On the Dienone Motif of Musks: Synthesis and Olfactory Properties of Partially and Fully Hydrogenated Dienone Musks

Abstract

AbstractMinimum‐energy calculations and the conformation of the (11Z)‐retinylidium moiety in bovine rhodopsin called into doubt that the function of the dienone motif of a new class of musk odorants 1–6 was to stiffen and planarize the compounds. To investigate the function and importance of these double bonds, the three most potent representatives of the family of dienone musks were partially and fully hydrogenated, and the products were evaluated for their olfactory properties. Stryker's method using the Osborn complex and the procedure of Evans and Fu utilizing catecholborane were used for the reduction of the α,β‐double bonds, palladium on CaCO3 was used for the reduction of the γ,δ‐double bonds, and palladium on charcoal was used for the complete hydrogenation of the dienone systems in 2–4. trans‐Configured cyclopentyl derivatives 23 and 24 were synthesized from 4,4‐dimethylcyclohex‐2‐en‐1‐one by Weitz–Scheffer epoxidation, sodium borohydride reduction, rearrangement to the corresponding carbaldehyde using lithium bromide in toluene/HMPT, cuprate alkylation with the tert‐butyl Gilman reagent, aldol condensation with acetone, and optional hydrogenation with palladium on charcoal. Of the synthesized derivatives, only the γ,δ‐unsaturated enones (i.e., 9, 12, and 15) have a typical musk odor, indicating that the γ,δ‐double bond interacts electronically with the musk receptor(s). As enones 9, 12, and 15 are, however, less intense than the parent compounds (i.e., 2–4), the α,β‐double bond seems to intensify the odor strength due to conformational effects. Conformational effects also seem to favor compounds with an endocyclic γ,δ‐double bond over acyclic dienone systems for their intensity and musk character. In acyclic compounds 10 and 13, the α,β‐double bond introduces violet–orris facets.