case is logical by considering the inertness of ruthenium
alkylidene 2 towards the RCM of terminally substituted
olefins.11
Therefore, to induce a productive RCM by using alkylidene
2, it was necessary to remove the olefinic gem-dimethyl sub-
stitution in diene 6. Accordingly, the alcohol 5, protected in
the form of its TBDMS ether 7, was subjected to ozonolysis
followed by Wittig olefination of the resulting dialdehyde to
furnish the desired diene substrate 9 after deprotection and
subsequent oxidation (Scheme 2). As anticipated, when 9 was
Experimental
Procedure for the RCM reaction
To a solution of acyclic diene 9 (30 mg, 0.114 mmol) in dry
degassed CH2Cl2 (25 ml) was added, via syringe, a solution of
ruthenium catalyst 2 (5 mg, 0.006 mmol) predissolved in
CH2Cl2 (6 ml). The purple solution was heated to 45 ЊC for 21 h
and concentrated under reduced pressure to afford an oily
brown residue. Purification by MPLC (pre-packed column
2 × 50 cm, 5% EtOAc–hexane) afforded 20 mg (78%) of 10 as
an oil with a musky odor.
5
Acknowledgements
We thank Soda Aromatics Co. Ltd., for the generous supply of
racemic muscone.
TBDMS chloride (1.2 equiv.)
Imidazole, DMF (86%)
OTBDMS
OTBDMS
References
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2 L. Ruzicka, Helv. Chim. Acta, 1926, 9, 715, 1008.
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1. O3, CH2Cl2, –78 °C
Me2S (75%)
2. Ph3PCH2Br
n-BuLi, THF (98%)
7
8
4 For some earlier syntheses see: (a) M. S. R. Nair, H. H. Mathur and
S. C. Bhattacharyya, J. Chem. Soc., 1964, 4154; (b) G. Ohloff,
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1. TBAF, THF (97%)
2. Jones reagent, acetone (98%)
O
O
2 (5 mol%), CH2Cl2
45 °C, 21 h (78%)
10
9
H2, 10% Pd/C
C2H5OH (98%)
5 N. A. Porter, B. Lacher, V. H.-T. Chang and D. R. Magnin, J. Am.
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O
(CH2)8
(CH2)8
7 W. Oppolzer and R. N. Radinov, J. Am. Chem. Soc., 1993, 115,
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O
O
8 For some other syntheses of (R)-(Ϫ)-muscone see: (a) Q. Branca
and A. Fishli, Helv. Chim. Acta, 1977, 60, 925; (b) A. Abad,
M. Arno, A. Pardo, J. R. Pedro and E. Seoane, Chem. Ind., 1985, 29;
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(d) H. Nozawa and H. Nohira, J. Org. Chem., 1987, 52, 1630;
(e) Z.-F. Xie, H. Suemune and K. Sakai, J. Chem. Soc., Chem.
Commun., 1988, 1638; ( f ) Z.-F. Xie and K. Sakai, J. Org. Chem.,
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and
11
head to tail isomers
1
Scheme 2
exposed to ruthenium catalyst 2 under the RCM reaction con-
ditions, it smoothly underwent ring closing olefin metathesis11
to yield the desired cyclic product 10 in 78% yield as a mixture
of E/Z isomers§ along with a small quantity of a mixture of
cyclic dimeric compound 11 obtained as a result of inter-
molecular metathesis. Finally, catalytic hydrogenation of 10
provided pure (R)-(Ϫ)-muscone 1 which was identical¶ in
all respects with an authentic sample.
Thus, a new simple synthesis of the rare and classical
perfumery compound (R)-(Ϫ)-muscone 1 has been achieved
starting from readily available synthons by utilizing ring
closing olefin metathesis. The key macrocyclization step in the
present synthesis proceeds under mild reaction conditions with
moderate catalyst loading in good yield. The evaluation of the
olfactory properties of some of the intermediate compounds
is currently in progress.
9 (a) R. H. Grubbs, J. S. Miller and G. C. Fu, Acc. Chem. Res., 1995,
28, 446; (b) M. Schuster and S. Blechert, Angew. Chem., Int. Ed.
Engl., 1997, 36, 2036; (c) S. K. Armstrong, J. Chem. Soc., Perkin
Trans. 1, 1998, 371.
10 (a) Z. Xu, C. W. Johannes, S. S. Salman and A. H. Hoveyda, J. Am.
Chem. Soc., 1996, 118, 10 926; (b) D. Meng, D. S. Su, A. Balog,
P. Bertinato, E. J. Sorensen, S. J. Danishefsky, Y. Zheng, T. Chou,
L. He and S. B. Horwitz, J. Am. Chem. Soc., 1997, 119, 2733;
(c) Z. Xu, C. W. Johannes, A. F. Houri, D. S. La, D. A. Cogan,
G. E. Hafilena and A. H. Hoveyda, J. Am. Chem. Soc., 1997, 119,
10 302; (d) D. Meng, P. Bertinato, A. Balog, D. Su, T. Kamenecka,
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11 T. Kirkland and R. H. Grubbs, J. Org. Chem., 1997, 62, 7310.
Paper 8/02891E
Received 17th April 1998
Accepted 2nd June 1998
§ All compounds gave satisfactory spectral analysis in agreement with
the assigned structures.
¶ [α]D18 Ϫ12.6 (c 0.9 in MeOH); lit.,8g [α]D18 Ϫ12.5 (c 5.0 in MeOH).
2254
J. Chem. Soc., Perkin Trans. 1, 1998