes, are observed if the two components are tethered in an intramolecular array. 

While a full discussion of radical-mediated C-glycoside synthesis is beyond both the space available and the general remit of this chapter, illustrative examples of the nature of the transformations available will be described. Comprehensive reviews are, however, available [3,4] and should be consulted for more detailed accounts. 

C-Glycoside synthesis via the intermolecular addition of anomeric radicals to activated alkenes has been pioneered by Giese and co-workers [120]. A wide variety of acceptors have been used in this area and both simple [131,132] and more complex (a C-disaccharide 290) [133] examples are shown (Scheme 77). 

In this review we have presented a complete and, as far as possible, up to date account of how C-glycosides may be synthesized using C(l) nucleophiles. Free radical based methods, which have provided numerous and useful procedures for C-glycoside synthesis, were beyond the scope of this review and only a few representative examples are mentioned. 

Beau J-M and Gallagher T (1997) Nucleophilic C-Glycosyl Donors for C-Glycoside Synthesis. 187 1-54... 

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