Utilization of natural sunlight and air in the aerobic oxidation of benzyl halides

Article abstract of DOI:10.1021/ol2002013

Chemical equations presented. A novel, efficient oxidation of α-aryl halogen derivatives to the corresponding α-aryl carbonyl compounds at room temperature has been disclosed. Natural sunlight and air are successfully utilized in this approach through the combination of photocatalysis and organocatalysis. A plausible mechanism was proposed on the basis of the mechanistic studies.

Full text of DOI:10.1021/ol2002013

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2168–2171
Utilization of Natural Sunlight and Air in
the Aerobic Oxidation of Benzyl Halides
Yijin Su,† Liangren Zhang,† and Ning Jiao*,†,‡
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical
Sciences, Peking University, Xue Yuan Road 38, Beijing 100191, China, and State Key
Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai
200032, China
jiaoning@bjmu.edu.cn
Received January 22, 2011
ABSTRACT
A novel, efficient oxidation of R-aryl halogen derivatives to the corresponding r-aryl carbonyl compounds at room temperature has been
disclosed. Natural sunlight and air are successfully utilized in this approach through the combination of photocatalysis and organocatalysis.
A plausible mechanism was proposed on the basis of the mechanistic studies.
The utilization of natural solar energy,1 as well as
molecular oxygen as the ideal oxidant,2 are arguably two
of the most important scientific and technical challenges
due to their secure, clean, green, and sustainable charac-
ters. Although employing visible light absorbing photo-
catalysts such as Ru(II)polypyridine complexes in the
photochemical synthesis for those substrates which cannot
absorb visible light has recently attracted great attention,3ꢀ5
visible light absorbing photocatalysts inducing aerobic oxi-
dative transformation with sunlight excitation are still
limited and pose a challenging task.6,7 Recently, Zen and
co-workers6a made a significant contribution toward the
visible light photocatalytic oxidation of sulfides to sulfox-
ides employing Ru(bpy)32þ as a photoredox catalyst, while
the group of Ma and Zhao7 developed the visible light
induced aerobic oxidation of alcohols in a dye-sensitized
TiO2 and TEMPO system. On the other hand, MacMillan
and co-workers pioneered the merger of the photoredox
catalysis and their enamine catalysis on the enantioselective
R-alkylation and R-fluoroalkylation of aldehydes.4b,c With
the booming of organocatalysis in the past decades,8 it is
† Peking University.
‡ Chinese Academy of Sciences.
(1) (a) Ciamician, G. Science 1912, 36, 385. (b) Esser, P.; Pohlmann,
B.; Scharf, H.-D. Angew. Chem., Int. Ed. 1994, 33, 2009. (c) Funken,
€
K.-H.;Ortner, J. Z. Phys. Chem. 1999, 213, 99. (d) Oelgelmoller, M.; Jung,
C.; Mattay, J. Pure Appl. Chem. 2007, 79, 1939. (e) Fagnoni, M.; Dondi,
D.; Ravelli, D.; Albini, A. Chem. Rev. 2007, 107, 2725. (f) Hoffman, N.
Chem. Rev. 2008, 108, 1052. (g) Protti, S.; Fagnoni, M. 2009, 8, 1499.
(2) (a) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Chem. Rev. 2005,
105, 2329. (b) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400.
(3) For some reviews, see: (a) Gust, D.; Moore, T. A.; Moore, A. L.
Acc. Chem. Res. 1993, 26, 198. (b) Zeitler, K. Angew. Chem., Int. Ed.
2009, 48, 9785. (c) Yoon, T. P.; Ischay, M. A.; Du, J. Nature Chem. 2010,
2, 527. (d) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev.
2011, 40, 104.
(5) For some other examples for visible light induced aerobic oxida-
tion reactions using halide salts as initiator, see: (a) Hirashima, S.; Itoh,
A. Green Chem. 2007, 9, 318. (b) Tada, N.; Ban, K.; Hirashima, S.;
Miura, T.; Itoh, A. Org. Biomol. Chem. 2010, 8, 4701. (c) Kanai, N.;
Nakayama, H.; Tadaþ, N.; Iꢀtoh, A. Org. Lett. 2010, 12, 1948. For an
example using AcrPh ClO4 as a photocatalyst, see: (d) Ohkubo, K.;
Fukuzumi, S. Org. Lett. 2010, 12, 3647.
(6) (a) Zen, J.-M.; Liou, S.-L.; Kumar, A. S.; Hsia, M.-S. Angew.
Chem., Int. Ed. 2003, 42, 577. (b) Perez, D.; Grau, M. M.; Arends, I. W.
C. E.; Hollmann, F. Chem. Commum. 2009, 6848.
(7) Zhang, M.; Chen, C. C.; Ma, W. H.; Zhao, J. C. Angew. Chem.,
Int. Ed. 2008, 47, 9730.
(8) For some recent reviews on organocatalysis, see: (a) List, B.
Chem. Rev. 2007, 107, 5413. (b) Dondoni, A.; Massi, A. Angew. Chem.,
Int. Ed. 2008, 47, 4638.
(4) For some recent examples, see: (a) Okada, K.; Okamoto, K.;
Morita, N.; Okubo, K.; Oda, M. J. Am. Chem. Soc. 1991, 113, 9401. (b)
Nicewicz, D. A.; MacMillan, D. W. C. Science 2008, 322, 77. (c) Nagib,
D. A.; Scott, M. E.; MacMillan, D. W. C. J. Am. Chem. Soc. 2009, 131,
10875. (d) Ischay, M. A.; Anzovino, M. E.; Du, J.; Yoon, T. P. J. Am.
Chem. Soc. 2008, 130, 12886. (e) Chen, W.; Rein, F. N.; Rocha, R. C.
Angew. Chem., Int. Ed. 2009, 48, 9672. (f) DeClue, M. S.; Monnard,
P. A.; Bailey, J. A.; Maurer, S. E.; Collis, G. E.; Ziock, H. J.; Rasmussen,
S.; Boncella, J. M. J. Am. Chem. Soc. 2009, 131, 931. (g) Narayanam,
J. M. R.; Tucker, J. W.; Stephenson, C. R. J. J. Am. Chem. Soc. 2009,
131, 8756. (h) Du, J.; Yoon, T. P. J. Am. Chem. Soc. 2009, 131, 14604. (i)
ꢀ
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Condie, A. G.; Gonzalez-Gomez, J. C.; Stephenson, C. R. J. J. Am.
Chem. Soc. 2010, 132, 1464.
r
10.1021/ol2002013
Published on Web 03/29/2011
2011 American Chemical Society

evident that the combination of photocatalysis and orga-
nocatalysis can substantially broaden the field of visible
light photochemistry. We describe herein a Ru(bpy)32þ-and
pyridine-cocatalyzed utilization of natural sunlight and air
in the aerobic oxidation of benzyl halides, in which a radical
is generated by the cooperation of the photocatalyst and
organocatalyst (Figure 1). Although pyridine derivatives as
bases or zwitterions have been used in organic catalysis,9 as
far as we know, this is not only a cooperation of photo-
catalyst and organocatalyst but also a novel pyridine deri-
vative catalyzed radical reaction.
Table 1. Screening on Different Parameters.a
entry
base
cocatalyst (mol %)
solvent yieldb (%)
CH3CN
1
2
Li2CO3 none
0
Li2CO3 pyridine (20)
CH3CN 55
CH3CN 42
CH3CN 80
3
none
pyridine (120)
4
Li2CO3 4-methoxypyridine (20)
5
Li2CO3 4-methoxypyridine (20) DMA
82 (75)
6
Na2CO3 4-methoxypyridine (20)
Li2CO3 4-methoxypyridine (20)
Li2CO3 4-methoxypyridine (20)
CH3CN 35
7c
8d
CH3CN
0
CH3CN trace
a Reaction conditions: 1a (0.2 mmol), Ru(bpy)3Cl2 (0.001 mmol),
base (0.2 mmol), and cocatalystwere added in solvent(1 mL) under air at
25 °C. Irradiation time using a 24 W compact fluorescent bulb at 20 cm
was 24 h. b Determined by GC; the number in parentheses is the isolated
yield. c In the absence of Ru(bpy)3Cl2 . d The reaction was carried out in
the dark.
Figure 1. Combining photocatalysis and organocatalysis.
reaction was carried out in DMA (entry 5). Other solvents,
such as DCE or DMF, showed low efficiencies (see the
Supporting Information). In addition, the case employing
1.2 equiv of pyridine as base and catalyst gave low yield
(entry 3). Although the stronger base was in favor of
quenching the produced acid, when a different base such
as Na2CO3 was used, the yield was low (35%, entry 6). We
envisioned that 1a could decompose in the presence of a
relatively stronger base. It is noteworthy that both Ru-
(bpy)3Cl2 and visible light are essential for this aerobic
oxidation (entries 7 and 8, Table 1).
Recently, we developed a Cu-catalyzed aerobic oxi-
dative
amidationꢀdiketonization
of
terminal
alkynes,10a in which O2 was employed as a radical trap
to introduce oxygen into organic molecules. On the
basis of these results, our continued efforts in the
application of dioxygen in organic synthesis10
prompted us to explore the possibility of aerobic oxida-
tion of R-aryl halogen derivatives through a Ru(bpy)3-
Cl2-catalyzed single-electron-transfer process induced
by visible light at room temperature.
Importantly, when the aerobic oxidation was executed
under ambient sunlight (Figure 2), the reaction of 1a
proceeded very well giving 2a in 78% yield. Therefore,
the utilization of natural sunlight and air in this organic
transformation is a practical strategy.
Initially, Ru(bpy)3Cl2 (0.5 mol %)-catalyzed aerobic
oxidation of 1a was investigated in CH3CN under air with
visible light irradiation. However, no desired oxidation
product was determined (entry 1, Table 1). Gratifyingly,
55% yield was achieved when catalytic amounts of pyr-
idine (20mol %) wereusedinthistransformation (entry 2).
This condition, based on what we know, is an interesting
pyridine-catalyzed oxidation reaction of R-aryl halogen
derivatives using air as oxidant in homocatalysis.11
When 4-methoxypyridine was used instead of pyridine,
the yield of 2a increased to 80% (entry 4). The yield
increased slightly to 82% (isolated yield: 75%) when the
Figure 2. Utilization of natural sunlight and air.
(9) For some reviews, see: (a) Spivey, A. C.; Arseniyadis, S. Angew.
Chem., Int. Ed. 2004, 43, 5436. (b) Nair, V.; Menon, R. S.; Sreekanth,
A. R.; Abhilash, N.; Biju, A. T. Acc. Chem. Res. 2006, 39, 520.
(10) For some of our recent results using O2 as the oxidant, see: (a)
Zhang, C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 28. (b) Shi, Z.; Zhang,
C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed.
2009, 48, 4572. (c) Shi, Z.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int.
Ed. 2009, 48, 7895. (d) Shi, Z.; Zhang, B.; Cui, Y.; Jiao, N. Angew.
Chem., Int. Ed. 2010, 49, 4036. (e) Zhang, C.; Jiao, N. Angew. Chem., Int.
Ed. 2010, 49, 6174.
(11) (a) For the oxidation of benzyl halids using dioxygen as the
oxidant in heterocatalysis, see: Itoh, A.; Kodama, T.; Inagaki, S.;
Masaki, Y. Org. Lett. 2000, 2, 2455. (b) For examples using other
oxidants, see: Li, C.; Zheng, P.; Li, J; Zhang, H.; Cui, Y.; Shao, Q.; Ji, X.;
Zhang, J.; Zhao, P.; Xu, Y. Angew. Chem., Int. Ed. 2003, 42, 5063.
With the optimal reaction conditions in hand, we then
probed the reaction scope using various benzyl halides
(Table 2). These reactions of R-haloarylacetic acid esters
proceeded smoothly producing the corresponding pro-
ducts in good yields (entries 1ꢀ6, Table 2). Both chloride
and bromide as a leaving group are tolerated in this
transformation. Additionally, the selectivity for the oxida-
tive dehalogenation is very high with the retention of the
chloro atom on the aryl ring (entry 4). Besides the
Org. Lett., Vol. 13, No. 9, 2011
2169

electronic property of the substitution at the aryl ring, the
expansion of R-aryl carbonyl compoundsformation chem-
istry to 2-halo-1, 2-diarylethanones provided moderate to
good yields (entries 7ꢀ11). Although the oxidation of
benzhydryl halides was not effective under these optimized
conditions, the desired products, benzophenone (2j),
9-fluorenone (2k), and 4,40-difluorobenzophenone (2l),
were obtained in 40%, 56%, and 39% yield, respectively,
when 2.5 equiv of pyridine was employed in the presence of
Cs2CO3 (entries 12ꢀ14). However, the reaction of 1o did
not generate the desired product 2m (entry 15, Table 2),
which is consistent with the previous study on this kind of
benzyl radical.12
Table 2. Synthesis of R-Aryl Carbonyl Compounds 2 from 1a
The pyridinium salt 3a was isolated (82%) from the
reaction of 1a with 2.5 equiv of pyridine in the absence of
the Ru(bpy)3Cl2 catalyst without the observation of 2a
(eq 1). Interestingly, 3a could undergo the oxidation
smoothly to form the desired product 2a in 70% yield
under these conditions (eq 2), which indicates that the
pyridinium salts could be the key intermediates during this
catalytic cycle. In addition, 2a was not observed in the
similar reaction of 3a in the absence of the photocatalyst
Ru(bpy)3Cl2 (eq 3). Hence, the cooperation of the catalysts
(Ru(bpy)3Cl2 and pyridine) is essential for this aerobic
oxidation.
a Reaction conditions: see entry 5 in Table 1. b Isolated yield.
c 4-Methoxypyridine (0.08 mmol) was used. d The irradiation time is
48 h. e Na2CO3 was used instead of Li2CO3. f 2.5 equiv of pyridine was
used. g Cs2CO3 was used instead of Li2CO3.
þ
the formation of the benzyl radical, either Ru(bpy)3 or
Ru(bpy)32þ* was needed to act as a reductant in our
catalytic system. Since a decrease in Ru(bpy)32þ* lumines-
cence was not observed in the presence of R-bromopheny-
lacetic acid ethyl ester or its pyridinium salt (see the
Supporting Information), the possibility that Ru(bpy)3þ is
participating as a reductant to form the benzyl radical was
supported. The Ru(bpy)32þ* excited state should behave as
an oxidant to close the photoredox catalytic cycle.
Although it has been known that the oxidative quench-
ing of Ru(bpy)32þ* to Ru(bpy)33þ by O2 can generate the
superoxide radical (O2ꢀ),13 the reactions in the absence of
pyridine did not work (entry 1, Table 1), even when 1.0
equiv of Ru(bpy)3Cl2 was employed (eq 4). On the con-
trary, the oxidation of R-aryl halogen derivatives employ-
ing KO2 as the oxidant in the similar conditions produced
Significantly, when the reaction of 3a in the absence Ru
catalyst under O2 was recorded by EPR (monitored with
the addition of the radical trap 5-,5-dimethyl-1-pyrroline
the desired product 2a in 65% yield (eq 5). Therefore,
2þ*
although the excited state Ru(bpy)3
can be easily
oxidized (Ru(bpy)33þ) or reduced (Ru(bpy)3þ),3b,13c thþe
photoredox catalysis between Ru(bpy)32þ*and Ru(bpy)3
is preferred in this novel transformation.
To further understand this transformation, some lumi-
nescence quenching experiments were conducted.4b,14 For
Figure 3. EPR studies: electroparamagnetic resonance (EPR)
spectra (X band, 9.7 GHz, rt). Sample a: reaction mixture
without Ru(bpy)3Cl2 in the presence of the radical trap DMPO
(2.5 ꢁ 10ꢀ2 M). Sample b: reaction of sample (a) with the
addition of Ru(bpy)3Cl2 catalyst in the presence of the radical
trap DMPO (2.5 ꢁ 10ꢀ2 M).
(12) Bejan, E. V.; Font-Sanchis, E.; Scaiano, J. C. Org. Lett. 2001, 3,
4059.
(13) (a) Kotkar, D; Joshi, V.; Ghosh, P. K. Chem. Commun. 1987, 4.
(b) Das, A.; Joshi, V.; Kotkar, D.; Pathak, V. S.; swayambunathan, V.;
Kamat, P. V.; Ghosh, P. K. J. Phys. Chem. A 2001, 105, 6945. (c) Ceroni,
P.; Bergamini, G.; Balzani, V. Angew. Chem., Int. Ed. 2009, 48, 8516.
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2170
Org. Lett., Vol. 13, No. 9, 2011

N-oxide (DMPO)), several signals of aradicalintermediate
can be obviously observed (sample a, Figure 3). However,
these reactions without the addition of Ru catalyst did not
afford the expected product (see eq 3 and eq S6
(Supporting Information)). In contrast, no signals were
detected in the absence of O2 (see Figure S5, Supporting
Information). It is noteworthy that with the addition of
Ru(bpy)3Cl2 into the above reaction mixture, the signals of
the radical intermediate disappeared completely (sample b,
Figure 3). Although the structure of the radical intermedi-
ate detected by EPR is difficult to identify, we believe that
this phenomenon maybe arise from a redox reaction
between the formed radical intermediate in situ and the
Ru catalyst 9 leading to the initial generation of Ru(I)
species 7 (Scheme 1).
4-methoxypyridine were then provided via the homolysis
of the CꢀN bond of 4.17 The aerobic oxidation of benzyl
radicals in the presence of O2 was widely reported.18 In this
case, 2a is efficiently produced from 5 with the formation
of the superoxide radical anions18b via the alkoxyl radical
intermediates 6 (Scheme S1, Supporting Information).18d
Because of the formation of acid, inorganic base is required
to protect 4-methoxypyridine from generating the corre-
sponding pyridinium salt. In the photoredox catalytic cycle,
[Ru(bpy)3]2þ (8) could readily accept a photon from visible
light to populate the excited state [Ru(bpy)3]2þ* (9) via
metal-to-ligand charge transfer (MLCT). Subsequently, the
O2ꢀ radicals, which could be oxidized,19 donate a electron to
the [Ru(bpy)3]2þ* excited state (9) to regenerate the active
reductant [Ru(bpy)3]þ (7) to close this catalytic cycle. In
addition, a decrease of the Ru(bpy)32þ* emission intensity at
low concentration of KO2 was observed (see the Supporting
Information, Figure S4), which supports the proposed path-
way that the generated O2ꢀ radicals in the right circle could
be as a reductant in the left circle to reduce 9 into 7.
Scheme 1. Proposed Mechanism for the Transformation
Two 18O labeling experiments were carried out (eq 6 and
7, determinedby HRMS; see the Supporting Information).
It was found that the oxygen of the new formed carbonyl
group was wholly from molecular oxygen rather than from
H2O. These results support that benzyl radical intermedi-
ate is involved in this transformation.
In summary, we have disclosed a novel, efficient oxidation
of R-aryl halogen derivatives to the corresponding R-aryl
carbonyl compounds at room temperature. Natural sunlight
and air are successfully utilized in this approach through the
combination of photocatalysis and organocatalysis. To the
best of our knowledge, this is not only a cooperation of
photocatalyst and organocatalyst but also a novel pyridine
derivative catalyzed radical reaction. For a clearer under-
standing of the reaction mechanism and the synthetic appli-
cations, further studies are ongoing in our laboratory.
On the basis of the above results, the catalytic cycle of
this transformation was proposed in Scheme 1. As we have
mentioned, 4-methoxypyridine can react with 1a to afford
the corresponding pyridinium salt 3b.15 A radical inter-
mediate generated under O2 from sacrificial 3b is consid-
ered to serve as the reductive quencher to reduce the
catalyst 9 into Ru(I) species 7 in the initial step of this
transformation (Scheme 1). The other formed 3b could
accept a single electron from Ru(I) species 7 to form the
dihydropyridyl radical 4.16 The benzyl radical 5 and
(15) For reviews on pyridinium salts, see: (a) Lavilla, R. Curr. Org.
Chem. 2004, 8, 715. (b) Damiano, T.; Morton, D.; Nelson, A. Org.
Biomol. Chem. 2007, 5, 2735.
Acknowledgment. Financial support from Peking Uni-
versity, National Science Foundation of China (Nos.
20702002, 20872003), and 973 Program (Grant No.
2009CB825300) are greatly appreciated. We thank Prof.
Zhang-Jie Shi’s (Peking University) and Prof. Li-Zhu
Wu’s (Technical Institute of Physics and Chemistry, Chi-
nese Academy of Sciences) laboratories for instrument
support. We also thank Wei Jia and Chong Qin in this
groupforreproducingtheresultsofentries1and8,Table1,
and entries 4 and 7, Table 2.
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Zgierski, M. Z.; Lusztyk, J. J. Am. Chem. Soc. 1995, 117, 2711. (b)
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Supporting Information Available. Experimental de-
tails and NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 9, 2011
2171