Crossing the Boundaries between Marine and Muguet: Discovery of Unusual Lily‐of‐the‐Valley Odorants Devoid of Aldehyde Functions

Abstract

Since 6‐isopropyl‐ (11) and 6‐isobutyl‐2H‐benzo[b][1,4]dioxepin‐3(4H)‐one (12) instead of the expected marine odor had been reported to possess lily‐of‐the‐valley notes, albeit weaker than benchmark odorants, the influence of a cyclopropyl ring instead of a methyl branching on the olfactory properties was investigated. 6‐Cyclopropyl‐ (27), 6‐(2′‐methylcyclopropyl)‐ (32) and 6‐(cyclopropylmethyl)‐2H‐benzo[b][1,4]dioxepin‐3(4H)‐one (39) were thus synthesized from 2,3‐dimethoxybenzaldehyde (22) by a synthetic sequence consisting of Wittig methylenation/ethylenation/homologation with (methoxymethyl)triphenylphosphonium chloride, followed by cyclopropanation, demethylation, Williamson etherification with 3‐chloro‐2‐(chloromethyl)prop‐1‐ene, and Katsuki–Sharpless oxidation. The odor thresholds of the target structures 27, 32, and 39, which are all floral‐green lily‐of‐the‐valley odorants, lie in the range of that of Lilial (1), with the 6‐cyclopropyl derivative 27 being the most potent (th 0.065 ng/l air). Particularly impressive was the close resemblance of the 6‐(cyclopropylmethyl) derivative 39 with Bourgeonal (3), which was rationalized by a superposition analysis.