Metal-Free, Visible-Light-Induced Selective C?C Bond Cleavage of Cycloalkanones with Molecular Oxygen

Article abstract of DOI:10.1002/chem.202001032

A metal-free, visible-light-induced oxidative C?C bond cleavage of cycloketones with molecular oxygen is described. Cooperative Br?nsted-acid catalysis and photocatalysis enabled selective C?C bond cleavage of cycloketones to generate an array of γ-, δ- and ?-keto esters under very mild conditions. Mechanistic studies indicate that singlet molecular oxygen (¹O₂) is responsible for this transformation.

Full text of DOI:10.1002/chem.202001032

Accepted Article
Accepted Article
Title: Metal-free, Visible Light-induced Selective C-C Bond Cleavage of
Cycloalkanones with Molecular Oxygen
Authors: Li-Na Guo, Hong Xin, Xin-Hua Duan, and Le Liu
This manuscript has been accepted after peer review and appears as an
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To be cited as: Chem. Eur. J. 10.1002/chem.202001032
Link to VoR: https://doi.org/10.1002/chem.202001032
01/2020

10.1002/chem.202001032
Chemistry - A European Journal
RESEARCH ARTICLE
Metal-free, Visible Light-induced Selective C-C Bond Cleavage of
Cycloalkanones with Molecular Oxygen
Hong Xin,[a] Xin-Hua Duan[a,b] Le Liu,[a] and Li-Na Guo*[a]
Dedicated to Professor Rof Huisgen on the occasion of his 100th birthday
[a]
[b]
H. Xin, Prof. Dr. X.-H. Duan, Dr. L. Liu, Prof. Dr. L.-N. Guo
Department of Chemistry, School of Science,
Xi'an Key Laboratory of Sustainable Energy Material Chemistry, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed
Matter,
Xi’an Jiaotong University, Xi’an 710049, China
E-mail: guoln81@xjtu.edu.cn
Prof. Dr. X.-H. Duan
State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000, P. R. China.
Supporting information for this article is given via a link at the end of the document.
Abstract: A metal-free, visible light-induced oxidative C-C bond
cleavage of cycloketones with molecular oxygen is described.
Cooperative Brønsted-acid catalysis and photocatalysis enabled
selectively C-C bond cleavage of cycloketones to generate an array
of γ-, δ- and ε-keto esters under very mild conditions. The
mechanistic studies indicate that singlet molecular oxygen (1O2) is
responsible for this transformation.
C−C bond cleavage in cycloalkanones remains highly
demanding and desirable.
Oxidation of cycloalkanones belongs to an important reaction
in organic synthesis and industrial applications, which could
provide a straightforward access to the dicarboxylic esters and
the keto esters via C(CO)−C bond cleavage.[7] Among them, the
molecular oxygen (O2) is undoubtedly the ideal oxidant, owing to
its abundant, natural, and environmental friendly merits.[8]
However, molecular oxygen (O2) is sometimes limited by its
reaction efficiency. As we know, singlet molecular oxygen (1O2)
Introduction
is
a more reactive oxygen species, which is probably
In recent years, selectively catalytic C(sp3)−C(sp3) bond
activation has emerged as an attractive and alternative strategy
for new chemical bonds formations.[1] For instance, the C−C
bond cleavage of cycloalkanones has been developed to
construct new C−C and C−heteroatom bonds.[2] However, due to
the inherent lack of ring strain tension, the unstrained C−C bond
cleavage is relatively challenging. Taking advantage of some
unique synergistic catalytic activity of transition metals and
ligands, the group of Jun and Dong disclosed several elegant
responsible for most of the oxidation reactions. To activate the
molecular oxygen, photocatalytic energy transfer was
recognized as an attractive and sustainable method.[9] As a part
of our interest in C−C bond cleavage,[10] we set out to explore
the oxidation of unstrained cycloalkanones with O2 by means of
visible-light driven photocatalysis. Herein, we report a metal-free,
visible-light induced selective C−C bond cleavage of
cycloalkanones with O2, which offers an environmental friendly
and sustainable approach to the keto esters. For this reaction,
the low-cost and easily available Rosolic acid was utilized as the
photosensitizer.
transition
metal-catalyzed
C−C
bond
activation
of
cycloalkanones through the formation of ketamine intermediates
to afford linear ketones or ring-expanded ketones, respectively.[3]
On the other hand, radical strategy has also displayed vast
potential in this area. For example, through modification Results and Discussion
cycloalkanones to the tertiary alcohols, the alkoxyl radical-
triggered C−C bond cleavage has been extensively investigated
to obtain versatile functionalized linear carbonyl compounds.[4]
Very recently, Zuo and co-workers reported an intriguing
example of C−C bond cleavage of ketones.[5] Therein the
Initially, we examined the reaction of 2-phenylcyclohexan-1-one
1a in the presence of 1 mol% of fac-Ir(ppy)3 as the photocatalyst,
8 mol% of AlCl3 as the co-catalyst in EtOH at room temperature
under irradiation of blue LEDs (10 W). To our delight, the
desired ε-keto ester 3a was obtained in 60% yield (Table 1,
entry 1). The screening of photocatalysts revealed that using
Mes-Acr-Me+ClO4 － instead of the expensive fac-Ir(ppy)3 also
furnished a comparable yield (Table 1, entries 2-6). Thus, we
evaluated the co-catalysts using Mes-Acr-Me+ ClO4 － as the
photocatalyst. Other Lewis acids such as VO(OEt)Cl2, FeCl3,
TiCl4 and Brønsted acid H2SO4 were also effective (Table 1,
entries 7-10). Among them, H2SO4 gave a slight higher yield
than AlCl3. The photocatalyst loading was also adjusted.
However, increasing the photocatalyst loading to 2 mol% or 5
mol% didn’t further improve the reaction efficiency (Table 1,
ketones underwent
a sequential nucleophilic addition and
alkoxyl radical-mediated C–C bond scission via combined
Lewis-acid catalysis with LMCT catalysis, offering a potential
opportunity for diverse transformations of the cleaved C–C bond.
Although direct photolysis of ketones was discovered more than
80 years ago, however, the further applications remains
undeveloped due to its harsh reaction conditions (high-energy
UV light) and complex conversions.[6] Given that cycloalkanones
are commonly occurring functionalities in organic synthons,
pharmaceuticals and natural products, the catalytic, selective
1
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10.1002/chem.202001032
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RESEARCH ARTICLE
entries 3 and 10). Interestingly, it was found that using 8 mol%
of low-cost Rosolic acid as the photocatalyst and 8 mol% of
H2SO4 as the co-catalyst raised the yield of 3a up to 76 %. As
we know, the Rosolic acid was commonly used as an acid-base
indicator, which was rarely applied as a photosensitizer in the
photocatalyzed reaction.[11] Remarkably, the reaction also
performed well under air atmosphere to give the product 3a in
67% yield (Table 1, entry 12). Finally, control experiments
revealed that visible light, photocatalyst and co-catalyst were all
essential for the success of this reaction (Table 1, entries 13-15).
It is worth mentioning that when we performed the reaction
under Matsumoto’s condition,[7d] only 51% yield of 3a was
obtained (for details, see supporting information).
desired products 4k and 4l in 50% and 40% yields, respectively.
It was found that the sterically hindered tertiary alcohols gave
poor yields of the esters (4m and 4n), which was attributed to
the formation of by-product 4q and the incomplete conversion of
1a. Furthermore, the phenols were also applicable, delivering
the phenolic esters 4o and 4p, albeit with somewhat low yields.
However, thiols and thiophenols failed to give the expected
Scheme 1. The Scope of alcohols.[a]
Table 1. Optimization of the reaction conditions.[a]
Entry
1
Photocatalyst
fac-Ir(ppy)3 (1 mol%)
Co-catalyst
AlCl3
Yield (%)
60
2
[Ru(bpy)3](PF6)2 (1 mol%)
Mes-Acr-Me+ClO4－ (1 mol%)
Methylene Blue (1 mol%)
Eosin Y (1 mol%)
AlCl3
49
3
AlCl3
57 (56)[b]
4
AlCl3
30
5
AlCl3
52
6
Rosolic Acid (1 mol%)
Mes-Acr-Me+ClO4－ (1 mol%)
Mes-Acr-Me+ClO4－ (1 mol%)
Mes-Acr-Me+ClO4－ (1 mol%)
Mes-Acr-Me+ClO4－ (1 mol%)
Rosolic Acid (8 mol%)
Rosolic Acid (8 mol%)
-
AlCl3
28
7
VO(OEt)Cl2
FeCl3
39
8
24
23
9
TiCl4
10
11
12[d]
13
14
15[e]
H2SO4
AlCl3 or H2SO4
H2SO4
H2SO4
-
62 (48) [b]
72, 76 (78)[c]
67
n.r.
Rosolic Acid (8 mol%)
Rosolic Acid (8 mol%)
n.r.
H2SO4
n.r.
[a] Reaction conditions: 1a (0.2 mmol, 1.0 equiv), photocatalyst (1 mol%), co-
catalyst (8 mol%), EtOH (2.0 mL), Blue LEDs(10 W), r.t., for 24 h, under O2.
Yields of isolated product were given. [b] 5 mol% photocatalyst. [c] Using 2.0
equiv of EtOH as nucleophiles in toluene (2.0 mL). [d] Under air atmosphere.
[e] In the dark.
With the optimal conditions in hand, the scope of alcohols 2
was evaluated with 1a. Satisfactorily, a range of structurally
diverse alcohols engaged in this reaction smoothly to give the
corresponding ε-keto esters 3 and 4. A variety of primary
alcohols delivered the ε-keto esters 3a-3x with yields ranging
from 24 to 95%. Functional groups such as unsaturated C-C
bonds (3n-3q), ethers (3r-3u) and halogens (3w and 3x)
survived well in this reaction. Both acyclic and cyclic secondary
alcohols gave the desired products 4a-4j in moderate yields.
The cholesterol and menthol were also amenable, providing the
[a] Reaction conditions: 1a (0.2 mmol, 1.0 equiv), 2 (0.4 mmol, 2.0 equiv), 8
mol% of Rosolic Acid, 8 mol% of H2SO4, toluene (2.0 mL), Blue LEDs (10 W),
r.t., for 24 h, under O2. Yields of isolated product were given. [b] Alcohols were
used as nucleophiles and solvents. [c] Yields of the 6-oxo-6-phenylhexanoic
acid 4q were given in parenthesis.
2
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10.1002/chem.202001032
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RESEARCH ARTICLE
products due to the formation of disulphides under the standard
conditions.[11c] In addition, using benzylamine as the nucleophile
also could not give the corresponding amide, along with the
formation of benzaldehyde[14]. However, other alkyl amines such
as n-amylamine and piperidine were used as substrates, none of
them gave the desired products under the standard conditions,
along with 83% and 89% of 1a were recovered, respectively (not
shown). Finally, it is worth mentioning that the 6-oxo-6-
phenylhexanoic acid (4q) was isolated as the major by-product
sometimes (3v, 4m and 4n). Surprisingly, using 2.0 equiv of
water instead of alcohol furnished only 13% yield of 4q with 83%
of 1a recovered. Notably, the esterification reaction of the 6-oxo-
6-phenylvaleric acid (4q) and phenylethyl alcohol also worked
under the standard conditions, giving the ester 3k in 60%
isolated yield (for details, see SI).
cyclohexanone reacted smoothly to give the product 5m in 45%
yield. When the menthone was used, relatively lower 33% yield
of the target 5n was isolated due to low conversion.
Unfortunately, the unsubstituted cyclohexanone only resulted in
trace amount of the anticipated product, which instead provided
25% yield of the ketal 5o’. We speculated that the existence of
substituent on the α position is probably beneficial to enhance
the stability of intermediates in this reaction. However, the steric
hindrance of the α-substituent could also be an unfavourable
factor, because it might prevent or slow down the formation of
the hemiacetal. 2-Tetralone participated in this reaction to give
the desired product 5p in 43% yield, along with 16% yield of the
diester 5p’ as by-product. In addition, cycloalkanones with
different ring sizes were also investigated. 2-Substituted
cyclopentanones underwent this reaction to afford the δ-keto
esters 5q-5s in 47-60% yields. The more strained 2-
phenylcyclobutan-1-one also worked, producing the γ-keto ester
5t in 54% yield. A comparison of the yield of 3j (90%), 5q (60%)
and 5t (54%) showed that there is not a positive correlation
between the yields and the strain force, implying that the ring
strain was not a crucial factor in this C-C bond cleavage reaction.
Furthermore, the acetophenone was also subjected to the
reaction system. However, no reaction occurred (not shown).
Scheme 2. The Scope of cycloalkanones.[a]
Scheme 3. Control experiments
To shed light on the mechanism of this reaction, a series of
experiments were performed carefully. When 2.0 equiv of
TEMPO, well-known radical scavenger, was subjected into the
reaction of 1a with ethanol, no product 3a was observed.
Meanwhile, 15% yield of the TEMPO-adduct 6a was isolated
and 78% of 1a was recovered. These results suggests that a
radical process might be involved in this reaction (Scheme 3,
Eq.1).[12] Additionally, using meso-tetraphenylporphyrin (TPP)
instead of Rosolic Acid, which was reported to be a singlet
oxygen generator[9][13] also led to the product 3a in 73% yield
(Scheme 3, Eq.2). Furthermore, the 1O2 generated from the
[a] Reaction conditions: 1 (0.2 mmol, 1.0 equiv), 2j (0.4 mmol, 2.0 equiv), 8
mol% of Rosolic Acid, 8 mol% of H2SO4, toluene (2.0 mL), Blue LEDs (10
W), r.t., for 24 h, under O2. Yields of isolated product were given. [b] 5.0
equiv of BnOH was used.
Subsequently, we examined the scope of this visible light-
induced oxidative C-C bond cleavage with various
cycloalkanones. A wide range of 2-aryl cyclohexanones reacted
regioselectively to afford the ε-keto esters 5a-5l in moderate to
good yields, except for 2-(2-methoxyphenyl) cyclohexanone (5f).
2-(2,6-Dimethylphenyl)cyclohexan-1-one also failed to give the
target product, probably due to the large steric effect. Not only 2-
aryl cyclohexanones but also 2-alkyl substituted cyclohexanones
were compatible under the standard conditions. The 2-methyl
catalytic
system
was
evidenced
by
using
1,3-
diphenylisobenzofuran (DPBF) as a trapping reagent (for details,
see SI). This result is consistent with the performance of the
reaction with TPP. Furthermore, the reaction could completely
shut down in the absence of oxygen or photocatalyst as well as
without irradiation (Table 1, entries 13-15). These results implied
that 1O2 was the reactive oxygen species in this oxidative C-C
3
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10.1002/chem.202001032
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RESEARCH ARTICLE
bond cleavage reaction. Moreover, the results of light on-off
experiments and relative low quantum yield ( = 0.12) indicated
that the reaction proceeded through a catalytic process rather
than a radical chain process (for details, see SI). Finally, to verify
the reaction intermediates the enol ester 7a and peroxy alcohol
8a were synthesized respectively. Both of them gave the desired
products under the standard reaction conditions (Scheme 3, Eq.
3 and Eq. 4), implying that they are the possible intermediates in
this reaction.
Acknowledgements
Financial support from the National Natural Science Foundation
of China (21971201), Natural Science Basic Research Plan in
Shaanxi Province of China (No. 2019JM-299), Key Laboratory
Construction Program of Xi'an Municipal Bureau of Science and
Technology (No. 201805056ZD7CG40) is greatly appreciated.
We also thank Mr Chang and Miss Lu at Instrument Analysis
Center of Xi’an Jiaotong University for their assistance with NMR
and HRMS analysis.
Scheme 4. Proposed two mechanistic pathways
Keywords: visible-light catalysis • metal-free • C-C bond
cleavage • singlet molecular oxygen • cycloalkanone
[1]
For selected reviews, see: a) P. Sivaguru, Z.-K. Wang, G. Zanoni, X.-H.
Bi, Chem. Soc. Rev. 2019, 48, 2615-2656. b) S. P. Morcillo, Angew.
Chem. 2019, 131, 14182-14192; Angew. Chem., Int. Ed. 2019, 58, 2-13.
c) X.-X. Wu, C. Zhu, Chin. J. Chem. 2019, 37, 171. d) F.-J. Song, T.
Gou, B.-Q. Wang, Z.-J. Shi, Chem. Soc. Rev. 2018, 47, 7078-7115. e)
F. Song, T. Gou, B.-Q. Wang, Z.-J. Shi, Chem. Soc. Rev. 2018, 47,
7078-7115. f) D.-S. Kim, W.-J. Park, C.-H. Jun, Chem. Rev. 2017, 117,
8977-8901. g) L. Souillart, N. Cramer, Chem. Rev. 2015, 115, 9410-
9464. h) A. Dermenci, J. W. Coe, G.-B. Dong, Org. Chem. Front. 2014,
1, 567-581. i) H. Liu, M.-H. Feng, X.-F. Jiang, Chem. Asian J. 2014, 9,
3360-3389. j) E. Leemans, M. D’hooghe, N. D. Kimpe, Chem. Rev.
2011, 111, 3268-3333. For select examples, see: k) J. B. Roque, Y.
Kuroda, L. T. Göttemann, R. Sarpong, Science 2018, 361, 171-174. l) J.
B. Roque, Y. Kuroda, L. T. Göttemann, R. Sarpong, Nature 2018, 564,
244-248. m) A.-H. Hu, Y.-L. Chen, J.-J. Guo, N. Yu, Q. An, Z.-W. Zuo, J.
Am. Chem. Soc. 2018, 140, 13580-13585.
On the basis of these results mentioned above and
literature,[2b, 9e-g] two possible reaction pathways were proposed
in Scheme 4. In pathway a: hemiketalization of ketone 1 in the
presence of sulfuric acid and alcohol delivers intermediate A,
which further undergoes dehydration to afford vinyl ether B.
Meanwhile, the visible light irradiation to RA gives rise to excited
3
RA* species, which activates O2 to provide the active singlet
[2]
a) P. Ghosh. ACS Omega 2019, 4, 8065-8070. b) A. S.-K. Tsang, A.
Kapat, F. Schoenebeck, J. Am. Chem. Soc. 2016, 138, 518-526. c) C.
R. Pitts, M. S. Bloom, D. D. Bume, Q. A. Zhang, T. Lectka, Chem. Sci.
2015, 6, 5225-5229. d) H. M. Ko, G.-B. Dong, Nat. Chem. 2014, 6, 739-
744. e) S. Hara, S.-Q. Chen, T. Hatakeyama, T. Fukuhara, Tetrahedro
Lett. 1995, 36, 6511-6514. f) T. Hirao, T. Fujii, T. Tanaka, Y. Ohshiro,
Synlett. 1994, 845-856. g) T. Hirao, T. Fujii, S. Miyata, Y. Ohshiro, J.
Org. Chem. 1991, 56, 2264-2266.
1O2 through an energy transfer process. Subsequently, the
reaction of singlet 1O2 with vinyl ether B leads to the formation of
dioxetane intermediate C. Finally, the fragmentation of the C−C
bond and O−O bond of dioxetane C produces the target keto
esters 3-5. Another plausible mechanistic pathway was
showcased in pathway b: enolization of 1 forms the enol D,
1
which reacts with singlet O2 to give the hydroperoxide E. Then,
[3]
[4]
a) Y. Xu, X.-T. Qi, P.-F. Zheng, C. Berti, P. Liu, G.-B. Dong, Nature
2019, 567, 373-378. b) Y. Xia, S. Ochi, G.-B. Dong, J. Am. Chem. Soc.
2019, 141, 13038-13042. c) Y. Xia, J.-C. Wang, G.-B. Dong, J. Am.
Chem. Soc. 2018, 140, 5347-5351. d) Y. Xia, G. Lu, P. Liu, G.-B. Dong,
Nature 2016, 539, 546-550. e) C.-H. Jun, H. Lee, S.-G. Lim, J. Am.
Chem. Soc. 2001, 123, 751-752.
peroxide E undergoes homolytic O−O bond scission, followed by
C−C bond fragmentation to afford the acetyl radical intermediate
G. The radical G rapidly converts to the keto esters 3-5 or acid
4q via an oxidation/nucleophilic attack cascade. Based on the
fact that poor yield of the 4q was obtained when water was
employed as the nucleophile and the results of 7a and 8a, we
speculated that the reaction is probably in favor of the pathway a
in the presence of alcohols.
For select reviews, see: a) X.-X. Wu, C. Zhu, Chem. Commun. 2019, 55,
9747-9756. b) X.-X. Wu, C. Zhu, Chem. Rec. 2018, 18, 587-589. c)
Murakami, M. Chem. Lett. 2017, 46, 1692-1700. d) J.-J. Guo, A. Hu, Z.-
W. Zuo, Tetrahedron Lett. 2018, 59, 2103-2111. e) J. Hartung, T.
Gottwald, K. Špehar, Synthesis 2002, 1469-1498. For select examples,
see: f) L. Huang, T.-F. Ji, M. Rueping, J. Am. Chem. Soc. DOI:
1021/jacs.9b12490. g) E. Ota, H.- J. Wang, N. L. Frye, R. R. Knowles, J.
Am. Chem. Soc. 2019, 141, 1457-1462. h) D.-P. Wang, J.-C. Mao, C.
Zhu, Chem. Sci. 2018, 9, 5805-5809. i) A.-H. Hu, Y.-L. Chen, J.-J. Guo,
N. Yu, Q. An, Z.-W. Zuo, J. Am. Chem. Soc. 2018, 140, 13580-13585.
j) J.-L. Wang, B.-B. Huang, C.-C. Shi, C. Yang, W.-J. Xia, J. Org. Chem.
2018, 83, 9696-9706. k) J.-J. Guo, A.-H. Hu, Y.-L. Chen, J.-F. Sun, H.-
M. Tang, Z.-W. Zuo, Angew. Chem. 2016, 128, 15545-15548; Angew.
Chem., Int. Ed. 2016, 55, 15319-15322. l) H. G. Yayla, H.-J. Wang, K. T.
Tarantino, H. S. Orbe, R. R. Knowles, J. Am. Chem. Soc. 2016, 138,
10794-10797. m) S. Chiba, M. Kitamura, K. Narasaka, J. Am. Chem.
Soc. 2006, 128, 6931-6937.
Conclusion
In conclusion, we have developed a visible light-induced C-C
bond cleavage of cycloketones with O2. This protocol features
low–cost catalytic systems, mild conditions (metal free, room
temperature) and operational simplicity, thus providing an
environmentally benign and sustainable method to achieve the
C-C bond cleavage of cycloketones for the distal keto ester
1
synthesis. The mechanistic studies suggest that the O2 would
be the real reactive oxygen species in this transformation.
Further mechanism investigation and possible application of this
method are ongoing in our laboratory.
[5]
[6]
Y.-L. Chen, J.-B. Du, Z.-W. Zuo, Chem DOI: 10.1016/j.chempr. 2019. 11.
009.
a) M. A. Miranda, E. F. Sanchis, J. P. Prieto, J. Org. Chem. 1999, 64,
3802-3803. b) J. C. Scaiano, Acc. Chem. Res. 1982, 15, 252-258.
4
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10.1002/chem.202001032
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RESEARCH ARTICLE
[7]
a) J. C. Lee, C. H. Ku, Synlett. 2002, 10, 1679-1680. b) L.-Y. He, M.
Kanamori, C. A. Horiuchi, J. Chem. Research (S), 1999, 122-123. c) T.
Hirao, M. Mori, Y. Ohshiro, Bull. Chem. Soc. Jpn. 1989, 62, 2399-2400.
d) S. Ito, M. Matsumoto, J. Org. Chem. 1983, 48, 1133-1135.
[8]
For select reviews see: a) C.-L. Bian, A. K. Singh, L.-B. Niu, H. Yi, A.-W.
Lei, Asian J. Org. Chem. 2017, 6, 386-396. b) Z.-Z. Shi, C. Zhang, C.-H.
Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3381-3430. c) T.
Punniyamurthy, S. Velusamy, J. Iqbal, Chem. Rev. 2005, 105, 2329-
2363. d) S. S. Stahl. Angew. Chem. 2004, 116, 3480-3501; Angew.
Chem., Int. Ed. 2004, 43, 3400-3420. For select examples concerning
on the oxidation reactions with O2, see: e) B.-C. Zhu, T. Shen, X.-Q.
Huang, Y.-C. Zhu, S. Song, N. Jiao, Angew. Chem. DOI: 10.1002/ange.
201903690; Angew. Chem., Int. Ed. DOI: 10.1002/anie. 201903690. f)
K.-X. He, T. Zhang, S.-W. Zhang, Z. Sun, Y.-X. Zhang, Y. Yuan, X.-D.
Jia, Org. Lett. 2019, 21, 5030-5034. g) B. Xu, J.-P. Lumb, B. A.
Arndtsen, Angew. Chem. 2015, 127, 4282-4285; Angew. Chem., Int. Ed.
2015, 54, 4208-4211. h) Y.-Q. Zou, J.-R. Chen, X.-P. Liu, L.-Q. Lu, R. L.
Davis, K. A. Jørgensen, W.-J., Xiao, Angew. Chem. 2012, 124, 808-
812; Angew. Chem., Int. Ed. 2012, 51, 784-788. i) H. Sundén, M.
Engqvist, J. Casas, I. Ibrahem, A. Córdova, Angew. Chem. 2004, 116,
6694-6697; Angew. Chem., Int. Ed. 2004, 43, 6532-6535.
[9]
For select reviews see: a) P. D. Mascio, G. R. Martinez, S. Miyamoto, G.
E. Ronsein, M. H. G. Medeiros, J. Cadet, Chem. Rev. 2019, 119, 2043-
2086. b) Q.-Q. Zhou, Y.-Q. Zou, L.-Q. Lu, W.-J. Xiao, Angew. Chem.
2019, 137, 1600-1619; Angew. Chem. Int. Ed. 2019, 58, 1586-1604. c)
F. S. Kalthoff, M. J. James, M. Teders, L. Pitzer, F. Glorius, Chem. Soc.
Rev. 2018, 47, 7190-7202. d) A. A. Ghogare, A. Greer, Chem. Rev.
2016, 116, 9994-10034. For select examples see: e) V. K. Soni, H. S.
Hwang, Y. K. Moon, S.-W. Park, Y.-M. You, E. J. Cho, J. Am. Chem.
Soc. 2019, 141, 10538-10545. f) J.-H. Xu, W.-B. Wu, J. Wu, Org. Lett.
2019, 21, 5321-5325. g) Q. Yu, Y.-T. Zhang, J.-P. Wan, Green Chem.
2019, 21, 3436-3441. h) W. Ding, L.-Q. Lu, Q.-Q. Zhou, Y. Wei, J.-R.
Chen, W.-J. Xiao, J. Am. Chem. Soc. 2017, 139, 63-66. i) S. Lerch, L.-
N. Unkel, M. Brasholz, Angew. Chem. 2014, 126, 6676-6680; Angew.
Chem., Int. Ed. 2014, 53, 6558-6562. j) A. Córdova, H. Sundén, M.
Engqvist, I. Ibrahem, J. Casas, J. Am. Chem. Soc. 2004, 126, 8914-
8915.
[10] For selected examples, see: a) J.-C. Yang, L. Chen, F. Yang, P. Li, L.-N.
Guo, Org. Chem. Front. 2019, 6, 2792-2795. b) P. Gao, H. Wu, J.-C.
Yang, L.-N. Guo, Org. Lett. 2019, 21, 7104-7108. c) J.-J. Zhang, X.-H.
Duan, Y. Wu, J.-C. Yang, L.-N. Guo, Chem. Sci. 2019, 10, 161. d) Y.-Q.
Tang, J.-C. Yang, L. Wang, L.-N. Guo, Org. Lett. 2019, 21, 5178-5182.
e) L. Yang, J.-Y. Zhang, X.-H. Duan, P. Gao, J. Jiao, L.-N. Guo, J. Org.
Chem. 2019, 84, 8615-8629. f) J.-F. Zhao, X.-H. Duan, Y.-R. Gu, P.
Gao, L.-N. Guo, Org. Lett. 2018, 20, 4614-4617. g) Y.-R. Gu, X.-H.
Duan, L. Yang, L.-N. Guo, Org. Lett. 2017, 19, 5908-5911. h) S. Wang,
L.-N. Guo, H. Wang, X.-H. Duan, Org. Lett. 2015, 17, 4798-4801.
[11] a) I. K. Astakhova, T. S. Kumar, M. A. Campbell, A. V. Ustinov, V. A.
Korshun, J. Wengel, Chem. Commun. 2013, 49, 511-513. b) G. F.
Ruda, C. Nguyen, P. Ziemkowski, K. Felczak, G. Kasinathan, A.
Musso-Buendia, C. Sund, X.-X. Zhou, M. Kaiser, L. M. Ruiz-pérez, R.
Brun, T. Kullikowski, N. G. Johansson, D. González-Pacanowska, L. H.
Gilbert, ChemMedChem 2011, 6, 309-320. c) W. M. Singh, J. B.
Baruah, Synth. Commun. 2009, 39, 325-331.
[12] TEMPO could also serve as a singlet oxygen scavenger, see: a) T.
Vidóczy, P. Baranyai, Helv. Chim. Acta 2001, 84, 2640-2652. b) A. P.
Darmanyan, A. S. Tatikolov, J. Photochem. 1986, 32, 157-163.
[13] A. Sagadevan, K.-C. Hwang, M.-D Su, Nat. Commum. 2017, 8, 1812-
1819.
[14]
a) X. Zhang, Z. Wang, K. Xu, Y. Feng, W. Zhao, X. Xu, Y. Yan, W. Yi,
Green Chem. 2016, 18, 2313-2316. b) S. Sobhani, M. F. Maleki, Synlett.
2010, 3, 383-386. c) R. Neumann, M. Levin, J. Org. Chem. 1991, 56,
5707-5710.
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10.1002/chem.202001032
Chemistry - A European Journal
RESEARCH ARTICLE
Entry for the Table of Contents
A metal-free, visible light-induced selective C-C bond cleavage of cycloketones with molecular oxygen is achieved through merging
Brønsted-acid catalysis and photocatalysis. This protocol features low–cost catalytic systems, mild conditions and operational
simplicity, thus providing an environmentally benign and sustainable approach to an array of γ-, δ- and ε-keto esters. The mechanistic
studies indicate that singlet molecular oxygen (1O2) is responsible for this reaction.
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This article is protected by copyright. All rights reserved.