9692
J. Am. Chem. Soc. 2001, 123, 9692-9693
Annulation of Aromatic Imines via Directed C-H
Activation with Wilkinson’s Catalyst
R. K. Thalji, K. A. Ahrendt, R. G. Bergman,* and
J. A. Ellman*
Center for New Directions in Organic Synthesis
Department of Chemistry, UniVersity of California†
Berkeley, California 94720
Table 1. Cyclization of Aromatic Imines Using Wilkinson’s
Catalysta
ReceiVed July 17, 2001
The application of transition metal-mediated C-H activation
to C-C bond formation has great potential for the preparation of
complex products from simple starting materials.1 One of the first
examples of such a transformation is Murai’s regioselective
ruthenium-catalyzed ortho alkylation of aromatic ketones with
alkenes, which is proposed to involve heteroatom-directed C-H
activation of the ortho-site.2 Brookhart has used Cp*Rh(C2H3-
SiMe3)2 (Cp* ) C5Me5) to catalyze this reaction with comparable
efficiency,3a and several groups have now expanded the scope of
these methodologies to include other directing groups such as
imines, esters, and pyridines.3b-e These reactions, however, give
only linear coupling products and are typically limited to terminal
alkenes bearing no allylic hydrogens. Recently, Jun reported a
more general imine-directed coupling reaction using Wilkinson’s
catalyst [(PPh3)3RhCl], that tolerates internal double bonds, yet
yields only linear products.4
Our group has been interested in intramolecular variants of
this methodology and recently reported the annulation of alkenyl-
substituted heterocyclic derivatives.5 Herein, we present the
annulation of aromatic imines in which the alkene is tethered meta
to the imine (eq 1). Coupling proceeds selectively to the more
hindered ortho site to provide functionalized bicyclic ring systems
that would be difficult to access by other methods. This
intramolecular reaction can provide linear or branched coupling
products depending on the alkene tether. Our results demonstrate
for the first time that allyl ethers and allylamine derivatives
function as efficient olefin coupling partners for the directed C-H
activation reaction. Remarkably, in contrast to the intermolecular
variant employing Wilkinson’s catalyst,4 an aldimine serves as
an effective directing group.6
† The Center for New Directions in Organic Synthesis is supported by
Bristol-Meyers Squibb as Sponsoring Member.
(1) For reviews on C-H activation, see: (a) Kakiuchi, F.; Murai, S.
Activation of Unreactive C-H Bonds. Top. Organomet. Chem. 1999, 3, 47-
79. (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)
Shilov, A. E.; Shul’pin G. B. Chem. ReV. 1997, 97, 2879-2932. (e) Arndtsen,
B. A.; Bergman, R. G.; Mobley, A.; Peterson, T. H. Acc. Chem. Res. 1995,
28, 154-162. (f) Ryabov, A. Chem. ReV. 1990, 90, 403-424. (g) Jia, C.;
Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001. In press.
(2) (a) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.;
Sonoda, M.; Chatani, N. Nature 1993, 366, 529-531. (b) Murai, S.; Kakiuchi,
F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Pure Appl.
Chem. 1994, 66, 1527-1534. (c) Kakiuchi, F.; Sekine, S.; Tanaka, Y.;
Kamatini, A.; Sonoda, M.; Chatani, N.; Murai, S. Bull. Chem. Soc. Jpn. 1995,
68, 62-83. (d) Murai, S.; Chatani, N.; Kakiuchi, F. Bull. Chem. Soc. Jpn.
1997, 69, 5589-594.
a Reactions were performed using 5 mol % (PPh3)3RhCl in toluene
(0.1 M). b 1H NMR yields were based on 2,6-dimethoxytoluene internal
standard. c Yield refers to an isolated mixture of 17 and 18 which appear
1
in a 1:1 ratio by H NMR.
(3) (a) Lenges, C. P.; Brookhart, M. J. Am. Chem. Soc. 1999, 121, 6616-
6623. (b) Lim, Y. G.; Kang, J. B.; Kim, Y. H. J. Chem. Soc., Perkin Trans.
1 1996, 2201-2206. (c) Lim, Y. G.; Kim, Y. H.; Kang, J. B. J. Chem. Soc.,
Chem. Commun. 1994, 2267-2268. (d) Trost showed that R,â-unsaturated
esters could also be functionalized in a similar fashion. Trost, B. M.; Imi, K.;
Davies, I. W. J. Am. Chem. Soc. 1995, 117, 5371-5372. (e) Jordan and Taylor
showed the coupling of pyridine to propene. Jordan, R. F.; Taylor, D. F. J.
Am. Chem. Soc. 1989, 111, 778-779.
Table 1 summarizes the results of our annulation experiments.
Treatment of the aromatic ketimine 1 (entry 1) with 5 mol %
(PPh3)3RhCl at 125 °C for 4 h affords, after hydrolysis, carbocycle
12 in high yield. The allyl-substituted ketimine 2 (entry 2) is
converted to indane 13, although a double bond isomer 14 is also
formed in a kinetic ratio of 3:1.7 Substrates containing longer
alkenyl tethers cyclize to either five- or six-membered rings,
(4) Jun, C. H.; Hong, J. B.; Kim, Y. H.; Chung, K. Y. Angew. Chem., Int.
Ed. 2000, 39, 3440-3441.
(5) (a) Tan, K. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2001,
123, 2685-2686. (b) Murai has demonstrated directed intramolecular cy-
clization of 1,5- and 1,6-dienes. Fujii, N.; Kakiuchi, F.; Yamada, A.; Chatani,
N.; Murai, S. Bull. Chem. Soc. Jpn. 1998, 71, 285-298. (c) Fujiwara has
successfully cyclized electron-deficient alkenes and alkynes to aromatic rings
with palladium. Jia, C. G.; Piao, D. G.; Oyamada, J. Z.; Lu, W. J.; Kitamura,
T.; Fujiwara, Y. Science 2000, 287, 1992-1995.
(6) (a) Murai used Ru3(CO)12 to couple aldimines intermolecularly to
terminal alkenes with no allylic hydrogens. Kakiuchi, F.; Yamauchi, M.;
Chatani, N.; Murai, S. Chem. Lett. 1996, 111. (b) Very recently, Lim has
shown that aldimines can be coupled to isomerizable alkenes using [RhCl-
(coe)2]2/PCy3 as the catalyst; however, bis-ortho alkylated products predominate
over the desired monoalkylated products. Lim, Y. G.; Han, J. S.; Yang, S. S.;
Chun, J. H. Tetrahedron Lett. 2001, 42, 4853-4856.
10.1021/ja016642j CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/06/2001