Vanilla oceanics: Synthesis and olfactory properties of (1E)-7-(prop-1-enyl)-2H-benzo[b][1,4]dioxepin-3(4H)-ones and homologues

(1E)-7-(Prop-1-enyl)-2H-benzo[b][1,4]dioxepin-3(4H)-one was synthesized from dimethyl 2,2-[(4-allyl-1,2-phenylene)bis(oxy)]diacetate by isomerization of the double bond and Dieckmann condensation followed by saponification and decarboxylation. It possessed an intense marine, spicy-vanillic odor, and served as starting material for the synthesis of homologues by protection as 1,3-dioxolane, Katsuki-Sharpless oxidation of the benzylic double bond, Grignard reaction, and dehydration/deprotection with 50% aqueous sulfuric acid. The olfactory properties and the extremely low odor thresholds of these resulting homologues are rationalized with an improved olfactophore model.