Iron-catalyzed benzylic oxidation with aqueous tert-butyl hydroperoxide

Article abstract of DOI:10.1002/adsc.200600553

A small amount of iron(III) chloride (2 mol%) catalyzes benzylic oxidations with tert-butyl hydroperoxide (TBHP) as oxidant in pyridine. The corresponding carbonyl compounds are obtained in high yields.

Full text of DOI:10.1002/adsc.200600553

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DOI: 10.1002/adsc.200600553
Iron-Catalyzed Benzylic Oxidation with Aqueous tert-Butyl
Hydroperoxide
a
a,
Masafumi Nakanishi and Carsten Bolm *
a
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52056 Aachen, Germany
Phone: (+49)-241-809-4675; fax: (+49)-241-809-2391; e-mail: Carsten.Bolm@oc.rwth-aachen.de
Received: October 25, 2006
[
12]
Abstract: A small amount of iron
A
H
R
U
G
by syringe pump; as in the Kim system) is unneces-
mol%) catalyzes benzylic oxidations with tert-butyl
hydroperoxide (TBHP) as oxidant in pyridine. The
corresponding carbonyl compounds are obtained in
high yields.
sary. A typical oxidation [the conversion of diphenyl-
methane (1) into diphenyl ketone (2)] is illustrated in
Eq. (1).
Keywords: carbonyl compounds; catalysis; CÀH ac-
tivation; ferric chloride; iron; oxidation
Benzylic oxidation is one of the most significant and
In the initial phase of the project, diphenylmethane
synthetically useful methods in organic chemistry. (1) was chosen as substrate for the optimization of
Classically, stoichiometric quantities of oxidants such the catalysis protocol. In the presence of 2 mol% of
as potassium permanganate or potassium dichromate iron(III) chloride, several oxidants such as hydrogen
A
H
R
U
G
[
1]
[14]
were used in these reactions. During the last dec- peroxide,
cumene hydroperoxide, NaOCl and di-
were tested (in pyridine at 828C). Under
these conditions the first oxidant decomposed, and
[
15]
ades a number of oxidation catalysts have been de- oxygen
scribed, but most of them involve toxic metals
[2]
[3–8]
and their applicability is limited in terms of substrate also the latter two gave no product at all. Only
range. Consequently, further improvements in this cumene hydroperoxide afforded ketone 2 in 58%
area are desirable. In particular on the industrial scale yield. Finally, the best result was achieved with TBHP
the application of environmentally benign oxidation (91% yield of 2). In the absence of this oxidant, no
catalysts in combination with “green oxidants” is es- reaction occurred. Surprisingly, an (open flask) aero-
sential. In that scenario, low cost and non-toxic iron bic atmosphere was beneficial, whereas under argon
[
9]
appears to be a prime element of choice. In 1983, the yield of 2 was only 13% (as determined by GC).
Barton introduced a particular type of iron-catalyzed Other iron salts proved also applicable independent
[
10]
oxidation,
further been developed.
workers demonstrated the applicabilty of a related yield of 2 was slightly higher with Fe
iron catalysis for the oxidation of activated methylene lyst, FeCl was used in subsequent studies in order to
and since then his “Gif chemistry” has of their oxidation states [Fe
A
H
R
U
G
A
T
E
N
4
2
[
11]
Recently, Kim and co- 94%; FeCl : 87%; Fe(acac) : 40%]. Although the
3
ACHTREUNG
A
H
R
U
G
2
(ClO ) as cata-
4 3
3
[12]
groups. Herein we report an alternative oxidation avoid the presence of the potentially dangerous per-
protocol, which allows one to efficiently oxidize ben- chlorate ion. Compared to other solvents such as ace-
zylic compounds under mild and convenient reaction tonitrile, acetic acid and N-methylimidazole, which af-
condition. The following characteristics are impor- forded 2 in 73, 48, and 42% yield, respectively, pyri-
tant: 1) Iron
A
C
H
T
R
E
U
N
G
(III) chloride is used as inexpensive, non- dine proved superior. In summary, use of a 2 mol%
toxic catalyst in small quantities (2 mol%). 2) Neither of FeCl ·6H O and 3 equivs. of TBHP (applied as a
3
2
[
10,11]
[12]
an acid (as in the systems by Barton
and Kim
)
70% aqueous solution) in pyridine at 828C under air
nor a ligand needs to be added. Probably, the solvent led to the formation of ketone 2 in 91% yield [Eq.
[
13]
[16]
(
pyridine) serves as coordinating agent. 3) A cheap (1)].
and convenient to use solution of TBHP in water (in-
These optimized conditions were then applied for
stead of TBHP in hydrocarbons) can be applied as the oxidative conversion of other substrates. Most dia-
oxidant. 4) A slow addition of reagents (for example, rylmethylene derivatives gave the corresponding
Adv. Synth. Catal. 2007, 349, 861 – 864
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861

Masafumi Nakanishi and Carsten Bolm
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[
a]
Table 1. . Benzylic oxidation of hydrocarbon derivatives.
Table 1. (Continued)
Entry Substrate
Product
Yield
[b]
Entry
Substrate
Product
Yield
[b]
[%]
[
%]
[a]
Reaction conditions for a 2 mmol scale: FeCl ·6 H O (2
3
2
mol%), TBHP (70%) in H O (3 equivs.), pyridine, 828C,
2
2
4 h.
products in excellent yields (up to >99%; Table 1, en-
tries 1–6). Less activated educts having one annelated
aryl group in a cyclic system led to benzylic oxidation
products in yield ranging between 30 and 74% (en-
tries 7–14). Acyclic compounds bearing one (hetero)-
aryl group were oxidized in the benzylic position with
moderate yields (entries 15–19). By-products were not
detected. The surprising reactivity difference between
[b]
All products were identified by comparison of their ana-
lytical data with those of previous reports or commercial
materials.
[7,8,18,19]
[c]
[d]
[e]
The reaction temperature was 1108C.
TBHP (70%) in H O (6 equivs.) was used.
The reaction was performed at ambient temperature for
0 min.
2
1
862
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Adv. Synth. Catal. 2007, 349, 861 – 864

running title
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ethylbenzene (entry 18) and p-methoxyethylbenzene References
(
entry 19) is attributed to the presence of the elec-
[
1] M. Hudlicky, Oxidations in Organic Chemistry, ACS
Monograph No. 186, American Chemical Society,
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tron-donating substituent. By oxidation of p-methoxy-
toluene the corresponding carboxylic acid was ob-
tained in 53% yield (entry 20). Diphenylmethanol
gave benzophenone (86% yield, entry 21), and, inter-
estingly, 1,4-dihydroxynaphthalene underwent oxida-
tion to give binaphthoquinone in high yield (82%)
under mild conditions (entry 22). The latter transfor-
mation is particularly important and might prove
useful for the synthesis of vitamin K analogues. Un-
expectedly, the oxidation of triphenylmethane afford-
ed tert-butyl triphenylmethyl peroxide (in 91% yield)
instead of the corresponding alcohol (entry 23).
In summary, we developed a clean iron-catalyzed
benzylic oxidation with TBHP as oxidant leading to
the corresponding carbonyl compounds in moderate
to excellent yields. The simplicity and use of environ-
mentally benign reagents renders this system attrac-
tive for large-scale applications.
[
[
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[
5] For Ru-catalyzed oxidations, see: a) S. Murahashi, Y.
Oda, T. Naota, T. Kuwabara, Tetrahedron Lett. 1993,
Materials
3
1
4, 1299; b) M. D. Nikalje, A. Sudaldai, Tetrahedron
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Most starting materials were purchased from commercial
suppliers and used without further purification. TBHP
[
6] For Mn-catalyzed oxidations, see: a) G. Blay, I. Fernµn-
dez, T. Gimenez, J. R. Pedro, R. Ruiz, E. Pardo, F.
Lloret, M. Muoz, Chem. Commun. 2001, 2102; b) J. F.
Pan, K. M. Chen, J. Mol. Catal. A: Chem. 2001, 176,
(
70% in water) was obtained from Fluka. Tosyl-, acetyl- and
butoxycarbonyl-protected substrates were prepared by gen-
eral procedures. Chroman (Table 1, entry 9) was prepared
by the previously reported protocol.
used after drying over KOH.
[19]
Pyridine has been
1
3
9; c) N. H. Lee, C.-S. Lee, D. Jung, Tetrahedron 1998,
9, 1385.
[
[
[
7] For Bi-catalyzed oxidations, see: Y. Bonvin, E. Callens,
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9] For a general overview on iron catalyses in organic
chemistry, see: C. Bolm, J. Legros, J. Le Paih, L. Zani,
Chem. Rev. 2004, 104, 6217.
Representative Procedure for the Benzylic Oxidation:
Conversion of Diphenylmethane
Diphenylmethane (84.1 mg, 83.3 mL, 0.5 mmol) was added
to the solution of FeCl ·6H O (2.7 mg, 0.01 mmol) in pyri-
3
2
dine (0.5 mL). After the addition of TBHP (70% in H O;
2
206 mL, 1.5 mmol), the reaction mixture was heated at 828C
for 24 h. The mixture was then allowed to cool to room tem-
perature and poured into a 1 N solution of aqueous HCl
[
10] a) P. Stavropoulos, R. C¸ elenligil- C¸ etin, A. E. Tapper,
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Kiani, A. Tapper, D. Pinnapareddy, P. Paraskevopou-
lou, in: Handbook of C-H Transformations, (Ed.: G.
(
10 mL) in order to remove the pyridine. The organic phase
was extracted with Et O (40 mL), washed with brine and
2
dried (MgSO ). After filtration, the solvents of the filtrate
4
were evaporated (rotary evaporator). The remaining mix-
ture was separated by column chromatography (silica gel;
diethyl ether:pentane=1:20 as eluent) affording benzophe-
none; yield: 83 mg (91%).
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Acknowledgements
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1
We are grateful to the Fonds der Chemischen Industrie and to
the Deutsche Forschungsgemeinschaft (DFG) within the SPP
jakowska, R. Krzyminiewski, J. Pietrzak, Inorg. Chim.
Acta 1991, 186, 27; c) S. A. Cotton, V. Franckevicius, J.
Fawcett, Polyhedron 2002, 21, 2055.
1118 for continuous support of our research program.
Adv. Synth. Catal. 2007, 349, 861 – 864
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
863

Masafumi Nakanishi and Carsten Bolm
COMMUNICATIONS
[
[
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16] These results refer to reaction performed on a 2 mmol
scale. Using 5 mmol of 1 under identical reaction condi-
tions afforded ketone 1 in 94% yield. On that scale, a
slight exothermicity was detected upon addition of the
oxidant.
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864
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Adv. Synth. Catal. 2007, 349, 861 – 864