Organocatalytic Chemoselective Primary Alcohol Oxidation and Subsequent Cleavage of Lignin Model Compounds and Lignin

Article abstract of DOI:10.1002/cssc.201700703

A one-pot two-step degradation of lignin β-O-4 model compounds initiated by preferred oxidation of the primary over the secondary hydroxyl groups with a TEMPO/DAIB system has been developed [TEMPO=2,2,6,6-tetramethylpiperidine-N-oxyl, DAIB=(diacetoxy)iodobenzene]. The oxidised products are then cleaved by proline-catalysed retro-aldol reactions. This degradation methodology produces simple aromatics in good yields from lignin model compounds at room temperature with an extension to organosolv beech-wood lignin (L1) resulting in known cleavage products.

Full text of DOI:10.1002/cssc.201700703

Accepted Article
Title: Organocatalytic Chemoselective Primary Alcohol Oxidation and
Subsequent Cleavage of Lignin Model Compounds and Lignin
Authors: Saumya Dabral, Jose Hernández, Paul Kamer, and Carsten
Bolm
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Link to VoR: http://dx.doi.org/10.1002/cssc.201700703
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ChemSusChem
10.1002/cssc.201700703
COMMUNICATION
Organocatalytic Chemoselective Primary Alcohol Oxidation and
Subsequent Cleavage of Lignin Model Compounds and Lignin
[
a]
[a]
[b]
[a]
Saumya Dabral, José G. Hernández, Paul C. J. Kamer,* Carsten Bolm*
OH
β O
Abstract: A one-pot two-step degradation of lignin β-O-4 model
compounds initiated by preferred oxidation of the primary over the
secondary hydroxyl groups with a TEMPO/DAIB system has been
developed. The oxidised products are then cleaved by proline-
catalysed retro-aldol reactions. This degradation methodology
produces simple aromatics in good yields from lignin model
compounds at room temperature with an extension to organosolv
α
R1
R2
γ
OH
1
Previous work
This work
oxidation /
dehydrogenation
secondary
oxidation
primary
oxidation
beech wood lignin L1 resulting in known cleavage products
.
O
OH
O
O
O
R1
R2
R1
R2
Lignin is the largest natural reservoir of aromatics and the
second most abundant biopolymer representing 30% of non-
fossil organic carbon on earth. Paper and pulp industries are
major producers of industrial lignin, which occurs as a waste by-
OH
2
3
acid-promoted
or reductive
retro-aldol
reaction
[
1]
product during wood-processing. Although lignin has been
used for obtaining low-added-value materials such as dispersing
O
aromatics
[
1a]
[1]
HO
O
O
or binding agents, the majority of it is burnt. Recently, more
and more research is focused on generating valuable co-
products (energy, chemicals and fuels) of high market value
H
R1
R2
+
R2
+
4
5
7
[
1,2]
from this renewable raw material.
At the same time, these
Scheme 1. Oxidations of lignin β-O-4 model compounds 1.
efforts are intended to decrease the existing dependence on
fossil-based raw materials and hence help to reduce carbon
[6g]
or DDQ
followed by acid promoted or reductive C
β
-O bond
[
3]
footprints.
[6d,6g]
cleavage reactions (Scheme 1, left).
Both routes proceeded
The variety of interconnecting bonds of the various building
blocks in lignin offer many possibilities for the production of bulk
chemicals and functional materials. In our group, the cleavage of
lignin at β-O-4 linkages has been of prime focus, because these
bonds are most dominant in the three-dimensional biopolymer
through common ketonic species such as 2 resulting from the
oxidation of secondary hydroxyl group at the benzylic position of
1
. However, attempts to address the oxidation of primary
[8-10]
hydroxyl group of 1 have only been met with limited success.
Realising that this process would lead to intermediates such as
[
4]
varying from 45% to 60% depending on the wood type.
3
5
prone for retro-aldol reactions, providing cleavage products 4,
and 7 (Scheme 1, right), we felt motivated to explore this less
However, due to the undefined amorphous nature of lignin,
which mainly consists of methoxylated aryl propane units, those
studied alternative. Herein we report the success of the
approach and a proof-of-principle study for a transition metal-
[
1,2,4]
degradation studies have been challenging.
In most of the
[
5]
cases, an initial application of lignin model compounds proved
useful for gaining a better understanding of the chemical
transformations taking place on the structurally complex lignin.
Recently, various groups reported on lignin depolymerization
studies that were initiated by oxidative ketone formations in
[11]
free (organocatalytic) lignin degradation process.
Lately iodine has been gaining considerable attention as a
cheap and environmentally benign element of choice for a
variety of catalytic chemical transformations. Around 16% of the
iodine produced yearly is utilised in various industrial catalytic
[
6]
β-O-4 units. DFT calculations revealed that such processes
weakened the connected –O linkages by ∼14 kcal/mol
Scheme 1), thereby facilitating subsequent bond cleavage
[12]
processes. In particular, hypervalent iodine reagents such as
C
β
(
diacetoxy)iodobenzene [PhI(OAc)
2
, DAIB] are versatile and
[
7]
(
environmental safe polyvalent iodine reagents used as mild and
reactions. Exemplified are such transformations by the works of
Stahl and Westwood, who independently described their two-
step depolymerisation pathways through alcohol oxidations
using catalytic amounts of AcNH- TEMPO (TEMPO = 2,2,6,6-
[12,13]
selective oxidants.
Following this idea, we were intrigued by
the fact that DAIB in combination with TEMPO enables the
selective catalytic oxidation of primary hydroxyl groups in the
[13]
presence of secondary ones. Applying this system to lignin
[
6b]
tetramethylpiperidine-N-oxyl), combined with inorganic acids
was foreseen to open new synthetic opportunities. To test this
hypothesis, we focused our attention on the chemoselective
oxidation of the γ-hydroxyl group present in the lignin model
compound erythro dilignol 1a (Scheme 2). Neither with TEMPO
(1.0 equiv) nor with DAIB (1.3 equiv) alone a considerable
conversion of 1a was observed after 24 h of stirring in
acetonitrile at ambient temperature. Combining both the
reagents, however, led to a significant increase in the activity.
With 0.3 equiv of TEMPO and 1.3 equiv of DAIB a 56%
conversion of 1a was observed after only 3 h at room
[
[
.
a]
S. Dabral, Dr. J. G. Hernández, Prof. Dr. C. Bolm
Institute of Organic Chemistry, RWTH Aachen University,
Landoltweg 1, D-52056 Aachen, Germany.
E-mail: carsten.bolm@oc.rwth-aachen.de
Prof. Dr. P. C. J. Kamer
School of Chemistry, EaStCHEM University of St Andrews, North
Haugh, St Andrews, Fife KY169ST (UK)
E-mail: pcjk@st-andrews.ac.uk
b]
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under .......
[14]
temperature providing aldehyde 3a in 43% yield.
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ChemSusChem
10.1002/cssc.201700703
COMMUNICATION
OH
OMe
OH
OMe
OH
OMe
conditions
(see text and SI)
TEMPO (0.1 equiv)
DAIB (1.3 equiv)
addition of
organocatalyst
MeO
MeO
O
MeO
MeO
O
O
MeO
MeO
O
3
a
MeCN, rt
MeCN, rt, 7 h
(0.2 equiv)
OH
OH
1
a
3a
1
a
O
OMe
O
O
O
OMe
OMe
O
MeO
MeO
MeO
MeO
MeO
MeO
HO
MeO
H
H
+
OH
MeO
H
O
2
a (not observed)
4a
4a
5a
6a
•
•
TEMPO (1 equiv) or DAIB (1.3 equiv): no conv. of 1a (24 h)
TEMPO (0.3 equiv) + DAIB (1.3 equiv): 56% conv. of 1a (3 h), 43% of 3a and traces of 4a
organocatalyst
DL-proline
DL-proline methyl ester
pyrrolidine
3a
%]
4a
[%]
5a
[%]
6a
[%]
[
•
optimal conditions:
---
40
---
7
0
26
5
10
5
14
58
TEMPO (0.1 equiv), DAIB (1.3 equiv): >99% conv. of 1a (7 h), 78% of 3a and 14% of 4a
23
2
5
[
13]
Scheme 2. Chemoselective oxidation of lignin β-O-4 model compound 1a.
Scheme 3. One-pot chemoselective oxidation of 1a followed by
[
16]
To our delight ketone 2a was not observed confirming the high
chemoselectivity of the oxidation. Apparently, the primary
hydroxyl group of 1a had been oxidised with great preference
organocatalytic retro-aldol reaction of 3a.
The latter product was formed predominantly, when the more
basic pyrrolidine was applied instead of DL-proline (Scheme
[
13]
over the secondary one. Trace quantities of veratraldehyde
4a) were detected as by-products, which were presumably
formed by the retro-aldol reaction of 3a catalysed by the AcOH
[
17]
(
3). To understand the overall reaction pathway, the progress
1
of the reaction for 1a was monitored by H-NMR and gas
[
15]
developed in situ from DAIB.
reaction parameters finally led to the optimal reaction
Further adjustments of the
chromatography-mass spectrometry (GC-MS) under the
optimised reaction conditions (Figure 1). The reaction profile
showed a good correlation between the consumption of 1a
(black line) and the formation of 3a (grey line), reaching its
maximum values (conv. of 1a = >99%, yield of 3a = 79%) after
7 h. Additionally, the formation of veratraldehyde (4a) (grey
dash) was traced from the start of the reaction, which
resulted in a 16% yield after the first 7 h. Thereafter the
addition of DL-proline led to a spontaneous retro-aldol
cleavage of 3a. The yield of (4a) increased to 50% after the
first hour of addition and plateaued out at 80% within the
next 5 h. A combined analysis of the reaction mixture also
led to the detection of the retro-aldol product 2-(2-
methoxyphenoxy) acetaldehyde (7a) (black dash), which
followed a pattern similar to 4a and resulted in a 10% yield
after 7 h. This reactive acetaldehyde derivative proved
unstable under column chromatographic conditions and
was thus quantified by GC with respect to the internal
standard n-octadecane (see ESI sections 7 and 8 for details).
[
16]
conditions, which involved the use of 0.1 equiv of TEMPO and
.3 equiv of DAIB in acetonitrile for 7 h at room temperature.
1
Next, we focused on the aforementioned retro-aldol step with the
goal to find a readily available organocatalyst, which could
directly be included into a one-pot reaction sequence starting
with the previously developed chemoselective oxidation of lignin
β-O-4 model compounds 1. Again, erythro dilignol 1a was
selected as a representative starting material. To our delight,
simple DL-proline proved applicable here, effectively catalysing
the cleavage of 3a, which had been generated in-situ from 1a
[
17]
before (Scheme 3). Thus, adding 0.2 equiv of DL-proline into
the reaction mixture obtained under the preceding oxidation
conditions followed by stirring for 5 h at ambient temperature
afforded veratraldehyde (4a) and guaiacol (5a) in 70% and 26%
yields respectively, over two steps. Additionally, 5% of
elimination product 6a was isolated by column chromatography
Using the methyl ester of DL-proline as catalysts slowed down
the retro-aldol reaction and favoured the formation of elimination
product 6a.
Figure 1. Reaction profile for the one-pot two-step chemoselective oxidation of lignin β-O-4 model compound 1a (0.250 mmol) under optimised reaction
conditions.
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10.1002/cssc.201700703
COMMUNICATION
[
16]
Table 1. One-pot two-step degradation of β-O-4 lignin model compounds.
OH
O
first: TEMPO (0.1 equiv)
DAIB (1.3 equiv), MeCN, rt
O
HO
O
H
R1
R2
R1
R2
R2
then: DL-proline (0.2 equiv), rt
OH
O
H
1
4
5
7
[a]
Entry
Substrate
Cleavage products [Yield]
OH
O
OMe
H
OMe
MeO
MeO
MeO
HO
O
H
O
1
1
MeO
HO
MeO
O
1
a
4a 76% (70%)
5a 40% (26%)
7a 20%
OH
OMe
OMe
H
OMe
MeO
MeO
O
O
MeO
MeO
HO
O
O
2
3
4
HO
MeO
5a 42% (20%)
H
O
O
4a 74% (67%)
7
a 19%
1
b
OH
H
OMe
HO
O
H
O
O
O
O
O
HO
MeO
4
b 70% (59%)
1
c
5a 35% (12%)
7a 14%
H
O
OMe
O
OH
OMe
MeO
MeO
HO
O
MeO
MeO
MeO
HO
H
O
H
OMe
c 79% (68%)
5a 46% (28%)
7a 18%
OMe 1d
4
MeO
OH
H
O
OMe
HO
OMe
O
MeO
MeO
O
MeO
MeO
O
5
6
MeO
HO
MeO
5b 29% (16%)
OMe
7b 32%
1
e
4a 73% (60%)
H
OH
OMe
OMe
HO
MeO
HO
MeO
HO
O
O
H
O
MeO
HO
O
1
f
4d 24% (15%)
5a 17% (5%)
7a 6%
[
a] Quantifications done by gas chromatography with respect to n-octadecane as an internal standard. Values within the parenthesis are obtained
after column chromatography and are based on an average of two runs.
Moreover, stirring a solution of 7a and DL-proline in MeCN
at room temperature resulted in the formation of guaiacol
Besides the above-mentioned products, minor oxidative by-
products from veratraldehyde (4a) and guaiacol (5a) were also
[
18]
(
5a) in 69% GC yield after 1 h (see ESI section 8.2.8). This
observed (see ESI Table S6 for details).
asserts the low stability of aldehyde 7a and the reduced yields
observed, in comparison to 4a, after the addition of DL-proline
during the second half of the reaction profile (see Figure 1).
With the aim of exploring the generality of the organocatalytic
primary alcohol hydroxyl oxidation/retro-aldol approach,
analogous cleavage reactions were performed with other β-O-4
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ChemSusChem
10.1002/cssc.201700703
COMMUNICATION
(
a)
6'
(d)
Aliphatic Region
Aromatic Region
(Before reaction)
HO
MeO
5'
4'
1'
2'
1'
6
'
2'
3'
(
Before reaction)
γ
HO
HO
α
5'
β
O
γ
OMe
3
'
4'
1
β
(
OMe)
α
O
6
2
6
5
5
3
1
2
(MeO)
OMe
(MeO)
4
O
4
O
3
OMe
A
C
(e)
HO
R
O
(
b)
MeO
6'
2
6
1'
2'
γ
5'
4'
HO
α
MeO
OMe
β
O
3
'
1
(
OMe)
6
5
2
S
3
Aliphatic Region
After reaction)
Aromatic Region
(After reaction)
(MeO)
OMe
4
O
(f)
(
O
A'
2
6
MeO
OMe
(c)
OMe
3
'
S'
O
2
'
4
'
1
'
5'
O
(OMe)
(g)
γ
α'
β'
γ'
6
'
HO
2
β
α
6
(
MeO)
5
6
O
1
2
4
5
O
MeO
3
B
OMe
G
’
Figure 2. 2D HSQC NMR spectra (in DMSO-d
6
) of beech wood lignin (L1): top: before the reaction; bottom: after the two-step degradation reaction; (a) β-O-4 aryl
’
ether linkages with a free-OH at the γ-carbon; (b) β-O-4 aryl ether linkages with acetylated and/or p-hydroxybenzoated -OH at γ-carbon; c) resinol substructures
formed by β−β-, α-O-γ-, and γ-O-α’-linkages; d) phenylcoumaran substructures formed by β-5- and α-O-4-linkages; e) syringyl units; f) syringyl unit with oxidised
’
’
’
’
benzylic position; g) guaiacyl units.
lignin model compounds having primary and secondary hydroxyl
groups but varying in the ratios of guaiacyl (G) and syringyl (S)
aromatic nuclei and their erythro and threo stereostructures
Applying G-type model compound 1f with a free phenolic
hydroxyl group as substrate led to a high conversion of the
[
20]
starting material, with the formation of 4d and 5a in 24% and
17% GC yields respectively (Table 1, entry 6; for details on
product distribution see ESI 8.2.6).
[
19]
(
Table 1). Also for those substrates the TEMPO/DAIB system
showed excellent selectivity towards the oxidation of the primary
hydroxyl groups of 1a-f. Furthermore, the subsequent addition of
DL-proline catalysed the retro-aldol cleavage reaction in all the
cases. Table 1 shows the yields for the resulting benzaldehyde
derivatives 4 along with the expected methoxyphenols 5 and 2-
aryloxyacetaldehydes 7 (component counterparts). The low
yields for products 7 and 5 after column purification can be
attributed to their low stability and volatile nature, respectively.
In general, all model compounds showed high degradations and
essentially full conversions (>98%) of 1 were observed after the
organocatalytic two-step reaction sequence. Threo dilignol 1b
showed a similar reactivity as its erythro counterpart 1a affording
veratraldehyde (4a) in 67% yield after column chromatography
Substituting DAIB by its immobilised variant poly[4-
[
13e,f]
(diacetoxyiodo)-styrene]
and performing the TEMPO
catalysis for 28 h at ambient temperature resulted in the
degradation of model compound 1a to a mixture of 4a and 5a in
80% and 48% yield respectively, under otherwise identical
reaction conditions (Scheme 4). Pleasantly, using the recycled
iodine reagent in a second run gave almost identical
[
21]
product yields (4a: 76%, 5a: 50%).
The success of the sequential organocatalytic oxidative
degradation strategy on lignin model compounds
encouraged us to test its applicability on the cleavage of an
organosolv beech wood lignin (L1) sample following the
one-pot procedure. Based on the 2D HSQC analysis of the
(
Table 1, entries 1 and 2). Also, model compounds 1c-e varying
in sterics and substitution pattern at the arenes reacted smoothly, first step, the oxidation of the lignin sample resulted in a
under similar reaction conditions, leading to the corresponding
aldehydes and methoxyphenol derivatives in good yields (Table
reduction of C
γ
–
H signals with a corresponding increase in
γ
the carbonyl content typical for aldehydes (δ = 9.5–10.0 and
175–200 ppm) (ESI, Figure S18). Furthermore, two new cross-
peaks at δ = 5.5/70.0 and 5.0/87.0 ppm were observed after the
primary oxidation step that could correspond to the shifted
1
, entries 3-5). For instance, cleavage of dilignol 1c with a
(
methylenedioxy) phenyl-capped arene provided 4b in 59% yield
after purification along with the detection of 14% of 7a and 35%
of guaiacol (5a) by GC (Table 1, entry 3). Furthermore, the
presence of the trioxygenated S-type nuclei in 1d had no effect
on the overall reaction time, and the expected 3,4,5-
trimethoxybenzaldehyde (4c) was isolated in 68% yield (see ESI
1
) TEMPO (10 mol%),
PS
I(OAc)2 (1.3 equiv)
MeCN, rt, 28 h
) DL-proline (20 mol%)
OH
OMe
O
OMe
MeO
MeO
O
MeO
MeO
HO
H
2
+
7
; Table 1, entry 4). Substrate 1e with bulkier ortho-substituents
OH
MeCN, rt, 5 h
4
a
5a
1
a
at the arene however required a longer reaction time, and finally
afforded the aldehydes 4a in 60% yield (see ESI 7; Table 1,
entry 5).
Run 1:
Run 2:
80%
76%
48%
50%
Scheme 4. Two-step degradation of 1a using TEMPO/immobilized DAIB
catalytic system.
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COMMUNICATION
C
α
–
H
α
and
C
β
–
H groups post primary-alcohol-oxidation step.
β
Furthermore, the aliphatic and aromatic regions in the 2D-
NMR HSQC spectra both before and after the one-pot two-
step degradation (reaction of lignin sample L1) are also
2
2
depicted in figure 2. As revealed by the disappearance of
their characteristic signals, several interconnecting bonds
including the β-O-4 linkages contained in substructures A
and A’, the resinol units B, and phenylcoumaran
substructure
C were cleaved following the two-step
degradation strategy. Since the exact structural modifications
after the two-step cleavage reaction could not be specified by
the NMR technique, the reaction mixture was analysed by gel
permeation chromatography (GPC) to determine the post
degradation change in the molecular weights of lignin L1. Figure
3
shows the mass distribution for the organosolv lignin L1 (top)
and the corresponding elugram (bottom). A double shift in the
mass maximum of the treated sample L1 towards lower
molecular weights was observed (grey line). The maximum
mass value in the original L1 sample at 3537 Dalton (black line)
was significantly reduced by 29% and 41%. In addition, a broad
peak having initially a mass maximum at approximately 10206
Dalton showed a decrease of 32% after the cleavage. Most
importantly, the absence of peaks at higher molecular weights
after the reaction, greater than the original L1 sample, precluded
the possibility of lignin re-polymerisation under the cleavage
reaction conditions. In addition to this, the organic fraction, which
accounted to 15 wt% of the starting lignin L1 was also analysed
by GC-MS. This confirmed the presence of low-molecular
monomeric aromatics such as 0.3 wt% guaiacol, 2.5 wt%
syringaldehyde and 1.1 wt% vanillin, with respect to the starting
lignin sample, which are typical products found in the cleavage
reactions of hardwood lignin (see ESI for details).
In conclusion, we developed an organocatalytic one pot two-step
degradation strategy for lignin β-O-4 model compounds and
Figure 3. GPC measurements of the ethanosolv beech wood lignin sample
before (black) and after the treatment (grey). The mass values acquired are
relative with respect to the external calibrations with polystyrene sulfonate
standards.
[
23]
representative lignin sample L1 at room temperature.
In
contrast to the prevalent oxidations of the benzylic secondary
hydroxyl groups, the reaction sequence is initiated by a TEMPO-
catalysed DAIB oxidation addressing the primary hydroxyl units.
For this step, also a recyclable polymer-bound oxidant can be
applied. Proline-catalysed retro-aldol reactions then lead to
lignin degradations by various C–C bond cleavages as
confirmed by 2D NMR (HSQC), GPC, GC-MS. analysis. We
realise that for applying this proof-of principle approach on an
industrially relevant scale, the reagent amounts are high and the
production of monoaromatic products low. Consequently, our
future efforts will be directed towards the screening and
optimisation of realiable lignin samples obtained from different
upstream processes along with increasing the overall efficiency
of the process in terms of both oxidation as well as the
subsequent base cleavage reaction. In this context, based on
our preliminary results with immobilised DAIB variant, an
important advancement would be to develop a chemoselective
catalytic primary hydroxyl oxidation using supported oxidants in
a flow reactor system.
Acknowledgements
This research was supported by the European Union (Marie
Curie ITN ‘SuBiCat’ PITN-GA-2013-607044, S.D.) and by the
Distinguished Professorship Program at RWTH Aachen
University funded by the Excellence Initiative of the German
federal and state governments. We thank Dr. N. Anders (RWTH
Aachen University) for the GPC measurements and Dr. C.
Räuber (RWTH Aachen University) for helpful discussions
during the NMR investigations. Prof. Dr. R. Rinaldi (formerly MPI
für Kohlenforschung, Mülheim a.d.R.) is acknowledged for
supplying organosolv lignin L1.
Keywords: lignin • organocatalysis • alcohol oxidation • one-pot
•
retro-aldol • C –C-bond cleavage
α
[
1]
a) J. Zakzeski, P. C. A. Bruijnincx, A. L. Jongerius, B. M. Weckhuysen,
Chem. Rev. 2010, 110, 3552–3599; b) C. Xu, R. A. D. Arancon, J.
Labidi, R. Luque, Chem. Soc. Rev. 2014, 43, 7485–7500; c) B. M.
Upton, A. M. Kasko, Chem. Rev. 2016, 116, 2275–2306; d) S. H. Li, S.
Liu, J. C. Colmenares, Y. J. Xu, Green Chem. 2016, 18, 594–607; e) R.
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COMMUNICATION
Rinaldi, R. Jastrzebski, M. T. Clough, J. Ralph, M. Kennema, P. C. A.
Buijnincx, B. M. Weckhuysen, Angew. Chem. 2016, 128, 8296–8354;
Angew. Chem. Int. Ed. 2016, 55, 8164–8215.
[11] Note that in the (organocatalytic) retro-aldol process reported here, a
central C–C-bond is broken that can also be cleaved under ruthenium-
catalysis (in xylene at 160 °C). The product composition, however,
differs. T. vom Stein, T. den Hartog, J. Buendia, S. Stoychev, J.
Mottweiler, C. Bolm, J. Klankermayer, W. Leitner, Angew. Chem. 2015,
127, 5957–5961; Angew. Chem. Int. Ed. 2015, 54, 5859–5863.
[
2]
a) G. W. Huber, S. Iborra, A. Corma, Chem. Rev. 2006, 106, 4044–
098; b) A. J. Ragauskas, G. T. Beckham, M. J. Biddy, R. Chandra, F.
4
Chen, M. F. Davis, B. H. Davison, R. A. Dixon, P. Gilna, M. Keller, P.
Langan, A. K. Naskar, J. N. Saddler, T. J. Tschaplinski, G. A. Tuskan,
C. E. Wyman, Science 2014, 344, 1246843; c) Z. Strassberger, S.
Tanase, G.
[12] a) V. V. Zhdankin, Hypervalent Iodine Chemistry: Preparation, Structure
and Synthetic Application of Polyvalent Iodine Compounds, Wiley, New
York, 2013; b) Hypervalent Iodine Chemistry, Top. Curr. Chem., vol.
373 (Ed. T. Wirth), Springer, Switzerland, 2015; c) M. Ochiai, Chem.
Rec. 2007, 7, 12–23; d) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008,
108, 5299–5358; e) M. Uyanik, K. Ishihara, Chem. Commun. 2009,
2086–2099; f) V. V. Zhdankin, ARKIVOC, 2009, 1, 1–62; g) M. Uyanik,
K. Ishihara, ChemCatChem 2012, 4, 177–185; h) F. V. Singh, T. Wirth,
Chem. Asian J. 2014, 9, 950–971; i) M. S. Yusubov, V. V. Zhdankin,
Resource-Efficient Technol. 2015, 1, 49-67; j) A. Yoshimura, V. V.
Zhdankin, Chem. Rev. 2016, 116, 3328–3435.
Rothenberg, RSC Adv. 2014, 4, 25310–25318; d) C. Li, X. Zhao, A.
Wang, G. W. Huber, T. Zhang, Chem. Rev. 2015, 115, 11559–11624.
C. D. Scown, A. A. Gokhale, P. A. Willems, A. Horvath, T. E. McKone,
Environ. Sci. Technol. 2014, 48, 8446–8455.
[
[
3]
4]
a) T. Kleine, J. Buendia, C. Bolm, Green Chem. 2013, 15, 160–166; b)
J. Mottweiler, M. Puche, C. Räuber, T Schmidt, P. Concepción, A.
Corma, C. Bolm, ChemSusChem. 2015, 8, 2106–2113; c) S. Dabral, J.
Mottweiler, T. Rinesch, C. Bolm, Green Chem. 2015, 17, 4908–4912; d)
J. Mottweiler, T. Rinesch, C. Besson, J. Buendia, C. Bolm, Green
Chem. 2015, 17, 5001–5008. For a recent application of lignins as
mediators for mechanochemical organic transformations, see: e) S.
Dabral, M. Turberg, A. Wanninger, C. Bolm, J. G. Hernández.
Molecules, 2017, 22, 146..
[13] For the selective oxidation of primary hydroxyl groups in the presence
of secondary ones using TEMPO and DAIB, see: a) A. De Mico, R.
Margarita, L. Parlanti, A. Vescovi, G. Piancatelli, J. Org. Chem. 1997,
62, 6974–6977; b) T. M. Hansen, G. J. Florence, P. L. -Mas, J. Chen, J.
N. Abrams, C. J. Forsyth, Tetrahedron Lett. 2003, 44, 57–59; c) C. I.
Herrerías, T. Y. Zhang, C. –J. Li, Tetrahedron Lett. 2006, 47, 13–17; d)
J. -M. Vatèle, Tetrahedron Lett. 2006, 47, 715–718; for immobilized
DAIB/TEMPO catalytic systems: e) K. Sakuratani, H. Togo Synthesis
2003, 21–23; f) T. Dohi, K. I. Fukushima, T. Kamitanaka, K. Morimoto,
N. Takenagab, Y. Kita, Green Chem. 2012, 14, 1493–150.
[
5]
For recent synthetic approaches towards 1,3-dilignol type lignin model
compounds, see: a) J. Buendia, J. Mottweiler C. Bolm, Chem. Eur. J.
2
011, 17, 13877–13882; b) C. N. Njiojob, J. L. Rhinehart, J. J. Bozell N.
K. Long, J. Org. Chem. 2015, 80, 1771–1780. For the use of advanced
model compounds, see: c) P. J. Deuss, M. Scott, F. Tran, N. J.
Westwood, J. G. de Vries and K. Barta, J. Am. Chem. Soc. 2015, 137,
[14] Aldehyde 3a was unstable to column chromatography. The formation of
1
7
456–7467; d) C. W. Lahive, P. J. Deuss, C. S. Lancefield, Z. Sun, D. B.
3a was therefore monitored by H NMR spectroscopy of the crude
Cordes, C. M. Young, F. Tran, A. M. Z. Slawin, J. G. de Vries, P. C. J.
reaction mixture using the signals for the α,β protons as indicators. The
structural assignment was further confirmed by reduction of 3a with
Kamer, N. J. Westwood and K. Barta, J. Am. Chem. Soc. 2016, 138,
8
900–8911.
4
NaBD to give 1a-D. For details, see Supporting Information (Fig. S1).
[
6]
For selected reports on the chemoselective secondary alcohol oxidation
in 1,3-dilignol type lignin model compounds, see: a) A. Wu, B. O.
Patrick, E. Chung, B. R. James, Dalton Trans. 2012, 41, 11093–11106;
b) A. Rahimi, A. Azarpira, H. Kim, J. Ralph, S. S. Stahl, J. Am. Chem.
Soc. 2013, 135, 6415–6418; c) J. D. Nguyen, B. S. Matsuura, C. R. J.
Stephenson, J. Am. Chem. Soc. 2014, 136, 1218–1221; d) A. Rahimi,
A. Ulbrich, J. J. Coon, S. S. Stahl, Nature 2014, 515, 249–252; e) K.
Walsh, H. F. Sneddon, C. J. Moody, Org. Lett. 2014, 16, 5224−5227; f)
M. Dawange, M. V. Galkin, J. S. M. Samec, ChemCatChem. 2015, 7,
The conversion of 1a and the yields of 2a and 4a presented in Scheme
1
2 were determined by H NMR with 1,4-dinitrobenzene as internal
standard.
[15] A chemoselective TEMPO/DAIB oxidation of 1a with in the presence of
2 equiv of AcOH led to the formation of 3a and 4 in 68% and 24% yield,
respectively, thereby confirming the role of AcOH in the retro-aldol
reaction of 3a. For details, see Supporting Information (Table S1, entry
11).
[16] See Tables S1 and S2 in the Supporting Information.
[17] For the results of the catalyst screening, see Table S3 in the Supporting
Information.
4
01–404; g) C. S. Lancefield, O. S. Ojo, F. Tran, N. J. Westwood,
Angew. Chem. 2015, 127, 260–264; Angew Chem. Int. Ed. 2015, 54,
58–262; h) R. Zhu, B. Wang, M. Cui, J. Deng, X. Li, Y. Ma, Y. Fu,
2
[18] Guaiacol (5a) reacted with DAIB (1.0 equiv) and TEMPO (0.1 equiv)
leading to a mixture of products (see ESI 8.2.7 ). These results were in
agreement with the reported investigations on DAIB-assisted oxidations
of 5a to benzoquinone derivatives. For details, see: a) S. Quideau, L.
Pouységu, D. Deffieux, A. Ozanne, J. Gagnepain, I. Fabre, M. Oxoby,
ARKIVOC 2003, 6, 106–119; b) T. –C. Kao, G. J. Chuang, C. C. Liao,
Angew. Chem. 2008, 120, 7435–7437; Angew. Chem. Int. Ed. 2008, 47,
7325–7327; c) S. Y. Gao, S. K. Chittimalla, G. J. Chuang, C. -C Liao, J.
Org. Chem. 2009, 74, 1632–1639; d) T. Dohi, T. Nakae, N. Takenaga,
T. Uchiyama, K. I. Fukushima, H. Fujioka, Y. Kita, Synthesis 2012, 44,
1183–1189; e) S. K. Chittimalla, R. Kuppusamy, N. Akavaram, Synlett
2015, 26, 613–618; f) S. K. Chittimalla, C. Bandi, Tetrahedron Lett.
2016, 57, 15–19.
Green Chem. 2016, 18, 2029–2036.
[
[
7]
8]
S. Kim, S. C. Chmely, M. R. Nimlos, Y. J. Bomble T. D. Foust, R. S.
Paton, G. T. Beckham, J. Phys. Chem. Lett. 2011, 2, 2846–2852.
For observations related to primary alcohol oxidations in β-O-4 and β-1
model compounds, see: a) (vanadium-based catalysts) B. Sedai, C.
Díaz-Urrutia, R. T. Baker, R. Wu, L. A. “Pete” Silks, S. K. Hanson, ACS
Catal. 2013, 3, 3111–3122; b) (TEMPO/copper catalysts) ref. 6b.
In batch pulping of wood, primary alcohol oxidation followed by
retro-aldol reaction has been suggested as reaction mechanism for
cleavage of α-aryl ether bonds. In those reactions, alkali
[
9]
(
14%)/anthraquinone mixtures were applied at 170 °C for 100 min.
Selectivity issues concerning primary versus secondary hydroxyl
group oxidations have not been in the focus of those studies. For
details, see: a) A. D. Venica, C.-L. Chen, and J. S. Gratzl,
Holzforschung 2008, 62, 627-636; b) A. D. Venica, C.-L. Chen, and
J. S. Gratzl, Holzforschung 2008, 62, 637-644 and references
therein.
[19] S. Shimizu, T. Yokoyama, T. Akiyama and Y. Matsumoto, J. Agric.
Food Chem. 2012, 60, 6471–6476.
[20] The degradation of phenolic 1f under basic conditions can also
involve a Grob-type heterolytic fragmentation although then, other
products could be expected to be formed as well. For details, see
refs. 9a–b.
[
10] In a recent manuscript, the merger of photoredox and palladium
catalysis was reported to lead to products stemming from
secondary and primary oxidation (with the former ones in
preference). For details, see: M. D. Kärkäs, I. Bosque, B. S.
Matsuura and C. R. J. Stephenson, Org. Lett. 2016, 18, 5166–5169.
[21] The supported catalyst was regenerated as follows: A peracetic acid
solution was prepared by the dropwise addition of 30% H
mL) to Ac O (6 mL) at 0 °C. The solution was slowly warmed to
room temperature and stirred overnight. Then, this solution was
2 2
O (2.0
2
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ChemSusChem
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COMMUNICATION
added to the recovered poly(4-iodostyrene) (220 mg, 0.325 mmol).
The reaction was stirred at 50 °C overnight. The resultant mixture
was precipitated with diethyl ether and filtered to give poly[4-
(
diacetoxyiodo)styrene] (300 mg) as a light yellow powder.
[
[
22] For the interpretation of the structural changes within the lignin
samples, see: T. Q. Yuan, S. N. Sun, F. Xu and R. C. Sun, J. Agric.
Food Chem. 2011, 59, 10604–10614.
23] For alternative two-step lignin degradation approaches using
Pt/alumina catalysis, see: a) F. P. Bouxin, A. McVeigh, F. Tran, N. J.
Westwood, M. C. Jarvis and S. D. Jackson, Green Chem. 2015, 17,
1
235–1242; b) A. McVeigh, F. P. Bouxin, M. C. Jarvis, and S. D.
Jackson, Catal. Sci. Technol. 2016, 6, 4141–4150.
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ChemSusChem
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COMMUNICATION
Saumya Dabral, José G. Hernández,
Paul. C. J. Kamer,* Carsten Bolm*
Organocatalytic Chemoselective
Primary Alcohol Oxidation and
Subsequent Cleavage of Lignin Model
Compounds and Lignin
β
γ
Follow your primary intuition! An
unprecedented route for the degradation of
lignin model compounds and lignin has
been developed, via catalytic oxidation of
the primary hydroxyl groups in β-O-4 lignin
STOP
α
- One-pot, two-step
Organocatalytic
Chemoselective oxidation
rt
-
-
-
OXIDATION
LIGNIN
β!O!4$models$$
β
γ
α
GO
CαꢀC
+"
units by
a TEMPO/DAIB system. This
Cleavage products
unique pathway widens the scope of the
existing strategies in the area of lignin
depolymerization.
Text for Table of Contents
This article is protected by copyright. All rights reserved.