8026
CH3
A. Okada et al. / Tetrahedron Letters 42 (2001) 8023–8027
2. For example, the enolate formation of cyclic ketone 28
OTMS
LDA
TMSCl
with LDA followed by trapping with TMSCl gave a
mixture of 18d and 18e (1:2.3).
cat. 7
O
THF
–78ºC
O
OTMS
OTMS
MeO2C CO2Me
16a
MeO2C CO2Me
LDA
TMSCl
18a
+
THF
–78ºC
CO2Me
CO2Me
CO2Me
PhCH(OMe)2
cat. TMSOTf
CH2Cl2
HCHO aq
cat. Yb(OTf)3
THF
NBS
THF
MeO2C
MeO2C
18d
MeO2C
(1 : 2.3)
28
18e
O
OH
O
O
OMe
3. For representative reviews on RCM, see: (a) Fu¨rstner, A.
Angew. Chem., Int. Ed. 2000, 39, 3012; (b) Grubbs, R. H.;
Chang, S. Tetrahedron 1998, 54, 4413; (c) Grubbs, R. H.;
Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446; (d)
Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34,
1833.
Br
Ph
MeO2C CO2Me
26
(75%, 3 steps)
MeO2C CO2Me
27
(89%, 3 steps)
MeO2C CO2Me
25
(93%, 3 steps)
4. Nicolaou, K. C.; Postema, M. H. D.; Claiborne, C. F. J.
Am. Chem. Soc. 1996, 118, 1565.
Scheme 3. Transformation of cyclic enol ether 18a.
5. RCM reactions of enol ethers using Ru and Mo catalysts
were also reported. For a representative example, see:
Rainier, J. D.; Cox, J. M.; Allwein, S. P. Tetrahedron
Lett. 2001, 42, 179 and references cited therein.
6. The alkenyl silyl esters 8 and 9 were prepared from the
corresponding alkenyl carboxylic acids in high yield
(>95%) according to the reported methods. See: Kita, Y.;
Haruta, J.; Segawa, J.; Tamura, J. Tetrahedron Lett.
1979, 20, 4311.
proceeded to afford the corresponding desired products
26 (75%, three steps) and 27 (89%, three steps), respec-
tively. Although overall yield of the transformation of
16a to 26 was moderate, the RCM process under mild
conditions appears to be a suitable candidate to synthe-
size b-hydroxy ketone instead of intramolecular nitrile
oxide cyclo addition followed by treatment with Raney
Ni.
7. The acyclic enol silyl ether 10 can be purified by quick
silica gel column chromatography (92% isolated yield).
8. (a) Pchwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R.
H. Angew. Chem., Int. Ed. Engl. 1995, 34, 2039; (b)
Pchwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1996, 118, 100.
In conclusion, we developed the first highly regioselective
synthesis of cyclic enol silyl ethers from readily accessible
acyclic alkenyl ketones or acyclic alkenyl silyl esters using
RCM. By changing the catalyst from Grubbs catalyst 6
to the second generation Grubbs catalyst 7 and the
solvent from CH2Cl2 to benzene, RCM of a variety of
acyclic enol silyl ethers proceeds smoothly to afford the
corresponding cyclic enol ethers in a highly regioselective
manner. The described method renders many types of
functionalized cyclic enol ethers readily available as a
pure form in terms of regiochemistry. Further investiga-
tion concerning applications of this strategy to other
kinds of metathesis and syntheses of complex bioactive
compounds are currently ongoing.
9. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953. Second generation Grubbs catalyst 7
was prepared from Grubbs catalyst 6 according to the
reference. We also used commercially available catalyst 7
(STREM Chemicals, Inc.), which had the same activity.
10. General procedure: To a solution of i-Pr2NH (0.14 mL,
1.0 mmol) in THF (10 mL) was added 1.54 M hexane
solution of n-BuLi (0.65 mL, 1.0 mmol) at 0°C. After 30
min, the reaction mixture was cooled to −78°C, to which
TMSCl (0.32 mL, 2.46 mmol) and a solution of 16a
(198.7 mg, 0.82 mmol) in THF (5 mL) were added in
order. After stirring at the same temperature for 2 h, the
reaction was quenched by addition of saturated NaHCO3
aqueous solution, allowed to warm to room temperature
(rt), and concentrated in vacuo. The residue was treated
with Et2O and water, extracted with Et2O twice. The
combined organic layers were washed with water and
brine, dried over Na2SO4 to afford the crude acyclic enol
silyl ether 17a (255 mg) (>99% yield determined by 1H
NMR): 1H NMR (500 MHz) (benzene-d6) l 0.15 (s, 9 H),
2.19 (m, 2 H), 2.43 (m, 2 H), 2.83 (d, J=7.3 Hz, 2 H),
3.29 (s, 6 H), 4.13 (s, 1 H), 4.16 (s, 1 H), 4.97 (d, J=10.7
Hz, 1 H), 5.01 (d, J=17.4 Hz, 1 H), 5.74 (m, 1 H); 13C
NMR (125 MHz) (benzene-d6) l 0.0, 30.6, 31.9, 37.7,
51.9, 57.6, 90.2, 118.9, 132.9, 158.9, 171.3. To a solution
of the crude 17a (20.3 mg, 64.6 mmol) in benzene (13 mL,
0.005 M) was added catalyst 7 (3.8 mg, 4.5 mmol) under
argon. The reaction mixture was stirred at 65°C for 1 h,
then cooled to rt, and concentrated in vacuo to afford the
Acknowledgements
This research was supported by CREST, The Japan
Science and Technology Corporation (JST), RFTF of
Japan Society for the Promotion of Science, and a
Grant-in-Aid for Scientific Research on Priority Areas
(A) ‘Exploitation of Multi-Element Cyclic Molecules’
from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
References
1. For recent reviews, see: (a) Fleming, I.; Barbero, A.;
Walter, D. Chem. Rev. 1997, 97, 2063; (b) Carreira, E. M.
In Comprehensive Asymmetric Catalysis; Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H., Eds.; Springer: Berlin, 1999;
Vol. 3, pp. 998–1065.