The conformational behaviour of 2-aryloxytetrahydropyrans and 2-acetoxytetrahydropyran, and barrier to ring inversion

Abstract

The 13C nuclear magnetic resonance data of a series of 2-(4-substituted-phenoxy)tetrahydropyrans at 156 K and in CF2Br2 and CHFCl2 solvents show that the axial preference increases with electron withdrawal in the aryloxy group: from 79% (ΔG°E→A = −0.4 kcal mol−1) (4-OCH3) to 90% (ΔG°E→A = −0.7 kcal mol−1) (4-NO2) in CF2Br2. The axial preference (anomeric effect) is smaller in the more polar CHFCl2 solvent, as expected, and the substituent effect is smaller also: change in ΔG°E→A from −0.3 (4-OCH3) to −0.5 (4-NO2) kcal mol−1. However, the axial preference of 2-acetoxytetrahydropyran is shown to be smaller than that of 2-phenoxytetrahydropyran in CF2Br2 solvent although the acetoxy group is expected to be more electronegative than the phenoxy group. Furthermore, the polarity of the solvent has no effect on the conformational equilibrium of 2-acetoxytetrahydropyran. The results are interpreted in terms of both orbital and electrostatic interactions. The ring-inversion barrier of 2-alkoxy and 2-aryloxytetrahydropyrans, determined by the temperature-coalescence method, is lower than that of tetrahydropyran by about 1.5 kcal mol−1. Key words: 2-substituted tetrahydropyrans, conformational analysis, anomeric effect, ring inversion.