Synthesis and Olfactory Evaluation of (4aR*,8aR*)-1,1,8a-Trimethyl­decahydronaphthalen-4a-ol: A cis-Decalol Intersection Structure of (-)-Patchoulol and (5R*,6S*)-1,1,6-Trimethylspiro[4.5]decan-6-ol

Abstract

Superposition analysis of (-)-patchoulol (1) and the spirocyclic patchouli odorant (5R*,6S*)-1,1,6-trimethylspiro[4.5]decan-6-ol (3) suggested the intersection structure (4aS*,8aS*)-1,1,8a-trimethyldecahydronaphthalen-4a-ol (4) as potential patchouli odorant. The synthesis commenced with the Robinson annulation of mesityl oxide with 2-cyanocyclohexanone, accessible by intramolecular cyclization of pimelonitrile. Weitz-Scheffer epoxidation of the resulting Michael system with hydrogen peroxide in the presence of sodium hydroxide and subsequent Wharton rearrangement employing hydrazine hydrate and acetic acid furnished with complete cis-selectivity (4aR*,8aR*)-8a-hydroxy-5,5-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene-4a-carbonitrile (14), possibly due to neighboring group participation of the cyano function in the epoxidation step. Subsequent hydrogenation of the allylic double bond with palladium on carbon as catalyst, followed by reduction of the nitrile group with DIBAL-H afforded (4aR*,8aR*)-8a-(aminomethyl)-1,1-dimethyldecahydronaphthalen-4a-ol (16), which was deaminated with hydroxylamine-O-sulfonic acid to afford the target compound 4 that possesses an interesting woody odor with green-mossy, camphoraceous, and patchouli-type facets.

Key words

annulations - cis-decalins - epoxidations - neighboring group effects - odorants

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Chemical Computing Group Inc., Molecular Operating Environment MOE 2007.09 software package, Montréal, Québec, Canada H3A 2R7, 2007. For more information, see http://www.chemcomp.com.

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Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publications no. CCDC-695876 (13) and CCDC-695877 (16). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone]; e-mail: [e-mail]].