Synthesis and Olfactory Evaluation of the Four Stereoisomers of 4-Acetoxy- and 4-Acetylthio-2-Hexyltetrahydrofuran

Abstract

Four stereoisomers of 4-acetoxy-2-hexyltetrahydrofuran and their sulfur analogues were synthesized. Odor evaluation showed that configuration governs properties: in the acetoxy series, (2R,4S) had the lowest thresholds (89 μg/L in water, 9.1 μg/L in air) with a peach-like sweet odor, while (2S,4R) had the highest (3.3 × 103 μg/L, 7.7 × 102 μg/L) with earthy notes; only (2R)-configured isomers exhibited the characteristic sweet peach note. In the acetylthio series, thresholds dropped dramatically: (2R,4S) showed the lowest (0.25 μg/L in water, 3.6 ng/L in air) with mushroom-celery odor, while (2S,4R) had a sulfurous, rotten-egg odor. The (2S,4S) and (2R,4R) isomers exhibited garlic-mushroom and plastic-metallic odors, respectively. Thus, sulfur substitution at the 4-position drastically lowers detection thresholds and shifts odor profiles from fruity toward sulfurous, mushroom-like notes.