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 (8 a) and its 2‐methyl (8 b), 2‐propyl (8 c), 2‐isobutyl (8 d), and 2,2,3,3‐tetramethyl derivative (8 e), as well as four 2,3‐annulated 1,4‐dioxepan‐6‐ones 8 h, 8 i, 8 j, and 8 k were synthesised. By etherification with ethyl diazoacetate and subsequent Dieckmann cyclisation, (5aS,9aS)‐9‐bromo‐ and 9‐iodo‐5a,6,7,9a‐tetrahydro‐2 H‐benzo[b][1,4]dioxepin‐3(4 H)‐one (8 f/g) as well as a 2,3‐annulated derivative 8 m from (+)‐limonene were prepared. 2‐Propyl‐1,4‐dioxepan‐6‐one (8 c) 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. Surprisingly green floralcy: The synthesis and olfactory properties of a series of 2‐substituted and 2,3‐annulated 1,4‐dioxepan‐6‐ones is reported. rac‐2‐Propyl‐1,4‐dioxepan‐6‐one was discovered to have an unexpected green‐floral, anisic odour with cinnamic aspects, which could be rationalised by superposition analysis with celery ketone and cis‐jasmone. The olfactory properties of further 1,4‐dioxepan‐6‐ones demonstrate the crucial importance of a benzenoid ring system for compounds to have marine odour characteristics.