Preparation and Olfactory Characterization of the Enantiomerically Pure Isomers of the Perfumery Synthetic Galaxolide

• Published in: Helvetica chimica acta Vol. 82; no. 10; pp. 1656 - 1665
• Main Authors: Fráter, Georg, Müller, Urs, Kraft, Philip
• Format: Journal Article
• Language: English
• Published: Basel Verlag Helvetica Chimica Acta 06.10.1999; Wiley
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; RING ENLARGEMENT; (12R)-(+)-12-METHYL-13-TRIDECANOLIDE
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/(SICI)1522-2675(19991006)82:10<1656::AID-HLCA1656>3.0.CO;2-M

The commercially important isochromane musk odorant Galaxolide® (=1,3,4,6,7,8‐hexahydro‐4,6,6,7,8,8‐hexamethylcyclopenta[g]‐2‐benzopyran; HHCB; 3) was separated into its diastereoisomers via the tricarbonyl(η6‐cyclopenta[g]‐2‐benzopyran)chromium complexes 10. Since GC/olfactometry indicated that only one enantiomer of each diastereoisomer (4RS,7RS)‐3 and (4RS,7SR)‐3 determines the odor characteristics of the commercial product, all four stereoisomers (4S,7R)‐, (4S,7S)‐, (4R,7S)‐, and (4R,7R)‐3 were synthesized by Friedel‐Crafts alkylation of 1,1,2,3,3‐pentamethylindane (11) with (S)‐ and (R)‐methyloxirane ((S)‐ and (R)‐12, resp.), acid‐catalyzed reaction of the resulting products with paraformaldehyde, and separation of the formed diastereoisomer pairs via the tricarbonyl(η6‐cyclopenta[g]‐2‐benzopyran)chromium complexes 10. The powerful musk odor of Galaxolide ® (3) was thus attributed to its (−)‐(4S)‐isomers (4S,7R)‐ and (4S,7S)‐3, while the (+)‐(4R)‐isomers (4R,7S)‐ and (4R,7R)‐3 were weak to almost odorless.