Synthesis of [4.3.3]Propellanes by Carbenium-Ion Rearrangement and Their Olfactory Characterization

• Published in: Helvetica chimica acta Vol. 86; no. 3; pp. 678 - 696
• Main Authors: Fráter, Georg, Helmlinger, Daniel, Kraft, Philip
• Format: Journal Article
• Language: English
• Published: Basel WILEY-VCH Verlag 01.03.2003; WILEY‐VCH Verlag; Wiley
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; KETONES; (+/-)MODHEPHENE; ACID; DIELS-ALDER REACTIONS; 2-METHYL-2-CYCLOHEXENONE; BIOSYNTHESIS; CYCLOALKENONES; SCLAREOL; POLYSPIRANES; CYCLIZATION
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.200390067

Treatment of (+)‐sclareolide (1) with polyphosphoric acid or Eaton's reagent furnished, besides the anticipated cyclopentenone (−)‐12 and its isomer (−)‐15, two diastereoisomeric [4.3.3]propellanes (−)‐13 and (−)‐14, which possess interesting woody‐ambery odors. The hydrogenated derivative (−)‐17 possessed an even more‐powerful odor reminiscent of natural ambergris tincture. Mechanistic insight into this rearrangement was provided by a by‐product 24 of the reaction of sclareolide (1) with Eaton's reagent. The carbenium ion rearrangement was then employed in the synthesis of four related [4.3.3]propellanes 40–43, illustrating the utility and scope of this reaction. The olfactory properties of the synthesized [4.3.3]propellanes as well as of the original target structures 10, 33, and 34, prepared from (−)‐12 and (−)‐15, are discussed. Especially the pronounced ambra odor of (−)‐17 vividly contradicts the ‘triaxial rule of amber sensation' and provides new insight into the structural requirements for ambra odorants.