Copper-Mediated Conversion of Complex Ethers to Esters: Enabling Biopolymer Depolymerisation under Mild Conditions

Article abstract of DOI:10.1002/chem.202000088

Selective processing of the β-O-4 unit in lignin is essential for the efficient depolymerisation of this biopolymer and therefore its successful integration into a biorefinery set-up. An approach is described in which this unit is modified to incorporate a carboxylic ester with the goal of enabling the use of mild depolymerisation conditions. Inspired by preliminary results using a Cu/TEMPO/O₂ system, a protocol was developed that gave the desired β-O-4-containing ester in high yield using certain dimeric model compounds. The optimised reaction conditions were then applied to an oligomeric lignin model system. Extensive 2D NMR analysis demonstrated that analogous chemistry could be achieved with the oligomeric substrate. Mild depolymerisation of the ester-containing oligomer delivered the expected aryl acid monomer.

Full text of DOI:10.1002/chem.202000088

Accepted Article
Accepted Article
Title: Copper-mediated conversion of complex ethers to esters:
Enabling biopolymer depolymerisation under mild conditions
Authors: Nicholas James Westwood, Ganyuan Xiao, James R. D.
Montgomery, Christopher S. Lancefield, and Isabella Panovic
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To be cited as: Chem. Eur. J. 10.1002/chem.202000088
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0
1/2020

Chemistry - A European Journal
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Copper-mediated conversion of complex ethers to esters:
Enabling biopolymer depolymerisation under mild conditions
[b]
[b]
[b]
[b]
Ganyuan Xiao, James R. D. Montgomery, Christopher S. Lancefield, Isabella Panovic, and
Nicholas J. Westwood*[a]
[a]
G. Xiao, Dr. J. R. D. Montgomery, Dr. C. S. Lancefield, Dr. I. Panovic and Prof. Dr. N. J. Westwood
School of Chemistry and Biomedical Sciences Research Complex
University of St Andrews and EaStChem
North Haugh, St Andrews, Fife KY16 9ST, U.K.
E-mail: njw3@st-andrews.ac.uk
Abstract: Selective processing of the β-O-4 unit in lignin is essential
for the efficient depolymerisation of this biopolymer and therefore its
successful integration into a biorefinery set-up. An approach is
described in which this unit is modified to incorporate a carboxylic
ester with the goal of enabling the use of mild depolymerisation
advantage of the presence of an ester in the lignin chain is that
the use of mild cleavage conditions could result in the formation
of smaller lignin chains which have not been condensed/
destroyed during a final depolymerisation step. We have therefore
been searching for ways to modify selectively the β-O-4 unit to
give lignin chains that contain ester functional groups.
conditions. Inspired by preliminary results using a Cu/TEMPO/O
2
system, a protocol was developed that gave the desired β-O-4-
containing ester in high yield using certain dimeric model compounds.
The optimised reaction conditions were then applied to an oligomeric
lignin model system. Extensive 2D NMR analysis demonstrated that
analogous chemistry could be achieved with the oligomeric substrate.
Mild depolymerisation of the ester-containing oligomer delivered the
expected aryl acid monomer.
(
A) Ester containing lignin
Ralph et. al. (2016)
O
MeO
HO
OMe MeO
+
O
OH
G/S
FA
G/S
Lignification
O
OH
HO
O
OMe
OMe
Lignin with readily
cleaved ester
Monolignol ferulates
Monolignols
(
B) NHC-catalyzed depolymerisation
Lancefield and Westwood et. al. (2019)
OBu OMe
OBu
O
OMe
OBu O
MeO
O
[O] MeO
O
MeO
NHC/BuOH
OBu
O
HO
OMe
O
HO
OMe
OMe
wt % (from a beech
butanosolv lignin -ox
aldehyde)
Introduction
5
γ
(
C) Cu-catalyzed cleavage of -O-4 lignin model
Koskinen et. al. (2019)
The efficient use of lignocellulosic biomass for the generation of
renewable chemicals and biofuels requires the use of the
biopolymer lignin. Whilst burning lignin remains one viable option,
its high aromatic ring content provides an opportunity for
renewable aromatic chemical feedstock production. However,
depolymerising lignin to deliver the aromatic components remains
challenging. A number of approaches exist including the ‘lignin-
first’ approach.[1] Alternatively, pretreatment of the lignocellulosic
biomass can be used to generate a lignin-rich product stream that
OMe
OMe
OMe
O
OMe
OMe
OMe
O
O
O
Cu cat.
+
O
EtO
HO
OMe
EtO
EtO
OMe
O
OMe
1
2
3
Conversion: 99 %
48 %
7 %
O
OMe
O
H
OMe
+
+
EtO
EtO
EtO
O
OMe
OMe
OMe
4
5
6
5
%
6 %
4 %
[
2]
[3]
[4]
can then be depolymerised in one , two or sometimes more
steps. For example, we[3b] and others[3e, 5] have reported α-
Scheme 1. A Incorporation of monolignol ferulates into lignin introduces
chemically labile esters into the polymer backbone.[
and subsquent NHC catalysis for the depolymerisation of butanosolv-derived
lignin β-aryl ether linkages.
8a, 8b]
B 1o alcohol oxidation
oxidation of the highly abundant β-O-4 followed by subsequent
α-OX
processing of the β-O-4
units as a means of depolymerising
[3a]
[9]
lignin. Others[
3c, 3d, 6]
C Koskinen’s experiment : 0.2 mmol scale in
/10 mol% BiPy (2,2’-
have used an initial γ-oxidation of the β-O-4
CH CN (0.1 M); Cu cat. = 10 mol% CuCl/10 mol% NaBF
3
4
unit as the first step in lignin depolymerisation. Whilst in the
majority of the current multistep approaches a relatively mild and
controllable initial step (e.g. selective α-oxidation) is used, it is
also important that the last processing step avoids high
temperatures and/or harsh chemical treatments. By combining
mild conditions in both steps, it is possible to isolate the desired
monomers and leave a residual lignin that can be used further.[7]
In this context, we have recently become inspired by Bartley
and Ralph’s reports[8] of ‘zip lignins’ that contain ester groups
bipyridine)/10 mol% TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl)/10 mol%
NMI (N-methylimidazole) under an oxygen atmosphere.
Our initial efforts in this area focused on the use of NHC
catalysed-redox esterification but were ultimately derailed by the
fact that the phenolic rebound reaction proved inefficient (Scheme
S1). In the end we compromised and used butanol as an
alternative rebound reactant leading to direct depolymerization
and delivery of aromatic monomers from lignin (Scheme 1B).[
However, during the course of our NHC studies we noticed a
report by Koskinen et al.[9] Their studies on the reaction of β-O-4
3a]
(
Scheme 1A). Their work was based on the introduction of
chemically labile ester bonds into the lignin polymer by encoding
a feruloyl-coenzyme A monolignol transferase into poplar trees
(
Populus alba × Populus grandidentata). The presence of the
model compounds under CuCl/TEMPO/O
CH CN conditions included the reaction of the methylated β-O-4
model 1 ((α-OMe)-β-O-4) to give the corresponding γ-aldehyde 2
2 4
/NaBF /BiPy/NMI/
ester group made the wood more prone to depolymerisation
under relatively mild, alkaline conditions.[8] An additional possible
3
1
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as the major product along with a 7% yield of the non-cleaved aryl
ester 3 (Scheme 1C). The formation of small amounts of aldehyde
of the reaction products still resulted from Cα-Cβ bond cleavage.
These conditions also efficiently converted the S-G (α-OBu)-β-O-
4 aldehyde 13 to the corresponding ester 14 (entry 7, 35% at
100% conversion of 13) with 15-17 also being formed. In contrast,
when these conditions were applied to the isomeric G-S (α-OBu)-
β-O-4 aldehyde 18 a much poorer outcome was obtained with an
overall conversion of 18 of only 18% and no observable formation
of the analogous aryl ester (entry 8). Butyl ester 11 (16 %) was
the only identifiable product from this reaction. To the best of our
knowledge this is the first time that a reactivity difference as a
function of the methoxy-substitution pattern in the β-O-4 unit has
been observed under this type of reaction conditions.
4
, methyl ester 5 and α, β-unsaturated aldehyde 6 was also
reported.
Despite the fact that production of 3 was not the focus of
Koskinen’s work, this observation was potentially relevant to our
quest. In a separate part of our lignin programme we have
focussed on a pretreatment protocol that uses butanol as a co-
solvent.[10] Whilst others[11] have used butanol in pretreatments,
the existing studies did not discuss the almost full conversion of
the β-O-4 unit to the corresponding (α-OBu)-β-O-4 unit that we
observe under our conditions. This has led us to lignins that are
rich in (α-OBu)-β-O-4 units analogous to the methylated unit ((α-
OMe)-β-O-4) 1 used by Koskinen. We therefore decided to revisit
Koskinen’s work but using the (α-OBu)-β-O-4 unit rather than 1.
Results and Discussion
We have previously reported the synthesis of a model of the (α-
OBu)-β-O-4 unit 7 as a mixture of diastereomers.[10a] This study
therefore started with the attempted conversion of 7 under
Koskinen’s conditions[9] (20 hour reaction time, Figure 1A, entry
1
). As expected, the outcome was very similar to that of
Koskinen’s with the major product being the known[3a, 12] γ-
aldehyde 8 (70 %, entry 1). Reassuringly, a small quantity of the
corresponding ester 9 (4 %) was also formed. It was decided to
repeat this reaction starting with 8 in an attempt to generate more
of the desired 9. After 20 hours (entry 2), overall conversion of 8
was low (20 %) and only small amounts of 9 (5 %) were formed.
At a 60-hour extended time point (entry 3), whilst conversion of 8
increased to 39 %, the amount of 9 (4 %) remained very low with
increased formation of ester 11 (14 %), resulting from cleavage of
α β
the C -C bond in the β-O-4 unit, in addition to a range of
unidentified products. Given the low yields of 9, it was decided to
abandon the Koskinen protocol.
Baker et al.[13] have reported catalytic systems for the
selective cleavage of lignin models using oxygen as the terminal
oxidant. In parallel work, Baker’s original protocol
(
2
CuCl/TEMPO/O /Py) was being explored by us to achieve
oxidative cleavage of 8 (Figures S7-S17 for a more detailed
discussion). Efficient conversion (100%) of 8 in the presence of
Figure 1. A Results of Koskinen’s conditions (CuCl/NaBF
4
/TEMPO/NMI (10
sub-stoichiometric amounts of CuCl and TEMPO in pyridine at
mol% each)/O /MeCN) for the conversion of 7 and 8 (The method used to
2
o
1
00 C under an oxygen atmosphere (Figure 1B, entry 4) resulted
calculate conversions and yields is discussed in Figures S1-S3 and full spectra
in the formation of butyl ester 11 as the major product (41 %; 36 %
isolated yield). Importantly in the context of the current work, an
increased yield of the desired ester 9 (28 %) was observed
compared to the Koskinen protocol. Aldehyde 10 (14 %) along
with trace amounts of known[3a] enal 12 (2 %) were also formed in
this reaction.
are shown in Figures S4–S6). B Results of the original Baker’s conditions
(CuCl/TEMPO (10 mol% each)/O
2
/pyridine) for the conversion of 8 (entry 4) and
modified Baker’s conditions – CuCl (10 %)/O
2
/pyridine in the absence of
TEMPO for the conversion of 8, 13 and 18 (Figures S10 and S18-S22 for full
a:
spectra). Reactions were performed on a 0.1 mmol scale. Conversions and
1
yields were determined by H NMR using 1,3,5-trimethoxybenzene as the
b:
internal standard. Isolation of products from 8 (150mg) using this condition
gave 9 (31%), 10 (12%) and 11 (36%).
2
The Baker system contains TEMPO, O and CuCl. Therefore
it was decided to assess the role of each component in the
reaction in the hope of biasing the system away from Cα-Cβ bond
cleavage in 8 and towards formation of ester 9. Initial studies
focussed on the use of CuCl under an oxygen atmosphere and in
the absence of TEMPO. Results showed that TEMPO was not
essential for the formation of 9 (c.f. Figure 1B, entries 4 and 5)
with high conversion (88 %) of 8 to 9 (29 %) and 11 (40 %) being
achieved with no TEMPO in the reaction. Extending the reaction
In the absence of both TEMPO and CuCl (Figure 1B, entry
), efficient conversion of 8 (88%) was still observed at 100 C but
o
9
none of the desired ester 9 was formed with the major product
resulting from elimination of butanol to give 12. This result
confirmed that the presence of CuCl is essential for the formation
of 9 under the Baker conditions. One possible mechanism
Scheme 2) involves the formation of the enolate[9, 14] 19, which
could be converted to form the corresponding radical. The radical
(
o
time to 15 hours at 100 C (entry 6) led to a slight increase in the
production of 9 (38 % at 95 % conversion of 8) but more than half
could be converted to the hydroperoxide intermediate 20.
2
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Subsequent deformylation would be expected to give 9. Possible
reasons for the apparent lack of reactivity of the G-S model 18
may be that the combination of the two radicals is more difficult
due to increased steric constraints around a β-carbon centred
radical.
production of 9 from 8 (Figure S24). As no oxygen was present
and hence no chance of establishing a catalytic cycle involving
oxygen, an excess of TEMPO was used. Under as carefully
controlled conditions as could be achieved in the absence of a
glove box (Figure S25 for a more detailed discussion), the model
(
α-OBu)-β-O-4 aldehyde 8 was efficiently converted to ester 9
using 1.5 equivalents of TEMPO, this time as the major product
62%, Figure 2, entry 1). Increasing the number of equivalents of
(
TEMPO led to a further increase in the yield of 9 (74 %, entry 2
and 77 %, entry 3) and these significant improvements in the
formation of the desired ester were also observed for S-G model
13 (entry 4). Very low conversions were again observed when the
G-S model 18 and the S-S model 21 (entries 5 and 6) were used.
Shortening the reaction time for the conversion of 8 under
optimised conditions (CuCl (10 mol%)/TEMPO (3.0 eq.)/Ar) to 3
hours led to the isolation of the TEMPO-adduct 22 by column
chromatography (39 % yield as a mixture of diastereomers, Figure
Scheme 2: One possible mechanism for the formation of
9
14b]
under cat.
). Generic
CuCl/O
nucleophile Nu: could be water or pyridine.
2
/pyridine conditions (based on literature findings[9,
3
A). Related α-ketone β-TEMPO-adducts have been reported
[9, 13a, 15]
previously.
A time course study supported a view that the
starting material 8 was first converted to the TEMPO-adduct 22
en route to ester 9 (Figure 3B). When 22 was resubmitted to the
reaction, ester 9 was obtained as expected (52 % yield, Figure
Whilst the presence of CuCl is not essential for the formation
of butyl ester 11 (Figure 1B, entry 9), the yield of 11 is significantly
decreased in its absence, indicating that 11 may be formed by two
alternative pathways (Scheme S2). In several of the reactions
3A).
(
1
Figure 2B, entries 5, 6 and 7), a small amount of aldehyde 10 (or
5 when 13 was used as the substrate) was formed in the
presence of CuCl. Koskinen proposed that under their conditions,
the formation of 10 from 1 is likely via 1,4-addition of H
1
2
O to enal
2 followed by a rapid retro-aldol reaction[ although other
9]
possible mechanisms could be considered (Scheme S3 and
Figure S23).
Figure 2: Results of catalytic CuCl/ stoichiometric TEMPO under Ar atmosphere
for the conversion 8, 13, 18 and 21. a: Reactions were performed on a 0.1 mmol
1
scale. Conversions and yields were determined by H NMR using 1,3,5-
trimethoxybenzene as the internal standard. b: additional data on the formation
of the small amount of cleavage products are presented in Figures S24-S35.
Figure 3: A The synthesis of TEMPO-adduct 22; B A graphical representation
of the relationship between time vs NMR yields (%) of 8, 22 and 9 (Figures S36-
S40 for a more detailed discussion); C One possible mechanism for the
CuCl/TEMPO-catalysed oxidation of 8 to form 9. Generic nucleophile Nu: used
in deformylation.
Returning to the original Baker reaction conditions (Figure 1B,
entry 4), it was decided to rerun this reaction in the absence of
oxygen to explore the contribution that TEMPO made to the
The benzylic oxidation and subsequent retro-aldol reaction
often proposed for these types of reactions when native β-O-4
3
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substrates are used[5, 9, 13c] is blocked in substrate 8 unless the α-
butoxylated lignin undergoes elimination of butanol and
subsequent addition of extraneous water. Another possible
mechanism could involve the formation of enolate[9, 14] 19 (Figure
3C) and formation of the corresponding radical 23. The adduct 22
could then be formed by radical coupling of 23 with TEMPO.
Subsequent deformylation, in an analogous manner to the
reaction of 20 (Scheme 2), would convert 22 to 9.
Having identified optimised conditions for the formation of the
desired esters 9 and 14 from the dimeric model compounds 8 and
13 respectively, the next challenge came in applying this
chemistry to a model β-O-4-containing oligomer. This step is
required to assess whether it is possible using this methodology
to prepare ester-containing chains with minimal initial cleavage of
the β-O-4 unit. Owing to the complexity of real samples of even
butanosolv lignin, it was decided to use an artificial all β-O-4-
containing oligomer. As the TEMPO-mediated ester formation
reaction did not work on G-S model 18 and S-S model 21 (Figure
2
(
, entries 5 and 6), studies focused on the all G β-O-4 oligomer
Scheme 3) which is a simplified model of a softwood lignin such
as that obtained from Douglas fir wood.[10b] Oligomer 24 (M
2880,
DP (degree of polymerisation) 8.13, Figures S41-S44 for a more
w
n
detailed discussion) was synthesized using the previously
reported route[3b, 17]. In an extension to previous literature 24,
which contains native β-O-4 units, was converted to the
corresponding α-functionalised butanosolv β-O-4 oligomer 25
(
Scheme
3
and Figure 4A) using a modified butanosolv
[
10a, 12]
pretreatment
in quantitative yield (Figures S45-S46). The
subsequent γ-oxidation reaction was then carried out using Dess-
Martin periodinane (DMP)[3a, 12] to give the required oligomeric
substrate 26 (Figures 4B and S47)
Figure 4：The oxygenated aliphatic region of the 2D HSQC NMR analysis of:
A) Butanosolv β-O-4 oligomer 25; (B) Butanosolv β-O-4 γ-aldehyde oligomer
(
Scheme 3: The oligomer synthesis: (A) 12 N. HCl: n-BuOH (1: 33), 117 °C, 1.5
h, ~100 %; (B) DMP (1.2 eq.), DCM, rt., 4.0 h, 75 %; (C) TEMPO (3.0 eq.), CuCl
26; (C) Oligomer 27 formed on reaction of 26 with 3.0 eq. TEMPO, 10 mol %
CuCl, Pyridine, 100 °C, 15 h; (D) Crude mixture of depolymerised products after
hydrolysis of 27. Full spectra are available in Figures S46-48 and S60. The
chemical shifts of peaks in the aldehyde region have been corrected due to
folding in the original analysis. a he assignment of signals in γA was determined
by comparison the 2D HSQC spectra of 25 with that of the corresponding dimer
model compound (Figures S45-S46). b The presence of signals corresponding
to the γ-ester unit (γE) was achieved by comparison with the 2D HSQC spectra
of the corresponding dimer model compound (Figures S44-S46). c The signals
corresponding to the α-protons in the benzyl alcohol (BE) end group and the α
and β-protons of the ethylene glycol (EG) end group were assigned based on
the literature.18 After the butanosolv step (Scheme 3, step A), R (in the ethylene
(10 mol %.), pyridine, 100 °C, 15 h, Ar., 100 %; (D) 0.5 M NaOH in MeOH, rt.,
12 h, 7.0 wt % of 28.
In brief, the key signals observed in the HSQC NMR analysis
1
13
of oligomer 25 included those corresponding to the α ( H/ C δ
1
13
4
.37 – 4.54 ppm/ 80.2 – 83.1 ppm), β ( H/ C δ 3.99 – 4.22 ppm/
8
5.1 – 88.2 ppm) and the diastereotopic γ-positions of the two
1
13
diastereomers ( H/ C δ 3.32 – 3.46 ppm/ 61.3 – 63.1 ppm and
2
glycol end group) = CH OH; after oxidation step (steps B and C), R (in the
ethylene glycol end group) = CHO; d In the dimer study, the HSQC NMR spectra
1
13
1
13
H/ C δ 3.32 – 3.46 ppm/ 61.3 – 63.1 ppm and H/ C δ 3.72 –
.92 ppm/ 60.7 – 62.6 ppm) of the γA unit. Signals corresponding
3
showed that the signal corresponding to the α-proton of ester 9 and the α-proton
of TEMPO-adduct 22 were overlapping (Figure S50, entry E), making it hard to
distinguish AE from TA using this signal. However, the presence of a TA unit
was clear due to the presence of the aldehyde proton. In addition, HMBC
to the two end groups (BE and EG) as well as small amounts of
γ-ester units (γE, Figures S45-S46 for a more detailed discussion),
remaining from incomplete ester reduction during the synthesis
e
analysis confirmed the formation of either AE or TA or both (Figures S51). the
formation of the acid unit AD is discussed in Figures S61.
4
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Chemistry - A European Journal
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FULL PAPER
of 25, were also present. On oxidation of 25 to 26, disappearance
of the signals corresponding to the γ- alcohol positions of unit γA
in 25 appeared linked to the presence of new signals
corresponding to the γ-aldehyde positions in the desired unit γO
(1
–
H/ C δ 9.57 – 9.68 ppm/ 199.6 – 201.5 ppm and H/ C δ 9.77
9.89 ppm/ 199.9 – 201.5 ppm, Figures 4B and S47).
13
1
13
Inspired by the dimer study (Figure 2, entry 2), an initial
attempt to form the ester using oligomer 26 started by reacting 26
with TEMPO (2.0 eq.) in the presence of CuCl (0.1 eq.) in pyridine
under an Ar atmosphere for 7 hours. The reaction outcome was
encouraging but the major product contained predominantly
TEMPO-adduct TA units (Figure S52). Whilst studies on the
simpler model 8 suggested that a reaction time of 7-9 hours may
be ideal (Figure 3B), it was clear that modified conditions would
be required for the successful preparation of 27 containing
predominantly ester units (Scheme 3). For example, when a
reaction time of 15 hours was tried (using 3.0 eq. TEMPO and 10
mol % CuCl) signals corresponding to the formation of the
TEMPO-adduct unit TA (minor component) and the desired ester
unit AE (major component) were observed (Figure 4C and Figure
S48-S51). Diagnostic changes in the HSQC analysis included the
modified β- Figure 5: 2D 1H DOSY spectrum of the 26, 27 and the crude
reaction mixture after hydrolysis of 27.
O-4 unit to the desired ester-containing unit, an effective method
was developed based using the CuCl/TEMPO system in the
absence of oxygen. This methodology was not only applicable to
a dimeric β-O-4 model unit but also to an oligomeric β-O-4 model,
leading to an oligomer chain (in 27) that contained a significant
number of internal ester units. A more detailed understanding of
the key aspects of the CuCl/TEMPO/pyridine system was
obtained. For example, the study confirmed that the desired ester
was formed via TEMPO-adduct 22 which was isolated and, on
resubmission to the reaction conditions, was converted to the
corresponding ester 9. Detailed 2D NMR (HSQC, HMBC and
DOSY) analysis showed that the reaction outcomes in both the
dimeric and oligomeric models were analogous. It is envisaged
that this method could be applied to a butanosolv lignin but
challenges associated with the successful removal of oxygen and
the amount of TEMPO are likely to limit the scale on which it can
be applied.
1
13
disappearance of the signals assigned to the β-( H/ C δ 4.34 –
1
13
4
.51 ppm/ 85.7 – 88.1 ppm and H/ C δ 4.14 – 4.30/ 86.9 – 89.0
1
13
ppm) and γ-positions of the two diastereomers ( H/ C δ 9.57 –
.68 ppm/ 199.6 – 201.5 ppm and H/ C δ 9.77 – 9.89 ppm/ 199.9
201.5 ppm) in γO units in 26 and new signals corresponding to
the α-position of the aryl ester (AE) units ( H/ C δ 4.97 – 5.16
ppm/ 79.3 – 81.8 ppm) were observed (c.f. Figures 4B and 4C).
Whilst the 2D HSQC analysis of 26 confirmed that the major
reaction on forming 27 involved formation of the desired ester unit
1
13
9
–
1
13
(
AE), evidence for the formation of units formed by cleavage of
the C -C bond (units CE and BA in Figure 4C) were also
α
β
obtained (Figures S57 for a more detailed discussion), consistent
with the dimer study result (Figures S24-S25). This was explored
further using a previously reported19 2D DOSY NMR approach
this time on 26 and 27 to determine any apparent change in the
molecular weight (MW) of the lignin models. There was, on
average, a small increase in the diffusion coefficient on going from
Experimental Section
For general considerations, the synthesis and characterisation of
dimeric and oligomeric substrates and products, the protocols for
the described ether to ester transformations and all spectroscopic
evidence in support of the data presented in Figures 1-3, see the
Supporting Information.
2
6 (blue signals) to 27 (green signals, Figure 5), indicating a
decrease in size during the reaction, which was consistent with
the appearance of the signals observed for the CE unit in the
HSQC analysis of 27 (Figure 4C). On hydrolysis of 27 (Scheme
4, step D), a significant increase in the average diffusion
coefficient of the crude product(s) was observed compared to
both 26 and 27 (Figure 5). Subsequent purification of the crude
products by column chromatography gave the expected acid 28 Acknowledgements
Scheme 3, 7.0 wt % isolated yield). No attempts to optimise this
yield have been made. In addition, a mixture of products (16.0 wt
isolated yield) that was shown to contain dimeric units was
(
The authors would like to thank the China Scholarship Council
G.X. studentship), the University of St Andrews (G.X. and
%
(
isolated from the column (Figures S59-S60 for a more detailed
discussion). The isolation of these dimeric units (albeit as part of
a mixture) was consistent with a relatively mild final step in the
depolymerisation process allowing fragments of model oligomer
chains to be obtained for potential future use (Figure S61 for a
more detailed discussion).
J.R.D.M. studentships) and the EPSRC-funded CRITICAT Centre
for Doctoral Training (studentship to I.P.; EP/L016419/1) for PhD
funding. C.S.L. thanks the Leverhulme Trust Early Career
Fellowship (ECF-2018-480) and the University of St Andrews. We
would like to thank Mrs Carolyn Horsburgh for mass spectrometric
analysis.
Keywords: biomass • lignin • mild depolymerization • TEMPO
Conclusion
oxidation • copper
In summary, whilst preliminary studies based on the
Koskinen protocol did not enable the efficient conversion of a
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Chemistry - A European Journal
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Ganyuan Xiao, James R. D. Montgomery, Christopher S.
Lancefield, Isabella Panovic and Nicholas J. Westwood
Page No.- page No.
Copper-mediated conversion of complex ethers to esters:
Enabling biopolymer depolymerisation under mild conditions
A Cu/TEMPO system was used to modify lignin’s β-O-4 unit to
give ester-containing chains that can be easily depolymerized.
This chemistry was successfully applied to relevant dimeric
and oligomeric substrates.
7
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