SCHEME 1
Reactivity of Grubbs’ Catalysts with Urea-
and Amide-Substituted Olefins. Metathesis
and Isomerization
Pilar Forment´ın,† Ne´lida Gimeno,‡
Joachim H. G. Steinke,*,† and Ramo´n Vilar*,‡,§
Department of Chemistry, Imperial College London, South
Kensington, London SW7 2AZ, United Kingdom, Institute of
Chemical Research of Catalonia (ICIQ), 43007 Tarragona,
Spain, and Institution for Research and Advanced Studies
of Catalonia (ICREA), Barcelona, Spain
derivatives have been shown to also catalyze other
nonmetathetic reactions such as olefin isomerization and
hydrogenation.5 Although these reactions broaden the
synthetic scope of the ruthenium-alkylidene catalysts,
they can be troublesome if the metathesis products are
the ones required.6
j.steinke@imperial.ac.uk; rvilar@iciq.es
Received June 3, 2005
We have a particular interest in using olefin metath-
esis to generate dynamic combinatorial libraries (DCL)7
of species containing hydrogen-bonding groups which can
potentially act as molecular receptors (in particular for
anionic species). Consequently, we have carried out a
systematic study of the products obtained when a series
of urea- and amide-substituted olefins are treated with
Grubbs’ catalysts. In particular, we have found that
complexes 1 and 2 under previously reported “standard”
experimental conditions catalyze mainly the isomeriza-
tion of the urea- and amide-substituted olefins. Since for
our goals, this is an unwanted reaction, we investigated
the conditions under which the reaction would mainly
give the metathesis products. Herein, we report that upon
addition of monophenyl phosphoester P(dO)(OPh)(OH)2
to the reaction mixture the course of the reaction changes
favoring the formation of the metathesis products and
suppressing completely the isomerization process. To the
best of our knowledge, this is the first time that a
phosphoester has been used to suppress completely the
isomerization reaction in favor of the metathesis process.
Since ureas have been widely used as building blocks
to generate molecular receptors with hydrogen-bonding
capabilities,8 we first investigated the reaction between
phenyl allyl urea 3 (which was prepared from allylamine
and PhNCO) and Grubbs’ catalyst 1. The aim of this
reaction was to obtain the metathesis product 4 (see the
reaction scheme in Table 1). This reaction was carried
out using conditions similar to those employed previously
for allylic substrates (CH2Cl2, at 40 °C and using 5 or 10
mol % of the catalyst). However, instead of the expected
The reactions of a series of urea- and amide-substituted
olefins with Grubbs’ catalysts are presented. Depending on
the substrate’s nature, the formation of either cross-metath-
esis or isomerization products is observed. To favor the cross-
metathesis products, the reactions have been carried out
using a wide range of experimental conditions. Upon addi-
tion of monophenyl phosphoester to these reactions, the
isomerization of the olefins is completely suppressed and the
cross-metathesis products are obtained in up to 60% yield.
Metal-catalyzed olefin metathesis has become one of
the most widely used organometallic transformations for
carbon-carbon bond formation.1 Although it has now
been several years since the first catalysts for this type
of reaction were developed,2 the initial scope of metath-
esis reactions was limited by the low functional group
tolerance that the catalysts had.3 However, over the past
decade, a series of ruthenium-based catalysts have been
developed (see Scheme 1) which combine high reactivity
with very good tolerance to a wide range of functional
groups.4 Several of these ruthenium complexes and their
† Imperial College London.
‡ Institute of Chemical Research of Catalonia (ICIQ).
§ Institution for Research and Advanced Studies of Catalonia
(ICREA).
(5) (a) Schmidt, B. Chem. Commun. 2004, 742. (b) Alcaide, B.;
Almendros, P. Chem. Eur. J. 2003, 9, 1258. Arisawa, M.; Terada, Y.;
Nakagawa, M.; Nishida, A. Angew. Chem., Int. Ed. 2002, 41, 4732. (c)
Cadot, C.; Dalko, P. I.; Cossy. J. Tetrahedron Lett. 2002, 43, 1839. (d)
Alcaide, B.; Almendros, P.; Alonso, J. M.; Aly, M. F. Org. Lett. 2001,
3, 3781. (e) Fu¨rstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H.-J.;
Nolan, S.-P. J. Org. Chem. 2000, 65, 2204. (f). Tallarico, J. A.; Malnick,
L. A.; Snapper, M. L. J. Org. Chem. 1999, 64, 344.
(1) (a) Astruc, D. New. J. Chem. 2005, 29, 42. (b) Grubbs, R.
Tetrahedron 2004, 60, 7117. (c) Trnka, T. M.; Grubbs, R. H. Acc. Chem.
Res. 2001, 34, 18. (d) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39,
3012. (e) Buchmeiser, M. R. Chem Rev. 2000, 39, 3012.
(2) See, for example: Katz, T. J. In Handbook of Metathesis; Grubbs,
R. H., Ed.; Wiley VCH: Weinheim, Germany, 2003; pp 47-60.
(3) Toste, F. D.; Chatterjee, A. K.; Grubbs, R. H. Pure Appl. Chem.
2002, 74, 7.
(6) McNaughton, B. R.; Bucholtz, K. M.; Camaan˜o-Moure, A.; Miller,
B. L. Org. Lett. 2005, 7, 733.
(4) (a) Connon S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003, 42,
1900. (b) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H.
J. Am. Chem. Soc. 2003, 125, 11360. (c) Weskamp, T.; Kohl, F. J.;
Hieringer, W.; Gleich, D. Herrmann, Angew. Chem., Int. Ed. 1999, 38,
2416. (d) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. 1997, 36,
2036. (e) Schwab, P.; Grubbs, R. H.; Ziller, W. J. J. Am. Chem. Soc.
1996, 118, 100.
(7) For reviews on DCL, see: (a) Lehn, J. M. Chem. Eur. J. 1999, 5,
2455. (b) Rowan, S. J.; Cantrill, S. J.; Cousins, G. R. L.; Sanders, J. K.
M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2002, 41, 898. (c) Cousins,
G. R. L.; Poulsen, S. A.; Sanders, J. K. M. Curr. Opin. Chem. Biol.
2000, 4, 270.
(8) (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486.
(b) Bondy, C. R.; Loeb, S. J. Coord. Chem. Rev. 2003, 240, 77.
10.1021/jo051120y CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/03/2005
J. Org. Chem. 2005, 70, 8235-8238
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