From Vetiver to Patchouli: Discovery of a NewHigh‐Impact Spirocyclic Patchouli Odorant

Abstract

AbstractIn the course of synthetic work on new vetiver odorants, a new, potent patchouli odorant was discovered. Its structure was elucidated as 1‐hydroxy‐1,4,7,7,9‐pentamethylspiro[4.5]decan‐2‐one (15/16), and both diastereoisomers were synthesized from the previously reported 4,7,7,9‐tetramethyl‐1‐methylenespiro[4.5]decan‐2‐one by epoxidation with m‐chloroperoxybenzoic acid, reduction with lithium aluminum hydride, and subsequent oxidation with pyridinium chlorochromate or Dess–Martin periodinane. The 1,4‐unlike‐isomer 15 was found to be the diastereoisomer with the most powerful odor, and its excellent odor threshold of 0.067 ng/L air triggered the synthesis of the derivatives 19, 22, 23, and 26 possessing a different methyl substitution pattern or ring size. Glycol cleavage in the oxidation step was circumvented by Swern oxidation. Three further 4‐demethylated derivatives, 32, 33, and 34, were prepared by a short sequence consisting of Diels–Alder reaction with 4‐methylene‐5‐oxohexanenitrile (28), reductive radical cyclization mediated by the titanocene(III) complex Cp2Ti(Ph)(iPr), and standard hydrogenation. Finally, the enantiomers of 15 were separated by forming their SAMP hydrazones, which were subsequently cleaved by ozonolysis. The odor of the racemate 15 was shown to be exclusively due to the (+)‐(1S,4R,5R,9S)‐configured enantiomer 38, the stereocenters of which superimpose well with those of (–)‐patchoulol (3), the odorous principle of patchouli oil. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)