title: Synthesis by ring-closing alkyne metathesis with selective hydrogenation, and olfactory comparison of (7E)- and (7Z)-cyclohexadec-7-enone (Aurelione(®) ).
abstract: Both C=C-bond isomers of cyclohexadec-7-enone (6, Aurelione(®) ) were selectively synthesized via cyclohexadec-7-ynol (16) by ring-closing alkyne metathesis of icosa-2,18-diyn-9-ol (15), employing an in situ-formed catalyst from Mo(CO)6 and 4-(trifluoromethyl)phenol. Pyridinium chlorochromate (PCC) oxidation and subsequent Lindlar hydrogenation afforded the (7Z)-configured isomer (7Z)-6, while hydrosilylation of the intermediate cyclohexadec-7-ynone (17), followed by desilylation, provided the (7E)-configured cyclohexadec-7-enone ((7E)-6). The substrate for the alkyne metathesis was prepared from cycloheptanone (7) by cycloaddition of chloromethylcarbene to its trimethylsilyl enol ether 8, and subsequent ring enlargement of the adduct 9 under rearrangement to 2-methylcyclooct-2-enone (10), which was subjected to Weitz-Scheffer epoxidation and Eschenmoser-Ohloff fragmentation to non-7-ynal (12). Its reaction with the Grignard reagent of 11-bromoundec-2-yne (14), prepared from the corresponding alcohol 13 by Appel-Lee bromination, furnished the icosa-2,18-diyn-9-ol (15). While both isomers of cyclohexadec-7-enone (6) possess warm and powdery musk odors with tobacco-type ambery accents, (7Z)-6 is more animalic and waxy, whereas (7E)-6 was found to be more floral, sweet, and hay-like in tonality. Interestingly, however, with odor detection thresholds of 2.0 ng/l air and 2.3 ng/l air, respectively, both (7Z)-6 and (7E)-6 were found to be almost identical in their odor strength, with the (7Z)-6 being only very slightly more powerful.
authors.affiliation: Givaudan Schweiz AG, Fragrance Research, Überlandstrasse 138, CH-8600 Dübendorf, (phone: +41-44-8242520; fax: +41-44-8242926).
authors.forename: Marion
authors.initials: M
authors.lastname: Mathys
authors.forename: Philip
authors.initials: P
authors.lastname: Kraft
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D006865:Hydrogenation; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009812:Odorants / Q000032:analysis*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000480:Alkynes; D007659:Ketones; D047028:Macrocyclic Compounds
keywords: Alkyne metathesis; Aurelione; EschenmoserOhloff fragmentation; Macrocycles; Musk odorants