On the Structure–Odor Correlation of Muguet Aldehydes: Synthesis of 3‐(4'‐Isobutyl‐2'‐methylphenyl)propanal (Nympheal) and Four Novel Derivatives from a Hagemann's Ester.

Lilybelle and Biomuguet are currently the only renewable and biodegradable non‐spermotoxic Lilial replacers. Being non‐aromatic, these lack however some of the green, aquatic aspects of Lilial that are present in the captive odorant Nympheal, 3‐(4‐isobutyl‐2‐methylphenyl)propanal, which is not available from renewable resources. Therefore, the influence of the aromatic nucleus on the odor of four new hydrogenated Nympheal derivatives was investigated, which were all accessible from the isobutyl Hagemann's ester that was synthesized in 75 % yield from isovaleraldehyde with two equivalents of ethyl acetoacetate. The respective Hagemann's ester was alkylated with 3‐bromopropanal dimethyl acetal and subjected to decarboxylative saponification, followed by hydride reduction and dehydration through the corresponding mesylate to furnish, after deprotection with formic acid, the corresponding exo‐ and endo‐dihydro‐Nympheal derivative. Full or partial hydrogenation of the central acetal‐protected intermediate provided after deprotection the analogous fully saturated analogue or the cyclohexene derivative. The olfactory properties of these four novel Nympheal derivatives are discussed and rationalized by computational olfactophore models. [ABSTRACT FROM AUTHOR]