Intramolecular Anomeric Radical Addition

If the radical addition reaction is performed in an intramolecular fashion, olefin activation with an electron-withdrawing group will not be a prerequisite for C-glycosylation, because the cyclization event competes well with hydrogen abstraction. In such examples, ring size and the stereochemistry of the ring substituents greatly influence the stereoselectivity and efficiency of the cyclization reaction. 

With the above points in mind, Sinay s group developed a direet approach to C-linked disaccharides employing a temporary silicon tether approach to graft the 

Because of the facile access to these C-dimers by use of this intramolecular approach, multigram quantities of the analogs are available and have been exploited for the synthesis of mixed C/0-glycosides of biologically relevant oligosaccharides. In this way, the analogs of sialyl Lewis and the pentasaccharide re- 

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Epoxides can also be reductively opened to form a radical. An example of an intramolecular cyclization of such a radical has recently been reported <06TL7755>. Treatment of 40 with Cp2TiCl generates an intermediate alkoxy radical, which then adds to the carbonyl of the formate ester. The product, 41, is formed as a 2 1 mixture of isomers at the anomeric carbon. This reaction is one of the first examples of a radical addition to an ester. The major byproduct of this reaction is the exo-methylene compound, 42, arising from a P-hydrogen elimination. 

In addition to intermolecular reactions, C-glycosides can also be synthesized by intramolecular sequences. A radical cyclization is a very fast reaction, in particular 5-exo-trig cyclizations. Thus, intermediate anomeric radicals have only a short time window of reactivity before undergoing the desired cyclization. 

In addition to the axial versus equatorial orientation of the but-3-enyl group, special stabilization of an intermediate radical can also play an important role in the stereochemical outcome of hex-5-enyl radical cyclizations. The surprising results of De Mesmaeker [28] on the stereochemistry of intramolecular C-glycosidation reactions (Fig. 7.16) can be satisfactorily explained if one also takes into account this important stabilization effect in considering the described models. For example, the anomeric radical from 53a would be expected to cyclize via chair-like transition state 55 leading to 56 as the major product, but up to 53 % of the exoisomer 58 is also formed in the reaction. 

Intramolecular radical cyclization followed by trapping of the intermediate with an enone has been investigated by Fraser-Reid and co-workers [95JOC3871] as a method for the synthesis of highly functionalized C-glycosyl derivatives. The control of the anomeric stereochemistry as well as the facial selectivity in the addition to the chiral enone is impressive. 

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