Total Synthesis of Junionone, a Natural Monoterpenoid from Juniperus communis L., and Determination of the Absolute Configuration of the Naturally Occurring Enantiomer by ROA Spectroscopy

• Published in: Chemistry & biodiversity Vol. 5; no. 1; pp. 126 - 139
• Main Authors: Lovchik, Martin A., Fráter, Georg, Goeke, Andreas, Hug, Werner
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01.01.2008; WILEY‐VCH Verlag
• Subjects: Cyclobutane; Cyclobutanone; Epoxy ketones; Junionone; Juniperus - chemistry; Juniperus communis; Ketones; Models, Chemical; Molecular Conformation; Monoterpenes - analysis; Monoterpenes - chemical synthesis; Monoterpenes - isolation & purification; Raman optical activity; SNi′ Reaction; Spectrum Analysis, Raman - instrumentation; Spectrum Analysis, Raman - methods; Stereoisomerism; Vibration
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.200890003

Recently, we reported a novel access to 2,2‐diethyl‐3‐[(E/Z)‐prop‐1‐en‐1‐yl]cyclobutanone by an intramolecular nucleophilic substitution with allylic rearrangement (SNi′) of (E)‐6‐chloro‐3,3‐diethylhept‐4‐en‐2‐one. The ring closure reaction was found to proceed with selective syn‐displacement of the leaving group. This method was now applied to the total synthesis of junionone, an olfactorily interesting cyclobutane monoterpenoid isolated from Juniperus communis, L. SNi′ Ring closure of the ketone enolate of (E)‐3,3‐dimethyl‐5‐[(2R,3R)‐3‐methyloxiran‐2‐yl]pent‐4‐en‐2‐one (R,R)‐(E)‐4′ proceeded only after the epoxide moiety had been activated by Lewis acid and led to the junionone precursors (3R)‐ and (3S)‐3‐[(1E,3R)‐3‐hydroxybut‐1‐en‐1‐yl]‐2,2‐dimethylcyclobutanone (S/R,R)‐(E)‐3. The ratio of syn‐ and anti‐conformers in the transitory molecular arrangement was found to depend on the nature of the Lewis acid. The absolute configuration of both the synthetic as well as the natural junionone, isolated from juniper berry oil, was determined by Raman Optical Activity (ROA) spectroscopy. Our experiments led to a novel synthetic route to both (+)‐ and (−)‐junionone, the first determination of the absolute configuration of natural junionone, and to the development of a practical ROA procedure for measuring milligram quantities of volatile liquids.