compound as a byproduct of the reaction (Scheme 1). State-
of-the-art systems following this approach have described
the use of aryl bromides and iodides, requiring elevated
7
temperatures (above 100 °C) and long reaction times. The
use of aryl chlorides as oxidants was recently reported with
use of biaryl phosphine ligands, but also requires those
8
elevated temperatures. Aryl chlorides are very appealing
substrates as they are readily available and much cheaper
than their bromo and iodo counterparts, although less reactive
due to the relative difficulty of activation of the C-Cl bond.
9
Figure 1. (NHC)Pd Complexes Tested
Herein, we report on the use of aryl chlorides for the
oxidation of a variety of secondary alcohols under anaerobic
conditions at very mild temperatures using (NHC)Pd or
Pd complexes (Figure 1) in the oxidation of 1-phenyl-1-
propanol to propiophenone in dioxane, using chorobenzene
as the oxidant (Table 1). Complex 1 allows for oxidation to
occur in high yield at 40 °C in 3 h, with a low catalyst
loading (0.5 mol %). The reaction could also be carried out
at room temperature, requiring nearly 24 h to reach comple-
tion. When complex 2 was used, known to be more active
1
0
(
NHC)Ni systems (NHC ) N-heterocyclic carbene).
Scheme 1
.
Metal-Catalyzed Oxidation of Alcohols with Aryl
Halides
1
4
at lower temperatures in cross-coupling reactions, the
reaction time was shortened to 17 h at room temperature.
Palladium dimer 3 allowed for the formation of only 45%
of the desired product under the same conditions. It is worth
mentioning that, for all complexes, similar results were
obtained when p-chlorotoluene was used as oxidant, leading
to the formation of toluene as a byproduct, more appealing
than benzene in large-scale applications due to safety and
health concerns.
The very effective use of (NHC)-Pd and (NHC)-Ni
complexes for the dehalogenation of aryl chlorides, an
Table 1. Performance Comparison of Different (NHC)Pd
Complexes
1
1
important transformation in organic chemistry and for
1
2
environmental remediation, has been previously reported
with use of 2-propanol as a hydride source, leading to the
7b,13
formation of acetone as a byproduct.
We decided to start
from those well-established systems and target the ketone
formation as a way to oxidize alcohols. We first tested the
activity of a variety of commercially available NHC-bearing
a
entry
[NHC-Pd]
temp (°C)
time (h)
yield (%)
1
2
3
4
5
a
1
1
2
2
3
40
25
25
25
25
3
24
17
11
24
92
90
92
91
45
(
6) For some early references, see: (a) Tamaru, Y.; Yamamoto, Y.;
Yamada, Y.; Yoshida, Z. Tetrahedron Lett. 1979, 16, 1401–1404. (b)
Bouquillon, S.; Henin, F.; Muzart, J. Organometallics 2000, 19, 1434–
b
1
437.
(
7) (a) Guram, A. S.; Bei, X.; Turner, H. W. Org. Lett. 2003, 5, 2485–
2
487. (b) Bei, X.; Hagemeyer, A.; Volpe, A.; Saxton, R.; Turner, H.; Guram,
b
Average of two runs, isolated yields. 1 mol % of 2.
A. S. J. Org. Chem. 2004, 69, 8626–8633.
8) In ref 7b, 96 different phosphines were tested as ligands with Pd(dba)
and with the exception of one substrate the best combination required 105
(
2
°
C.
Regarding the scope of the reaction, preliminary results
are depicted in Table 2. A variety of alcohols were oxidized
to the corresponding ketones at room temperature (25 °C)
or slightly above in high yields. Catalyst loadings, reaction
times and isolated yields of products are comparable to those
reported with use of the most common state-of-the-art Pd-
(
9) (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176–
4
211. (b) Grushin, V. V.; Alper, H. Chem. ReV. 2000, 100, 3009–3066.
(
10) For general reviews on NHCs, see : (a) Nolan, S. P., Ed.
N-Heterocyclic Carbenes in Synthesis; Wiley-VCH: Weinheim, Germany,
2
006. (b) Glorius, F., Ed. Top. Organomet. Chem. 2007, 21.
11) (a) Parry, R. J.; Li, Y.; Gomez, E. E. J. Am. Chem. Soc. 1992,
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(
1
Y.; Ahem, D. G. J. Org. Chem. 1995, 60, 2292–2297.
1
5
(
12) (a) Hutzinger, O.; Safe, S.; Zitko, V. The Chemistry of PCBs; CRC
catalyzed aerobic oxidation systems. Interestingly, with
these initial reaction conditions our (NHC)Pd system did not
Press: Cleveland, OH, 1974. (b) Morra, M. J.; Borek, V.; Koolpe, J. J.
EnViron. Qual. 2000, 29, 706–715.
(
13) (a) Navarro, O.; Marion, N.; Oonishi, Y.; Kelly, R. A.; Nolan, S. P.
J. Org. Chem. 2006, 71, 685–692. (b) Navarro, O.; Kaur, H.; Mahjoor, P.;
Nolan, S. P. J. Org. Chem. 2004, 69, 3173–3180. (c) Desmarets, C.; Kuhl,
S.; Schneider, R.; Fort, Y. Organometallics 2002, 21, 1554–1559. (d) For
a review in metal-mediated hydrodehalogenation, see: Alonso, F.; Be-
(14) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.;
Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101–4111.
(15) For an excellent, substrate-dependent comparison of Pd-catalyzed
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M. S. J. Org. Chem. 2005, 70, 3343–3352.
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