the RCM method.4 With microwaves, otherwise sluggish
RCM protocols have been reported to be completed within
minutes or even seconds, instead of hours at room
temperature.5-9 Examples include microwave-enhanced
standard olefin metathesis reactions in solution phase,5-7
the use of poly(ethylene glycol)-supported olefinic sub-
strates,8 polystyrene-bound ruthenium catalysts,5 domino
RCM reactions involving dienynes,9 and alkyne metath-
esis protocols.3b In all these cases, significant rate
enhancements were observed using microwave heating.
Because of the experimental simplicity of RCM trans-
formations and the fact that metathesis chemistry is
typically carried out in homogeneous solution in unpolar
solvents that are weak absorbers of microwave energy,
RCM reactions seem ideally suited to study the existence
of so-called nonthermal microwave effects.10 Several
groups have suggested that the direct activation of one
or both of the polar reagents in the RCM process (i.e.,
the catalyst and/or the olefin) is responsible for the
observed rate enhancements.5,7 Here we report a thor-
ough reinvestigation of microwave-assisted RCM chem-
istry employing dedicated single-mode microwave appli-
cators, specifically addressing the issue of the involvement
of nonthermal microwave effects.
Our starting point in these investigations involved
RCM reactions of six standard model substrates 1a -f
producing five-, six-, or seven-membered carbo- or het-
erocycles 2a -f (Scheme 1). Apart from the well-investi-
gated Grubbs type II catalyst 3,2 we have also employed
the cationic ruthenium allenylidene catalyst 4 in our
studies. This family of cationic ruthenium metathesis
initiators is readily prepared from commercially available
precursors and can be applied to the formation of es-
sentially all rings with five or more members in good to
excellent yields.11,12 However, RCM reactions with this
catalyst generally require prolonged heating at elevated
temperatures.11,12 We were particularly interested to see
if the polar cationic nature of catalyst 4, allowing for
interaction with microwaves by an ionic conduction
Micr ow a ve-Assisted Rin g-Closin g
Meta th esis Revisited . On th e Qu estion of
th e Non th er m a l Micr ow a ve Effect
Stefania Garbacia,† Bimbisar Desai,‡
Olivier Lavastre,*,† and C. Oliver Kappe*,‡
Institut de Chimie, UMR 6509 Universite de Rennes
1 - CNRS, Campus de Beaulieu, 35042 Rennes, France,
and Institute of Chemistry, Karl-Franzens-University Graz,
Heinrichstrasse 28, A-8010 Graz, Austria
lavastre@univ-rennes1.fr; oliver.kappe@uni-graz.at
Received August 1, 2003
Abstr a ct: The ring-closing metathesis reactions (RCM) of
six standard diene substrates leading to five-, six-, or seven-
membered carbo- or heterocycles were investigated under
controlled microwave irradiation. RCM protocols were per-
formed with standard Grubbs type II and a cationic ruthe-
nium allenylidene catalyst in neat and ionic liquid-doped
methylene chloride under sealed vessel conditions. Very
rapid conversions (15 s) were achieved utilizing 0.5 mol %
Grubbs II catalyst under microwave conditions. Careful
comparison studies indicate that the observed rate enhance-
ments are not the result of a nonthermal microwave effect.
In recent years, the olefin metathesis reaction has
attracted widespread attention as a versatile carbon-
carbon bond-forming method.1 Many new applications
have become possible because of major advances in
catalyst design. In particular, the advent of well-defined
ruthenium-based metathesis precatalysts has triggered
an explosive growth of interest in this transformation
both from the organic and polymer chemist communities.2
Among the numerous different metathesis methods, ring-
closing metathesis (RCM) has emerged as very powerful
method for the construction of small, medium, and
macrocyclic ring systems.1 Of particular interest in this
context are the syntheses of complex natural products
using RCM strategies,3a including the preparation of the
effective DNA cleaving agents turrianes,3b the piperidine
alkaloid (-)-halosaline,3c or the odoriferous (R)-(+)-
muscopyridine.3d
(4) For general references on microwave synthesis, see: (a) Lid-
stro¨m, P.; Tierney, J .; Wathey, B.; Westman, J . Tetrahedron 2001, 57,
9225-9283. (b) Hayes, B. L. Microwave Synthesis: Chemistry at the
Speed of Light; CEM Publishing: Matthews, NC, 2002. (c) Microwaves
in Organic Synthesis; Loupy, A., Ed.; Wiley-VCH: Weinheim, 2002.
(d) For online resources on microwave-assisted organic synthesis, see:
Microwave-Assisted Organic Synthesis (MAOS) Webpages. http://
In general, metathesis reactions are carried out at
room temperature or at slightly elevated temperatures
(e.g., at 40 °C in refluxing methylene chloride), sometimes
requiring several hours of reaction time to achieve full
conversion. Very recently, microwave irradiation has
been introduced as a tool to enhance the effectiveness of
(5) Mayo, K. G.; Nearhoof, E. H.; Kiddle, J . J . Org. Lett. 2002, 4,
1567-1570.
(6) Yang, C.; Murray, W. V.; Wilson, L. J . Tetrahedron Lett. 2003,
44, 1783-1786.
(7) Grigg, R.; Martin, W.; Morris, J .; Sridharan, V. Tetrahedron Lett.
2003, 44, 4899-4901.
(8) Varray, S.; Gauzy, C.; Lamaty, F.; Lazaro, R.; Martinez, J . J .
Org. Chem. 2000, 65, 6787-6790.
(9) Efskind, J .; Undheim, K. Tetrahedron Lett. 2003, 44, 2837-2839.
(10) For a discussion of nonthermal or specific microwave effects,
see: (a) Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9225-9283. (b)
Kuhnert, N. Angew. Chem., Int. Ed. 2002, 41, 1863-1866. (c) Strauss,
C. R. Angew. Chem., Int. Ed. 2002, 41, 3589-3590. (d) Langa, F.; de
la Cruz, P.; de la Hoz, A.; D´ıaz-Ortiz, A.; D´ıez-Barra, E. Contemp. Org.
Synth. 1997, 4, 373-386.
† Universite de Rennes 1.
‡ Karl-Franzens-University Graz.
(1) (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-4450.
(b) Armstrong, S. K. J . Chem. Soc., Perkin Trans. 1 1998, 371-388.
(c) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012-3043.
(2) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29.
(3) (a) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012-3043.
(b) Fu¨rstner, A.; Stelzer, F.; Rumbo, A.; Krause, H. Chem. Eur. J . 2002,
8, 1856-1871. (c) Stragies, R.; Blechert, S. Tetrahedron 1999, 55,
8179-8188. (d) Fu¨rstner, A.; Leitner, A. Angew. Chem., Int. Ed. 2003,
42, 308-3011.
(11) Fu¨rstner, A.; Liebl, M.; Lehmann, C. W.; Picquet, M.; Kunz,
R.; Bruneau, C.; Touchard, D.; Dixneuf, P. H. Chem. Eur. J . 2000, 6,
1847-1857.
(12) Semeril, D.; Olivier-Bourbigou, H.; Bruneau, C.; Dixneuf, P. H.
Chem. Commun. 2002, 146-147.
10.1021/jo035135c CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/09/2003
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J . Org. Chem. 2003, 68, 9136-9139