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Nickel-Catalyzed Stereoselective Formation of α-2-Deoxy-2-amino Glycosides.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Mensah, Enoch Akuamoah Nguyen, Hien M. |
| Copyright Year | 2009 |
| Abstract | The R-2-deoxy-2-amino glucosides and galactosides are the structural units found within a variety of biologically important glycoconjugates. The stereoselective synthesis of R-1,2-cis-glycosides of D-glucosamine and D-galactosamine is challenging because it requires a nonassisting neighboring group effect at the C(2)-amino functionality on the glycosyl donor to direct the R-selectivity. Early work in this area employs the C(2)-azide functionality on the glycosyl donor as a nonparticipatory group. However, the stereochemical outcome can be difficult to predict and often resulted in moderate R-selectivity. In 2001, Kerns reported an elegant strategy utilizing a glycosyl donor incorporated with the C(2)-oxazolidinone group. This approach requires 2 equiv of the activating reagent (PhSOTf), and undesired N-glycosylation and sulfenylation are also observed in the reaction. Later, Schmidt reported the conjugate addition of alcohols to C(2)nitro-galactals in the presence of t-BuOK to afford R-2-deoxy-2-nitrogalactosides in good yields. Gin has recently reported the opening of aziridine with C(1)-hemiacetal nucleophiles to form R-O-glycosyl serine conjugates in good diastereoselectivity. Despite the variety of methods available, selective synthesis of R-2-dexoy-2-amino glycosides continues to be a challenge because each of the above methodologies has its own advantages and disadvantages. The use of para-methoxybenzylidene as the protecting group for the C(2)-nitrogen on glycosyl bromide was investigated over 40 years ago. However, its use was complicated due to the low stability of the Schiff base as well as the multistep synthesis required for the preparation of glycosyl bromide. Additionally, the stereochemical outcome of the coupling process depends on the nature of the promoters as well as the alcohol acceptors. For instance, utilizing stoichiometric amounts of HgCN provides the desired glucosides selectively either as the R-isomers12 or as the -isomers13 depending on the nature of the alcohol acceptors. In contrast, the use of AgOTf (2 equiv) as a promoter provides glucosides exclusively as -isomers. On the other hand, the n-pentenyl glycoside approach provides R-glucoside in moderate yield. In this communication, we report the use of C(2)para-methoxybenzylideneamino trichloroacetimidates 5 and 6 as the donors (Scheme 1) for the stereoselective synthesis of R-2-deoxy-2amino glycosides. This strategy relies on the nature of the ligand on nickel to control the R-selectivity. This method requires only a catalytic amount of the cationic nickel catalyst to activate trichloroacetimidate donors at ambient temperature. Furthermore, its application is widespread to a variety of alcohol nucleophiles. The straightforward synthesis of 5 and 6 commenced with Dglucosamine (1) and D-galactosamine (2), respectively. Exposure of 1 and 2 to p-anisaldehyde and NaOH followed by acetylation provided 3 and 4 in good yields (Scheme 1). Chemoselective 1-O-deacetylation with NH3 in MeOH and subsequent treatment of the resulting hemiacetals with trichloroacetonitrile in the presence of DBU afforded trichloroacetimidates 5 and 6. With these donors in hand, our attention was focused on the glycosylation reactions. Initial experiments were performed with trichloroacetimidate 5 as the donor and primary alcohol of galactoside 7 as the acceptor (Table 1). Upon treatment of both coupling partners 5 and 7 with 5 mol % of cationic Pd(PhCN)2(OTf)2, 16 the reaction proceeded sluggishly at 0 °C to give the desired disaccharide 8 in poor yield with moderate diastereoselectivity (entry 1). Warming the reaction to 25 °C shortened the reaction time and increased the yield (entry 2). Switching to the cationic nickel catalyst improved the yield and the R-selectivity, and 8 was isolated in 95% yield with R: ) 8:1 (entry 4). We then investigated the nature of the ligands on nickel to influence the anomeric selectivity. The more electron-withdrawing substituted benzonitrile ligands decreased the reaction time and increased the R-selectivity (entries 5 and 6). On the other hand, the more electronrich ligands increased the reaction time (entries 7 and 8). These results clearly demonstrate the efficiency of the nickel method, with the formation of disaccharide 8 with excellent R-diastereoselectivity. It has been reported that coupling of the C(2)-azide donor derivative of 5 with 7 provided a 2:1 mixture of Rand -isomers. Glycosylation of alcohol acceptor 9 with 5 has been attempted under Lewis acid conditions. The reaction did not occur in the presence of TMSOTf as a promoter, and the use of BF3 ·OEt2 resulted in only a trace amount of the desired disaccharide 10. Encouraged by the results Scheme 1 a |
| File Format | PDF HTM / HTML |
| DOI | 10.1002/chin.200948195 |
| Alternate Webpage(s) | https://nguyenresearchgroup.lab.uiowa.edu/sites/nguyenresearchgroup.lab.uiowa.edu/files/ja903123b.pdf |
| Alternate Webpage(s) | https://doi.org/10.1002/chin.200948195 |
| Volume Number | 40 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
