Synthesis and Olfactory Properties of Spirocyclic Georgywood® Analogues

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-l,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).