Anomeric bromides

The reaction of phosphines and alkyl halides presents an alternative way to generate phosphonium electrophiles (Scheme 3.8). In particular, the combination of a phosphine and carbon tetrabromide (the Appel reaction) allows for in situ formation of a phosphonium dibromide salt (48, X = Br). Treatment of a hemiacetal donor 1 with the phosphonium halide 48 initially provides the oxophosphonium intermediate 38 (X = Br). However, the oxophosphonium intermediate 38 can react with bromide ion to form the anomeric bromide intermediate 49 (X = Br) with concomitant generation of phosphine oxide. With the aid of bromide ion catalysis (i.e. reversible, catalytic formation of the more reactive P-anomeric bromide 50) [98], the nucleophile displaces the anomeric bromide to form the desired glycoside product 3. The hydrobromic add by-product is typically buffered by the presence of tetramethyl urea (TMU). 

For the synthesis of CIO carba derivatives, a better leaving gronp than hydroxyl is nsnally preferred. The anomeric finoride , bromide, acetate, benzoate and phenyl-snlphonyl gronps have all been nsed and some of the chemistry that has been achieved is shown in Scheme 25. AllylsUanes tend to provide /S-confignred prodncts by axial attack on the oxoninm ion species (Scheme 25C) whereas larger nncleophiles snch as electron-rich aromatics add by attack on the a face (Scheme 25D). For nitrogen nncleophiles, Haynes and CO workers have employed the CIO anomeric bromide intermediate that gives the ClO-a hemi-aminal prodncts (Scheme 25E), some of which exhibit remarkable stability (Chart 1) . ... 

A second method is based on the abnormal course of the Koenigs-Knorr reaction with fluoroalkyl alcohols. Indeed, when there are two or three methylenes between the Rf group and the hydroxyl, the reaction does not lead to substitution of the anomeric bromide but instead affords an orthoester. In the presence of mercuric bromide, this orthoester can undergo a rearrangement into an (9-fluoroalkyl glycoside (Figure 6.47). 

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... 

Demchenko reported the synthesis of the benzoylated STaz glycosides from the corresponding anomeric bromides (27) and NaSTaz or KSTaz in the presence of a crown ether (76). In these syntheses, the STaz glycosides of the D-gluco, D-galacto, and D-manno series were isolated in 60, 90, and 70 % yield, respectively. Subsequently, it was determined that direct conversion of the anomeric acetates into STaz glycosides is by far more efficient for the D-gluco... 

Notes and discussion. This procedure is an oxalyl bromide-mediated bromination of the free anomeric hydroxyl of tetra-O-benzylglucose. Presumably, an anomeric bromooxalate ester is a primary intermediate in the process, which is then displaced by bromide ion to yield the anomeric bromide. As such the oxalyl bromide is also acting as a source of in situ generated HBr. Once again the a-bromide is the major,... 

Insoluble silver salts such as silver silicate favor direct Sn displacement of an anomeric bromide by alcohols [88]. When applied to 2-deoxy-pyranosyl bromides, this procedure can lead to 2 -deoxy-P-disaccharides with a good stereoselectivity. For instance (Scheme 32), bromide 141, where an ester group at 0-4 can also favor [85] P-glycoside formation, reacted with the sugar alcohol 142 in the presence of silver silicate to give the disaccharide 143 in 85% yield (P a 5.4 1) [89]. 

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