The effect of electrostatic interactions on conformational equilibria of multiply substituted tetrahydropyran oxocarbenium ions

Abstract

The three-dimensional structures of dioxocarbenium ions related to glycosyl cations were determined by an analysis of spectroscopic, computational, and reactivity data. Hypothetical low-energy structures of the dioxocarbenium ions were correlated with both experimentally determined (1)H NMR coupling constants and diastereoselectivity results from nucleophilic substitution reactions. This method confirmed the pseudoaxial preference of C-3 alkoxy-substituted systems and revealed the conformational preference of the C-5 alkoxymethyl group. Although the monosubstituted C-5 alkoxymethyl substituent preferred a pseudoequatorial orientation, the C-5-C-6 bond rotation was controlled by an electrostatic effect. The preferred diaxial conformer of the trans-4,5-disubstituted tetrahydropyranyl system underscored the importance of electrostatic effects in dictating conformational equilibria. In the 2-deoxymannose system, although steric effects influenced the orientation of the C-5 alkoxymethyl substituent, the all-axial conformer was favored because of electrostatic stabilization.

Figure 1

Preferred conformations of the oxocarbenium ion intermediates in nucleophilic substitution reactions of monosubstituted tetrahydropyran oxocarbenium ions.

Figure 2

Monosubstituted lactones

Figure 3

Relative energy of conformers at different level of theory.

Figure 4

Theoretical and experimental J-values for C-3 alkoxy dioxocarbenium ion (B3LYP/6-31G*)

Figure 5

Relative low-energy conformers of C-5 alkoxymethyl dioxocarbenium ion (B3LYP/6-31G*).

Figure 6

Comparison of theoretical and experimental J-values of C-5 alkoxymethyl dioxocarbenium ion.

Figure 7

Theoretical and experimental J-values of C-5 alkoxymethyl rotamers.

Figure 8

Relative low-energy conformers of the 4,5-disubstituted dioxocarbenium ion (B3LYP/6-31G*).

Figure 9

Comparison of theoretical and experimental J-values for 4,5-disubstituted dioxocarbenium ion.

Figure 10

Calculated low-energy conformers of the 2-deoxymannosyl oxocarbenium ion (B3LYP/6-31G*).

Figure 11

Comparison of theoretical and experimental J-values of the 2-deoxymannosyl oxocarbenium ion.

Figure 12

Nucleophilic addition to oxocarbenium ions derived from 2-deoxymannolactone.