Relative rate profile for ring-closing metathesis of a series of 1-substituted 1,7-octadienes as promoted by a 4,5-dihydroimidazol-2-ylidene-coordinated ruthenium catalyst

Article abstract of DOI:10.1021/ol0272794

(Matrix presented) This report details the kinetic responses of nine compounds of type 6 to ring-closing metathesis as promoted by 2 to give the identical product 7. The experimental observations have been subjected to Hammett analysis. The ρ value for the composite aromatic derivatives (R = p-XC₆H₄-) differs from that of the aliphatic series, although both are negative because electron-donating groups accelerate the reaction.

Full text of DOI:10.1021/ol0272794

ORGANIC
LETTERS
2003
Vol. 5, No. 6
789-792
Relative Rate Profile for Ring-Closing
Metathesis of a Series of 1-Substituted
1,7-Octadienes as Promoted by a
4,5-Dihydroimidazol-2-ylidene-Coordinated
Ruthenium Catalyst
Xin Guo, Kallol Basu, Jose A. Cabral,* and Leo A. Paquette*
EVans Chemical Laboratories, The Ohio State UniVersity, Columbus, Ohio 43210
paquette.1@osu.edu
Received November 14, 2002
ABSTRACT
This report details the kinetic responses of nine compounds of type 6 to ring-closing metathesis as promoted by 2 to give the identical
product 7. The experimental observations have been subjected to Hammett analysis. The G value for the composite aromatic derivatives (R
) p-XC H −) differs from that of the aliphatic series, although both are negative because electron-donating groups accelerate the reaction.
6
4
The adaptability and widespread popularity of ring-closing
metathesis (RCM) has been widely attributed to the excellent
functional group tolerance of ruthenium-based catalysts such
as 1.1 Indeed, the striking power of this methodology is
extensively reflected in the synthesis of nitrogen heterocycles
(including azasugars and alkaloids),2 structurally modified
carbohydrates,3 lactones and lactams,4 sulfones,5 sulfon-
amides,6 and the like. While the range of substrates amenable
to this chemical transformation is very broad, there has
existed a tacit limitation. The heteroatomic functionality has
almost invariably been intentionally positioned in a relatively
remote relationship to the double bonds taking part in the
metathesis process. While this restriction has led to a more
advanced definition of RCM reactions such as the large
activating effect of an allylic hydroxyl substituent,7a sub-
strates carrying an electron-donating or electron-withdrawing
group directly attached to a key center of unsaturation have
largely been unexplored.7b
(1) For recent reviews, consult: (a) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18. (b) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000,
39, 3012. (c) Wright, D. L. Curr. Org. Chem. 1999, 3, 211. (d) Grubbs, R.
H.; Chang, S. Tetrahedron 1998, 54, 4413.
(2) Reviews: (a) Pandit, U. K.; Overkleeft, H. S.; Borer, B. C.; Biera¨ugel,
H. Eur. J. Org. Chem. 1999, 959, 9. (b) Philips, A. J.; Abell, A. D.
Aldrichimica Acta 1999, 32, 75.
(3) Reviews: (a) Roy, R.; Das, S. K. Chem. Commun. 2000, 519. (b)
Jorgensen, M.; Hadwiger, P.; Madsen, R.; Stu¨tz, A. E.; Wrodnigg, T. M.
Curr. Org. Chem. 2000, 4, 565.
(4) Some representative examples include: (a) Houri, A. F.; Xu, Z.;
Cogan, D. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1995, 117, 2943. (b)
Miller, J. F.; Termin, A.; Koch, K.; Piscopio, A. D. J. Org. Chem. 1998,
63, 3158. (c) White, J. D.; Hrnciar, P.; Yokochi, A. F. T. J. Am. Chem.
Soc. 1998, 120, 7359. (d) Ripka, A. S.; Bohacek, R. S.; Rich, D. H. Bioorg.
Med. Chem. Lett. 1998, 8, 357. (e) Sukkari, H. E.; Gesson J. P.; Renoux,
B. Tetrahedron Lett. 1998, 39, 4043.
The deemphasis surrounding the possible adaptation of
functionalized ring-closing metathesis is seemingly rooted
(5) For illustrative case studies, see: (a) Paquette, L. A.; Fabris, F.; Tae,
J.; Gallucci, J.; Hofferberth, J. E. J. Am. Chem. Soc. 2000, 122, 3391. (b)
Fu¨rstner, A.; Gastner, T.; Weintritt, H. J. Org. Chem. 1999, 64, 2361. (c)
Grela, K.; Bieniek, M. Tetrahedron Lett. 2001, 42, 6425.
10.1021/ol0272794 CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/22/2003

in various observations cited in the prior art. The feasibility
of engaging acrylate esters in productive cross metathesis
has been recognized for some time.8 Correspondingly,
examples of the involvement of R,â-unsaturated esters in
RCM are rather numerous.9 In contrast, acrylonitrile is a
substituted alkene that has eluded virtually all attempts to
effect comparable reaction.10 No examples of the participa-
tion of R,â-unsaturated nitriles in RCM have consequently
been reported, even when the cyano functionality is situated
on the terminus of a 1,3-diene.11 Conjugated amides appear
to enjoy an intermediate position.12 The ability of R,â-
unsaturated ketones to exhibit comparable high performance
behavior has surfaced only recently,13 chiefly as the result
of improved catalyst design.
Enol ethers14a and enamides14b have been reported not to
undergo RCM when exposed to 1. In fact, ethyl vinyl ether
has been utilized to terminate living ROMP reactions.15 These
phenomena have been attributed to the ability of ruthenium
alkylidenes to generate metathesis-inactive Fischer carbenes
such as 3 under these circumstances.16 This transformation
is quantitative and essentially irreversible.17 For this reason,
recourse has been made to other catalysts such as 4 and 5 in
order to provide an alternate driving force for RCM in such
cases.18
In light of these developments, a systematic investigation
of the relative rates of RCM of a series of dienes of type 6
has been undertaken to allow for proper comparative analysis.
Use has been made of the highly active N-heterocyclic
carbene-coordinated metathesis catalyst 219 in order to
address steric and electronic effects that might affect this
particular promoter.20 Our guidelines provide not only for
attachment of an R- or p-XC6H4- group directly to a
reacting double bond but also for generation of the identical
product 7 in every instance.21
(6) (a) Paquette, L. A.; Ra, C. S.; Schloss, J. D.; Leit, S. M.; Gallucci,
J. C. J. Org. Chem. 2001, 66, 3564. (b) Paquette, L. A.; Leit, S. M. J. Am.
Chem. Soc. 1999, 121, 8126.
(7) (a) Hoye, T. R.; Zhao, H. Org. Lett. 1999, 1, 1123. (b) Kirkland, T.
A.; Grubbs, R. H. J. Org. Chem. 1997, 62, 7310.
(8) Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymeri-
zation; Academic Press: New York, 1997.
(9) (a) Ghosh, A. K.; Lei, H. J. Org. Chem. 2000, 65, 4779. (b) Ghosh,
A. K.; Cappiello, J.; Shin, D. Tetrahedron Lett. 1998, 39, 4651. (c) Nicolaou,
K. C.; Rodriguez, R. M.; Mitchell, H. J.; Suzuki, H.; Fylaktakidou, C.;
Baudouin, O.; Delft, F. L. van, Chem. Eur. J. 2000, 6, 3095. (d) Cossy, J.;
Bauer, D.; Bellosta, V. Tetrahedron Lett. 1999, 40, 4187. (e) Bassindale,
M. J.; Hamley, P.; Leitner, A.; Harrity, J. P. A. Tetrahedron Lett. 1999,
40, 3247. (f) Fu¨rstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H.-J.; Nolan,
S. P. J. Org. Chem. 2000, 65, 2204. (g) Ramachandran, P. V.; Reddy, M.
V. R.; Brown, H. C. Tetrahedron Lett. 2000, 41, 583. (h) Brouard, I.;
Hanxing, L.; Martin, J. D. Synthesis 2000, 883. (i) Ghosh, A. K.; Bilcer,
G. Tetrahedron Lett. 2000, 41, 1003. (j) Greer, P. B.; Donaldson, W. A.
Tetrahedron Lett. 2000, 41, 3801.
(14) (a) Fujimura, O.; Fu, G. C.; Grubbs, R. H. J. Org. Chem. 1994, 59,
4029. (b) Kinderman, S. S.; van Maarseveen, J. H.; Schoemaker, H. E.;
Hiemstra, H.; Rutjes, F. P. J. T. Org. Lett. 2001, 3, 2045.
(15) Steltzer, F. J. Macromol. Sci. Pure Appl. Chem. 1996, A33, 941.
(16) (a) Wu, Z.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1995, 117, 5503. (b) Lynn, D. M.; Mohr, B.; Grubbs, R. H.; Henling,
L. M.; Day, M. W. J. Am. Chem. Soc. 2000, 122, 6601.
(17) Sanford, M. S.; Ulman, M.; Grubbs, R. H. J. Am. Chem. Soc. 2001,
123, 749.
(10) Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc. 1995, 117, 5162.
(11) Basu, K.; Cabral, J. A.; Paquette, L. A. Tetrahedron Lett. 2002, 43,
5453.
(12) (a) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc.
1993, 115, 9856. (b) Rutjes, F. P. J. T.; Schoemaker, H. E. Tetrahedron
Lett. 1997, 38, 677. (c) Grossmith, C. E.; Senia, F.; Wagner, J. Synlett 1999,
1660. (d) Agami, C.; Couty, F.; Rabasso, N. Tetrahedron Lett. 2000, 41,
4113. (e) Martin, S. F.; Follows, B. C.; Hergenrother, P. J.; Franklin, C. L.
J. Org. Chem. 2000, 65, 4509.
(18) (a) Rainier, J. D.; Allwein, S. P. J. Org. Chem. 1998, 63, 5310. (b)
Nicolaou, K. C.; Postema, M. H. D.; Claiborne, C. F. J. Am. Chem. Soc.
1996, 118, 1565.
(19) (a) Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. H.
Tetrahedron Lett. 1999, 40, 2247. (b) Scholl, M.; Ding, S.; Lee, C. W.;
Grubbs, R. H. Org. Lett. 1999, 1, 953.
(20) Ruthenium catalyst 2 is recognized to alleviate certain limitations
brought on by substitution and to promote the metathesis of vinyl siloxanes
and fluorinated alkenes.
(13) (a) Efremov, I.; Paquette, L. A. J. Am. Chem. Soc. 2000, 122, 9324.
(b) Morgan, J. P.; Grubbs, R. H. Org. Lett. 2000, 2, 3153. (c) Paquette, L.
A.; Efremov, I. J. Am. Chem. Soc. 2001, 123, 4492.
(21) Presence of the remotely positioned benzyloxy substitutent is
purposeful. In this way, the volatility of the reactant and particularly the
product is reduced sufficiently to facilitate quantitation of the process.
790
Org. Lett., Vol. 5, No. 6, 2003

Table 1. Summary of Kinetic Data and Isolated Yield of 7a
k/min
k/min
regression
isolated yield
substrate 6, R )
[1 mol % run]
[5 mol % run]
t
1/2, min
analysis, r
kR/kH
of 7, %
σb
A. aromatics
p-CH3OC6H4-
C6H5-
p-CF3C6H4-
p-O2NC6H4-
B. aliphatics
-CH3
-COOCH2CH3
-H
-COCH3
0.2647
0.2582
0.2335
0.2069
1.3235
1.2910
1.1675
1.0345
0.5237
0.5369
0.5937
0.6700
0.997
0.959
0.994
0.996
20.9
20.4
18.5
16.4
73
89
94
76
-0.268
-0.010
0.540
0.778
0.0573
0.0175
0.2865
0.0814
0.0632
0.0432
0.0280
2.4194
8.5153
10.9675
16.0451
24.7553
0.967
0.999
0.991
0.942
0.996
4.5
1.3
1.0
0.68
0.44
90
87
83
88
88
-0.170
0.450
0.000
0.502
0.686
-SO2C6H5
a Cyclizations were performed with freshly prepared CD2Cl2 solutions of both the substrate and catalyst at 300 K in the probe of a Bruker 400 MHz
spectrometer under N2. Measurement of the rates of the carboethoxy derivative at both catalyst loadings allowed for extrapolation of the 1 mol % rates to
the 5 mol % level. b Values of σ employed for the aromatic series are those of the para substituents (Gordon, A. J.; Ford, R. A. The Chemist’s Companion;
Wiley and Sons: New York, 1972; pp 145-147).
The dienes 6 examined in this study exhibit rates that are
more than 100-fold faster than rates determined in our earlier
investigation11 (Table 1). Also, k(C6H5)/k(H) ) 20.4, indicating
that the aromatic and aliphatic series differ considerably in
their rate profiles. These observations are consistent with the
inherently greater proximity of the vinyl substituent R to the
reaction center. More significantly, the kinetic data reveal
that electron-donating groups enhance the overall reaction
rates. This effect is only moderate for the para substituents
where faster rates are manifested in the aromatic series. For
example, the kR/kH ratio for p-CH3OC6H4- is 20.9 and
changes to 16.4 for p-O2NC6H4-, a factor of 1.3. The
electronic effects are more pronounced for the substituents
in the aliphatic series. The kR/kH ratio for R ) CH3 is 4.5,
while it is 0.68 for the methyl ketone, a factor of 6.7.
possible explanation is that the R group in the aliphatic series,
being closer to the reacting double bond, hinders generation
of the ruthenium alkylidene. Chen has observed that electron-
withdrawing substituents on the carbene moiety accelerate
ring-opening metathesis.22 The present results do not conform
to this trend, are not compatible with a process involving
polarization of the ruthenium species as in 8, and also do
not find rate acceleration by an intramolecular Michael-type
cyclization to be kinetically viable.
Bulky R substituents in aliphatics have been shown to
severely hinder cyclization with ruthenium alkylidenes.7b
Presently, the COOC2H5-, COCH3-, and SO2C6H5- sub-
stituted dienes proved to be unreactive to 1. The F value
remains constant.
A Hammett plot of reaction rates relative to R ) H (Figure
1) is seen to be fragmented into two parts, one for aliphatic
and one for aromatic substituents. The F values in both
segments are negative, suggesting that electron-donating
substituents accelerate the reaction. This conclusion is
consistent, for example, with the faster reaction rates for
p-CH3OC6H4- and CH3- in the aromatic and aliphatic
series, respectively. A small F ) -0.0970 (r ) 0.924) for
aromatic substituents and a larger F ) -0.8801 (r ) 0.695)
for aliphatic substituents have been found.
The two different F values need not indicate that the
presence of an aromatic ring effects a change in the reaction
sequence. The problem may lie in the unavailability of a
consistent set of σ values for all of the compounds in the
study. The decreased sensitivity to substitution in the
aromatic series may be due to the involvement of a ruthenium
benzylidene derivative as the cyclization progresses. Another
Figure 1. Hammett plot with both series referenced against H.
The upper line is defined by the aromatic series and the lower by
the aliphatic congeners of 6.
Org. Lett., Vol. 5, No. 6, 2003
791

In summary, the reactivity of a series of structurally related
dienes has been studied in detail. However, the multistep
nature of the process, the fact that the aromatic and aliphatic
series are defined by different F values, and the accelerating
effect of electron-donor groups make detailed mechanistic
analysis a challenging endeavor at this time.
Acknowledgment. The authors thank Dr. Claudio Sturino
(Merck Frosst Canada) for a generous gift of 2.
Supporting Information Available: Experimental pro-
cedures for the preparation of 6, pertinent spectroscopic
data, and a description of the kinetic studies. This ma-
terial is available free of charge via the Internet at
http://pubs.acs.org.
(22) Adlhart, C.; Hinderling, C.; Baumann, H.; Chen, P. J. Am. Chem.
Soc. 2000, 122, 8204.
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Org. Lett., Vol. 5, No. 6, 2003