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

The commercially important isochromane musk odorant Galaxolide^® (=1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopentag]-2-benzopyran; HHCB; 3 ) was separated into its diastereoisomers via the tricarbonyl(η⁶-cyclopentag]-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-cyclopentag]-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.