Lovchik, Martin A. Fráter, Georg Goeke, Andreas Hug, Werner 2008-01-18 Recently, we reported a novel access to 2,2-diethyl-3-[(<i>E</i>/<i>Z</i>)-prop-1-en-1-yl]cyclobutanone by an intramolecular nucleophilic substitution with allylic rearrangement (<i>S</i>_N<i>i</i>′) of (<i>E</i>)-6-chloro-3,3-diethylhept-4-en-2-one. The ring closure reaction was found to proceed with selective <i>syn</i>-displacement of the leaving group. This method was now applied to the total synthesis of junionone, an olfactorily interesting cyclobutane monoterpenoid isolated from <i>Juniperus communis</i>, L. <i>S</i>_N<i>i</i>′ Ring closure of the ketone enolate of (<i>E</i>)-3,3-dimethyl-5-[(2<i>R</i>,3<i>R</i>)-3-methyloxiran-2-yl]pent-4-en-2-one (<i>R</i>,<i>R</i>)-(<i>E</i>)-<b>4′</b> proceeded only after the epoxide moiety had been activated by <i>Lewis</i> acid and led to the junionone precursors (3<i>R</i>)- and (3<i>S</i>)-3-[(1<i>E</i>,3<i>R</i>)-3-hydroxybut-1-en-1-yl]-2,2-dimethylcyclobutanone (<i>S</i>/<i>R</i>,<i>R</i>)-(<i>E</i>)-<b>3</b>. The ratio of <i>syn-</i> and <i>anti-</i>conformers in the transitory molecular arrangement was found to depend on the nature of the <i>Lewis</i> acid. The absolute configuration of both the synthetic as well as the natural junionone, isolated from juniper berry oil, was determined by <i>Raman</i> 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. application/pdf https://folia.unifr.ch/global/documents/300803 https://folia.unifr.ch/documents/300803/files/hug_tsj.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1002/cbdv.200890003 info:eu-repo/semantics/openAccess License undefined Chemistry & Biodiversity. - 2008, vol. 5, no. 1, p. 126-139 Junionone <i>S</i>_N<i>i</i>′ Reaction epoxy ketones ketones cyclobutanone cyclobutane Raman optical activity Juniperus communis info:eu-repo/classification/udc/54 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 http://purl.org/coar/resource_type/c_6501