Synthesis and Olfactory Properties of Spirocyclic Georgywood^® Analogues

Abstract

Spirocyclic analogues of Georgywood^® (3) and unlike-10-acetyl-9,10-dimethylbicyclo[6.4.0]dodec-1(8)-ene (4), in which the acetyl moiety and the methyl substituent of C-10 are part of a cyclopentyl­ or cyclohexyl ring, were synthesized from 8a-homomyrcene (6) and 4-methylenespiro[2.7]decane (13), respectively. 2-(Dimethylaminomethyl)cyclopentanone (7) or the allyl 1-(acetoxymethyl)-2-oxocycloalkanecarboxylates 14 and 18 were employed as methylene cycloalkanone precursors in an ordinary Diels-Alder reaction or in [4+2] cycloadditions on the vinyl cyclopropane system 13 in the presence of Wilkinson’s catalyst. By simple LDA-mediated alkylation of the resulting spirocycles with methyl iodide, further analogues were prepared that provided additional insight into the structural and stereochemical requirements for the typical woody-ambery odor character of Iso E Super^® (1), and that call a binding model proposed by Hong and Corey into question. The best odorants found in this study were (1R*,3S*,1′R*)-3,1′,8′,8′-tetramethyl-3′,4′,5′,6′,7′,8′-hexahydro-1′H-spiro[cyclopentane-1,2′-naphthalen]-2-one (10) and (1R*,1′S*,3′S*)-1,3′-dimethyl-3,4,5,6,7,8,9,10-octahydro-1′H-spiro[benzo[8]annulene-2,1′-cyclohexan]-2′-one (17).

Key words

cyclizations - Diels-Alder reactions - Georgywood - odorants - spiro compounds

References

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13

Crystallographic data (excluding structure factors) for the X-ray structure of oxime 9 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 234419. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB1 1EZ, UK [Fax: [phone]; E-mail: [e-mail]].