Table 1 Optimisation in the RCM of trisubstituted diene 9 with the
IL-catalyst 8 and ruthenium contaminant level in cyclised product 10
Table 2 Activity and recyclability of IL-catalyst 9 in the RCM of
various dienes
Entry Substrate Product
1
Conditions Cycle/conversion (%)a
[2.5 mol%]
25 uC,3 h
1
2
3
4
1
2
3
4
w98
w98
w98
w98
w98
w98
w98
w98
5
6
7
8
5
6
7
8
w98
w98
95
95
Cycle/conversion (%)a
2
3
[2.5 mol%]
40 uC,6 h
w98
w98
83
Entry Solvent
Conditions 1
2
3
4
5
6
7
8
33
1
2
3
4
BMI?PF6 60 uC,3 h w98 97 91 68 16
BMI?PF6 40 uC,4 h 76 —
—
—
— —
— —
[2.5 mol%]
25 uC,3 h
1
2
3
4
w98
w98
w98
w98
5
6
7
8
w98
94
81
—
—
BMI?NTf2 40 uC,4 h w98 w98 91 89 74 50 — —
BMI?PF6 40 uC,3 h w98 w98 w98 96 85 63 — —
36
/toluene
50/50
5
6
[2 mol%]
25 uC,3 h
1
2
3
4
w98
w98
w98
w98
w98
w98
w98
w98
5
6
7
8
w98
w98
96
5
BMI?PF6 25 uC,3 h w98 w98 w98 w98 w98 w98 95 95
/toluene
25/75
Ru
94
[2 mol%]
25 uC,3 h
1
2
3
4
5
6
7
8
w98
w98
94
16.9 5.4 1.6 3.3 1.2 22 5.7 2.3
residue
(ppm)b
92
a Determined by 1H NMR (400 MHz). b Determined by ICP-MS
spectroscopic analysis.
7
8
[5 mol%]
60 uC,7 h
1
2
65
0
94
90
3b
4b
active compounds) is the toxic ruthenium waste, which is very
difficult to remove from the product (even after repeated
purification by silica gel column chromatography). Several
research groups have developed efficient methods for removal of
ruthenium by-products9 and the residual ruthenium levels have
been reduced, in the best case, to 200–40 ppm of products. In our
work, after each cycle using IL-catalyst 8 in the above biphasic
approach, the residual ruthenium levels were determined. ICP-MS
spectroscopic analysis of RCM product 10, obtained employing
optimum reaction and recycling conditions (entry 3), revealed very
low residual ruthenium levels (between 1.2 to 22 ppm). The average
value over eight cycles (7.3 ppm) is approximately an order of
magnitude lower than the best previously reported methods.9b–d
Having established the recyclability and reuse of IL-catalyst 8,
we evaluated its activity in the RCM of several diene substrates at
room temperature or at 40 uC (Table 2). Excellent conversions were
obtained in all cases (entries 1 to 6) for up to eight cycles. As an
example, we also measured the residual ruthenium level for the first
run of diethyl diallylmalonate 11 and only 2.5 ppm were detected in
the cyclised product 12. Finally, to examine the scope of IL-catalyst
8, we focused on its performance with the tetra-substituted dienes
21 and 23, which are known to be extremely difficult substrates.
The IL-catalyst proved to be efficient only for the first run for 21,
and inactive for 23 (entries 7 and 8), showing the limitation of
the catalyst activity. Nevertheless, remarkably, as shown by the
excellent conversions observed in successive runs with the disub-
stituted diene 17, the recovered catalyst still remained highly active,
attestingtothestabilityandthehighlevelofrecyclabilityofIL-cat8in
the BMI?PF6/toluene medium at higher temperature.
[5 mol%]
1
0
60 uC,24 h 2b
w98
w98
3b
a Determined by 1H NMR spectroscopic analysis at 400 MHz.
b Reaction performed with 17 at 25 uC for 3 h.
Notes and references
1 Selected reviews on olefin metathesis: (a) R. R. Schrock and
A. H. Hoveyda, Angew. Chem., Int. Ed., 2003, 42, 4592;
(b) T. M. Trnka and R. H. Grubbs, Acc. Chem. Res., 2001, 34, 18.
2 (a) P. Schwab, M. B. France, J. W. Ziller and R. H. Grubbs, Angew.
Chem., Int. Ed. Engl., 1995, 34, 2039; (b) P. Schwab, R. H. Grubbs and
J. W. Ziller, J. Am. Chem. Soc., 1996, 118, 100.
3 Catalyst 2a: (a) S. P. Nolan, J. Huang, E. D. Stevens and J. L. Petersen,
J. Am. Chem. Soc., 1999, 121, 2674; Catalyst 2b: (b) M. Scholl,
T. M. Trnka, J. P. Morgan and R. H. Grubbs, Tetrahedron Lett., 1999,
40, 2247; (c) L. Ackermann, A. Fu¨rstner, T. Weskamp, F. J. Kohl and
W. A. Herrmann, Tetrahedron Lett., 1999, 40, 4787.
4 (a) J. S. Kingsbury, J. P. A. Harrity, P. J. Bonitatebus and
A. H. Hoveyda, J. Am. Chem. Soc., 1999, 121, 791; (b) S. B. Garber,
J. S. Kingsbury, B. L. Gray and A. H. Hoveyda, J. Am. Chem. Soc.,
2000, 122, 8168.
5 For a review on styrene ether Ru complexes and their supported
versions, see: A. H. Hoveyda, D. G. Gillingham, J. J. Van Veldhuizen,
O. Kataoka, S. B. Garber, J. S. Kingsbury and J. P. A. Harrity, Org.
Biomol. Chem., 2004, 2, 8.
6 Ionic Liquids in Synthesis, eds. P. Wasserscheid and T. Welton, Wiley-
VCH, Weinheim, 2003.
7 N. Audic, H. Clavier, M. Mauduit and J. C. Guillemin, J. Am. Chem.
Soc., 2003, 125, 9248.
In summary, we have developed a powerful recyclable IL-
phosphine free N-heterocyclic carbene ruthenium complex to
perform metathesis reactions in a BMI?PF6/toluene biphasic
medium. High level of recyclability and reusability combined
with a high reactivity were obtained for the RCM of several
substrates including tri-substituted and/or oxygen-containing
dienes. The low residual ruthenium levels in the RCM products
promote this environmentally friendly RCM process in synthesis.
A study of its use in cross-metathesis reaction is under way in our
laboratory and will be reported in due course.
8 Q. Yao and Y. Zhang, Angew. Chem., Int. Ed., 2003, 42, 3395.
9 Ru residual level after chromatography, see: (a) J. H. Cho and
B. M. Kim, Org. Lett., 2003, 5, 531 and references cited therein. Ru
residual level with supported catalyst, see: (b) S. J. Connon, A. M. Dunne
and S. Blechert, Angew. Chem., Int. Ed., 2002, 41, 3835; (c)
J. S. Kingsbury, S. B. Garber, J. M. Giftos, B. L. Gray,
M. M. Okamoto, R. A. Farrer, J. T. Fourkas and A. H. Hoveyda,
Angew. Chem., Int. Ed., 2001, 42, 4251; (d) M. Ahmed, A. G. M. Barrett,
D. C. Braddock, S. M. Cramp and P. A. Procopiou, Tetrahedron Lett.,
1999, 40, 8657.
C h e m . C o m m u n . , 2 0 0 4 , 2 2 8 2 – 2 2 8 3
2 2 8 3