Glycosides products

Although the Koenigs-Knorr reaction appears to involve a simple backside S 2 displacement of bromide ion by alkoxide ion, the situation is actually more complex. Both a and /3 anomers of tetraacetyl-o-glucopyranosyl bromide give the same /3-glycoside product, implying that they react by a common pathway. 

We saw in Section 25.6 that reaction of a monosaccharide with an alcohol yields a glycoside in which the anomeric -OH group is replaced by an -OR substituent. If the alcohol is itself a sugar, the glycosidic product is a disaccharide. 

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). 

In an extension beyond hetaryl onium salt promoted hemiacetal activation, Ishido and coworkers have reported the carbodiimide activation of hemiacetals [141]. In the method (Scheme 3.13), the hemiacetal donor 1 is treated with a carbodiimide electrophile 83 and copper(I) chloride to provide glycosyl isourea intermediate 85. Highly susceptible to hydrolysis, the isourea 85 was not isolated but could be detected by 13C NMR and IR spectroscopy [142,143], Accordingly, the reaction between intermediate 85 and the glycosyl acceptor (NuH) provides glycoside product 3, along with urea by-product 84. 

Often, ethers are constructed by alkoxide displacement of a stereodefined leaving group. Hirakazu Arimoto of Nagoya University has found (Chem. Commun. 2004, 1220) that it is possible to effect diastereocontrolled construction of cyclic benzylic ethers such as 2 by oxidation of 1 to the o-quinone methide. The more stable equatorial C-glycoside product 2 is formed in near quantitative yield. 

The stereochemistry of the C-glycosidic products, obtained with the above-mentioned procedure, depends on the structure of the starting sugar and on the experimental conditions. In general, base catalyzed cyclizations afford a mixture of anomers, which on prolonged reaction time is converted into the thermodynamic product. For example, in the case of 4,6-O-isopropylidene-D-glucose,... 

In contrast, the Barbier reactions of 2-acetamido-2-deoxy sugars with ketones showed a preference for the formation of 1,2-m-C-glycoside products (Scheme 7.39). This was attributed to the complexation of the C2-acetamido group to the glycosyl samarium, thereby reducing the configurational lability of the organometallic species.78,80,81... 

Next, the scope of this C-glycosylation reaction was investigated. The NeuSAc chloride was found to serve as a donor in samarium mediated C-glycosylation, unfortunately, purification of C-glycoside from excess chloride donor is often problematic, making the NeuSAc phenyl sulfone the donor of choice. A variety of acceptors were also evaluated including alkenes, epoxides, vinyl esters, aldehydes and ketones. Only the aldehydes and ketones afforded the desired C-glycoside products. 

Acceptor C-Glycoside product Yield C-fil coside (a fi) Yield O-glycoxide ([Pg.86]

In order to lower water activity and therefore favor synthesis over hydrolysis, the effect of the addition of a high concentration of lithium chloride in the )3-galactosidase-catalyzed reaction between phenylethanol and lactose was studied [18]. Concentrations of LiCl in the range 0.4 and 0.7 M did not improve the yield of phenylethyl o-galactopyranoside however, it prevented the disappearance of the glycoside product, which may facilitate the control of product formation. 

All of the above-mentioned reactions using glycals derived from hexopyranoses gave stere-oelectronically controlled a-C-glycoside products. On the other hand, it is difficult to synthesize the corresponding -C-glycoside by using the same method. Recently, reaction of... 

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