Synthesis and ActiVity of (IPr)Pd(acac)Cl
stirred at 50 °C unless otherwise indicated. When the reaction
reached completion, or no further conversion could be observed
by gas chromatography, water was added to the reaction mixture,
the organic layer was extracted with tert-butylmethyl ether (MTBE)
dried over magnesium sulfate, and the solvent was evaporated in
vacuo. When necessary the product was purified by flash chroma-
tography on silica gel. The reported yields are the average of at
least two runs.
Furthermore, the present catalytic system was found compat-
ible with di-ortho-substituted substrates, highlighting its high
tolerance for extremely hindered substrates as we previously
noticed in the Buchwald-Hartwig reaction. As an added
advantage, a heteroaromatic ketone was R-arylated without loss
of activity (entry 11). Finally, we focused on the use of
polyaromatic halides as coupling partners and produced three
propiophenones possessing respectively the 1-naphthyl, 2-naph-
thyl, and 4-biphenylyl moiety at the R position in near
quantitative yields (entries 12-14). Interestingly, we isolated
these products without purification by column chromatography
on silica gel. Taking advantage of the low solubility of the
product in alkanes, a simple pentane wash followed by a
filtration was sufficient to isolate pure compounds (entries 12,
13, and 14). To the best of our knowledge, this is the first time
that such compounds have been synthesized with a Pd-catalyzed
cross-coupling reaction.26
r-Ketone Arylation of Aryl Halides: General Procedure. In
a glovebox, (IPr)Pd(acac)Cl (1) (0.01 mmol, 6.3 mg), sodium tert-
butoxide (1.5 mmol, 144 mg), and anhydrous toluene (1 mL) were
added in turn to a vial equipped with a magnetic bar and sealed
with a screw cap fitted with a septum. Outside the glovebox, the
ketone (1.1 mmol) and the aryl halide (1 mmol) were injected in
turn through the septum. If one of the two starting materials was a
solid, it was added to the vial inside the glovebox and toluene and
the second starting material were added outside the glovebox under
argon. The reaction mixture was then stirred at 60 °C. When the
reaction reached completion, or no further conversion could be
observed by gas chromatography, water was added to the reaction
mixture, the organic layer was extracted with tert-butylmethyl ether
(MTBE) dried over magnesium sulfate, and the solvent was
evaporated in vacuo. When necessary, the product was purified by
flash chromatography on silica gel. The reported yields are the
average of at least two runs.
Conclusion
In summary, we have described a new synthetic route leading
to a PdII precatalyst in one step from a stable NHC salt and the
commercially available Pd(acac)2. The resulting complex, (IPr)-
Pd(acac)Cl, has shown excellent catalytic activity in the
Buchwald-Hartwig and the R-ketone arylation reactions, using
aryl chlorides under mild reaction conditions. The activity of
this family of palladium precatalysts in related reactions is
currently under investigation.
2-(2,6-Dimethylphenyl)-1-(1-methyl-1H-pyrrol-2-yl)-etha-
none (Table 3, entry 10). The above general procedure yielded,
after a pentane wash, 218 mg (96%) of the title compound.
1H NMR (300 MHz, CDCl3): δ 7.12-7.10 (m, 1H, HAr), 7.04-
7.02 (m, 3H, HAr), 6.75 (s, 1H, HAr), 6.14-6.12 (m, 1H, HAr), 4.28
(s, 2H, C(O)-CH2), 3.96 (s, 3H, N-CH3), 2.32 (s, 6H, CAr-CH3).
13C NMR (75 MHz, CDCl3): δ 188.0 (C, CdO), 137.3 (C, CAr),
132.9 (C, CAr), 131.0 (CH, CAr), 130.7 (C, CAr), 128.0 (CH, CAr),
126.8 (CH, CAr), 118.8 (CH, CAr), 108.0 (CH, CAr), 39.7 (CH2,
C(O)-CH2), 37.8 (CH3, N-CH3), 20.6 (CH3, CAr-CH3). Anal.
Calcd for C15H17NO (MW 227.30): C, 79.26; H, 7.54; N, 6.16.
Found: C, 79.39; H, 7.24; N, 5.74.
Experimental Section
Synthesis of (IPr)Pd(acac)Cl (1). A Schlenk flask equipped with
a magnetic bar was loaded with the imidazolium salt IPr‚HCl (2.96
g, 7 mmol) and Pd(acac)2 (1.53 g, 5 mmol). The vessel was purged
by a sequence of three vacuum-argon refill-evacuation cycles and
dry dioxane (100 mL) was added with a syringe. The reaction
mixture was stirred at 100 °C for 24 h. The solvent was evaporated
in vacuo and the remaining solid was dissolved in diethyl ether,
some impurities being insoluble. The mixture was then filtered and
the solid further washed with diethyl ether (2 × 10 mL). The filtrate
was collected and the solvent was evaporated in vacuo to yield
2.99 g (95%) of the desired compound as a yellow powder.
1H NMR (400 MHz, CDCl3): δ 7.51 (t, J ) 7.8 Hz, 2H), 7.35
(d, J ) 7.8 Hz, 4H), 7.12 (s, 2H), 5.12 (s, 1H), 2.95 (q, J ) 6.4
Hz, 4H), 1.84 (s, 3H), 1.82 (s, 3H), 1.34 (d, J ) 6.4 Hz, 12H),
1.10 (d, J ) 6.4 Hz, 12H). 13C NMR (100 MHz, CDCl3): δ 187.1,
184.1, 156.4, 147.0, 135.5, 134.8, 130.9, 125.7, 124.7, 124.6, 99.9,
29.1, 30.0, 27.6, 26.8, 23.7, 23.5. Anal. Calcd for C32H43ClN2O2-
Pd (MW 629.57): C, 61.05; H, 6.88; N, 4.45. Found: C, 60.78;
H, 7.15; N, 4.29.
2-(Naphthalen-2-yl)-1-phenylpropan-1-one (Table 3, entry
13). The above general procedure yielded, after a pentane wash,
253 mg (97%) of the title compound.
1H NMR (300 MHz, CDCl3): δ 7.96 (d, J ) 5.7 Hz, 2H, HAr),
7.73-7.69 (m, 4H, HAr), 7.39-7.31 (m, 4H, HAr), 7.26 (t, J ) 5.7
Hz, 2H, HAr), 4.77 (q, J ) 5.1 Hz, 1H, CH-CH3), 1.58 (d, J ) 5.1
Hz, 3H, CH-CH3). 13C NMR (75 MHz, CDCl3): δ 200.3 (C,
CdO), 139.1 (C, CAr), 136.5 (C, CAr), 133.7 (C, CAr), 132.9 (CH,
CAr), 132.4 (C, CAr), 128.9 (CH, CAr), 128.8 (CH, CAr), 128.5 (CH,
CAr), 127.8 (CH, CAr), 127.7 (CH, CAr), 126.5 (CH, CAr), 125.2
(CH, CAr), 126.0 (CH, CAr), 125.8 (CH, CAr), 48.0 (CH, CH-CH3),
19.6 (CH3, CH-CH3). Anal. Calcd for C19H16O (MW 260.33): C,
87.66; H, 6.19. Found: C, 87.90; H, 6.35.
Buchwald-Hartwig Cross-Coupling of Aryl Halides with
Primary and Secondary Amines: General Procedure. In a
glovebox, (IPr)Pd(acac)Cl (1) (0.01 mmol, 6.3 mg), potassium tert-
butoxide (1.1 mmol, 124 mg), and anhydrous 1,2-dimethoxyethane
(DME) (1 mL) were added in turn to a vial equipped with a
magnetic bar and sealed with a screw cap fitted with a septum.
Outside the glovebox, the amine (1.1 mmol) and the aryl halide (1
mmol) were injected in turn through the septum. If one of the two
starting materials was a solid, it was added to the vial inside the
glovebox and DME and the second starting material were added
outside the glovebox under argon. The reaction mixture was then
Acknowledgment. The National Science Foundation is
gratefully acknowledged for financial support of this work. Eli
Lilly and Co. and Lonza are gratefully acknowledged for their
gifts of materials. Boehringer Ingelheim Pharmaceuticals Inc.
is gratefully thanked for their support of this work in the form
of an unrestricted grant. O.N. acknowledges the International
Precious Metals Institute for a Student Award. We would also
like to thank the University of Ottawa for hosting our group
while UNO is recovering from hurricane Katrina.
Supporting Information Available: Details for experimental
procedures and products isolation. This material is available free
(26) (a) 3i was previously synthesized by thermolysis of benzoylben-
zocycloheptene, see: Battye, P. J.; Jones, D. W. J. Chem. Soc., Perkin Trans.
1 1986, 8, 1479-1489. (b) 3j has not been reported. (c) 3k was previously
synthesized by a Friedel-Craft/methylation sequence, see: Garcia-Garibay,
M. A.; Shin, S.; Sanrame, C. N. Tetrahedron Lett. 2000, 56, 6729-6737.
JO060190H
J. Org. Chem, Vol. 71, No. 10, 2006 3821