(-)-(9R,10S)-10-Acetyl-9,10-dimethylbicyclo[6.4.0]dodec-1(8)-ene: Optical Resolution, Catalyst Systems, Derivatives and Olfactory Properties

Abstract

By separation of the enantiomers of the woody-ambery odorant 10-acetyl-9,10-dimethylbicyclo[6.4.0]dodec-1(8)-ene (rac-12) via their diastereomeric (-)-camphanoates, the (-)-(9R,10S)-isomer (9R,10S)-12 was determined to be the most powerful enantiomer. With an odor threshold of 0.19 ng/L it is about one hundred times stronger than its antipode. Racemic 10-acetyl-9,10-dimethylbicyclo[6.4.0]dodec-1(8)-ene (rac-12) was synthesized by an unusual [4+2]-cycloaddition of 4-methylenespiro[2.7]decane (10) and 3-methylbut-3-en-2-one (11) in the presence of Wilkinson’s catalyst. However, attempts to induce optical activity with chiral rhodium(I) catalysts proved futile. Platinum(II)-DIOP catalysts furnished traces (0.05% GC yield) of (-)-(9R,10S)-10-acetyl-9,10-dimethylbicyclo[6.4.0]dodec-1(8)-ene [(9R,10S)-12] with an enantiomeric excess of around 40% ee. For further studies on the structure-odor correlation of woody odorants, two new tricyclic analogs of rac-12, (±)-(2R*,3S*,7S*)-2-methyltricyclo[7.6.0.0^3,7]pentadec-1(9)-en-4-one (18) and (±)-(2R*,3S*,7S*)-2,3-dimethyl-tricyclo[7.6.0.0^3,7]pentadec-1(9)-en-4-one (20) were synthesized and characterized.

catalysis - cycloadditions - enantiomeric resolution - odorants - polycycles

References

<A NAME="RT12003SS-1">1</A> Gallo S. Diploma Thesis   Eidgenössische Technische Hochschule Zürich, Dept. XAf; Switzerland: 2003. 

<A NAME="RT12003SS-2A">2a</A> Fráter G. Bajgrowicz JA. Kraft P. Tetrahedron  1998,  54:  7633 

<A NAME="RT12003SS-2B">2b</A> Kraft P. Bajgrowicz JA. Denis C. Fráter G. Angew. Chem. Int. Ed.  2000,  39:  2980 ; Angew. Chem. 2000, 112, 3106

<A NAME="RT12003SS-3">3</A> Nussbaumer C. Fráter G. Kraft P. Helv. Chim. Acta  1999,  82:  1016 

<A NAME="RT12003SS-4">4</A> Kraft P. Synthesis  1999,  695 

<A NAME="RT12003SS-5">5</A> Ruder SM. Ronald RC. Tetrahedron Lett.  1984,  25:  5501 

<A NAME="RT12003SS-6">6</A> Doering WVE. Schreiber KC. J. Am. Chem. Soc.  1955,  77:  514 

<A NAME="RT12003SS-7">7</A> Fitjer L. Quabeck U. Synth. Commun.  1985,  15:  855 

<A NAME="RT12003SS-8A">8a</A> Wender PA. Takahashi H. Witulski B. J. Am. Chem. Soc.  1995,  117:  4720 

<A NAME="RT12003SS-8B">8b</A> Wender PA. Baryza JL. Brenner SE. Clarke MO. Gamber GG. Horan JC. Jessop TC. Kan C. Pattabiraman K. Williams TJ. Pure Appl. Chem.  2003,  75:  143 

<A NAME="RT12003SS-8C">8c</A> Wender PA. Williams TJ. Angew. Chem. Int. Ed.  2002,  41:  4550 ; Angew. Chem. 2002, 114, 4732

<A NAME="RT12003SS-9A">9a</A> Job A. Janeck CF. Bettray W. Peters R. Enders D. Tetrahedron  2002,  58:  2253 

<A NAME="RT12003SS-9B">9b</A> Djuric SW. Docter SH. Yu SS. Spangler D. Tsai B.-S. Anglin CP. Gaginella TS. Kachur JF. Keith RH. Masiasz TJ. Villani-Price D. Rao TS. Walsh RE. Widomski DL. Fretland DJ. Bioorg. Med. Chem. Lett.  1994,  4:  811 

<A NAME="RT12003SS-9C">9c</A> Domínguez D. Ardecky RJ. Cava MP. J. Am. Chem. Soc.  1983,  105:  1608 

<A NAME="RT12003SS-10A">10a</A> Gerlach H. Helv. Chim. Acta  1968,  51:  1587 

<A NAME="RT12003SS-10B">10b</A> Gerlach H. Müller W. Helv. Chim. Acta  1972,  55:  2277 

<A NAME="RT12003SS-10C">10c</A> Helmchen G. Staiger G. Angew. Chem. Int. Ed. Engl.  1977,  16:  116 ; Angew. Chem. 1977, 89, 119

<A NAME="RT12003SS-10D">10d</A> Oppolzer W. Chapuis C. Dupuis D. Guo M. Helv. Chim. Acta  1985,  68:  2100 

<A NAME="RT12003SS-10E">10e</A> Tochtermann W. Mattauch A.-K. Kasch M. Peters E.-M. Peters K. von Schnering HG. Liebigs Ann.  1996,  317 

<A NAME="RT12003SS-11">11</A> Boaz NW. Debenham SD. Mackenzie EB. Large SE. Org. Lett.  2002,  4:  2421 

<A NAME="RT12003SS-12A">12a</A> Periana RA. Bergman RG. J. Am. Chem. Soc.  1984,  106:  7272 

<A NAME="RT12003SS-12B">12b</A> Periana RA. Bergman RG. J. Am. Chem. Soc.  1986,  108:  7346 

<A NAME="RT12003SS-12C">12c</A> Stang PJ. Song L. Lu Q. Halton B. Organometallics  1990,  9:  2149 

<A NAME="RT12003SS-13A">13a</A> Miyashita A. Takahashi M. Takaya H. J. Am. Chem. Soc.  1981,  103:  6257 

<A NAME="RT12003SS-13B">13b</A> Burton JT. Puddephatt RJ. Organometallics  1983,  2:  1487 

<A NAME="RT12003SS-13C">13c</A> Wilker CN. Hoffmann R. J. Am. Chem. Soc.  1983,  105:  5285 

<A NAME="RT12003SS-13D">13d</A> Burton JT. Puddephatt RJ. Organometallics  1986,  5:  1312 

<A NAME="RT12003SS-13E">13e</A> Parsons EJ. Jennings PW. J. Am. Chem. Soc.  1987,  109:  3973 

<A NAME="RT12003SS-13F">13f</A> Neilsen WD. Larsen RD. Jennings PW. J. Am. Chem. Soc.  1988,  110:  3307 

<A NAME="RT12003SS-13G">13g</A> Parsons EJ. Jennings PW. Organometallics  1988,  7:  1435 

<A NAME="RT12003SS-13H">13h</A> Neilsen WD. Larsen RD. Jennings PW. J. Am. Chem. Soc.  1988,  110:  8657 

<A NAME="RT12003SS-14">14</A>

Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supple-mentary publication no. CCDC-217321, CCDC-218099, and CCDC-219739. 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]].