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

Since 6‐isopropyl‐ ( 11 ) and 6‐isobutyl‐2 H ‐benzo[ b ][1,4]dioxepin‐3(4 H )‐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)‐2 H ‐benzo[ b ][1,4]dioxepin‐3(4 H )‐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.