chromatography on silica gel (2 g/0.01 mmol of catalyst,
eluent ) hexanes:ethyl acetate ) 4:1) gave a clear, colorless
liquid or a white solid in the reported yields (Scheme 2).7-9
In all three cases, the colored byproducts were successfully
removed from the products [ICP-MS data: 7 (0.5 µg/5 mg),
9 (1.1 µg/5 mg), and 11 (2.1 µg/5 mg)].
In summary, our results demonstrate that Ph3PdO and
DMSO can be used effectively to remove the colored
ruthenium byproducts of ruthenium catalysts 1 and 2, which
are formed after RCM, when followed by simple filtration
through silica gel or column chromatography. With this
method, residual ruthenium levels from metathesis reactions
are lowered to approximately 1-2 µg/5 mg of product. The
advantage of the method is that Ph3PdO and DMSO are
very stable and inexpensive reagents. Both reagents have
limited chemical reactivity and should therefore be compat-
ible with a wide variety of functional groups.
(5) Procedure for RCM of 3 and purification of crude product 4
with triphenylphosphine oxide or dimethyl sulfoxide: A solution of
diethyl diallylmalonate (3, 120 mg, 0.5 mmol) in CH2Cl2 (100 mL) was
degassed with argon for 5 min and then catalyst 1 (20.5 mg, 5 mol %) was
added to the solution. The reaction flask was sealed with a rubber septum.
After the reaction was complete (approximately after 2 h at rt, monitored
by TLC), the reaction mixture was treated with Ph3PdO (350 mg, 50 equiv,
relative to catalyst 1) or DMSO (90 µL, 50 equiv, relative to catalyst 1)
overnight. The solution was concentrated in vacuo and purified by column
chromatography on silica gel (2 g/0.01 mmol of catalyst 1) using hexanes:
EtOAc ) 8:1 as the eluent to provide the RCM product 5 in 95-98% yield.
(6) Samples (approximately 5-10 mg) were accurately weighed, digested
with distilled 6 N nitric acid overnight, and diluted to a total volume of
approximately 100 mL with the distilled acid and distilled deionized water
to a final acid concentration of about 2%. Samples were analyzed on a
PQII+XS inductively coupled plasma mass spectrometer (ICP-MS). Masses
96, 98, 99, 100, 101, 102, and 104 were monitored in all samples and
standards. Drift (corrected according to the method by Cheatham, M. M.;
Sangrey, W. F.; White, W. M. Spectrochim. Acta, Part B 1993, 48B, E487-
E506) was usually less than 5% and always less than 10% during a single
run. The reported concentration is the average of the total Ru concentration
as calculated from each of the individual isotopes after drift correction.
The average usually had a percent relative standard deviation (%RSD) of
less than 2% and always less than 4%.
Acknowledgment. We gratefully acknowledge financial
support for this work by the National Institutes of Health
(CA84173). We wish to thank Dr. Apurba Datta and Dr.
Paul R. Hanson for helpful discussions. We also thank Dr.
Paul R. Hanson for providing RCM substrate 10 in Scheme
2. We are grateful to Professor Gwendolyn L. Macpherson,
Director of the Plasma Analytical Laboratory at the Univer-
sity of Kansas, for carrying out the ICP-MS measurements.
OL010045K
(8) Georg, G. I.; Ahn, Y. M.; Blackman, B.; Farokhi, F.; Flaherty, P.
T.; Mossman, C. J.; Roy, S.; Yang, K. Chem. Commun. 2001, 255-256.
(9) Dougherty, J. M.; Probst, D. A.; Robinson, R. E.; Moore, J. D.; Klein,
T. A.; Snelgrove, K. A.; Hanson, P. R. Tetrahedron 2000, 56, 9781-9790.
(7) Ackermann, L.; Fu¨rstner, A.; Weskamp, T.; Kohl, F. J.; Herrmann,
W. A. Tetrahedron Lett. 1999, 40, 4787-4790.
Org. Lett., Vol. 3, No. 9, 2001
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