Anomerically stabilized radical

In most cases the radical generated after cyclization is quenched by H-abstraction. However, another possibility is to utilize the cyclized radical in another C-C bond-forming event. Fraser-Reid and co-workers utilized a silyl-tethered radical cyclization of the (L)-rhamnal-derived silyl ether 142 to generate the anomerically. stabilized radical 143, which could be trapped in the presence of an excess of acrylonitrile to generate acetate 144 after tether cleavage and peracetylation (Scheme 10-48) [55a]. This reaction sequence occurred with complete regio- and stereoselectivity. The same group has also used an acetal tether (vide infra) to effect similar transformations [55 b, 56]. 

This anomeric stabilization of radicals is also observed using halonitrosugars such as 1-C-nitroglycosyl halides [22] 15. Captodative stabilization of the alcoxy nitro radicals explains the radical-chain substitution with mild nucleophiles such as ma-lonate or nitroalkane anions to form 16 (Scheme 8). 

Generally, the reactions are carried out in refluxing benzene solution, since the yield in benzene is better than that in other solvents. Probably, the radicals formed may be somewhat stabilized by the weak orbital-orbital interaction between the radicals and benzene. However, from the environmental point of view, toluene or dioxane is recently used. As substrates, alkyl bromides or alkyl iodides are used, and the reactivity increases in the order prim-alkyl < seoalkyl < te/t-alkyl. Sugar anomeric bromide (3) is generally not so stable, so the reaction is carried out under irradiation conditions with a mercury lamp at room temperature (eqs. 4.2 and 4.3). There are two types of anomeric glycosyl radicals as shown in Figure 4.1. One is the axial radical [I], and the other is the equatorial radical [I ]. The axial radical is more nucleophilic than the equatorial radical due to the stereoelectronic effect, where this effect comes... 

The stability of azides in radical reactions is further illustrated by the radical fragmentation of carbohydrate anomeric aUcoxyl radicals bearing an azido substituent at position 3 reported by Suarez (Scheme 8.2). After fragmentation, the 2-azido-substituted radical is iodinated and no jS-fragmentation of the azide is observed. 

The anomeric configuration is set in the reductive lithiation step, which proceeds via a radical intermediate. Hyperconjugative stabilization favors axial disposition of the intermediate radical, which after another single electron reduction leads to a configurationally stable a-alkoxylithium intermediate. Protonation thus provides the j9-anomer. The authors were unable to determine the stereoselectivity of the alkylation step, due to difficulty with isolation. However, deuterium labeling studies pointed to the intervention of an equatorially disposed a-alkoxylithium 7 (thermodynamically favored due to the reverse anomeric effect) which undergoes alkylation with retention of configuration (Eq. 2). 

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

In contrast, the mannosyl radical 8 does not undergo such a conformational change, and the observed a-attack results from the shielding effect of the axial C-2 substituent in the chair conformation and the stereoelectronic effects mentioned earlier. In radicals 7b and 8 the C-O bonds adjacent to the radical center are coplanar with the singly occupied orbital. This reminds us of the anomeric effect in which an interaction between the nonbonding electron pair of the ring oxygen and the LUMO of the C-O bond stabilizes the conformation. 

Cyclic carbohydrates bearing a cyano group at the anomeric center have, at this position, captodative radical-stabilizing groups similar to those at C-5 of the hexopyranuronic add compounds (see Section 11,2). In consequence,... 

Because the aromatic rings of compounds of this class render the anomeric centers benzylic, and also conceivably subject to captodative radical stabilization, photobromination results might be expected to correlate with those observed for the glycosyl cyanides (see Section 11,6). 

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