NHC ligands, due to their enhanced stability and reactivity,
have been successfully applied to palladium and other
transition metal-catalyzed reactions.6 These include Heck,7
Suzuki-Miyaura,8 Stille, and Kumada couplings,6 hydroge-
nation reactions,9 and ring-closing metathesis reactions.10 We
recently reported base-free conditions with NHC catalysts
for Heck and Suzuki couplings using reactive aryl diazonium
ions.11 Imidazolium carbene ligands provide strong σ-bond
donation to the metal, together with attenuated back-bonding
due to donation of the N1 and N3 lone pair electrons.12 This
arrangement renders the metal more electron-rich, allowing
for a more favorable oxidative insertion step. Typical NHC-
palladium complexes, formed by treatment of an imidazolium
salt with base, are air stable and can be chromatographed in
some cases. Alternatively, the NHC-Pd complex can be
formed in situ without added base. Comparisons with
substituted NHC ligands have been previously made between
bis-mesityl and the 2,6-diisopropylimidazolium ligands and
between the aromatic 4,5-dehydro and the saturated, non-
aromatic 4,5-dihydro versions.13 A dramatic effect is now
demonstrated with the novel phenanthrenyl NHC ligands,
where the most sterically hindered, extended aromatic ligand
produces Sonogashira coupling product in high yields at
moderate temperatures and short reaction times.
Table 1. Effect of Ligand and Conditions
Shown in Table 1 are the effects of ligand substitution
and reaction conditions. The known NHCs, N,N-bis-mesityl
1 and 2,6-diisopropylimidazolium hexafluoro phosphate 2,
were reacted with Pd(PPh3)2Cl2 (3 mol %) and used in situ.14
Other forms of palladium, were found to be less effective in
this case, including Pd(OAc)2, Pd(PPh3)4, PdCl2, and Pd-
(dba). The optimal base was potassium t-butoxide (1.5 equiv)
used with 18-crown-6 in THF heated at reflux for 12 h using
bromobenzene as a test substrate. Other bases explored
included K2CO3, Et3N, Cs2CO3, and CsF, which proved to
be inferior. When the solvent was changed to DMF or
toluene, a comparable yield was obtained, while dioxane and
methanol gave much lower yields. When the ligand is left
out, a low yield was obtained following a 24 h reaction.
a All yields are for isolated, chromatographed materials. b Pd(OAc)2 was
used for catalyst formation. c Chloride salt of dihydroimidazolium 5 was
used.
improved 51% yield under similar conditions. 10-Cyclo-
hexyl-9-phenanthryl NHC 4, a significantly more hindered
variation, gave a 61% yield after only 3 h of reaction time.
When used at room temperature, ligand 4 gave a modest
48% yield with bromobenzene. Finally, the more hindered
2,9-dicyclohexyl-10-phenanthryl ligand 5 gave a 90% yield
of product after only 2 h of reaction time at 65 °C. After 12
h at room temperature, a 67% yield was obtained. Other
variations, including Pd(OAc)2 or the use of the chloride salt
of 5, gave lower yields. Use of Pd(dba)2 gave a lower 71%
yield under these conditions. The aromatic 4,5-dehydro
analogue of 5 gave a reduced 82% yield after 2 h at reflux
and a 51% yield at room temperature.
The optimal coupling conditions with phenanthryl ligand
5 were used with numerous aryl bromides at 65 °C and
iodides, reacted at room temperature, with terminal acetylenes
to produce substituted alkynes (Table 2).16 The iodides in
general gave higher yields even when reacted at the lower
temperature. Electron-rich and -deficient substrates were
coupled with equal success with this system. Ortho substit-
uents were well tolerated, including 2,6-dimethyl bromoben-
zene. 2-Bromothiophene also reacted with success. 1-Bro-
mocyclohexene was investigated to demonstrate potential for
The most significant improvement was found when the
new extended aromatic phenanthryl NHC ligands were
explored.15 Bis-9-phenanthryl ligand 3 gave only a slightly
(5) For previous NHC-catalyzed Sonogashira reactions, see: (a) McGuiness,
D. S.; Cavell, K. J. Organometallics 2000, 19, 741. (b) Batey, R. A.; Shen,
M.; Lough, A. J. Org. Lett. 2002, 4, 1411. (c) Hukuyama, T.; Shinmen,
M.; Nishitani, S.; Sato, M.; Ryu, I. Org. Lett. 2002, 4, 1691.
(6) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(7) Yang, C.; Lee, H. M.; Nolan, S. P. Org. Lett. 2001, 3, 1511.
(8) (a) Fu¨rstner, A.; Leitner, A. Synlett 2001, 290-292. (b) Grasa, G.
A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3, 1077-1080.
(9) Perry, M. C.; Cui, X.; Powell, M. T.; Hou, D. R.; Reibenspies, J. H.;
Burgess, K. J. Am. Chem. Soc. 2003, 125, 113.
(10) Seiders, T. J.; Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225.
(11) (a) Andrus, M. B.; Song, C. Org. Lett. 2001, 3, 3761. (b) Andrus,
M. B.; Song, C.; Zhang, J. Org. Lett. 2002, 4, 2079.
(12) Herrmann, W. A.; Kocher, C. Angew. Chem., Int. Ed. Engl. 1997,
36, 2162.
(13) Ref 8a and: Furstner, A.; Krause, H. AdV. Synth. Catal. 2001, 343,
343.
(14) Ligands 1 and 2 were formed following the known method:
Arduengo, A. J. Acc. Chem. Res. 1999, 32, 913.
(15) New bis-phenanthryl ligands 3-5 were formed using the method
of Arduengo (ref 14) from the corresponding phenanthrylamines. See
Supporting Information.
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Org. Lett., Vol. 5, No. 18, 2003