J. Am. Chem. Soc. 2000, 122, 3783-3784
3783
Table 1. Cross-Metathesis Reactions with Esters, Aldehydes and
Ketonesa
Synthesis of Functionalized Olefins by Cross and
Ring-Closing Metatheses
Arnab K. Chatterjee, John P. Morgan, Matthias Scholl, and
Robert H. Grubbs*
Arnold and Mabel Beckman Laboratories of
Chemical Synthesis, DiVision of Chemistry and
Chemical Engineering, California Institute of Technology
Pasadena, California 91125
ReceiVed NoVember 11, 1999
The generation of olefins with electron-withdrawing functional-
ity, such as R,â-unsaturated aldehydes, ketones, and esters,
remains a difficult task in organic chemistry. A practical method
to approach this problem would involve olefin metathesis,1
utilizing well-defined alkylidenes such as ((CF3)2MeCO)2(ArN)-
ModCH(t-Bu) (1)2 and (PCy3)2Cl2RudCHPh (2).3 However, the
generation of olefins with vinylic functionality through the use
of cross-metathesis4 (CM) has met with limited success. In one
of the few reports of this reaction, Crowe and Goldberg5 demon-
strated that acrylonitrile participated in cross-metathesis reactions
with a variety of terminal olefins. Other π-conjugated olefins,
such as enones and enoic esters, were not functional group com-
patible with alkylidene 1 and failed to react with 2 in cross-
metathesis. Recently, the highly active ruthenium-based olefin
metathesis catalyst 3,6 which contains a 1,3-dimesityl-4,5-dihydro-
a Reactions with 5 mol% of 3. Reactions with geminally disubstituted
olefins utilize the same stoichiometry as those reported in ref 7. b Ratio
based on NMR spectra.
intermolecular cross-metathesis and intramolecular ring-closing
metathesis using ruthenium alkylidene 3.
In the exploration of a variety of 1,1-geminally disubstituted
olefins as substrates for CM, we discovered that methyl meth-
acrylate 7 participates in CM with terminal olefin 4 to generate
the trisubstituted enoic ester 13 in moderate yield with excellent
stereoselectivity (Table 1, entry 1). This positive result led us to
examine the cross-metathesis of various R-carbonyl containing
compounds (Table 1). Particularly noteworthy are the generally
excellent yields attained with ketones and aldehydes (Table 1,
entries 3-6). Extended reaction times were necessary in order to
ensure these high yields.8
Additionally, the efficiency of the reactions suggest that the
highly unstable â-carbonyl-carbene species [Ru]dCH(CO)R is
not involved in the cross-metathesis. It was recently shown that
ester-carbene complexes decompose within a few hours at room
temperature, in contrast to the long lifetime of catalyst 3 in cross
metathesis.9 The typically low degree of conversion to an ester-
carbene, coupled with its instability, strongly suggests that
â-carbonyl-carbenes are not responsible for the bulk of product
formation.10
imidazol-2-ylidene ligand, was found to efficiently catalyze the
cross-metathesis of 1,1-geminally disubstituted olefins.7 Because
ruthenium alkylidene 3 displayed unique activity toward previ-
ously metathesis-inactive substrates, we decided to investigate
the metathesis of R-functionalized olefins. In this communication,
we report the single-step synthesis of R-functionalized olefins by
(1) For a recent review of olefin metathesis see: Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413-4450.
(2) (a) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.; Dimare,
M.; O’Regan, M. J. Am. Chem. Soc. 1990, 112, 3875-3886. (b) Bazan, G.
C.; Khosravi, E.; Schrock, R. R.; Feast, W. J.; Gibson, V. C.; O’Regan, M.
B.; Thomas, J. K.; Davis, W. M. J. Am. Chem. Soc. 1990, 112, 8378-8387.
(c) Bazan, G. C.; Oskam, J. H.; Cho, H. N.; Park, L. Y.; Schrock, R. R. J.
Am. Chem. Soc. 1991, 113, 6899-6907.
(3) (a) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2039-2041. (b) Schwab, P.; Grubbs, R. H.;
Ziller, J. W. J. Am. Chem. Soc. 1996, 118, 100-110. (c) Belderrain, T. R.;
Grubbs, R. H. Organometallics 1997, 16, 4001-4003.
(4) Recent developments in cross-metathesis include: (a) Crowe, W. E.;
Zhang, Z. J. J. Am. Chem. Soc. 1993, 115, 10998-10999. (b) Crowe, W. E.;
Goldberg, D. R.; Zhang, Z. J. Tetrahedron Lett. 1996, 37, 2117-2120. (c)
Brummer, O.; Ruckert, A.; Blechert, S. Chem. Eur. J. 1997, 3, 441-446. (d)
O’Leary, D. J.; Blackwell, H. E.; Washenfelder, R. A.; Grubbs, R. H.
Tetrahedron Lett. 1998, 39, 7427-7430. (e) O’Leary, D. J.; Blackwell, H.
E.; Washenfelder, R. A.; Miura, K.; Grubbs, R. H. Tetrahedron Lett. 1999,
40, 1091-1094. (f) Roy, R.; Dominique, R.; Das, S. K. J. Org. Chem. 1999,
64, 5408-5412. (g) Blanco, O. M.; Castedo, L. Synlett 1999, 557-558. (h)
Huwe, C. M.; Woltering, T. J.; Jiricek, J.; Weitz-Schmidt, G.; Wong, C.-H.
Bioorg. Med. Chem. 1999, 7, 773-788. (i) Oguri, H.; Sasaki, S.; Oishi, T.;
Hirama, M. Tetrahedron Lett. 1999, 40, 5405-5408. (j) Blackwell, H. E.;
O’Leary, D. J.; Chatterjee, A. K.; Washenfelder, R. A.; Bussmann, D. A.;
Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 58-71.
Overall, the stereoselectivities of the reactions are excellent,
making them synthetically practical. Although numerous factors
control the stereochemistry of the ultimate products, simple steric
arguments provide a first level of analysis. Presumably the alkyl
chain (from the unfunctionalized olefin) and the carbonyl group
(8) In entry 3 (Table 1), productive CM was still observed (1H NMR) to
be occurring after 8 hours. As previously reported in a related CM system
using Ru catalyst 2, productive cross-metathesis continues to be observed after
10 hours.4j This result is also consistent with previous experiments which
indicate that the propagating species, the methylidene derivative of 3, has a
lifetime in excess of 12 hours: Ulman, M.; Grubbs, R. H. Unpublished results.
(9) Ulman, M.; Belderrain, T. R.; Grubbs, R. H. Manuscript in preparation.
(10) NMR scale experiments were performed in J. Young valve NMR tubes
under an N2 atmosphere, with 20 equivalents of functionalized olefin to 1
equivalent of 3 in CD2Cl2. After 1 hour at 45 °C, the reaction of 3 and methyl
acrylate forms less than 7% of the ester carbene, which decomposes rapidly
(4 hours). Characteristic 1H NMR shifts include: 17.87 ppm (methylidene of
3); 17.33 ppm (ester-carbene, RudCHCO2Me).
(5) Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc. 1995, 117, 5162-
5163.
(6) Scholl, M.; Ding, S.; Lee C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
953-956. The dimethylvinyl carbene 3 is prepared by analogy to the synthesis
of the benzylidene reported therein. Details are included in the Supporting
Information.
(7) Chatterjee, A. K.; Grubbs, R. H. Org. Lett. 1999, 1, 1751-1753.
10.1021/ja9939744 CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/04/2000