C O M M U N I C A T I O N S
We thank Dr. Fred Hollander and Dr. Allen Oliver of the UC
Berkeley CHEXRAY facility for carrying out the X-ray diffraction
studies.
Supporting Information Available: Experimental details, including
ananlytical data for all compounds described in the article, X-ray
diffraction data for 3, kinetic data for the cyclization of 1 to 2, and
details for the calculated structures 4, 5‡, 6, 7‡, 8, 9‡, and 10 (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(1) For recent reviews of C-H activation, see: (a) Kakiuchi, F.; Murai, S.
Topics in Organometallic Chemistry, 1999; Vol. 3. (b) Guari, Y.; Sabo-
Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047-1055. (c)
Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1699-1712. (d) Ryabov, A.
D. Chem. ReV. 1990, 90, 403-424. (d) Shilov, A. E.; Shul’pin, G. B.
Chem. ReV. 1997, 97, 2879-2932. (e) Jia, C. G.; Piao, D. G.; Oyamada,
J. Z.; Lu, W. J.; Kitamura, T.; Fujiwara, Y. Science 2000, 287, 1992-
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Figure 2. Calculated reaction coordinate diagram for cyclization.
(2) (a) Heterocyclic substrates: Tan, K. L.; Bergman, R. G.; Ellman, J. A. J.
Am. Chem. Soc. 2001, 123, 2685-2686. (b) Aromatic substrates: Thalji,
R. K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc.
2001, 123, 9692-9693.
(3) (a) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991,
113, 361-363. (b) Lappert, M. F. J. Organomet. Chem. 1988, 358, 185-
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W.; Schonher, H. J. Angew. Chem., Int. Ed. 1968, 7, 141.
(4) Several groups have shown that NHCs are useful ligands in a variety of
catalytic reactions: (a) Herrmann, W. A.; Kocher, C. Angew. Chem., Int.
Ed. Engl. 1997, 36, 2163-2187. (b) Herrmann, W. A.; Fischer, J.; Ofele,
K.; Artus, G. R. J. J. Organomet. Chem. 1997, 530, 259-262. (c)
Weskamp, T.; Bohm, V. P. W.; Herrmann, W. A. J. Organomet. Chem.
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(5) McGuinness et. al. have shown that NHCs undergo stoichiometric
reductive elimination and oxidative addition at a metal center: (a)
McGuinness, D. S.; Saendig, N.; Yates, B. F.; Cavell, K. J. J. Am. Chem.
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a single imaginary vibrational frequency. The first transition state
(5‡) is rate limiting with an energy 47 kcal/mol higher than resting
state 4. Although 5‡ resembles a metallocyclobutane, resulting from
a [2 + 2] cycloaddition between an alkene and carbene, visualiza-
tion of the transition-state imaginary frequency11 reveals that 5‡ is
more aptly described as a transition state leading to insertion of
the alkenyl group into the Rh-C bond. Going from 4 to 5‡ the Rh-
Ccarbene bond is lengthened from 2.01 to 2.13 Å, whereas the distance
from the carbene carbon to the internal alkene carbon decreases
dramatically from 2.93 to 1.69 Å. The alkene insertion leads to the
formation of zwitterion 6, which lies only 24 kcal/mol above
carbene 4 in part due to the aromatic character of the imidazolium
ring. Intramolecular proton transfer generates neutral hydride 8.
The free energy required to reach 7‡ from 6 was calculated to be
9 kcal/mol. C-H reductive elimination occurs at the Rh(III) center
in complex 8 through 9‡, with a decrease in the H-Rh-C angle
from 75.3° to 44.1°. Presumably, the catalytic cycle is then renewed
by the displacement of the product by another molecule of alkene
with subsequent C-H activation to form the NHC complex 4.
In summary, the cooperative use of experiment and theory has
led to the discovery of a novel carbene insertion mechanism in the
intramolecular coupling of an alkene to a benzimidazole. Further-
more, an N-heterocyclic carbene complex was found to be the
resting state of the catalyst, and the carbene insertion was calculated
to be the rate-limiting step of the reaction. Surprisingly, the NHC
complex is formed in situ under mild thermal conditions via C-H
activation of the heterocycle without necessitating pre-formation
of the imidazolium salt. Currently, we are investigating the
application of this annulation methodology to other heterocycles
that are known to form N-heterocyclic carbenes, as well as
investigating the mechanism of the formation of the carbene.
(6) Furstner et.al. has reported a ruthenium-NHC complex with a tethered
alkene which undergoes intramolecular metathesis at elevated temperatures
(a) Furstner, A.; Ackermann, L.; Gabor, B.; Goddard, R.; Lehmann, C.
W.; Mynott, R.; Stelzer, F.; Thiel, O. R. Chem.sEur. J. 2001, 7, 3236-
3253. (b) Furstner, A.; Krause, H.; Ackermann, L.; Lehmann, C. W. Chem.
Commun. 2001, 2240-2241.
(7) Herrmann, W. A.; Fischer, J.; Ofele, K.; Artus, G. R. J. J. Organomet.
Chem. 1997, 530, 259-262.
(8) Although the reaction was performed at 135 °C, the 31P NMR spectrum
was monitored at room temperature.
(9) Although compound 1 undergoes a formal 6-endo-trig cyclization, it has
been previously reported that removal of the geminal methyl groups favors
a formal 5-exo-trig cyclization (see ref 2). Therefore, in this paper the
5-exo-trig cyclization was studied. A more complete DFT study is currently
underway.
(10) The structures were characterized at B3LYP/LACVP**++// B3LYP/
LACVP** level of theory. Zero point and Gibbs free energy (1 atm, 298
K) corrections were applied based on unscaled frequency calculations.
For further details see references below as well as the Supporting
Information. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652. (b)
Vosko, S. H.; Wilk, L.; Nusair, M. Can. J. Phys. 1980, 58, 1200-1211.
(c) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. ReV. B 1988, 37, 785-
789. (d) Frisch, M. J.; Pople, J. A.; Binkeley, J. S. J. Chem. Phys. 1984,
80, 3265. (e) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.
(11) Molden: Schaftenaar, G.; Noordik, J. H. J. Comput.-Aided Mol. Des. 2000,
14, 123.
Acknowledgment. This work was supported by NIH grant
GM50353 (to J.A.E), and by the Director, Office of Energy
Research, Office of Basic Energy Sciences, Chemical Sciences
Division, U.S. Department of Energy, under Contract No. DE-
AC03-76SF00098 (to R.G.B) Bristol-Myers Squibb is the founding
member of the UC Berkley Center for New Directions in Synthesis.
JA017351D
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