Is there a generalized reverse anomeric effect?: Substituent and solvent effects on the configurational equilibria of neutral and protonated N-arylglucopyranosylamines and N-aryl-5-thioglucopyranosylamines

The effects of substitution and solvent on the configurational equilibria of neutral and protonated N-(4-Y-substituted-phenyl) peracetylated 5-thioglucopyranosylamines (Y = OMe, H, CF3, NO2) 1-4 and N-(4-Y-substituted-phenyl) peracetylated glucopyranosylamines (Y = OMe, H, NO2) 9-11 are described. The configurational equilibria were determined by direct integration of the resonances of the individual isomers in the H-1 NMR spectra after equilibration of both alpha- and beta-isomers. The equilibrations of the neutral compounds 1-4 in CD3OD, CD3NO2, and (CD3)(2)CO were achieved by HgCl2 catalysis and those of the neutral compounds 9-11 in CD2Cl2 and CD3OD by triflic acid catalysis. The equilibrations of the protonated compounds in both the sulfur series (solvents, CD3OD, CD3NO2, (CD3)(2)CO, CDCl3, and CD2Cl2) and oxygen series (solvents, CD2Cl2 and CD3OD) were achieved with triflic acid. The substituent and solvent effects on the equilibria are discussed in terms of steric and electrostatic effects and orbital interactions associated with the endo-anomeric effect. A generalized reverse anomeric effect does not exist in neutral or protonated N-aryl-5-thioglucopyranosylamines and N-arylglucopyranosylamines. The anomeric effect ranges from 0.85 kcal mol(-1) in 2 to 1.54 kcal mol(-1) in 10. The compounds 1-4 and 9-11 show an enhanced endoanomeric effect upon protonation, ranging from 1.73 kcal mol(-1) in 2 to 2.57 kcal mol(-1) in 10. We estimate the increase in the anomeric effect upon protonation of 10 to be approximately 1.0 kcal mol(-1) However, this effect is offset by steric effects due to the associated counter ion which we estimate to be approximately 1.2 kcal mol(-1). The values of K-eq(axial-equatorial) in protonated 1-4 increase in the order OMe < H < CF3 < NO2, in agreement with the dominance of steric effects (due to the counterion) over the endo-anomeric effect. The values of K-eq(axial-equatorial) in protonated 9-11 show the trend OMe < H < NO2 that is explained by the balance of the endoanomeric effect and steric effects in the individual compounds. The trends in the values of the C-1-H-1 coupling constants for 1-4 and the corresponding deacetylated compounds 5-8 as a function of substituent and alpha- or beta-configuration are discussed in terms of the Perlin effect and the interplay of the endo- and exo-anomeric effects.