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 o f neutral and protonated N-(4-Y-substituted-phenyl) peracetylated 5-thioglu copyranosylamines (Y = OMe, H, CF3, NO2) 1-4 and N-(4-Y-substituted-phenyl) peracetylated glucopyranosylamines (Y = OMe, H, NO2) 9-11 are described. T he configurational equilibria were determined by direct integration of the resonances of the individual isomers in the H-1 NMR spectra after equilibra tion of both alpha- and beta-isomers. The equilibrations of the neutral com pounds 1-4 in CD3OD, CD3NO2, and (CD3)(2)CO were achieved by HgCl2 catalysi s and those of the neutral compounds 9-11 in CD2Cl2 and CD3OD by triflic ac id catalysis. The equilibrations of the protonated compounds in both the su lfur series (solvents, CD3OD, CD3NO2, (CD3)(2)CO, CDCl3, and CD2Cl2) and ox ygen series (solvents, CD2Cl2 and CD3OD) were achieved with triflic acid. T he substituent and solvent effects on the equilibria are discussed in terms of steric and electrostatic effects and orbital interactions associated wi th the endo-anomeric effect. A generalized reverse anomeric effect does not exist in neutral or protonated N-aryl-5-thioglucopyranosylamines and N-ary lglucopyranosylamines. 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 t o 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 e ffect is offset by steric effects due to the associated counter ion which w e estimate to be approximately 1.2 kcal mol(-1). The values of K-eq(axial-e quatorial) 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 protonat ed 9-11 show the trend OMe < H < NO2 that is explained by the balance of th e endoanomeric effect and steric effects in the individual compounds. The t rends in the values of the C-1-H-1 coupling constants for 1-4 and the corre sponding 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.