Synthesis and olfactory properties of 2-substituted and 2,3-annulated 1,4-dioxepan-6-ones

The synthesis and olfactory properties of a series of 2-substituted and 2,3-annulated 1,4-dioxepan-6-ones is reported. By Williamson etherification with 3-chloro-2-(chloromethyl)prop-1-ene (6) and subsequent Katsuki-Sharpless oxidation, 1,4-dioxepan-6-one (8a) and its 2-methyl (8b), 2-propyl (8c), 2-isobutyl (8d), and 2,2,3,3-tetramethyl derivative (8e), as well as four 2,3-annulated 1,4-dioxepan-6-ones 8h, 8i, 8j, and 8k were synthesised. By etherification with ethyl diazoacetate and subsequent Dieckmann cyclisation, (5aS,9aS)-9-bromo- and 9-iodo-5a,6,7,9a-tetrahydro-2H-benzo[b][1,4]dioxepin-3(4H)-one (8f/g) as well as a 2,3-annulated derivative 8m from (+)-limonene were prepared. 2-Propyl-1,4-dioxepan-6-one (8c) was discovered to have a green floral odour with anisic and cinnamic nuances, which could be rationalised by a superposition analysis. The olfactory properties of the 1,4-dioxepan-6-ones synthesised underline the crucial importance of a benzenoid ring system for marine odorants.