Metal-Free catalyst for visible-light-induced oxidation of unactivated alcohols using Air/Oxygen as an oxidant

Article abstract of DOI:10.1021/acscatal.8b01067

9-Fluorenone acts as a metal-free and additive-free photocatalyst for the selective oxidation of primary and secondary alcohols under visible light. With this photocatalyst, a plethora of alcohols such as aliphatic, heteroaromatic, aromatic, and alicyclic compounds has been converted to the corresponding carbonyl compounds using air/oxygen as an oxidant. In addition to these, several steroids have been oxidized to the corresponding carbonyl compounds. Detailed mechanistic studies have also been achieved to determine the role of the oxidant and the photocatalyst for this oxidation.

Full text of DOI:10.1021/acscatal.8b01067

Subscriber access provided by Kaohsiung Medical University
Letter
Metal-Free Catalyst for Visible-Light-Induced Oxidation
of Unactivated Alcohols Using Air/Oxygen as Oxidant
Waldemar Schilling, Daniel Riemer, Yu Zhang, Nareh Hatami, and Shoubhik Das
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b01067 • Publication Date (Web): 02 May 2018
Downloaded from http://pubs.acs.org on May 2, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 7
ACS Catalysis
1
2
3
4
5
6
7
8
9
Metal-Free Catalyst for Visible-Light-Induced Oxidation of Unacti-
vated Alcohols Using Air/Oxygen as Oxidant
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Waldemar Schilling, Daniel Riemer, Yu Zhang, Nareh Hatami, and Shoubhik Das*
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttin-
gen, Germany
ABSTRACT: 9-Fluorenone acts as a metal-free and additive free photocatalyst for the selective oxidation of primary and secondary
alcohols under visible light. With this photocatalyst, a plethora of alcohols such as aliphatic, heteroaromatic, aromatic and alicyclic
compounds have been converted to the corresponding carbonyl compounds using air/oxygen as an oxidant. In addition to these,
several steroids have been oxidized to the corresponding carbonyl compounds. Detailed mechanistic studies have also been achieved
to find out role of the oxidant and the photocatalyst for this oxidation.
KEYWORDS: O2 • alcohols • photocatalysts • oxidations • metal-free
Ir, Cu, TiO2, Pt, Nb-
based photocatalysts
Syntheses of carbonyl compounds via alcohol oxidation is one
of the major important reactions in the pharmaceuticals as well
Limited to benzylic
and allylic alcohols
(Ref. 38-46)
as in the fine chemical industries.1 So far, stoichiometric oxi-
dants such as MnO2, hypochlorite, permanganate, osmium ox-
ide, activated DMSO etc. prevail in this reaction.2-9 In compar-
ison to these stoichiometric oxidants, O2 or air acts as better ox-
idants due to the avoidance of hazardous, toxic and stoichio-
metric by-products. Based on this approach, several homogene-
ous and heterogeneous transition metal-based catalysts have
been reported.10-20 However, requirement of precious metals,
expensive ligands, costly and toxic additives always hinder
their application in the pharmaceutical industries. In contrast,
transition metal-free catalysts can be attractive due to their
cheaper price, non-toxicity and easy separation from the reac-
tion mixture. In fact, TEMPO-based and nitroxyl radical based
transition metal-free systems have already been reported. How-
ever, the reaction needed several co-catalysts, high temperature
and corrosive solvents.21-29
Macromolecular based
organic semiconductors
OH
O
Limited to benzylic
and allylic alcohols
R1
H
R1
H
(Ref. 47-51)
Aliphatic, hetero-
aromatic and
alicyclic alcohols
This work
Fluorenone (3 mol%)
DMSO, rt
Figure 1: Visible-light mediated photocatalysts for the oxida-
tion of alcohols
Inspired by this information, several metal-based photocatalysts
have been reported based on Ir, Cu, TiO2, Pt, Nb, Pt-function-
alized porphyrinic MOF etc (Figure 1).41-48 However, utiliza-
tion of precious metals and limited reactivity of these photo-
catalysts forced scientists towards the development of organic
semiconductor-based photocatalysts. Advantageously, these
photocatalysts are non-metal in nature and exhibit high tunable
physicochemical properties. In fact, small molecular or macro-
molecular based organic semiconductors such as porous carbon
nitrides, graphene/carbon nitride, thiophene-based covalent tri-
azine framework have also shown reactivity for the oxidation
of alcohols to the carbonyl compounds.50-54 However, often
these organic semiconductors needed high temperatures, tedi-
ous syntheses of the catalysts and more importantly, only
showed reactivity towards activated alcohols such as benzylic
and allylic alcohols. Therefore, there is a strong requirement for
an alternative metal-free photocatalyst, which shows wide sub-
strates scope and reactivity towards aliphatic, heteroaromatic
and alicyclic alcohols.
Compared to the thermal reactions, photocatalysis has powerful
impact for the requirement of clean energy and environmental
applications. Over the past two decades, number of applications
based on photocatalysis has been increased sharply especially
for the hydrogen fuel generation and CO2 reduction.30-33 Signif-
icant efforts have also been paid for the development of visible
light mediated reactions to achieve sustainable syntheses of
chemicals.34-39 Therefore, there is always strong interest for the
findings of cheap and commercially available photocatalyst for
the selective oxidation of alcohols. In fact, O2 molecule can be
activated by photocatalysts to transform it into reactive oxygen
species (ROS) such as superoxide anion radical, hydrogen per-
oxide, singlet oxygen and hydroxy radical which are the key
oxidants in many organic reactions.40
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 7
1
2
3
4
5
6
7
8
9
Small organic molecules have also shown their activity towards
formation of over-oxidized carboxylic acid product was ob-
served after the reaction.
the activation of O2 molecule under visible light and this con-
cept has already shown powerful applications in organic syn-
theses via C–H bond activation and others.55-59 These small or-
ganic molecules show unique reactivity and unparalleled selec-
tivity in organic reactions. Advantageously, various commer-
cially available structures of these molecules enhance easy op-
timization of the desired reaction. Based on all these infor-
mation and our own interest to explore metal-free catalysis, we
became interested to find a mild photocatalytic system for the
selective oxidation of alcohols.60-65
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization for the visible light induced oxidation of
benzyl alcohol to benzaldehyde.[a-e]
Entry
1c
Catalysts
Solvents
DMSO
Atmosphere Yield [%]
9,10-dicyano-
anthracene
oxygen
0
2
3
rose bengal
riboflavine
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMA
oxygen
oxygen
oxygen
oxygen
oxygen
air
1
7
4
fluorescein
22
23
99
98
0
5
rhodamine 6G
9-fluorenone
9-fluorenone
9-fluorenone
9-fluorenone
9-fluorenone
9-fluorenone
6
7
8d
9e
10f
11
air
DMF
air
4
THF
air
3
Toluene
air
0
[a] Reaction conditions: Benzyl alcohol (0.29 mmol), photocatalysts
(3 mol%), solvent (1 mL), O2 (balloon) or air, rt, 18 h. [b] Yield determined
by GC using n-dodecane as an internal standard. [c] DMSO
=
Dimethylsulfoxide. [d] DMA = N,N-dimethylacetamide. [e] DMF = N,N-
dimethylformamide. [f] THF = Tetrahydrofuran.
At the outset of the project, several organic photocatalysts were
investigated for the reaction of benzyl alcohol (1a) with O2 as
the oxidant for the model system to identify and optimize po-
tential reaction parameters (Table 1). To our delight, in the
presence of 3 mol% of 9-fluorenone, corresponding benzalde-
hyde (1b) was obtained in 99% yield within 18 h. Among other
photocatalysts, rhodamine 6G and fluorescein (Table 1, entries
4-5) showed activity under our reaction conditions. We at-
tributed the high activity of 9-fluorenone to its high life-time for
the excited state, which was reported with up to 17.8 ns, with
an additional stabilizing effect of DMSO in our case.66 The re-
action was also investigated under air and to our delight, in pres-
ence of 3 mol% of 9-fluorenone, 98% of the desired benzalde-
hyde was obtained. The reaction yield was suppressed in DMF,
DMA, toluene and THF (Table 1, entries 8-11). In addition, no
Reaction conditions: Substrates (0.25 mmol), 9-fluorenone (3-6 mol%),
DMSO (1 mL), 16-72 h. All are isolated yields except 22a and 27a. Entries
19-25a, 27-33a were performed under O2 atmosphere. 13a* 10 mmol scale
see supporting info for more information.
Scheme 1. General substrates scope for the oxidations of pri-
mary and secondary alcohols.
With these optimized conditions in hand, the scope of this alco-
hol oxidation reaction was explored (Scheme 1). A number of
alcohols including aromatic, heteroaromatic, alicyclic, and ali-
phatic were smoothly oxidized with high yields up to 99%.
2
ACS Paragon Plus Environment

Page 3 of 7
ACS Catalysis
1
2
3
4
5
6
7
8
9
Different benzylic primary alcohols reacted faster under the op-
oxygen as the oxidant. In most of the cases, stoichiometric oxi-
dants and/or metal-based catalysts have been used.69-71 There-
fore, owing to the interest of pharmaceutical companies, this
catalyst can find strong interest in steroid chemistry.
timized conditions (Scheme 1; entries 2a, 6a, 7a, 10a, and 16a).
To our delight, reaction also showed high selectivity in the pres-
ence of aldehyde functional group in the aromatic ring (Scheme
1; entry 10a). In fact, attachment of aliphatic, heteroaromatic,
aromatic and alicyclic ring in the benzylic or allylic position did
not hamper the reaction yield (Scheme 1; entries 3-5a, 8-9a, 11-
12a, 14-15a, and 17-18a).
Table 2: Control experiments for the oxidation of benzyl alco-
hol.[a,b]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
entry Controlled parameter yield [%]
1
2
3
4
Standard conditions
N2 atmosphere
No light
98
0
After successfully investigating different benzylic and allylic
alcohols, we became interested to find out the potential of 9-
fluorenone towards unactivated alcohols. For this purpose, ali-
phatic, alicyclic and heteroaromatic alcohols were applied un-
der our optimized reactions conditions (Scheme 1; entries 21-
33a). To our delight, different aliphatic secondary alcohols
showed excellent reactivity under our optimized reaction con-
ditions. In fact, the desired oxidized products were easily iso-
lated in case of both the internal and terminal aliphatic second-
ary alcohols in good to excellent yield (Scheme 1; entries 21-
25a). Notably, unactivated cyclic alcohols were also oxidized
to the corresponding ketones with an excellent yield up to 83%
(Scheme 1; entries 26-29a). In addition to these, both primary
and secondary heteroaromatic alcohols reacted excellently un-
der our conditions (Scheme 1; entries 30-33a). The sole by-
product for this oxidation reaction was DMSO2, which was gen-
erated after the oxidation of DMSO by the in situ generated
H2O2. The by-product was removed by aqueous work up fol-
lowed by column chromatography.
1
No catalyst
0
[a] Reaction conditions: Substrates (0.29 mmol), 9-fluorenone (3 mol%),
DMSO (1 mL), 18 h. [b] Yield determined by GC using n-dodecane as an
internal standard.
After substrates scope evaluation, we became interested to find
out the actual role of the catalyst and the light source. Control
experiments proved no formation of the product in the absence
of light or photocatalyst (Table 2). In addition to these, no for-
mation of product was observed under N2 atmosphere, which
clearly suggested the significant role of O2. These control ex-
periments led us to find out the effect of different quenchers to
recognize the reactive oxygen species (Table 3).54 In fact, reac-
tion showed slight decrease in the yield in the presence of ter-
tiary butanol, which ruled out the presence of hydroxide radical.
However, using sodium azide and benzoquinone as quenchers
revealed the presence of singlet oxygen radical and superoxide
radical anion in the reaction system. Further application of
CuCl2 in the reaction exhibited lower yield that clearly sug-
gested the interplay of a single electron in this photocatalytic
system. We presume that this electron could be generated from
the photocatalyst to generate the real oxidant such as singlet ox-
ygen radical and superoxide radical anion from O2 molecule.
Finally, reaction with catalase detected the presence of peroxide
species in the reaction. However, direct introduction of H2O2
into oxidation reaction resulted in lower activity, indicating that
H2O2 was not responsible oxidant in our reaction system but a
peroxo species could be involved in the reaction.
Reaction conditions: Substrates (0.25 mmol), 9-fluorenone (6 mol%),
DMSO (1 mL), 16-72 h. All are isolated yields.
Scheme 2: Oxidation of alcohol moiety in steroids.
Further investigation by Stern-Volmer fluorescence quenching
experiments revealed that excited state of the photocatalyst was
not quenched by oxygen rather by benzyl alcohol (Figure 2).72
Fluorescence intensity was dramatically decreased with the in-
crease of benzyl alcohol concentration and no change was ob-
served with saturated oxygen/air solution. In addition to this,
KH/KD value of 3.0 in the kinetic isotope effect (KIE) experi-
ment strongly suggested the C–H bond cleavage in the rate-de-
termining step (Scheme 3).
Furthermore, we decided to apply our catalytic oxidation strat-
egy to more complex steroids as selective oxidation of saturated
steroidal alcohols is highly important in steroid chemistry.67
Major steroidal hormones contain ketone functionality and the
oxidation of Δ5-3β-alcohols to the corresponding Δ4-3-ketones
is highly important for the commercial synthesis of hormones.68
Based on this information, we applied our photocatalyst on tes-
tosterone, stanelone, androsterone and to our delight all these
three steroids showed high formation of the desired ketones
(Scheme 2). To the best of our knowledge, currently there is no
metal-free catalyst known for the oxidation of steroids using
Table 3: Quenching experiments for the oxidation of benzyl al-
cohol.[a,b]54
3
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 7
1
2
3
4
5
experiment under 18O2 atmosphere confirmed this mechanism
via the formation of DMSO18O (Scheme 3).
6
7
8
9
Quenchers
BHT
equivalents yields
notes
0.5
1.0
37%
9%
radical scav.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
BHT
radical scav.
TEMPO
0.5
31%
11%
81%
4%
radical scav.
TEMPO
1.0
radical scav.
Tert-butanol
CuCl2
1.0
hydroxide radical scav.
electron scav.
1.0
Sodium azide
Catalase
1.0
22%
0%
singlet oxygen scav.
peroxide radical scav.
100 mg
1.0
Benzoquinone
5% superoxide radical anion scav.
[a] Reaction conditions: Substrates (0.29 mmol), 9-fluorenone (3 mol%),
DMSO (1 mL), quenchers, 18 h. [b] Yield determined by GC using n-
dodecane as an internal standard.
1,35
c(SM)
saturation with O2
1,30
1,25
1,20
1,15
1,10
1,05
1,00
0,95
linear fit of c(SM)
linear fit of oxygen
Scheme 3. Mechanistic experiments and proposed reaction
mechanism.
In conclusion, we have demonstrated 9-fluorenone as a com-
mercially available and cheap metal-free photocatalyst for the
selective oxidation of alcohols to the corresponding carbonyl
compounds. Notably, our photocatalyst showed wide substrates
scope especially high reactivity towards aliphatic, alicyclic and
heteroaromatic alcohols. In fact, this catalyst can also be applied
to the oxidation of steroids, which is the key step for many phar-
maceuticals. Finally, detailed mechanistic studies clearly
demonstrated the role of O2 in the reaction. We believe this
methodology could find interest in the syntheses of pharmaceu-
ticals and in the syntheses of natural products.
0,00
0,05
0,10
0,15
0,20
0,25
c(quencher) / mmol
Figure 2: Stern-Volmer plot for the oxidation of benzyl alco-
hol.
Combining all these mechanistic information, we rationalized
that at first the photocatalyst reached the excited state by irradi-
ation of visible light. The excited state of the photocatalyst ren-
dered single electron transfer (SET) to benzyl alcohol and trans-
formed itself to the corresponding radical anion. This flu-
orenone radical anion generated the real oxidants singlet oxy-
gen radical and superoxide radical anion from O2. The activated
benzyl alcohol then reacted with the superoxide anion to gener-
ate peroxide radical and further abstraction of one more hydro-
gen atom by the peroxide radical generated the final desired
product. The reported value for the reduction-potential of ex-
cited state 9-fluorenone resides at -0.61 V vs SCE,54 which is
sufficient for the reduction of molecular oxygen to its superox-
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS publications website.
Experimental details, characterization data and spectra for the
compounds of the synthesized compounds (PDF).
AUTHOR INFORMATION
-
ide radical form (•O2/ O2 ) with the reduction potential residing
Corresponding Author
at -0.56 V vs SCE.54,56,73 The fact, that without substrate no sin-
glet oxygen radical, nor superoxide radical anion, could be de-
tected indicates the pivotal role of the substrate in combination
with the photocatalyst. The postulated radical intermediates
should be short lived and are only effective due to the direct and
close generation of the oxidant by the activated catalyst. Final
*E-mail: shoubhik.das@chemie.uni-goettingen.de
Author Contributions
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the manu-
script.
4
ACS Paragon Plus Environment

Page 5 of 7
ACS Catalysis
1
2
3
4
5
6
7
8
9
(21) Liu, R.; Liang, X.; Dong, C.; Hu, X. Transition-Metal-Free: A Highly Efficient
Funding Sources
Catalytic Aerobic Alcohol Oxidation Process. J. Am. Chem. Soc. 2004, 126, 4112-
4113.
We thank Fonds der Chemischen Industrie (FCI, Liebig-Fellow-
ship to S.D.) and Chinese Scholarship Council (CSC to Y.Z.) for
the
(22) Karimi, B.; Biglari, A.; Clark, J. H.; Budarin, V. Green, Transition-Metal-Free
Aerobic Oxidation of Alcohols Using a Highly Durable Supported Organocatalyst.
Angew. Chem. Int. Ed. 2007, 46, 7210-7213.
financial
support.
ACKNOWLEDGMENTS
(23) Ludger, T.; Studer, A. Nitroxides: Applications in Synthesis and in Polymer
Chemistry. Angew. Chem. Int. Ed. 2011, 22, 5034-5068.
We are highly thankful to Prof. Dr. Lutz Ackermann for his kind
support behind our work.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(24) Laeini, M. S.; Shaabani, A. A Transition-Metal-Free Homogeneous TEMPO-
Based Catalyst: Aerobic Oxidation of Alcohols in Aqueous Media. Chem. Select 2017,
2, 9084-9087.
REFERENCES
(1) Bäckvall, J.-E. Modern Oxidation Methods, Wiley-VCH, New York, 2004.
(2) Tojo, G.; Fernandez, M. I. Oxidation of Alcohols to Aldehydes and Ketones,
Springer science, 2006.
(25) Wertz, S.; Studer, A. Nitroxide-catalyzed Transition-Metal-Free Aerobic Oxi-
dation Processes. Green Chem. 2013, 15, 3116-3134.
(26) Yan, Y.; Tong, X.; Wang, K.; Bai, X. Highly Efficient and Selective Aerobic
Oxidation of Alcohols in Aqueous Media by TEMPO-Containing Catalytic Systems.
Catal. Commun. 2014, 43, 112-115.
(3) Friedrich, H. B. The Oxidation of Alcohols to Aldehydes or Ketones. Platinum
Metals Rev. 1999, 43, 94-102.
(27) Zhu, J.; Zhao, X.-J.; Wang, P.-C.; Lu, M. Synthesis of Fibrous Nano-Silica-
supported TEMPO and its Application in Selective Oxidation of Alcohols. Chem. Lett.
2013, 42, 1505-1507.
(4) Alfonsi, K.; Colberg, J.; Dunn, P. J.; Fevig, T.; Jennings, S.; Johnson, T. A.;
Kleine, H. P.; Knight, C.; Nagy, M. A.; Perry, D. A.; Stefaniak, M. Green Chemistry
Tools to Influence a Medicinal Chemistry and Research Chemistry Based Organisa-
tion. Green Chem. 2008, 10, 31-36.
(28) Wang, X.; Liu, R.; Liang, X. TEMPO/HCl/NaNO2 Catalyst: A Transition-
Metal-Free Approach to Efficient Aerobic Oxidation of Alcohols to Aldehydes and
Ketones Under Mild Conditions. Chem. Eur. J. 2008, 14, 2679-2685.
(29) He, X.; Shen, Z.; Mo, W.; Sun, N.; Hu, B.; Hu, X. TEMPO-tert-Butyl Nitrite:
An Efficient Catalytic System for Aerobic Oxidation of Alcohols. Adv. Synth. Catal.
2009, 351, 89-92.
(5) Omura, K.; Swern, D. Oxidation of Alcohols by “Activated” Dimethyl Sulfox-
ide. A Reparative, Steric and Mechanistic Study. Tetrahedron 1978, 34, 1651-1660.
(6) Gorini, L.; Caneschi, A.; Menichetti, S. TPAP/NMO System as a Novel Method
for the Synthesis of Nitronyl Nitroxide Radicals. Synlett 2006, 6, 948-950.
(7) Pfitzner, K. E.; Moffatt, J. G. A New and Selective Oxidation of Alcohols. J.
Am. Chem. Soc. 1963, 85, 3027-3028.
(30) Kuehnel, M. F.; Reisner, E. Solar Hydrogen Generation from Lignocellulose.
Angew. Chem. Int. Ed. 2018, 57, 3290-3296.
(31) Osterloh, F. E. Inorganic Nanostructures for Photoelectrochemical and Photo
Catalytic Water Splitting. Chem. Soc. Rev. 2013, 42, 2294-2320.
(32) Hutton, G. A. M.; Martindale, B. C. M.; Reisner, E. Carbon Dots as PhotoSen-
sitisers for Solar-Driven Catalysis. Chem. Soc. Rev. 2017, 46, 6111-6123.
(33) White, J. L.; Baruch, M. F.; Pander, J. E.; Hu, Y.; Fortmeyer, I. C.; Park, J. E.;
Zhang, T.; Liao, K.; Gu, J.; Yan, Y.; Shaw, T. W.; Abelev, E.; Bocarsly, A. B. Light-
Driven Heterogeneous Reduction of Carbon Dioxide: Photocatalysts and Photoelec-
trodes. Chem. Rev. 2015, 115, 12888-12935.
(8) Parikh, J. R.; Doering, W. v. E. Sulfur Trioxide in the Oxidation of Alcohols by
Dimethyl Sulfoxide. J. Am. Chem. Soc. 1967, 89, 5505-5507.
(9) Albright, J. D.; Goldman, L. Dimethyl Sulfoxide-Acid Anhydride Mixture. New
Reagents for Oxidation of Alcohols. J. Am. Chem. Soc. 1965, 87, 4214-4216.
(10) Schröder, K.; Junge, K.; Bitterlich, B.; Beller, M. Fe-Catalysed Oxidation Re-
actions of Olefins, Alkanes, and Alcohols: Involvement of Oxo- and Peroxo Com-
plexes. Topics in Organometal. Chem. 2011, 33, 83-111.
(11) Engelmann, X.; Monte-Perez, I.; Ray, K. Oxidation Reactions with Bioinspired
Mononuclear Non-Heme Metal-Oxo Complexes. Angew. Chem. Int. Ed. 2016, 55,
7632-7649.
(34) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Visible Light Photoredox
Catalysis with Transition Metal Complexes: Applications in Organic Synthesis. Chem.
Rev. 2013, 113, 5322-5363.
(12) Yuan, Y.; Yan, N.; Dyson, P. J. pH-Sensitive Gold Nanoparticle for the Aero-
bic Oxidation of Alcohols. Inorg. Chem. 2011, 50, 11069-11074.
(13) Jagadeesh, R. V.; Junge, H.; Pohl, M. M.; Radnik, J.; Brückner, A.; Beller, M.
Selective Oxidation of Alcohols to Esters Using Heterogeneous Co3O4-N@C Catalysts
under Mild Conditions. J. Am. Chem. Soc. 2013, 135, 10776-10782.
(14) Gowrisankar, S.; Neumann, H.; Goerdes, D.; Thurow, K.; Jiao, H.; Beller, M.
A Convenient and Selective Palladium-Catalyzed Aerobic Oxidation of Alcohols.
Chem. Eur. J. 2013, 19, 15979-15984.
(35) Xi, Y.; Yi, H.; Lei, A. Synthetic Applications of Photoredox Cataysis with Vis-
ible Light. Org. Biomol. Chem. 2013, 11, 2387-2403.
(36) Xuan, J.; Xiao, W. -J. Visible-Light Photoredox Catalysis. Angew. Chem. Int.
Ed. 2012, 51, 6828-6838.
(37) Tucker, J. W.; Stephenson C. R. J. Shining Light on Photoredox Catalysis:
Theory and Synthetic Applications. J. Org. Chem. 2012, 77, 1617-1622.
(38) Ischay, M. A.; Yoon, T. P. Accessing the Synthetic Chemistry of Radical Ions.
Eur. J. Org. Chem. 2012, 3359-3372.
(15) Mannel, D. S.; Ahmed, M. S.; Root, T. W.; Stahl, S. S. Discovery of Multi-
component Heterogeneous Catalysts via Admixture Screening: PdBiTe Catalysts for
Aerobic Oxidative Esterification of Primary Alcohols. J. Am. Chem. Soc. 2017, 139,
1690-1698.
(39) Reckenthaler, M.; Griesbeck, A. G. Photoredox Catalysis for Organic Synthe-
ses. Adv. Synth. Catal. 2013, 355, 2727-2744.
(40) Nosaka, Y.; Nosaka, A. Y. Generation and Detection of Reactive Oxygen Spe-
cies in Photocatalysis. Chem. Rev. 2017, 117, 11302-11336.
(16) Das, A.; Stahl, S. S. Noncovalent Immobilization of Molecular Electrocatalysts
for Chemical Synthesis: Efficient Electrochemical Alcohol Oxidation with a Pyrene-
TEMPO Conjugate. Angew. Chem. Int. Ed. 2017, 56, 8892-8897.
(17) Sikari, R.; Sinha, S.; Jash, U.; Das, S.; Brandao, P.; de Bruin, B.; Paul, N. D.
Deprotonation Induced Ligand Oxidation in a NiII Complex of a Redox Noninnocent
N1-(2-Aminophenyl)benzene-1,2-diamine and its Use in Catalytic Alcohol Oxidation.
Inorganic Chem. 2016, 55, 6114-6123.
(41) Chen, Y.; Wang, Z. U.; Wang, H.; Lu, J.; Yu, S.; Jiang, H. Singlet Oxygen-
Engaged Selective Photo-Oxidation over Pt Nanocrystals/Porphyrinic MOF: The
Roles of Photothermal Effect and Pt Electronic State. J. Am. Chem. Soc. 2017, 139,
2035-2044.
(42) Meng, C.; Yang, K.; Fu, X.; Yuan, R. Photocatalytic Oxidation of Benzyl Al-
cohol by Homogeneous CuCl2/Solvent: A Model System to Explore the Role of Mo-
lecular Oxygen. ACS Catal. 2015, 5, 3760-3766.
(18) Guo, Z.; Liu, B.; Zhang, Q.; Deng, W.; Wang, Y.; Yang, Y. Recent Advances
in Heterogeneous Selective Oxidation Catalysis for Sustainable Chemistry. Chem.
Soc. Rev. 2014, 43, 3480-3524.
(43) Furukawa, S.; Shishido, T.; Teramura, K.; Tanaka, T. Photocatalytic Oxidation
of Alcohols over TiO2 Covered with Nb2O5. ACS Catal. 2012, 2, 175-179.
(44) Yurdakal, S.; Palmisano, G.; Loddo, V.; Augugliaro, V.; Palmisano, L.
Nanostructured Rutile TiO2 for Selective Photocatalytic Oxidation of Aromatic Alco-
hols to Aldehydes in Water. J. Am. Chem. Soc. 2008, 130, 1568-1569.
(45) Tamaki, Y.; Furube, A.; Murai, M.; Hara, K.; Katoh, R.; Tachiya, M. Direct
Observation of Reactive Trapped Holes in TiO2 Undergoing Photocatalytic Oxidation
of Adsorbed Alcohols: Evaluation of the Reaction Rates and Yields. J. Am. Chem. Soc.
2006, 128, 416-417.
(19) Li, X.; Shi, J.-L.; Lang, X. Visible Light-Induced Selective Oxidation of Al-
cohols with Air by Dye-Sensitized TiO2 Photocatalysis. Applied Catalysis, B: Envi-
ronmental 2018, 232, 260-267.
(20) Gogoi, N; Borah, G.; Gogoi P. K.; Chetia, T. R. TiO2 Supported Gold Nano-
Particles: An Efficient Photocatalyst for Oxidation of Alcohol to Aldehyde and Ketone
in Presence of Visible Light Irradiation. Chem. Phys. Lett. 2018, 692, 224-231.
5
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 7
1
2
3
4
5
6
7
8
9
(46) Lang, X.; Ma, W.; Chen, C.; Ji, H.; Zhao, J. Selective Aerobic Oxidation Me-
Oxidation and Remote Functionalization Reactions. Curr. Org. Chem. 2006, 10, 2227-
2257.
(70) Suzuki, K.; Shimizu, T.; Nakata, T. The Cholesterol Metabolite Cholest-4-en-
diated by TiO2 Photocataysis. Acc. Chem. Res. 2014, 47, 355-363.
(47) Tsukamoto, D.; Shiarishi, Y.; Sugano, Y.; Ichikawa, S.; Tanaka, S.; Hirai, T.
Gold Nanoparticles Located at the Interface of Anatase/Rutile TiO2 Particles as Active
Plasmonic Photocatalysts for Aerobic Oxidation. J. Am. Chem. Soc. 2012, 134, 6309-
6315.
3-one and its 3-oxo Derivates Suppress Body Weight Gain, Body Fat Accumulation
and Serum Lipid Concentration in Mice. Bioorg. Med. Chem. Lett. 1998, 8, 2133-2138.
(71) Kontiza, I.; Abatis, D.; Malakate, K.; Vagias, C.; Roussis V. 3-Keto Steroids
from the Marine Organisms Dendrophyllia Cornigera and Cymodecea Nodosa. Ster-
oids 2006, 71, 177-181.
(48) Hering, T.; Slanina, T.; Hancock, A.; Wille, U.; Konig, B. Visible Light Pho-
tooxidation of Nitrate: The Dawn of a Nocturnal Radical. Chem. Commun. 2015, 51,
6568-6571.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(72) Arias-Rotondo, D. M.; McCusker, J. K. The Photophysics of Photoredox Ca-
talysis: a Roadmap for Catalyst Design. Chem. Soc. Rev. 2016, 45, 5803-5820.
(73) Ghosh, S.; Kouamé, N. A.; Ramos, L.; Remita, S.; Dazzi, A.; Deniset-Besseau,
A.; Beaunier, P.; Goubard, F.; Aubert, P.H.; Remita, H. Conducting Polymer
Nanostructures for Photocatalysis under Visible Light. Nat. Mater. 2015, 14, 505-511.
(49 Rueping, M.; Vila, C.; Szadkowska, A.; Koenigs, R. M.; Fronert, J. Photoredox
Catalysis as an Efficient Tool for the Aerobic Oxidation of Amines and Alcohols: Bi-
oinspired Demethylations and Condensations. ACS Catal. 2012, 2, 2810-2815.
(50) Su, F.; Mathew, S. C.; Lipner, G.; Fu, X.; Antonietti, M.; Blechert, S.; Wang,
X. mpg-C3N4-Catalyzed Selective Oxidation of Alcohols Using O2 and Visible Light.
J. Am. Chem. Soc. 2010, 132, 16299-16301.
(51) Walsh, K.; Sneddon, H. F.; Moody, C. J. Solar Photochemical Oxidations of
Benzylic and Allylic Alcohols Using Catalytic Organo-Oxidation with DDQ: Appli-
cation to Lignin Models. Org. Lett. 2014, 16, 5224-5227.
(52) Wang, Y.; Wang, X.; Antonietti, M. Polymeric Graphitic Carbon Nitride as a
Heterogeneous Organocatalyst: From Photochemistry to Multipurpose Catalysis to
Sustainable Chemistry. Angew. Chem. Int. Ed. 2012, 51, 68-89.
(53) Chen, Y.; Zhang, J.; Zhang, M.; Wang, X. Molecular and Textural Engineering
of Conjugated Carbon Nitride Catalysts for Selective Oxidation of Alcohols with Vis-
ible Light. Chem. Sci. 2013, 4, 3244-3248.
(54) Huang, W.; Ma, B. C.; Lu, H.; Li, R.; Wang, L.; Landfester, K.; Zhang, K. A.
I. Visible-Light-Promoted Selective Oxidation of Alcohols Using a Covalent Triazine
Framework. ACS Catal. 2017, 7, 5438-5442.
(55) Nicewicz, D. A.; Nguyen, M. T. Recent Applications of Organic Dyes as Pho-
toredox Catalysts in Organic Synthesis. ACS Catal. 2014, 4, 355-360.
(56) Romero, N.; Nicewicz, D. A. Organic Photoredox Catalysis. Chem. Rev. 2016,
116, 10075-10166.
(57) Neumann, M.; Füldner, S.; König, B.; Zeitler, K. Metal-Free, Cooperative
Asymmetric Organophotoredox Cataysis with Visible Light. Angew. Chem. Int. Ed.
2011, 50, 951-954.
(58) Romero, N. A.; Margrey, K. A.; Tay, N. E.; Nicewicz, D. A. Site-Selective
Arene C-H Amination via Photoredox Catalysis. Science, 2015, 349, 1326-1330.
(59) Ghosh, I.; Ghosh, T.; Bardagi, L. J.; König, B. Reduction of Aryl Halides by
Consecutive Visible Light-Induced Electron Transfer Processes. Science, 2014, 346,
725-728.
(60) Riemer, D.; Mandaviya, B.; Schilling, W.; Götze, A. C.; Kühl, T.; Finger, M.;
Das, S. CO2-Catalyzed Oxidation of Benzylic and Allylic Alcohols with DMSO. ACS
Catal. 2018, 8, 3030-3034.
(61) Hirapara, P.; Riemer, D.; Hazra, N.; Gajera, J.; Finger, M.; Das, S. CO2-
Assisted Synthesis of Non-Symmetric α-Diketones from Aldehydes via C-C Bond
Formation. Green. Chem. 2017, 19, 5356-5360.
(62) Riemer, D.; Hirapara, P.; Das, S. Chemoselective Synthesis of Carbamates us-
ing CO2 as Carbon Source. ChemSusChem 2016, 9, 1916-1920.
(63) Das, S.; Bobbink, F. D.; Bulut, S.; Soudani, M.; Dyson, P. J. Thiazolium Car-
bene Catalysts for the Fixation of CO2 onto Amines. Chem. Commun. 2016, 52, 2497-
2500.
(64) Karakulina, A.; Gopakumar, A.; Akok, I.; Rouliner, B. L.; LaGrange, T.; Kat-
syuba, S. A.; Das, S.; Dyson, P. J. A Rhodium Nanoparticle-Lewis Acidic Ionic Liquid
Catalyst for the Chemoselective Reduction of Heteroarenes. Angew. Chem. Int. Ed.
2016, 128, 300-304.
(65) Addis, D.; Zhou, S.; Das, S.; Junge, K.; Kosslick, H.; Harloff, J.; Lund, H.;
Beller, M. Hydrosilylation of Ketones: From Metal-Organic Frameworks to Simple
Base Catalysts. Chem. Asian. J. 2010, 5, 2341-2345.
(66) Ghosh, I.; Mukhopadhyay, A.; Koner, A. L.; Samanta, S.; Nau, W. M.; Moor-
thy, J. N. Excited-State Properties of Fluorenones: Influence of Substituents, Solvent
and Macrocyclic Encapsulation. Phys. Chem. Chem. Phys. 2014, 16, 16436-16445.
(67) Lednicer, D.; Mitscher, L. A.; Georg, G. I. The Organic Chemistry of Drug
Synthesis; John Wiley & Sons, Inc., 1990.
(68) Brodie, A. M. H.; Njar, V. C. O. Aromatase Inhibitors and their Application in
Breast Cancer Treatment. Steroids, 2000, 65, 171-179.
(69) Salvador, J. A. R.; Silvestre, S. M.; Moreira, V. M. Catalytic Oxidative Pro-
cesses in Steroid Chemistry: Allylic Oxidation, β-Selective Epoxidation, Alcohol
6
ACS Paragon Plus Environment

Page 7 of 7
ACS Catalysis
1
2
3
4
Table of contents:
5
O
OH
6
R1
H
R1
H
7
8
Metal-free catalyst
Unactivated alcohols
Commercially available
air/oxygen
Fluorenone (3 mol%)
9
Air/oxygen as the oxidant
Visible light mediated
Blue LED
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
OH
R2
Oxidation of steroids
R1
R2
R1
7
ACS Paragon Plus Environment