Anomeric nitriles

In addition to the formation of anomeric nitriles, similar chemistry allows for the formation of anomeric isocyanides. Requirements for these reactions include utilizing acetates, halides, and imidates as activating groups. Some Lewis acids used to effect these transformations include SnCU, TMSOTf, TMSCN, Et2AlCN, and HgCN. Additionally, both benzylated and acetylated sugars may be used. 

While the steric explanation is consistent with the observed selectivity, it nonetheless presents an incomplete explanation, as alkylation of 2-methyl-4-cyano-l,3-dioxane 17 also proceeded with very high syn-selectivity [11] (Eq. 5). The selective equatorial alkylation can be rationalized as an anfz-anomeric effect that disfavors axial alkylation of the ketene iminate through filled-shell repulsion. Simple lithiated nitriles are known to exist as ketene iminates, but it would be easy to rationalize the preference for equatorial alkylation by considering the relative stability of hypothetical equatorial and axial alkyllithium reagents, vide infra. Preferential equatorial alkylation was also observed by Beau... 

Dipolar addition of ethyl propiolate to the nitrile oxide 285, prepared by chlorination of the corresponding oxime, gave, after removal of protecting groups, the C-glycosyl-isoxazole205 (286). These reactions further demonstrate the utility of anomerically functionalized C-/3-D-ribofuranosyl derivatives that can be prepared from the versatile aldehyde 100. 

The fact that each monosaccharide may give more than one peak owing to the formation of anomeric derivatives has led to a search for means to eliminate this complication. The anomeric center may be removed either by conversion into the oxime5 or the nitrile,394,3943 by oxidation followed by formation of the lactone (see Section IX, p. 71), or by reduction to the alditol. The last method is simpler than oxidation, and the separation of alditols and of aldononitriles will be discussed here additional examples are given in Table V (see p. 119). The early work on the separation of alditols has been discussed by Bishop.4 The necessity of decomposing borate complexes... 

Fused or spiro sugar oxazolines have been synthesized by treating D-fructopyranose or D-fructofuranose 1,2-0-acetonides with nitriles in triflic acid773 (Scheme 5.73). First the activation of the anomeric center takes place with simultaneous isopropy-lidene cleavage to form the oxocarbenium ion intermediate, which is attacked by the nitrile. The resulting nitrilium ion is then trapped by the hydroxyl group in an intramolecular Ritter-like reaction to yield the final product. 

Photolysis of the azide 54 in benzene gave the tctrahydro-l,3-oxazepine 55 in moderate yield. The rearrangement proceeded by migration of the endocyclic carbon atom attached to the anomeric center, independent of the anomeric configuration (Equation 10). Unfortunately, when the nitrile group was replaced either by a carboxamido or a tetrazolyl group, complex mixtures of products resulted <2000TA533>. 

Starting with phosphite 59 stannous triflate catalyzes the formation of an oxenium ion 60, which is stabilized by the solvent (61). The complex 61 is more favored than 63, justified by the reverse anomeric effect until now. But as it is shown there is no possibility for 61 to react in an SN2 reaction to 62. The intermediate 63 can be attacked by the alcohol functionality of the glycosyl acceptor, and with MeCN as leaving group you get 64. Ultimately the equilibrium between 61 and 63 shifts completely to 63. This kind of stereocontrol during a glycosylation is known as the nitrile effect.28... 

The anomeric forms derived from equilibration of aldoses give rise to multiple peaks when trimethylsilylated and gas chromatographed [311]. A method of overcoming this problem, assuming that mutarotation itself is not under study, is to modify the aldose. It can be oxidised and lactonised to the aldonolactone, for example, and characterised as its TMS derivative [322]. Alternatively for the identification of aldoses and alditols, more use may be made in the future of the separations achievable on open tubular columns of the poly-0-acetylaldonic nitriles (18) produced from aldoses and the poly-acetyl esters from alditols [323]. Figure 1.18 shows the separation of 32 assorted polyols and aldoses. 

While tin reagents have provided ample methods for the generation of anomeric radicals, the variety of structures useful as radical acceptors is extremely diverse. In addition to the conjugated nitriles and conjugated carbonyl compounds, oximes have also been used. As shown in Scheme 5.2.14, Hart, et al.,22 effected a C-glycosidation utilizing an O-benzyl oxime and a tin reagent. The reaction proceeded in 80% yield with a anomeric selectivity. 

With respect to 1,3-dipolar cycloadditions, several approaches have been utilized in the preparation of C-glycosides. As shown in Scheme 6.5.4, Kozikowski, et al.,18 effected the reaction of the ribose-derived nitrile oxide with the olefin, shown. The reaction provided a 70% yield of the isoxazoline glycoside with no deleterious effects on the configuration at the anomeric center. 

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