PNNP-Ligated RuII Complexes as Efficient Catalysts for Mild Benzylic C-H Oxidation

Full text of DOI:10.1002/cctc.201200590

CHEMCATCHEM
COMMUNICATIONS
DOI: 10.1002/cctc.201200590
PNNP-Ligated RuII Complexes as Efficient Catalysts for
Mild Benzylic CÀH Oxidation
Shih-Fan Hsu and Bernd Plietker*[a]
The selective transformation of a CÀH bond into a defined
functional group offers the chance to streamline organic syn-
theses by an overall reduction in the number of synthetic op-
erations. Amongst the various functional groups present in or-
ganic chemistry, the carbonyl group occupies an eminent posi-
tion as a result of the plethora of subsequent reaction possibil-
ities.[1] Hence, the direct transformation of, for example, a meth-
ylene group into a ketone is a desirable synthetic goal for
which a variety of methods have been reported within the
past years. Metal complexes based on Ru,[2] Fe,[3] Rh,[4] Bi,[5]
Mn,[6] Cr,[7] and Co[8] in conjunction with tert-butylhydroperox-
Scheme 1. Synthesis of PNNP ligand 4.
ide (TBHP) have shown moderate to good reactivities. Howev-
er, with regard to substrate scope and reactivity there is an on-
going interest in finding more potent, new catalysts that
enable this catalytic transformation to take place. Herein we
report a novel class of PNNP-ligated RuII–acetonitrile com-
plexes that allow the direct oxidation of benzylic CÀH groups
into the corresponding ketones in good yields at room tem-
perature (RT) with catalyst loadings as low as 1 mol%.
We envisioned a tetradentate ligand to be a suitable starting
point for the preparation of defined RuII complexes, as the
rigid complex structure might prevent fast catalyst decomposi-
tion through ligand dissociation and subsequent ligand or
metal oxidation.[9] Furthermore, we chose a mixed-valent N,P
ligand and believed this would serve as a good ligand scaffold
because the RuÀP bond might be able to stabilize the complex
to a greater extent than a RuÀN bond, as is the case in most
other defined oxidation catalysts. The ligand scaffold that was
chosen as a starting point and its synthesis are shown in
Scheme 1.
Ligand 4 was subsequently treated with RuCl2(dmso)4 in ace-
tonitrile under thermal conditions to give the corresponding
RuII(PNNP)(CH3CN)Cl2 complex. The outer-sphere coordinated
chloride was exchanged with a PF6 anion to improve the solu-
bility of the complex (Scheme 2).[10]
Having in hand pure complex 5-PF6, we subsequently set
out to investigate its catalytic activity in the direct oxidation of
benzylic CÀH bonds to the corresponding ketones (Table 1). In-
itial results indicated that this complex was highly active; the
desired product was obtained in moderate yield at a catalyst
Scheme 2. Synthesis and X-ray analysis of the [RuII(PNNP)(CH3CN)Cl]PF6 com-
plex. Selected bond lengths [ꢀ] and angles [8]: Ru1–N3 2.0175(16), Ru1–N2
2.2653(16), Ru1–N1 2.2962(16), Ru1–Cl1 2.3997(5), Ru1–P1 2.3102(5), Ru1–P2
2.3033(5), N2–C2–C3–N1 68.67(19), N3–Ru1–Cl1 179.24(5), N1–Ru1–N2
82.43(6), P1–Ru1–P2 100.955(19).
concentration of only 1 mol% at RT in benzene (Table 1, en-
[a] S.-F. Hsu, Prof. Dr. B. Plietker
Institut fꢀr Organische Chemie
Universitꢁt Stuttgart
Pfaffenwaldring 55, D-70569 Stuttgart (Germany)
Fax: (+49)711-685-64285
E-mail: bernd.pliekter@oc.uni-stuttgart.de
tries 1 and 2). The oxidant TBHP proved to be a good first
choice,[11] as no other oxidant gave comparable results (Table 1,
entries 3–6). A surprising result was the effect of the catalyst
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201200590.
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 126 – 129 126

CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
Table 1. Ru-catalyzed CÀH oxidation: Influence of the solvent and
Table 2. Ru-catalyzed CÀH oxidation: Scope and limitations.[a]
oxidant.[a]
Entry Substrate
Product
TBHP
Yield
[equiv.] [%][b]
1
3
3
96
93
Entry
Catalyst
[mol%]
Oxidant
[equiv.]
Solvent
Yield
[%][b]
2[c]
1
2
3
4
5
6
7
8
5-PF6 [5]
5-PF6 [1]
5-PF6 [1]
5-PF6 [1]
5-PF6 [1]
5-PF6 [1]
5-PF6 [1]
5-PF6 [1]
(Ph3P)3RuCl2 [1]
(dmso)4RuCl2 [1]
(H2O)3RuCl3 [1]
5-PF6 [1]
5-PF6 [1]
5-PF6 [1]
–
TBHP [3]
TBHP [3]
H2O2 [3]
NaOCl [3]
PhI=O [3]
O2
TBHP [6]
TBHP [8]
TBHP [6]
TBHP [6]
TBHP [6]
TBHP [6]
TBHP [6]
TBHP [6]
TBHP [6]
–
benzene
benzene
benzene
benzene
benzene
benzene
benzene
benzene
benzene
benzene
benzene
toluene
CH3CN
32
57
0
5
1
0
3
4
R=Ts
R=Boc
6
6
72
73
74 (72)[c]
76 (75)[c]
9
20
18
13
40
2
36
0
0
5
6
7
8
6
3
6
3
69
45
49
62
10
11
12[d]
13
14
15
16
CH2Cl2
benzene
benzene
5-PF6 [1]
[a] All reactions were performed with the substrate (0.5 mmol), oxidant,
and catalyst in solvent (2 mL). 4.8m TBHP in benzene was used. [b] Deter-
mined by GC integration. [c] Isolated yield. [d] Benzaldehyde was detect-
ed in the product mixture.
concentration on the formation of the product. An increase in
the concentration of the catalyst led to a significantly lower
isolated yield of the product (Table 1, entry 1 vs. 2). This finding
might be explained by assuming that the Ru-catalyzed decom-
position of the peroxide reagent is a highly competing back-
ground reaction. As a consequence, the yield of the product
increased as the amount of the reoxidant was increased, even
at a catalyst concentration of only 1 mol% (Table 1, entries 7
and 8).
9
3
65
10
6
6
6
63
30
58
11
A screening of the solvents indicated benzene to be the op-
timum choice (Table 1, entries 7 and 8). Relative to other Ru
sources, the novel [(PNNP)Ru(CH3CN)Cl]PF6 catalyst proved to
be superior. After some final optimizations, the standard proce-
dure for the direct benzylic CÀH oxidation involved the use of
a catalyst loading of 1 mol% at RT over 18 h by using benzene
as the solvent and TBHP as the stoichiometric reoxidant
(Scheme 3).
12[d]
13
14
15
R’=OMe
R’=CO2H
R’=CO2Me
6
6
6
57
35
31
[a] All reactions were performed with the substrate (0.5 mmol), TBHP
(4.8m in benzene), and catalyst (1 mol%) in benzene (0.25m) at RT for
18 h unless otherwise specified. [b] Isolated yield. [c] 6.0m TBHP in ben-
zene was used. [d] The reaction was performed at 1008C.
With the optimized conditions in hand, we turned our atten-
tion towards the scope and limitations of this process (Table 2).
The catalytic system proved to be applicable to the selective
oxidation of various aromatic alkanes. In general, diarylalkanes
were found to be more reactive than monoarylalkanes. If both
aryl substituents were part of a tricyclic substrate in which the
two aryl groups were coplanar, almost quantitative yields were
observed with the use of only 3 equivalents of TBHP (Table 2,
entries 1 and 2). Bicyclic arylalkanes were more reactive than
the corresponding acyclic arylalkanes; this indicates that the
aromatic substituent plays a pivotal role in controlling reactivi-
ty. Notably, a-tetralone underwent oxidation to give the dione
in moderate yield (Table 2, entry 7) without overoxidation to
Scheme 3. Ru-catalyzed benzylic CÀH oxidation.
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 126 – 129 127

CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
1,4-naphthoquinone.[12] Moreover,
a variety of functional
groups was tolerated under the reaction conditions. Ethers,
carboxylic acids, esters, carbamates, and even pyridine rings
were stable under the reaction conditions. Oxidation or hydrol-
ysis products were not observed.
Although the exact mechanism of the oxidation remains elu-
sive at the current stage of research, the following results indi-
cate a radical mechanism to be most likely (Scheme 4). In the
Figure 1. a) 31P NMR chemical shift of pure complex 5-PF6. b) 31P NMR chemi-
cal shift of complex 5-PF6 after the oxidation reaction (Table 1, entry 1).
tion mixture was filtered through a short column of silica gel and
washed with ethyl acetate to remove the excess amount of the
peroxide. The solvent of the filtrate was removed under reduced
pressure, and the crude reaction mixture was purified by flash
column chromatography on silica gel to give desired 4-chroma-
none 6b (53.2 mg, 72%).
Scheme 4. Ru-catalyzed benzylic CÀH oxidation.
oxidation of tetraisohydroquinoline derivatives 7a and 8a, cor-
responding peroxides 7b and 8b were isolated as the sole
products in moderate to good yields [Eq. (1), Scheme 4]. Appa-
rently, the decomposition of the peroxide is slow because of
stabilizing s*CÀO,nN interactions. In the oxidation of the tertiary
CÀH bond in 9a, corresponding triphenylmethylperoxide 9b
was isolated in moderate yield [Eq. (2), Scheme 4]. However,
these are preliminary results, and in-depth studies aimed to-
wards the understanding of the mechanistic details of these re-
actions are currently underway.
Synthesis of complex 5-PF6
To a solution of RuCl2(dmso)4 (300 mg, 0.62 mmol) in CH3CN
(62 mL) was added ligand 4 (488 mg, 0.62 mmol) under an atmos-
phere of N2 at RT. The mixture was degassed with N2 for 10 min
and heated at reflux for 3 h. The resulting yellow solution was fil-
tered through Celite and washed with CH3CN (3ꢂ20 mL). The sol-
vent of the filtrate was removed under reduced pressure, and the
crude reaction mixture was redissolved in a minimal amount of
methanol (ꢀ2–3 mL). To the resulting yellow solution was added
dropwise a solution of NH4PF6 (202 mg, 1.24 mmol) in water
(25 mL), and the mixture was stirred under an atmosphere of N2
for 12 h at RT. The resulting yellow suspension was filtered and
washed with water (3ꢂ20 mL). The yellow solid was redissolved in
CH2Cl2 (30 mL), and the solution was dried with Na2SO4, filtered,
and evaporated. The obtained crude product was purified by flash
column chromatography on silica gel (CH2Cl2/acetone=100:2) to
give a yellow solid that was then dried under high vacuum for 5 h
at 1208C. The resulting pale brown solid was redissolved in CH2Cl2
(30 mL), and the solvent was evaporated. The residue was dried
under high vacuum for 5 h at 1208C and redissolved in CH2Cl2
(30 mL). The solvent was once again evaporated, and the resulting
solid was dried under high vacuum for 1 h at RT to give desired
complex 5-PF6 (655 mg, 95%). To obtain crystals for X-ray diffrac-
tion analysis, the complex was crystallized from CH3CN and Et2O.
In this manuscript we report the synthesis, characterization,
and catalytic activity of a new class of defined, sterically crowd-
ed RuII complexes for the selective oxidation of benzylic CÀH
bonds. The complex was prepared from inexpensive starting
materials in a straightforward manner and was found to toler-
ate oxygen and water in the solid state. Hence, no special pre-
cautions in handling this catalyst are required. Moreover, de-
composition of the catalyst was not observed under the oxida-
tion conditions (Figure 1). A variety of arylalkanes was oxidized
into the corresponding ketones at low catalyst concentration
at RT. Further investigations to elucidate the mechanism and
to broaden the scope of the reaction are currently being per-
formed in our group.
Experimental Section
General procedure for Ru-catalyzed CÀH oxidation
Acknowledgements
To a flame-dried, 10-mL Schlenk tube under an atmosphere of N2
charged with 3,4-dihydro-2H-1-benzopyran (6a; 67.1 mg,
0.5 mmol) and complex 5-PF6 (5.6 mg, 0.005 mmol) in benzene
(2 mL) was added TBHP (4.8m in benzene; 625 mL, 3.0 mmol) in
one portion at RT, and the mixture was stirred for 18 h. The reac-
Financial support by the Deutscher Akademischer Austausch-
dienst (Ph.D. grant to S.-F.H.), the Deutsche Forschungsgemein-
schaft (SFB 706), and the Dr-Otto-Rçhm-Gedꢁchtnisstiftung is
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 126 – 129 128

CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
[7] a) A. Pearson, G. R. Han, J. Org. Chem. 1985, 50, 2791–2792; b) J.
Muzart, Tetrahedron Lett. 1986, 27, 3139–3142; c) R. Rathore, N. Saxena,
S. Chandrasekaran, Synth. Commun. 1986, 16, 1493–1498; d) J. Muzart,
Tetrahedron Lett. 1987, 28, 2131–2132; e) J. Muzart, A. N. A. Ajjou, J.
Mol. Catal. 1991, 66, 155–161; f) B. M. Choudary, A. D. Prasad, V. Bhuma,
V. Swapna, J. Org. Chem. 1992, 57, 5841–5844; g) T. K. Das, K. Chaud-
hari, E. Nandanan, A. J. Chandwadkar, A. Sudalai, T. Ravindranathan, S.
Sivasanker, Tetrahedron Lett. 1997, 38, 3631–3634; h) G. Rothenberg, H.
Wiener, Y. Sasson, J. Mol. Catal. A 1998, 136, 253–262.
gratefully acknowledged. We are also grateful to Dr. W. Frey (Uni-
versitꢁt Stuttgart, Institut fꢀr Organische Chemie) for X-ray struc-
ture analyses.
Keywords: CÀH activation
ligands · ruthenium
· oxidation · peroxides · N,P
[1] a) R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidation of Organic Com-
pounds, Academic Press, New York, 1981; b) Modern Oxidation Methods,
2nd ed. (Ed.: J.-E. Bꢃckvall), Wiley-VCH, Weinheim, 2010.
[2] a) S.-I. Murahashi, T. Naota, K. Yonemura, J. Am. Chem. Soc. 1988, 110,
8256–8258; b) S.-I. Murahashi, Y. Oda, T. Naota, T. Kuwabara, Tetrahe-
dron Lett. 1993, 34, 1299–1302; c) C. S. Yi, K.-H. Kwon, D. W. Lee, Org.
Lett. 2009, 11, 1567–1569.
[3] a) M. Nakanishi, C. Bolm, Adv. Synth. Catal. 2007, 349, 861–864; b) T.
Nagano, S. Kobayashi, Chem. Lett. 2008, 37, 1042–1043.
[4] a) A. J. Catino, J. M. Nichols, H. Choi, S. Gottipamula, M. P. Doyle, Org.
Lett. 2005, 7, 5167–5170; b) A. Wusiman, X. Tusun, C.-D. Lu, Eur. J. Org.
Chem. 2012, 3088–3092.
[8] a) P. Li, H. Alper, J. Mol. Catal. 1990, 61, 51–54; b) M. Jurado-Gonzalez,
A. C. Sullivan, J. R. H. Wilson, Tetrahedron Lett. 2003, 44, 4283–4286;
c) E. Modica, G. Bombieri, D. Colombo, N. Marchini, F. Ronchetti, A.
Scala, L. Toma, Eur. J. Org. Chem. 2003, 2964–2971.
[9] A. Mezzetti, Dalton Trans. 2010, 39, 7851–7869.
[10] CCDC 903901 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[11] a) K. B. Sharpless, T. R. Verhoeven, Aldrichimica Acta 1979, 12, 63–74;
b) J. G. Hill, B. E. Rossiter, K. B. Sharpless, J. Org. Chem. 1983, 48, 3607–
3608.
[12] Dione must be purified in time by flash column chromatography on
silica gel and stored in a freezer to avoid decomposition.
[5] Y. Bonvin, E. Callens, I. Larrosa, D. A. Henderson, J. Oldham, A. J. Burton,
A. G. M. Barret, Org. Lett. 2005, 7, 4549–4552.
[6] a) G. Blay, I. Fernꢄndez, T. Gimꢅnez, J. R. Pedro, R. Ruiz, E. Pardo, F.
Lloret, M. C. MuÇoz, Chem. Commun. 2001, 2102–2103; b) J.-F. Pan, K.
Chen, J. Mol. Catal. A 2001, 176, 19–22.
Received: August 30, 2012
Published online on November 30, 2012
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 126 – 129 129