C O M M U N I C A T I O N S
Table 1. Diene Metathesis by 1 (5 mol %)a
substrate. Polyether 14 undergoes preferential ADMET at 2.5-20
mM, consistent with the literature report,2j but diluting to 0.5 mM
yields >90% 15 in 0.5 h.
While submillimolar substrate concentrations might be used to
minimize oligomerization and enforce direct RCM, this would retard
the bimolecular reaction between substrate and catalyst. The
opposite approach greatly improved RCM efficiency for 4a. By
mixing 4a and 1 at 100 mM, and diluting to 5 mM to promote
backbiting, we obtained 5a in 1 h (cf. 9 h for the Ziegler method).
Oligomers are overwhelmingly regarded as inimical to formation
of RCM products. The foregoing demonstrates that this is a false
premise. At dilutions compatible with efficient metathesis, ADMET
oligomers provide a key vector for efficient synthesis of medium
or large rings. Protocols designed to impede oligomerization prolong
reaction times and potentially limit yields. An intriguing inference
is the possibility that some “failed” RCM reactions may be more
promising than they originally seemed. Failure may be an artifact
of an inappropriately high concentration regime, or not permitting
sufficient time for the reaction to evolve toward equilibrium.
Preliminary results reveal similar behavior for other (Mo, Ru)
metathesis catalysts. Detailed studies are under way, and will be
reported in due course.
Acknowledgment. This work was supported by NSERC, the
Canada Foundation for Innovation, and the Ontario Innovation
Trust. J.D.S. thanks CAPES and CNDCT of Brazil for a fellowship.
Supporting Information Available: Synthetic details.This material
a Diene, 1 mixed in CH2Cl2 (22 °C); heated to reflux after 15 min. GC-
FID quantification;4 identity of RCM products confirmed by GC-MS. E/Z
ratios in RCM products: 5a/c, 72:28; 5b, 89:11; 7a, 41:59; 7c, 9a/b, 11a/
b, 0:100; 15, 53:47. For EM values, see refs 3b and 11. b Calculated by
difference.
References
(1) Recent reviews: (a) Grubbs, R. H. Handbook of Metathesis; Wiley-
VCH: Weinheim, Germany, 2003. (b) Nicolaou, K. C.; Bulger, P. G.;
Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4490. (c) Prunet, J. Angew.
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(2) Selected examples: Dimerization driven by unsymmetrical diene substitu-
tion: (a) Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62, 7310.
(b) Yamamoto, K.; Biswas, K.; Gaul, C.; Danishefsky, S. J. Tetrahedron
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Cogan, D. A.; Hofilena, G. E.; Hoveyda, A. H. J. Am. Chem. Soc. 1997,
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Michrowska, A.; Wawrzyniak, P.; Grela, K. Eur. J. Org. Chem. 2004,
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ROMP of cyclooctadiene, polymer chains dominate at 1.8 M, but
C12 rings are extruded at 0.13 M.9b Likewise, an unsaturated 21-
membered macrocycle underwent ROMP at 0.7 M, but at 20 mM,
the polymer liberated cyclomonomer and decreasing amounts of
cyclodimer, trimer, and tetramer.10 For oligomers of 4a-c, the
smallest rings (5a-c) form at 5 mM, but oligomers emerge at
intermediate concentrations.
The kinetic bias of 4a-c toward ADMET at 5 mM suggests
that other macrocyclic or medium-ring compounds, for which
effective molarity (EM) values are comparable or lower,3b,11 should
also undergo RCM via the oligomerization-backbiting mechanism.
Of the ester, malonate, catechol, and polyether substrates shown
in Table 1, all oligomerize at 5 mM except diethyl diallylmalonate
8b (EM > 106)11a and catechol 10b (EM 750).3b For 8b, the gem-
dimethyl and Thorpe-Ingold effects exert a powerful bias toward
cyclization, and solely RCM is observed even at 100 mM. For 10b,
the small ring size and backbone rigidity favor cyclization, but
oligomers emerge at 100 mM.
(3) (a) Conrad, J. C.; Parnas, H. H.; Snelgrove, J. L.; Fogg, D. E. J. Am.
Chem. Soc. 2005, 127, 11882. (b) For the importance of Ziegler conditions
in classic cyclization chemistry, see Illuminati, G.; Mandolini, L. Acc.
Chem. Res. 1981, 14, 95 and references therein. For protocols, see
Experimental section in the Supporting Information.
(4) GC retention times and response factors for all substrates and RCM
products were confirmed by analysis of authentic materials.
Equilibrium EMeq values for saturated lactones tend to track the
more usual, kinetic, EM values. The latter thus serve as a guide to
the relative dilutions required to maximize backbiting. An exception
is hexalactone, which has an EMeq value ca. tenfold lower than
expected from the kinetic EM value.11b Higher dilutions are indeed
required for seven-membered 7c, as well as 9a. The presence of
the metal in the cyclic transition state may increase the strain
energies for these substrates. Where ring strain is too high, or the
probability of encounter too low, cyclization fails, even at high
dilution. Thus, oligomers of 12 do not cyclize at 0.5 mM, and
formation of eight-membered 7b fails even at 0.05 mM. Finally,
we note that the oligomerization-backbiting mechanism does not
require a conformational predisposition toward backbiting in the
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