Solar photochemical oxidations of benzylic and allylic alcohols using catalytic organo-oxidation with DDQ: Application to lignin models

Article abstract of DOI:10.1021/ol502664f

Visible light has a dramatic effect on the oxidation of benzylic and allylic alcohols, including those deactivated by electron-withdrawing groups, and β-O-4 lignin models, using catalytic amounts of the organo-oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Sodium nitrite or tert-butyl nitrite is used as cocatalyst, and oxygen is employed as the terminal oxidant.

Full text of DOI:10.1021/ol502664f

Letter
pubs.acs.org/OrgLett
Solar Photochemical Oxidations of Benzylic and Allylic Alcohols
Using Catalytic Organo-oxidation with DDQ: Application to Lignin
Models
†
‡
,†
Katie Walsh, Helen F. Sneddon, and Christopher J. Moody*
†
School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.
‡
Green Chemistry Performance Unit, GlaxoSmithKline R&D Ltd., Medicines Research Centre, Gunnels Wood Road, Stevenage SG1
2NY, U.K.
*
S Supporting Information
ABSTRACT: Visible light has a dramatic effect on the oxidation of benzylic
and allylic alcohols, including those deactivated by electron-withdrawing
groups, and β-O-4 lignin models, using catalytic amounts of the organo-
oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Sodium nitrite or tert-
butyl nitrite is used as cocatalyst, and oxygen is employed as the terminal
oxidant.
xidation is a fundamental process in chemistry and
biology. In chemical synthesis, the oxidation of alcohols
are some toxicity concerns associated with its use on a large
scale; the compound has an LD of 82 mg/kg and can release
O
50
1
−4
to carbonyl compounds is a core transformation,
and one
HCN on contact with water. Consequently, the use of DDQ in
catalytic quantities, alongside a benign terminal oxidant, is an
particular example that has attracted much attention recently is
5
26
the OH groups in lignin. Lignin is a biopolymer that has been
attractive, safer, and more sustainable alternative.
5
−7
the subject of interest due to its potential as a feedstock. The
most common connectivity in lignin is the β-O-4 link, which
features a primary aliphatic alcohol and a secondary benzylic
alcohol and constitutes up to 50% of connectivities in lignin.
Recent literature has demonstrated that oxidation of the
benzylic position of β-O-4 lignin models results in easier C−C
Previous attempts at oxidations using substoichiometric
quantities of DDQ have been reported. However, many of
these processes have resorted to using an excess of metal-based
27
28
29
oxidants, such as Mn(OAc)3, MnO2, and FeCl3 in order
to reoxidize the DDQH , and therefore offer few advantages. In
2
contrast, other reports demonstrate the use of nitrite
8
−12
2
4,30,31
bond cleavage
aromatic materials.
Oxidation of alcohols is often carried out using high-
and, as a result, allows access to high-value
cocatalysts.
In one example, DDQ and sodium nitrite
1
3,14
32
are utilized for the oxidation of benzylic and allylic alcohols.
However, the authors note that the use of alcohols containing
electron-withdrawing groups gave unsatisfactory yields
2
,3
oxidation-state metal salts usually in excess. These metal-
based reagents are not ideal since many, such as chromium(VI),
lead(IV), and manganese(VII) compounds, are toxic and pose
some serious health risks. In addition, they can be expensive,
require the use of relatively scarce elements, and produce
hazardous waste streams. As a result, considerable efforts have
been made to use metals in catalytic amounts or nonmetallic
(
Scheme 1). This is most likely due to the one-electron
33
reduction potential of DDQ (Ered = 0.51 V vs SCE), which
may be too low to oxidize these electron-poor alcohols. We
now report the remarkable effect of visible light on such
catalytic DDQ oxidations that allows the oxidation not only of
less reactive benzylic and allylic alcohols (Scheme 1) but also of
β-O-4 lignin models under mild conditions.
15−18
reagents to effect the oxidation of alcohols.
Examples of
the nonmetallic methods, a process that we term organo-
oxidation, include DMSO-based oxidations, hypervalent iodine
Of the methods that employ substoichiometric amounts of
2
,3
DDQ, the most attractive appeared to be the nitrite-based
reagents, and TEMPO-based protocols.
2
4,30,31
protocols.
In the presence of oxygen, these generate
One particular organo-oxidant that is capable of performing a
wide variety of oxidative transformations is 2,3-dichloro-5,6-
nitrogen dioxide, a sufficiently strong oxidant to efficiently
1
9,20
recycle the DDQH . However, under these conditions, our test
2
dicyano-1,4-benzoquinone (DDQ).
Examples of its use
2
1,22
23
reaction, the oxidation of 1-phenylethanol to acetophenone
(Table S1), resulted in only a 13% conversion. Recently,
Fukuzumi and co-workers have shown that triplet-excited DDQ
include oxidative cyclizations,
aromatizations, and de-
However, the stoichiometric use of this
2
4,25
hydrogenations.
oxidant results in equimolar quantities of the corresponding
hydroquinone (DDQH ) byproduct that makes purification
2
difficult on a large scale. In addition, DDQ is moderately
expensive with a cost of $680/mol (August 2014), and there
Received: September 9, 2014
Published: September 24, 2014
©
2014 American Chemical Society
5224
dx.doi.org/10.1021/ol502664f | Org. Lett. 2014, 16, 5224−5227

Organic Letters
Letter
Scheme 1. Alcohol Oxidations Using Catalytic DDQ
Table 1. Visible-Light-Enhanced Oxidation of Allylic and
Benzylic Alcohols with Catalytic Amounts of DDQ
(
Reactions Carried out on 1 mmol Scale in Pyrex Vessels)
(3
DDQ*) has a much stronger oxidizing ability (E = 3.18 V
red
34
vs SCE). As a result, we sought to develop a procedure in
which benzylic and allylic alcohols could be oxidized under
visible light irradiation using catalytic amounts of DDQ and
sodium nitrite or tert-butyl nitrite as efficient cocatalysts, with
oxygen as the terminal oxidant.
For consistency of irradiation, we initially used a “sunlight-
mimicking” lamp, a commonly employed light source in
commercial glasshouses. The effect was dramatic in that
conversion to acetophenone increased to 55% compared to
the “dark” reaction. Further experimentation included the
screening of catalyst loadings, solvents, and concentrations, as
well as a range of control experiments, and the results are
summarized in the Supporting Information.
With the photochemical conditions established, we inves-
tigated the reactivity of a variety of alcohol substrates (Table
1
); reactions under dark conditions (method A) are shown for
comparison. Benzylic alcohols were found to give good to
excellent yields, such as 1-phenyl-2-propyn-1-ol (entry 2),
benzyl alcohol (entry 3), and diphenylmethanol (entry 4). In
addition, some improvement in yield was also seen when using
allyl alcohols, such as (S)-perillyl alcohol (entry 6) and 3,5,5-
trimethylcyclo-2-hexen-1-ol (entry 7), which afforded yields of
8
1 and 87%, respectively. In all cases, conversions were
significantly higher and reaction times were lower in
comparison with the dark reaction.
With benzylic alcohols containing electron-withdrawing
groups, the effects of light were even more marked. Thus, for
4
-chlorobenzyl alcohol (entry 8) and 1-(4-chlorophenyl)-
ethanol (entry 9), very little reaction was observed without
irradiation, even with stoichiometric quantities of DDQ.
However, in 6−10 h, complete conversion was achieved using
the visible light source, affording yields of 88 and 94%,
respectively. Interestingly, if 4-chlorobenzyl alcohol was left for
longer than 6 h, a significant quantity of 4-chlorobenzoic acid
was isolated. This process requires no DDQ or NaNO and
2
occurs readily when a sample of 4-chlorobenzaldehyde in
dimethyl carbonate is irradiated with visible light.
a
b
1
20 mol % of DDQ and nitrite used. Conversion measured by H
c
Due to the poor reactivity of some highly electron-deficient
alcohols even under irradiation using method B, an alternative
set of conditions was developed. In these conditions (method
C), the sodium nitrite and acetic acid were replaced with tert-
NMR integration. Same result obtained when using 5 mol % of
DDQH
mol % of DDQ and nitrite used.
d e
in place of DDQ. 15 mol % of DDQ and nitrite used. 10
2
3
0
butyl nitrite, affording high yields of the corresponding
aldehydes. In particular, reactions of 4-(trifluoromethyl)benzyl
alcohol (entry 12) and 4-nitrobenzyl alcohol (entry 13), which
have been reported as unsuccessful with catalytic DDQ with
27
Mn(OAc) (8 equiv) as co-oxidant, afforded yields of 74 and
77%, respectively. Since the conditions are chosen to reoxidize
the DDQH as it is formed, it is no surprise that the oxidation
3
2
5
225
dx.doi.org/10.1021/ol502664f | Org. Lett. 2014, 16, 5224−5227

Organic Letters
Letter
reaction can be carried out by starting from DDQH as reagent
in place of DDQ (entry 10) without loss of efficiency or yield.
sea level). Although routinely carried out on 1 mmol scale, no
reduction in conversion is observed on 10 mmol scale (entries
4 and 7; 90 and 47% conversion in sunlight after 5.5 h,
respectively).
2
Given that DDQ is believed to oxidize substrates via a SET
3
5,36
mechanism,
we sought evidence of radical intermediates.
When using (4-chlorophenyl)(cyclopropyl)methanol as sub-
strate (entry 14), no cyclopropane ring opening was observed.
On the other hand, when butylated hydroxytoluene (BHT) was
added, little or no oxidation was observed. For example, with 1-
We also investigated the relative rates of reaction of allylic
alcohols versus benzylic alcohols (see Supporting Information
for details). In these competition experiments, using perillyl
alcohol and 3,5,5-trimethylcyclohex-2-en-1-ol combined with
either benzyl alcohol or 4-chlorobenzyl alcohol, the allylic
alcohols are oxidized faster.
(
4-chlorophenyl)ethanol, a conversion of 56% was observed as
opposed to 100% when no BHT was added, but with all other
examples, including activated benzyl alcohols that ordinarily
undergo complete conversion, no conversion was observed.
Subsequently, we explored how the reactions performed in
sunlight compared with the visible light source (Table 2).
Finally, we sought to apply the procedure to several β-O-4
lignin models (Table 3) to determine its applicability and
Table 3. Lignin Model Oxidations with Catalytic Amounts of
DDQ
Table 2. Photochemical Alcohol Oxidations in Natural Light
(Reactions Carried out on 1 mmol Scale in Pyrex Vessels)
a
b
Synthesized using method C. synthesized using method A.
selectivity. A number of lignin models have been employed
37
ranging from simple benzylic alcohols to complex oligomers,
and various oxidative methods for lignin degradation have been
12
a
b
c
developed recently. These include vanadium oxo catalysts,
2
0 mol % of DDQ and nitrite used. 10 mmol scale, 5.5 h. 10 mol %
9
8,10
of DDQ and nitrite used.
cobalt complexes, TEMPO-based oxidants,
and biotrans-
11
formations. Under our conditions, vanillyl alcohol (Table 3,
entry 1) oxidized cleanly to the aldehyde to give vanillin in 78%
yield. Reactions with simple diols (entries 2 and 3) showed
complete selectively to give the benzylic ketones in high yields
of 89−93%. In addition, some alternative β-O-4 lignin models
were investigated (entries 4 and 5), both of which afforded
excellent yields. In particular, one lignin model (entry 5)
required only 1.5 mol % of the DDQ catalyst, with no
irradiation, to afford an excellent 92% yield of the ketone,
Results demonstrate that even with a relatively low natural
illuminance of 32 000 lx, good conversions were observed in
just 4.5 h. These results are comparable to the sunlight-
mimicking lamp that produced an average of 80 000 lx.
Alcohols such as 1-phenylethanol (entry 1) and 4-methylbenzyl
alcohol (entry 2) afforded slightly higher conversions of 79 and
77%, respectively, under sunlight. 4-Chlorobenzyl alcohol
(
entry 4) was found to give a 90% conversion in natural
8
,10
light, compared with a lower 64% conversion under artificial
illumination. The highly electron-deficient 4-trifluoromethyl
benzyl alcohol and 4-nitrobenzyl alcohol (entries 6 and 7) were
found to give conversions of 62 and 40%, respectively. These
conditions allow a fast and highly efficient synthesis, even in
relatively poor sunlight (March, latitude 52°56′ N, 32 m above
comparable to other methods.
In summary, we have developed a highly efficient oxidation
of benzylic and allylic alcohols under visible light irradiation
using catalytic amounts of DDQ and sodium nitrite or tert-butyl
nitrite. The procedure can be performed effectively even in
relatively poor sunlight or alternatively using a visible light
5
226
dx.doi.org/10.1021/ol502664f | Org. Lett. 2014, 16, 5224−5227

Organic Letters
Letter
source; substrates which are usually unreactive with DDQ, such
as 4-nitrobenzyl alcohol, afford high yields upon irradiation
with visible light. The method can also be applied to β-O-4
lignin models, potential precursors to high-value aromatic
compounds, selectively oxidizing the secondary benzylic alcohol
in high yield.
(20) Buckle, D. R.; Collier, S. J.; McLaws, M. D. 2,3-Dichloro-5,6-
dicyano-1,4-benzoquinone. e-EROS Encyclopedia of Reagents for
Organic Synthesis; Wiley: New York, 2005.
(
21) Lewis, J. R.; Paul, J. G. J. Chem. Soc., Perkin Trans. 1 1981, 770−
75.
22) Chang, J.; Zhao, K.; Pan, S. Tetrahedron Lett. 2002, 43, 951−
54.
7
(
9
(
23) Haldar, P.; Guin, J.; Ray, J. K. Tetrahedron Lett. 2005, 46, 1071−
ASSOCIATED CONTENT
■
1074.
*
S
Supporting Information
(24) Zhang, W.; Ma, H.; Zhou, L.; Sun, Z.; Du, Z.; Miao, H.; Xu, J.
Full experimental details and copies of H and 13C NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
1
Molecules 2008, 13, 3236−3245.
(25) Pi, H.-J.; Liu, H.; Du, W.; Deng, W.-P. Tetrahedron Lett. 2009,
5
(
0, 4529−4531.
26) Adams, J. P.; Alder, C. M.; Andrews, I.; Bullion, A. M.;
Campbell-Crawford, M.; Darcy, M. G.; Hayler, J. D.; Henderson, R.
K.; Oare, C. A.; Pendrak, I.; Redman, A. M.; Shuster, L. E.; Sneddon,
H. F.; Walker, M. D. Green Chem. 2013, 15, 1542−1549.
AUTHOR INFORMATION
Corresponding Author
■
*
(27) Cosner, C. C.; Cabrera, P. J.; Byrd, K. M.; Thomas, A. M. A.;
E-mail: c.j.moody@nottingham.ac.uk.
Notes
Helquist, P. Org. Lett. 2011, 13, 2071−2073.
(28) Liu, L.; Floreancig, P. E. Org. Lett. 2010, 12, 4686−4689.
(29) Chandrasekhar, S.; Sumithra, G.; Yadav, J. S. Tetrahedron Lett.
The authors declare the following competing financial
interest(s): C.J.M. and H.F.S. are are stockholders in
GlaxoSmithKline.
1
(
996, 37, 1645−1646.
30) Shen, Z.; Dai, J.; Xiong, J.; He, X.; Mo, W.; Hu, B.; Sun, N.; Hu,
X. Adv. Synth. Catal. 2011, 353, 3031−3038.
31) Shen, Z.; Sheng, L.; Zhang, X.; Mo, W.; Hu, B.; Sun, N.; Hu, X.
(
ACKNOWLEDGMENTS
We thank the Engineering and Physical Science Research
Council and GlaxoSmithKline for support of this work.
■
Tetrahedron Lett. 2013, 54, 1579−1583.
(32) Wang, L.; Li, J.; Yang, H.; Lv, Y.; Gao, S. J. Org. Chem. 2012, 77,
7
90−794.
33) Fukuzumi, S.; Ohkubo, K.; Tokuda, Y.; Suenobu, T. J. Am.
Chem. Soc. 2000, 122, 4286−4294.
34) Ohkubo, K.; Fujimoto, A.; Fukuzumi, S. J. Am. Chem. Soc. 2013,
(
REFERENCES
■
(
(
1) Ba
̈
ckvall, J.-E. Modern Oxidation Methods; Wiley-VCH:
1
(
(
(
35, 5368−5371.
Weinheim, Germany, 2010.
35) Cheng, D.; Bao, W. Adv. Synth. Catal. 2008, 350, 1263−1266.
36) Zhang, Y.; Li, C.-J. J. Am. Chem. Soc. 2006, 128, 4242−4243.
37) Forsythe, W. G.; Garrett, M. D.; Hardacre, C.; Nieuwenhuyzen,
(
2) Tojo, G.; Fernan
Ketones: A Guide to Current Common Practice; Springer Science
Business Media: New York, 2010.
3) Haines, A. H. Methods for Oxidation of Organic Compounds V2:
́
dez, M. Oxidation of Alcohols to Aldehydes and
+
(
M.; Sheldrake, G. N. Green Chem. 2013, 15, 3031−3038.
Alcohols, Alcohol Derivatives, Alkyl Halides, Nitroalkanes, Alkyl Azides,
Carbonyl Compounds Hydroxyarenes and Aminoarenes; Academic Press:
London, 1988.
(
4) Fuchs, P. L. Handbook of Reagents for Organic Synthesis: Catalytic
Oxidation Reagents; Wiley & Sons: Chichester, UK, 2013.
5) Zakzeski, J.; Bruijnincx, P. C. A.; Jongerius, A. L.; Weckhuysen, B.
M. Chem. Rev. 2010, 110, 3552−3599.
6) Yan, N.; Zhao, C.; Dyson, P. J.; Wang, C.; Liu, L.-t.; Kou, Y.
ChemSusChem 2008, 1, 626−629.
7) Crestini, C.; Crucianelli, M.; Orlandi, M.; Saladino, R. Catal.
Today 2010, 156, 8−22.
8) Rahimi, A.; Azarpira, A.; Kim, H.; Ralph, J.; Stahl, S. S. J. Am.
(
(
(
(
Chem. Soc. 2013, 135, 6415−6418.
(
(
9) Biannic, B.; Bozell, J. J. Org. Lett. 2013, 15, 2730−2733.
10) Nguyen, J. D.; Matsuura, B. S.; Stephenson, C. R. J. J. Am. Chem.
Soc. 2014, 136, 1218−1221.
11) Sainsbury, P. D.; Hardiman, E. M.; Ahmad, M.; Otani, H.;
Seghezzi, N.; Eltis, L. D.; Bugg, T. D. H. ACS Chem. Biol. 2013, 8,
151−2156.
12) Son, S.; Toste, F. D. Angew. Chem., Int. Ed. 2010, 49, 3791−
794.
(
2
(
3
(
(
13) Kleinert, M.; Barth, T. Energy Fuels 2008, 22, 1371−1379.
14) Hanson, S. K.; Wu, R.; Silks, L. A. P. Angew. Chem., Int. Ed.
2
(
012, 51, 3410−3413.
15) Chorghade, R.; Battilocchio, C.; Hawkins, J. M.; Ley, S. V. Org.
Lett. 2013, 15, 5698−5701.
16) Gowrisankar, S.; Neumann, H.; Goerdes, D.; Thurow, K.; Jiao,
H.; Beller, M. Chem.Eur. J. 2013, 19, 15979−15984.
17) Liang, S.; Wen, L.; Lin, S.; Bi, J.; Feng, P.; Fu, X.; Wu, L. Angew.
Chem., Int. Ed. 2014, 53, 2951−2955.
18) Prebil, R.; Stavber, G.; Stavber, S. Eur. J. Org. Chem. 2014, 2014,
95−402.
19) Walker, D.; Hiebert, J. D. Chem. Rev. 1967, 67, 153−195.
(
(
(
3
(
5
227
dx.doi.org/10.1021/ol502664f | Org. Lett. 2014, 16, 5224−5227