Olefin metathesis involving ruthenium enoic carbene complexes [16]

Full text of DOI:10.1021/ja016386a

J. Am. Chem. Soc. 2001, 123, 10417-10418
Scheme 1. Direct Generation of Enoic Carbene
10417
Olefin Metathesis Involving Ruthenium Enoic
Carbene Complexes
Tae-Lim Choi, Choon Woo Lee, Arnab K. Chatterjee, and
Robert H. Grubbs*
Arnold and Mabel Beckman Laboratories of Chemical
Synthesis DiVision of Chemistry and Chemical Engineering
California Institute of Technology
Table 1. Dimerization of R,â-Unsaturated Carbonyl Compoundsa
Pasadena, California 91125
ReceiVed June 11, 2001
Olefin metathesis has become a valuable reaction in organic
synthesis, as has been demonstrated by its frequent use as the
key bond constructions for total syntheses of many natural
products.1 With the recent discovery of highly active catalyst 1,
trisubstituted and functionalized alkenes have been synthesized
efficiently by cross-metathesis (CM), further expanding the
substrate scope for this reaction.2 With these successes in hand,
unprecedented metathesis reactions were explored. There have
been no previous reports of the dimerization of R,â-unsaturated
carbonyl compounds by a metathesis mechanism. Molybdenum-
and tungsten-based catalysts form metallocyclobutane with acry-
lates, but they are inactive due to carbonyl oxygen chelation.3
Our group reported the synthesis of ester carbene 4 by a
nonmetathesis route and showed that 4 was extremely reactive.
In fact, ester carbene 4 was the first carbene to ring-open
cyclohexene but did not react in a catalytic fashion.4 The nontrivial
synthesis, lack of stability, and the ineffective catalytic activity
of ester carbene 4 has limited its uses in organic synthesis.
a 5 mol % catalyst 1 in refluxing CH2Cl2 for 3 h. b Only the E isomer
1
was obtained. c Yield was determined by H NMR.
to dimerize of n-butyl acrylate at 0.2 M in refluxing CH2Cl2 only
gave 44% of the desired product of E isomer, and the balance as
starting material. GC analysis showed the reaction was completed
1
in less than 2 h, and no carbenes were observed by H NMR.
This suggests enoic carbene 5 is still unstable, with a much shorter
lifetime than other alkylidene or benzylidene carbenes. To our
delight, an attempt to increase the rate by doubling the concentra-
tion to 0.4 M resulted in 87% yield of dimer (Table 1, entry 1).
Other solvents such as CHCl3, CCl4, C6H6, and THF were tried,
but they all produced much poorer results than CH2Cl2.5 Various
acrylates were effectively dimerized by this procedure (Table 1,
entries 1-4).
Previous reports on the mechanism of cross-metathesis reac-
tions between terminal olefins and R,â-unsaturated carbonyl
compounds, state that catalyst 1 reacts preferentially with terminal
olefins to form an alkylidene which crosses onto R,â-unsaturated
carbonyl compounds to form methylidene and CM product.2c At
that time, the formation of the unstable enoic carbene 5 was
believed to be less likely. However, it was recently discovered
that the electron-rich catalyst 1 was, in fact, able to react with
R,â-unsaturated carbonyl compounds directly to form enoic
carbene 5 effectively under certain conditions. Herein, we report
the first efficient generation of enoic carbenes 5 in situ with
catalyst 1 (Scheme 1), and successful catalytic CM and ring-
opening reactions of previously inactive metathesis substrates.
The formation of enoic carbene 5 was initially discovered in
the dimerization of acrylates to form fumarates. Initial attempts
Interestingly, vinyl ketones behaved quite differently from
acrylates. Dimerization of hexyl vinyl ketone at 0.4 M gave only
29%, and increasing concentration further decreased the yield (less
than 5% at 0.6 M by 1H NMR). However, decreasing the
concentration increased the yield where optimized yield was
obtained at 0.05 M (Table 1, entries 5-7).
1
Following the reactions by H NMR revealed that at 0.05 M,
the rate of formation of keto-carbene was at least 5 times faster
than that of acrylates.6 Therefore, a high concentration is required
for acrylates to speed up the reactions, whereas at that condition,
a much higher concentration of unstable keto-carbene leads to
bimolecular decomposition.4
(1) For recent reviews on organic applications, see: (a) Grubbs, R. H.;
Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446. (b) Schuster, M.;
Blechert, S. Angew. Chem. 1997, 109, 2124; Angew. Chem., Int. Ed. Engl.
1997, 36, 2067. (c) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(d) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371. (e) Blechert,
S. Pure Appl. Chem. 1999, 71, 1393. (f) Furstner, A. Angew. Chem., Int. Ed.
2000, 39, 3013.
(2) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
953. (b) Chatterjee, A. K.; Grubbs, R. H. Org. Lett. 1999, 1, 1751. (c)
Chatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H. J. Am. Chem.
Soc. 2000, 122, 3783. (d) Choi, T.-L.; Chatterjee, A. K.; Grubbs, R. H. Angew.
Chem. 2001, 113, 1317; Angew. Chem. Int. Ed. 2001, 40, 1277. (e) Chatterjee,
A. K.; Choi, T.-L.; Grubbs, R. H. Synlett 2001, 1034.
(5) An opposite solvent effect was observed previously. See Furstnet, A.;
Thiel, O. R.; Ackermann, L.; Schanz, H.-J.; Nolan, S. P. J. Org. Chem. 2000,
65, 2204.
(6) The faster formation of keto-carbene can be explained by the following
arguments. To form 5, the complex has to adopt A conformation, not B, and
ab initio calculation (HF6-31G**) suggests that olefins of vinyl ketones are
more polarized than those of acrylates, favoring state A. Also acrylates have
more electron-rich carbonyls, and the chelation effect C may slow down the
formation. See ref 2d.
(3) Feldman, J.; Murdzek, J. S.; Davis, W. M.; Schrock, R. R. Oranome-
tallics 1989, 8, 2260.
(4) Ulman, M.; Belderrain, T. R.; Grubbs, R. H. Tetrahedron Lett. 2000,
41, 4689.
10.1021/ja016386a CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/26/2001

10418 J. Am. Chem. Soc., Vol. 123, No. 42, 2001
Communications to the Editor
Scheme 2. Ring Opening of Cyclohexene with 5
Table 2. Ring-Opening or Cross Metathesis Reactions of Enoic
Carbenesa
To access more synthetically useful hetero-coupled products,
we attempted the CM between different R,â-unsaturated carbonyl
compounds. Cross couplings of methyl acrylates and methyl vinyl
ketones were attempted, and only a statistical mixture of 41% of
the cross-coupled products was obtained (Table 2, entries 4, and
5). Cross-metathesis reactions between R,â-unsaturated carbonyl
compounds and R-methyl disubstituted olefin were also studied.
Unlike CM between terminal olefins and acrylates, analogous
conditions gave the acrylate dimer as a major product and only
a trace amount of desired cross product, suggesting the catalyst
1 reacted with acrylates preferentially to form enoic carbene 5.
Although the formation of 5 is thermodynamically less favorable,
it is kinetically preferred over reaction with bulky disubstituted
alkenes.2b However, increasing the stoichiometry of the disub-
stituted olefins produced CM products with good yields. For
example, with 2 equiv of R-methyldisubstituted olefin, a 5:4
mixture of acrylate dimer and the cross product yield was
obtained, whereas up to 83% yield of the cross product was
achieved by using 4 equiv of R-methyldisubstituted olefin with
an E-to-Z ratio of 2:1 (entries 6-8). Not surprisingly, less
sterically hindered methylenecyclohexane proved to be a better
cross partner, producing up to 99% of the CM products with 2
equiv of the gem-disubstituted olefin. Compared to terminal R,â-
unsaturated carbonyl compounds, â-methyl-disubstituted R,â-
unsaturated carbonyl compounds improved the CM yields by
2-40% because the rate of dimerization was suppressed by the
methyl group, thereby increasing the relative rate of CM reaction.
This observation is particularly useful in the reactions where dimer
was a substantial side-product (Table 2, entries 3, 6, 8, and 11).9
In conclusion, we have demonstrated that the highly active
catalyst 1 reacts with R,â-unsaturated carbonyl compounds
directly to form enoic carbene 5. It illustrates that the more
electron-donating ligand stabilizes the electron-deficient enoic
carbene 5. With the in situ generation of enoic carbenes, enone
dimerization, cross-coupling with gem-disubstituted olefins, and
catalytic ring-opening of cyclohexene are now attainable.
a 5 mol % catalyst 1 at 0.1-0.3 M in refluxing CH2Cl2 for 3 h.
b Only the E isomer was observed by 1H NMR. c 3 equiv of cyclohexene
was used. d 2 equiv of acrylates was used. e 4 equiv of R-methyl
disubstituted olefin was used. f E/Z ) 2.0. g 2 equiv of methylenecy-
clohexene was used.
GC analysis showed dimethyl maleate (Z isomer) isomerized
to dimethyl fumarate (E isomer) very slowly when compared to
unfunctionalized internal cis olefins.7 Also, only the E isomer
was obtained even at early conversion in dimerization reactions,
suggesting that the E isomer is the kinetic as well as thermody-
namic product in theses CM reactions.
Applications of the enoic carbene to various metathesis
reactions beyond simple enone dimerization are shown in Table
2. Although cyclohexene is unique compared to other cycloalkenes
because it is not polymerized by ROMP,8 our group previously
reported that catalyst 4, unlike catalysts 1-3, could ring-open
thermodynamically stable cyclohexene.4 However, this reaction
required a stoichiometric amount of catalyst 4 because the product
of one turnover is an alkylidene which was unreactive toward
cyclohexene or acrylates. However, now that enoic carbene 5
could be generated in situ by catalyst 1, ring-opening of
cyclohexene could be achieved catalytically (Scheme 2) yielding
linear C-10 chains of R,â-unsaturated carbonyl compounds being
doubly crossed (Table 2, entries 1-3). An excess of cyclohexene
(3 equiv) was used to minimize the dimerization of R,â-
unsaturated carbonyl compounds since the ring-opening reaction
competes with dimerization to products that slowly undergo
secondary metathesis reactions.
Acknowledgment. We thank the NIH for generous support of this
research, and Dr. M. Scholl, J. P. Morgan, Dr. S. D. Goldberg, Dr. F. D.
Toste, Dr. M. S. Sanford and C. Morrill for helpful discussions.
Supporting Information Available: Experimental procedures and
characterization data (1H and 13C NMR, HRMS) (PDF). This material is
available free of charge via the Internet at http://pub.acs.org.
JA016386A
(9) Acrolein and acrylamide also worked but with less efficiency. Unfor-
tunately attempted ring-closing metathesis of bis-acrylates failed, only resulting
in mixtures of linear dimer, trimer, and oligoners. However, macrocyclization
of bis-acrylate was achieved in modest yield: Lee, C. W.; Grubbs, R. H.
Unpublished result.
(7) Blackwell, H. E.; O’Leary, D. J.; Chattejee, A. K.; Washenfelder, R.
A.; Bussmann, D. A.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 58.
(8) Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization,
2nd ed.; Academic: San Diego, 1997.