C-Glycosides, formation

While transition metals have been used extensive ) in C-gly coside construction, assigning a precise reactivity profile to C(l) can be difficult and this section will cover cases where nucleophilic character is apparent, albeit loosely defined. The use of palladium-mediated synthesis of C-glycosides has been reported and this topic, which involves an anomeric tin intermediate, has been covered in Sect. 2.2.2. The insertion of carbon monoxide into a carbon-metal (C(l)-metal) bond is, however, an important aspect of transition metal-mediated C-glycoside formation, and this process has been observed and exploited in a number of situations. 

D. Mazdas, T. Skrydstrup, O. Doumeix, and J.-M. Beau, Samarium iodide induced intramolecular C-glycoside formation Efficient radical formation in the absence of an additive, Angew. Chem. hit. Ed. Engl. 33 1383 (1994). 

Scheme 2 Use of anomeric phosphorous compounds in C-glycoside formation.

In their review, Rohr and Thiericke classified the angucyclinones based on the degree of oxygenation and C-glycoside formation (Scheme 1) [3]. 

To organize the review of this vast research field, we wiU draw a distinction between C-glycosyl compounds with and without an anomeric hydroxyl group. As will be discussed, the latter can be prepared from the former by reduction at the anomeric center. Many excellent reviews have appeared on the methods of C-glycoside formation [212-219] and their properties [220]. 

Since sialyl C-glycoside formation results in a quaternary carbon atom, it is synthetically a difficult subject. In addition, as mentioned earlier, due to the electron-withdrawing carboxylate group, the generation of the carbenium ion is also problematic. 

Both new cascade reactions were carried out in basic medium (tertiary amines). However, the key difference of this two cascade processes is as follows. The initial reaction step in the C-glycoside formation process is a Knoevenagel condensation, whereas the chain elongation cascade starts with a Knoevenagel-addition reaction of the acyclic form of the carbohydrates. This difference is dictated by the application of either 2-hydroxypyridine (Knoevenagel-addition reaction) or proline (Knoevenagel condensation). The intermediately formed Knoevenagel addition or condensation products determinate the subsequent reaction steps. Based on that, a different outcome of these cascade reactions is observed (Scheme 2.17). 

Ding, F. and Jennings, M.P. (2008) Total synthesis of (-)-dactylolide and formal synthesis of (—)-zampanolide via target oriented P-C-glycoside formation. J. Org. Chem., 73, 5965-5976. 

---