Stephen J. Connon et al.
COMMUNICATIONS
6H), 1.28 0d, J 6.1 Hz, 6H), 1.26 0d, J 6.1 Hz, 6H); anal.
calcd. for C34H44N2Cl2O2Ru 0684.72): C 59.64, H 6.48, N 4.09%;
found: C 59.34, H 6.85, N 3.51%.
OH
3a (5 mol %)
MeOH/H2O (4:1),
(0.1 M), 22 °C, 12 h in air
OH
OH
16
17 35%
RCM General Procedure
O
Me3Si
O
A solution of the substrate 00.06 mmol) in solvent 01.2 mL) was
added to the catalyst 00.003 mmol) in air and stirred at rt for 12
h. Ethyl vinyl ether 02 mL) was added, the solution evaporated
to dryness under vacuum, and the residue analysed by 1H NMR
spectroscopy. Where DMF was used as solvent, MTBE
010 mL) and H2O 05 mL) were added after the ethyl vinyl
ether addition. Separation of the layers and washing of the
organic extracts with H2O 03 Â 5 mL) gave a crude solution
which could be dried 0MgSO4), concentrated under vacuum
and analysed by 1H NMR.
3a (5 mol %)
OTBS
MeOH, (0.05 M)
OTBS
TBSO
22 °C, 12 h in air
OTBS
SiMe3
(2.0 equivs.)
19 >98%
18
Scheme 2. CM in protic solvents catalysed by 3a.
moted by 3a in the presence of water, which proceeded
with only modest conversion to yield 17 0Scheme 2).[14]
In general we found that across a range of substrates, the
promotion of conventional CM reactions under these
conditions was beyond the capability of either 2 or 3a.
However, in methanol it was possible to quantitatively
ring-open norbornene 18 in the presence of 3a and
allyltrimethylsilane to give 19 in a selective ring-opening
cross-metathesis 0ROM-CM) reaction 0Scheme 2). To
the best of our knowledge this represents the first
example of an efficient and selective CM reaction in a
protic solvent. In summary, it has been demonstrated
that commercially available catalyst 2 is capable of
effecting the homo- or heterogeneous RCM of previ-
ously challenging substrates in non-degassed DMF or
methanol, respectively, in air. This catalyst possesses
many advantages over current methanol-soluble sys-
tems[5aÀf] in terms of superior activity/substrate scope,
ready availability and ease of manipulation. The novel
methanol-soluble catalyst 3a can also be used effectively
under these conditions, with the added advantage that it
retains considerable metathesis activity in aqueous
media 0methanol-water and DMF-water mixtures),
and has been shown to promote CM reactions in protic
media. The application of these catalysts in the synthesis
of biologically important molecules in aqueous solvent
mixtures is currently being pursued.
Acknowledgements
S. J. C. thanks the Alexander von Humboldt foundation for
financial support.
References and Notes
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Â
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Experimental Section
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Synthesis of 3a
A stirred mixture of 2 0200 mg, 0.235 mmol), 2,4-diisopropoxy-
styrene 0104 mg, 0.472 mmol) and CuCl 023.3 mg, 0.235 mmol)
in CH2Cl2 030 mL) under nitrogen was heated at 458C for 1 h.
After cooling, evaporation of the solvent and flash chroma-
tography 0CH2Cl2/hexane 1:1) of the residue gave 3a as a green
1
solid; yield: 135 mg 081%); H NMR 0500 MHz, CDCl3): d
16.17 0s, 1H), 7.05 0s, 4H), 6.80 0d, J 8.5 Hz, 1H), 6.37 0dd, J
8.5, 1.8 Hz, 1H), 6.30 0s, 1H), 4.81 0septet, J 6.1 Hz, 1H), 4.51
0septet, J 6.1 Hz, 1H), 4.17 0s, 4H), 2.47 0bs, 12H), 2.39 0s,
574
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asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 572 ± 575