Design, Synthesis and Olfactory Properties of 2-Substituted 2-tert-Butyl-5-­methyl-2,5-dihydrofurans: seco-Derivatives of Theaspiranes

Abstract

Two seco-theaspiranes with pronounced blackcurrant notes, 2-tert-butyl-5-methyl-2-propyl-2,5-dihydrofuran (7) and 2-tert-butyl-5-methyl-2-propyltetrahydrofuran (8), were synthesized by a synthetic sequence consisting of Grignard reaction, Lindlar hydrogenation, and cyclization followed by optional Pd-catalyzed hydrogenation. The sequence was modified for the synthesis of the oxygenated analogs 2-(2¢-tert-butyl-5¢-methyltetrahydrofuran-2¢-yl)propan-2-ol (9) and 3-(2¢-tert-butyl-5¢-methyltetrahydrofuran-2¢-yl)butan-2-one (10). The first modification featured trimethylsilyl ether protection and stepwise construction of the alkyne moiety necessitated by steric hindrance. In the second modification, a but-2-en-2-yl group was utilized as latent 3-hydroxybut-1-en-2-yl functionality, and the steric constraint around the tertiary hydroxy group was exploited to introduce a stereocenter by S N 2 ring closure. As for the parent compounds 7 and 9, the odor of the oxygenated secotheaspiranes was shifted towards a woody tonality. The likediastereomer 9a even had a typical patchouli profile, and the enantiomers 10a and 10b differed significantly in their olfactory properties.

Novel Silicon‐Based Patchouli Odorants of the Trialkyl(1‐hydroxy‐1‐methylethyl)silane Type: Design, Synthesis, and Olfactory Properties

“…In addition, one should note that a 2,3,4,4‐tetramethylpentan‐2‐ol substructure is already present in the former lead structure 3 , highlighted in red (Scheme ). Similar motifs, again highlighted in red, can also be found in two recently described monocyclic patchouli odorants, the tetrahydrofuran derivative 6 10 and the campholyt aldehyde derivative 7 14 (Scheme ). Therefore, the structural motif of the first target compound 5 seemed to be quite meaningful.…”

“…To further explore lead structure 4 , it now seemed interesting to increase the molecular flexibility by dissecting some bonds while preserving the hydrophobic groups around the quaternary carbon atoms, which probably address the corresponding hydrophobic binding pockets at the receptor site(s). In the ionone family, such seco strategies worked out very well,8 and led, for instance, to the commercial odorants pomarose9 and cassyrane,10 respectively. However, the odors of seco derivatives of (−)‐patchoulol ( 1 ) have so far shifted either towards the woody, the earthy, or the camphoraceous side, and did not represent balanced patchouli notes 11.…”

What's Hot, What's Not: The Trends of the Past 20 Years in the Chemistry of Odorants

“…[183] With 17.2 ng L À1 air, 211 also had ar ather high odor threshold. Ab ifunctional donor/ acceptor unit can however convey ac haracteristic patchouli note,asdemonstrated by the theaspirane-related tetrahydrofuranyl alcohols 212 [184] and 213 ( Figure 19). [185,186] Such structures are generally associated with fruity blackcurrant odors (cf.Section 3.2).…”

Heiße Luft oder cooler Duft? Die Trends der letzten 20 Jahre in der Riechstoffchemie

“…[183] Mit 17.2 ng L À1 Luft besaß 211 allerdings einen ziemlich hohen Schwellenwert. Eine bifunktionelle Donor/Acceptor-Einheit kann dennoch eine charakteristische Patchouli-Note vermitteln, wie die mit Theaspiran verwandten Tetrahydrofuranylalkohole 212 [184] und 213 beweisen (Abbildung 19). [185,186] (206).…”