Copper catalysts for selective c-c bond cleavage of b-o-4 lignin model compounds

Article abstract of DOI:10.1002/adsc.201400463

The reactivity of homogeneous copper catalysts towards the selective C-C bond cleavage of both phenolic and non-phenolic arylglycerol b-aryl ether lignin model compounds has been explored. Several copper precursors, nitrogen ligands, and solvents were evaluated in order to optimize the catalyst system. Using the optimized catalyst system, copper(I) trifluoromethanesulfonate [CuACHTUNGTRENUNG(OTf)]/L/TEMPO (L=2,6-lutidine, TEMPO=2,2,6,6-tetramethyl-piperidin-1-yl-oxyl), aerobic oxidation of the non-phenolic b-O-4 lignin model compound proceeded with good selectivity for Ca-Cb bond cleavage, affording 3,5-dimethoxybenzaldehyde as the major product. Aerobic oxidation of the corresponding phenolic b-O-4 lignin model proceeded with different selectivity, affording 2,6-dimethoxybenzoquinone and a,b-unsaturated aldehyde products resulting from cleavage of the CaCaryl bond. At low catalyst concentrations, however, a change in selectivity was observed as oxidation of the benzylic secondary alcohol predominated with both substrates.

Full text of DOI:10.1002/adsc.201400463

FULL PAPERS
DOI: 10.1002/adsc.201400463
À
Copper Catalysts for Selective C C Bond Cleavage of b-O-4
Lignin Model Compounds
a
a,
Baburam Sedai and R. Tom Baker *
a
Department of Chemistry and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, ON,
K1N 6N5 Canada
Fax : (+1)-613-562-5613; phone: (+1)-613-562-5698; e-mail: rbaker@uottawa.ca
Received: May 7, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400463.
Abstract: The reactivity of homogeneous copper cat- product. Aerobic oxidation of the corresponding
alysts towards the selective CÀC bond cleavage of phenolic b-O-4 lignin model proceeded with differ-
both phenolic and non-phenolic arylglycerol b-aryl ent selectivity, affording 2,6-dimethoxybenzoquinone
ether lignin model compounds has been explored. and a,b-unsaturated aldehyde products resulting
Several copper precursors, nitrogen ligands, and sol- from cleavage of the C ÀC bond. At low catalyst
a
aryl
vents were evaluated in order to optimize the cata- concentrations, however, a change in selectivity was
lyst system. Using the optimized catalyst system, observed as oxidation of the benzylic secondary alco-
copper(I) trifluoromethanesulfonate [Cu ACHUTNGRENNUG( OTf)]/L/ hol predominated with both substrates.
TEMPO (L=2,6-lutidine, TEMPO=2,2,6,6-tetra-
methyl-piperidin-1-yl-oxyl), aerobic oxidation of the
non-phenolic b-O-4 lignin model compound proceed- Keywords: aerobic oxidation; CÀC bond cleavage;
ed with good selectivity for C ÀC bond cleavage, af- copper catalysts; lignin models; TEMPO; 2,2,6,6-tet-
a
b
fording 3,5-dimethoxybenzaldehyde as the major ramethyl-piperidin-1-yl-oxyl
[
10]
Introduction
white rot fungi, and most recently with Mn-depen-
[11]
dent bacterial enzymes.
The investigation of metal complex-catalyzed aero-
The efficient conversion of heterogeneous biomass re-
sources to chemicals and fuels is presenting new chal- bic oxidation of a variety of lignin model compounds
[
1]
lenges for catalysis science and engineering. As has demonstrated some intriguing selectivity differen-
[
7a]
a main constituent of lignocellulosic biomass, lignin – ces vs. traditional base-catalyzed methods.
a random mixture of macromolecules containing me- the use of simple lignin models has allowed for evalu-
While
[
2]
thoxylated phenoxypropanoid units – is readily sep- ations of catalyst reactivity, recent work has demon-
[
3]
arated in the wood pulping process. However, isolat- strated that the selectivity observed with simple b-O-4
ed lignins differ widely in their molecular composition lignin models, for example, may not pertain with
[
12]
depending on the tree species and details of the pulp- more complex arylglycerol b-aryl ethers such as 1a
ing method. As a result, value-added products derived and 1b (Figure 1), which are commonly employed as
[31]
from lignin will likely need to be families of chemicals models for the most prevalent lignin linkage.
For
such as alkylphenols, aromatic aldehydes and acids, instance, Son and Toste showed that a five-coordinate
[
4]
rather than single compounds. While reductive ap- salen-type oxo-vanadium complex catalyzed CÀO
proaches have focused on selective production of al- bond cleavage of a non-phenolic model compound, to
[
5]
[6]
kylphenols or aromatic fuel components, oxidative
[
7]
processes have also met with some success with
a simple mixed Cu-Fe homogeneous catalyst system
affording 14 wt% aldehydes in one report
[
8]
and
CuSO in an ionic liquid yielding up to 30% alde-
4
[
9]
hydes in another. Biocatalysis continues to play an
important role in oxidative lignin conversion; first in
investigations of lignin peroxidase enzymes found in Figure 1. Syringyl b-O-4 lignin model compounds.
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give 2-methoxyphenol and the functionalized ene- Results and Discussion
[13]
one In contrast, we found that a five-coordinate di-
picolinate oxovanadium complex afforded CÀC bond Copper Catalyst Optimization for Oxidation of Non-
cleavage products through the intermediacy of the Phenolic b-O-4 Lignin Model (1a)
[14]
ketone. Hanson et al. subsequently reported dispa-
rate reactivity with similar catalysts using phenolic In previous work, we built on diol oxidation studies
[
15]
[21a]
[21b]
lignin models.
Using a simple CuCl/pyridine/ by Kinoshita
and by Prati and Rossi
to show
TEMPO catalyst with 1a led instead to direct C ÀC
that aerobic oxidation of lignin model compounds
a
b
bond cleavage to afford the substituted benzaldehyde using CuCl/TEMPO catalyst in pyridine proceeded by
[
16]
[
TEMPO=(2,2,6,6-tetramethylpiperidin-1-yl)oxyl].
direct CÀC bond cleavage, affording aldehydes as
[
16]
Direct C ÀC bond cleavage has also been observed major products (Scheme 1). Note that the pyridine
a
b
in the oxidation of 1a using lignin peroxidase en- serves as ligand, base, and solvent in these reac-
[10]
[22]
13
zymes. These catalysts have been shown to operate tions. Use of the doubly C-labeled substrate (1a*)
through a single-electron transfer mechanism and sub- allowed us to determine that additional, partially
[
10,17]
[16]
sequent decomposition of the aryl cation radical.
In contrast, manganese peroxidase generates an aim of maximizing the aldehyde yield, we thus con-
Mn(III) carboxylate that effects hydrogen atom ab- ducted a series of experiments to optimize the copper
straction to afford the phenoxy radical.
studies using Co(salen) catalysts, Canevali et al. noted
characterized side-products were formed. With the
ACHTUNGTRENNUNG
[
18]
In their catalyst system.
Initially, we evaluated the stoichiometric oxidation
ACHTUNGTRENNUNG
that the electron-rich aromatic rings in these sub- of 1a at 1008C with several different copper precur-
strates promoted electron transfer from Co(II) to O2 sors, solvents and N-donor ligands (Table 1). The re-
followed by H atom abstraction to afford the coordi- action products were identified and quantified by
1
nated phenoxy radical in the case of the phenolic
lignin models.
H NMR, GC/MS, and LC/MS; yields are expressed
as a percentage of the theoretical maximum based on
[19]
The diversity of oxidative reaction pathways ob- the initial amount of substrate. Moving first from pyr-
served for substrates 1a and 1b suggested that further idine to the bulkier 2,6-lutidine afforded higher yields
catalyst development might allow for increased con- of aldehyde (2) (entry 2). However, additional prod-
trol over the distribution of aldehyde and acid prod- ucts (5, 6) that derived from the decarboxylative cou-
ucts from real lignin extracts. In their ability to cata- pling of the solvent were also observed (Figure 2; see
lyze CÀC bond cleavage and utilize dioxygen, copper also the Supporting Information, Figures S3–S6). A
aerobic oxidation catalysts have the potential to control experiment performed without substrate 1a
mimic the selectivity of peroxidase enzymes without using CuCl/TEMPO under oxygen in 2,6-lutidine at
the need for hydrogen peroxide. As previous optimi- 1008C afforded the same coupling products 5 and 6.
zations of copper oxidation catalysts involved alcohol Using ca. 10 equiv. of 2,6-lutidine as ligand and base
[20]
oxidation, we sought to identify the best conditions in toluene solvent maintained the aldehyde yield with
for aerobic oxidative CÀC bond cleavage in phenolic only a trace of 5 and 6 (entry 3), but a significant
and non-phenolic b-O-4 models (1a and 1b) and to amount of 1a was formylated to product 7 (Figure 3).
see if detailed characterization of the products and Compound 7 is the result of catalyzed formylation of
soluble copper species could shed additional light on the secondary alcohol in 1a with formic acid that is
the operative reaction pathways.
produced along with 2-methoxyphenol following CÀC
Scheme 1. Selective CÀC bond cleavage using CuCl/TEMPO in pyridine.
2
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Copper Catalysts for Selective CÀC Bond Cleavage of b-O-4 Lignin
bond cleavage of 1a. A control reaction performed by
The nature of the copper precursor and solvent also
heating 1a with two equivalents of formic acid in the played a significant role in these homogeneous reac-
presence of 10 equivalents of 2,6-lutidine under tions with the best results obtained using Cu(I) tri-
oxygen in toluene at 1008C for 18 h without catalyst flate in toluene (entry 5); the divalent triflate and sul-
afforded only 5% of formylation product 7.
fate derivatives gave low conversions of 1a even after
[a]
Table 1. Screening of N-donor ligands, copper precursors, and solvents for the aerobic oxidation of 1a.
Entry N-Donor
Ligand
Catalyst
(+1 equiv.
TEMPO)
Time Solvent
[h]
Conversion
[%]
2
8
9
7
10
4a
4b
[b] [b]
[b]
[b]
[b]
[b]
[b]
[%] [%] [%] [%] [%] [%] [%]
[
16]
1
2
3
pyridine
CuCl
CuCl
CuCl
40
40
40
pyr
2,6-lut
toluene
89
79
84
43
52
51
1
–
1
2
–
10
2
4
14
–
–
1
7
8
7
–
–
5
2,6-lutidine
2,6-lutidine
(
10 equiv.)
2,6-lutidine
10 equiv.)
2,6-lutidine
10 equiv.)
2,6-lutidine
2,6-lutidine
2,6-lutidine
4
5
6
7
8
9
CuCl (20 mol%) 40
toluene
68
99
15
6
24
62
7
8
6
19
16
–
1
3
–
–
–
–
8
6
–
–
8
–
3
(
CuOTf
Cu(OTf)
18
40
40
18
18
toluene
3
5
10
–
(
A
H
U
G
R
N
U
G
2,6-luti-
dine
2,6-luti-
dine
–
–
2
CuSO4
CuOTf
CuOTf
1
–
–
–
–
DMF
80
5
44
–
14
–
0.2
–
13
–
–
(
10 equiv.)
2,6-lutidine
10 equiv.)
DMF/
water
–
(
(
1:1)
1
0
1
2,6-lutidine
10 equiv.)
diazabutadiene CuOTf
5 equiv.)
CuOTf
40
18
CH CN
56
76
20
53
9
5
0
1
4
8
–
–
2
5
–
2
3
(
1
toluene
(
1
1
2
3
bipy (5 equiv.) CuOTf
bis(oxazoline) CuOTf
18
18
toluene
toluene
67
50
36
24
5
1
0
0
12
10
–
3
2
nd
3
2
(
5 equiv.)
neocuproine
5 equiv.)
2,6-lutidne
10 equiv.)
1
4
CuOTf
18
toluene
21
4
12
0
0
–
nd
–
(
15
CuOTf
(20mol%)
40
toluene
95
54
7
5
18
2
10
5
(
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Table 1. (Continued)
Entry N-Donor
Ligand
Catalyst
(+1 equiv.
TEMPO)
Time Solvent
[h]
Conversion
[%]
2
8
9
7
10
4a
4b
[b] [b]
[b]
[b]
[b]
[b]
[b]
[%] [%] [%] [%] [%] [%] [%]
[
[
c]
1
6
7
2,6-lut (10
equiv.)
2,6-lutidine
CuOTf
CuOTf
18
18
toluene
toluene
60
62
30
29
3
3
1
12
4
–
–
5
8
4
d]
1
19
10
(10 equiv.)
[
[
[
[
a]
Temperature=1008C except for entries 8 (1108C) and 10 (828C).
NMR yields.
No TEMPO added.
b]
c]
d]
1
equiv. 2-methoxyphenol added; traces of 3,5-dimethoxybenzoic acid also formed.
Figure 2. Aerobic oxidation of 1a in 2,6-lutidine mediated by stoichiometric CuCl/TEMPO (yields of 5 and 6 are based on
the initial amount of 1a).
Figure 3. Copper complex-catalyzed aerobic oxidation of 1a.
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Copper Catalysts for Selective CÀC Bond Cleavage of b-O-4 Lignin
4
8 h in 2,6-lutidine solvent (entries 6 and 7). The se- containing the dimethoxylated aryl ring is 87%,
lectivity to 2 dropped significantly in DMF solvent whereas that for the monomethoxylated ring is only
entry 8) and both activity and selectivity decreased 47%, suggesting that the benzoquinone product (4b)
(
in acetontrile (entry 10). No additional benefits ac- undergoes further conversion under our reaction con-
crued from the use of bidentate ligands such as dii- ditions. Finally, the identity of the oxidation products
[
23]
mine, bipyridine, bis(oxazoline), or neocuproine,
was confirmed by carrying out the reaction on
with lower conversions and selectivities observed (en- a larger scale and isolating the products using column
tries 11–14).
chromatography.
Next, we tested the oxidation of 1a using the opti-
mized copper precursor and ligand combination, but
under catalytic conditions. Using 20 mol% Cu ACHUTNRGNENUG( OTf)/ Oxidation of Phenolic Lignin Model 1b
TEMPO in the presence of 10 equivalents of 2,6-luti-
dine, 95% conversion of 1a and 54% yield of 3,5-di- Phenolic b-O-4 lignin model (1b) was heated at
methoxybenzaldehyde (2) were observed after 40 h 1008C using a stoichiometric amount of Cu
entry 15, Figure 3). In another experiment, 1a was lutidine/TEMPO with oxygen in toluene (Figure 4).
heated using Cu(OTf)/2,6-lutidine without TEMPO After 18 h, complete consumption of 1b was ob-
ACHTUNGTRENNUNG( OTf)/2,6-
(
ACHTUNGTRENNUNG
under oxygen in toluene. After 18 h, only 60% of the served, with 2,6-dimethoxybenzoquinone (11) and
starting material had been consumed, thus illustrating ene-al (12) formed as the major products. In a control
the role of TEMPO as co-catalyst (entry 16). In con- reaction omitting the copper triflate, no reaction was
trast, heating 1a with 10 equivalent of 2,6-lutidine observed after 18 h. When the catalyst loading was
under oxygen in toluene with no catalyst afforded decreased to 10 mol%, approximately 98% conver-
only ~2% conversion. The reaction rate drops signifi- sion of (1b) was observed after 6 h, with formation
cantly at lower catalyst concentrations and given the primarily of ketone (13) (55%) along with 2,6-dime-
[
24a–d]
extensive phenol oxidation to quinone (4b),
we thoxybenzoquinone (11) (20%), ene-al (12) (6%), and
surmised that the latter could be one source of the 4-hydroxy-3,5-dimethoxybenzaldehyde (3%) from CÀ
rate decrease. Indeed, heating 1a with stoichiometric C bond cleavage of the ketone. After 18 h, the prod-
Cu
under oxygen in toluene for 18 h at 1008C gave only droxy-3,5-dimethoxybenzaldehyde or 2-methoxyphe-
0% conversion (entry 17). Note also that for the re- nol were detected (Figure 5). The poor carbon bal-
action in Figure 3, the carbon balance of products ance for the 2-methoxyphenoxy aromatic ring may be
ACHTUNGTRENNUNG( OTf)/2,6-lutidine/TEMPO and 2-methoxyphenol uct distribution was largely unchanged but no 4-hy-
6
Figure 4. Aerobic oxidation of 1b mediated by stoichiometric Cu AHCUTNGRNENGU( OTf)/2,6-lutidine/TEMPO.
Figure 5. Copper complex-catalyzed aerobic oxidation of 1b.
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due to instability of ene-al (12) under the reaction most relevant to this work are the recent reports by
[15]
conditions. An LC/MS trace of the reaction mixture Stahl et al. that account for the higher activity of
showed several peaks corresponding to higher molec- Cu(I) precursors in the absence of very strong bases
[
26]
ular masses.
such as KO-t-Bu. While their proposed mechanism
pertains to alcohol oxidation under mild conditions,
several steps are likely to play key roles in the more
demanding CÀC bond cleavage reactions described
Activity of Copper Catalysts
here. These include use of nitrogen donor ligands to
As described above, the copper complex cleaved the modulate the Cu(I)/Cu(II) redox couple, activation of
C ÀC bond in non-phenolic b-O-4 lignin model (1a) dioxygen by two different Cu(I) centers, and im-
a
b
to afford 3,5-dimethoxybenzaldehyde as the major proved catalyst performance using the weakly coordi-
À
product. The other half of the molecule underwent nating triflate ligand (vs. Cl ). Under our harsh reac-
further conversion to generate 2-methoxyphenol and tion conditions (1008C), the lability of both Cu(I) and
formic acid. Subsequent experiments indicated that Cu(II) complexes with N-donor ligands reduce their
the 2-methoxyphenol or its oxidation products such as impact as a potential source of improved catalyst ac-
[
27]
2-methoxy-1,4-benzoquinone (4b) may deactivate the tivity and selectivity.
Cu catalyst. In order to gain insight into copper speci-
Recently, Stahl and co-workers reported the aero-
ation in the presence of 2,6-lutidine (L) we recorded bic oxidation of a complex b-O-4 lignin model com-
the ESI-mass spectra using both Cu(I) and Cu(II) pound similar to 1a using their Cu(OTf)/bpy/
precursors (see Supporting Information, Figures S36– TEMPO/N-methylimidazole catalyst system to afford
AHCTUNGTRENNUNG
[
28]
S41). The results for CuCl, Cu ACHTUNGRENNUG( OTf) and Cu ACHTUNGTERNNUN(G OTf) re- veratryl aldehyde as the major product. They pro-
2
vealed a mixture of mono- and divalent species with posed that oxidation of the primary alcohol followed
one or two coordinated ligands; isotope patterns were by a retro-aldol reaction led to cleavage of the CaÀC
b
+
+
[29]
consistent with [CuL ] (A), [(CuL)
ACHTUNGERTNNUNG( m-Cl)] (B) and bond.
2
This then provides an alternate mechanism
2
2+
[
CuL S ] (C) where S=MeCN, H O (Figure 6, Sup- (Scheme 2) to the well-studied single electron transfer
2
4
2
porting Information, Figures S37, S38, and S40). At- mechanism in which reagents like ceric ammonium ni-
tempts to grow crystals from the reaction mixture af- trate generate aryl cations that undergo subsequent
[
10,17]
forded resting state complex bis(2,6-lutidine)- cleavage of the CaÀC bond.
b
[
25]
Cu(II)Cl , confirmed by X-ray diffraction.
After
Although the complexity of copper speciation
2
heating CuCl in the presence of TEMPO at 1008C makes it difficult to test electrochemically if the diva-
under O for 18 h both mono- and dinuclear cations lent Cu 2,6-lutidine cations are sufficiently oxidizing
2
are still observed (Supporting Information, Fig- to generate aryl cations from substrates 1a and 1b, an-
ure S42). Finally, mass spectra recorded after oxida- other observation tends to disfavor the primary alco-
tion of 2-methoxyphenol (HOAr) at 1008C under O2 hol oxidation route. We recently showed that oxida-
for 40 h using CuCl/L/TEMPO/showed formation of tion of b–1 models (which bear an aryl group in the
several additional ions such as [Cu(II)ACTHUNGTRENNUNG
+
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
inhibitor rather than a catalyst poison.
while the stoichiometric reaction led to cleavage of
the C ÀC bond. Moreover, use of the Cu catalyst
a
aryl
Mechanistic Considerations
with simple lignin models that lack the electron-rich
aromatic ring, such as 1-phenyl-2-phenoxyethanol, af-
A variety of copper/TEMPO catalyst systems has forded primarily oxidation products with the CaÀC
b
[
16c]
been utilized for the aerobic oxidation of alcohols, bond still intact.
Thus, while Cu/TEMPO catalyst
diols, and lignin model compounds, and several systems are well recognized for their primary alcohol
[
17,20,26]
[20n]
common mechanisms have been proposed.
The selectivity under mild conditions,
at the elevated
Figure 6. Mono- and divalent cations derived from CuX and 2,6-lutidine.
6
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Copper Catalysts for Selective CÀC Bond Cleavage of b-O-4 Lignin
Experimental Section
General Considerations
Unless specified otherwise, all reactions were carried out in
1
13
the presence of air. H and C NMR spectra were recorded
at room temperature on a Bruker AV400 MHz spectrome-
ter, with chemical shifts (d) referenced to the residual sol-
vent signal. GC-MS analysis was obtained using a Hewlett
Packard 6890 GC system equipped with a Hewlett Packard
5
973 mass selective detector. 2-Methoxyphenol was quanti-
fied with response factors using GC/MS. HPLC-MS analyses
were performed on a Dionex Ultimate 3000 Liquid Chroma-
tograph and an Applied Biosystem API2000 triple quadru-
pole mass spectrometer (LC-MS delay 0.27 min), using a re-
versed-phase gradient column (RSLC PA2 2.2 mm 120 ꢁ,
2
.1ꢂ150 mm) and 0.5% acetic acid in H O, acetonitrile/
2
methanol as mobile phases. The analysis employed a DAD
UV-Vis detector or mass spectrometry (Q1MS) with electro-
spray ionization (ESI-MS) in positive mode (ion spray volt-
age: 5000 V, TEM: 4008C, declustering potential: 11.00 V
and focusing potential: 300.0 V). ESI-MS analyses were per-
formed using in an Applied Biosystem API2000 with triple
quadrupole mass spectrometer in positive mode using
Scheme 2. Two routes to oxidative CÀC bond cleavage.
temperatures employed in this study, we suggest that
an alternate pathway predominates. Also unclear is
the origin of the selectivity dependence on the sub-
strate to catalyst ratio observed in this study and with
the b–1 substrates. Previous work has demonstrated
that basic nitrogen ligands are capable of reducing di-
CH CN solvent. CuCl, Cu ACHUTNGRENUN(G OTf), Cu ACHTUTGNRENNUN(G OTf) , CuSO4,
3
2
TEMPO, 2,2’-bipyridine, and neocuproine were used as re-
ceived from Aldrich. Deuterated solvents were purchased
from Cambridge Isotope Laboratories and dried with molec-
ular sieves. The b-O-4 lignin models compounds 1-(3,5-di-
methoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol 1a
[
20k,26b]
valent copper to its monovalent state
and our
goal in catalyst optimization was to employ excess and 1-(4-hydroxy-3,5-dimethoxy-phenyl)-2-(2-methoxyphe-
ligand to favor mononuclear copper centers. Multinu- noxy)propane-1,3-diol 1b were synthesized according to the
[
13,15]
clear copper catalysts have been reported to promote literature procedures.
Oxygen was purchased from
[
30]
CÀC bond formation which would be deleterious to
lignin depolymerization. The MS studies, however, in-
dicate significant amounts of dinuclear Cu cations
even with excess L and the weakly coordinating tri-
flate anion.
Linde Canada.
Oxidation of Non-Phenolic b-O-4 Lignin Model 1a
using CuCl/TEMPO in 2,6-Lutidine
In an NMR tube, non-phenolic lignin model 1a (40 mg,
0
.12 mmol) was dissolved in CDCl (1 mL) containing dime-
3
Conclusions
thylsulfone (3 mg, 0.03 mmol) as an internal standard. An
initial spectrum was recorded and solvent was removed. The
reaction mixture was transferred to a thick-walled 50 mL
Schlenk tube equipped with Teflon stopcock containing
CuCl (11 mg, 0.11 mmol) and TEMPO (9 mg, 0.06 mmol) in
In this study we demonstrate that the promising selec-
tivity for oxidative CÀC bond cleavage exhibited by
[
16a]
soluble copper catalysts with simple lignin models
2
,6-lutidine (4 mL) under air. Oxygen was bubbled into the
is hampered by several additional factors with more
complex b-O-4 models such as 1a and 1b. Although
catalyst optimization improved the yields of the target
reddish orange reaction mixture for 2 min and the reactor
sealed. The reaction mixture was heated at 1008C with con-
stant stirring. After 40 h, the reaction was cooled to room
aromatic aldehyde, the catalyst was inhibited by the temperature and solvent was removed under vacuo. To an
phenol by-product and reduction of the catalyst load- aliquot of the reaction mixture, CDCl (1 mL) was added
3
1
ing led primarily to the ketone derived from oxidation and filtered thorough glass wool and examined by H NMR
spectroscopy (Supporting Information, Figure S1). A second
of the secondary benzylic alcohol. Moreover, while
aliquot was dissolved in acetonitrile and passed through
Co salen-type catalysts oxidize lignin-derived phenols
a silica plug to remove copper salts. The solvent was re-
to benzoquinones in good yields under mild condi-
moved under vacuum and the residue dissolved in CDCl
3
[
24c,d]
tions,
the elevated temperatures required for CÀC
for NMR analysis (Supporting Information, Figure S2). Con-
version and product yields (expressed as a percentage of the
theoretical maximum based on the initial amount of sub-
bond cleavage of 1a and 1b leads to futher reactivity
of the phenol oxidation products.
1
strate) are shown in Figure 2. H NMR resonances not as-
signed to products 2–7: d=6.55 (d, J=2 Hz), 6.30 (br), 4.69
(
br), 4.66 (s), 4.63 (s), 4.62 (br), 4.59 (br), 4.43 (d, J=
Adv. Synth. Catal. 0000, 000, 0 – 0
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ÞÞ
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Baburam Sedai and R. Tom Baker
FULL PAPERS
3
2
.2 Hz), 4.41 (d, J=2.4 Hz), 4.35 (br), 4.16 (br), 3.95 (s),
.66 (s), 2.50 (s), 1.72 (br), 1.54 (br).
not assigned to products 2–4, 7–10 or 1a: d=6.62 (br), 6.60
(br), 6.56 (br), 5.93 (s), 5.82 (d, J=2 Hz), 5.63 (br), 5.50 (d,
J=2 Hz), 4.44 (br), 4.51 (br), 3.71 (s), 1.58 (br), 1.32 (br),
1.23 (s), 1.19 (br).
New 2,6-lutidine decarboxylative coupling products 5 and
were isolated from a large-scale reaction (500 mg 1a in
0 mL of 2,6-lutidine) by column chromatography with silica
6
1
gel using 85:15 mixture of hexanes: ethyl acetate.
-Methyl-6-[(6-methylpyridin-2-yl)methoxy]pyridine (5):
colorless solid; isolated yield: 20%; H NMR: d=7.95, 7.33,
Catalytic Oxidation of 1a using CuCl/TEMPO with
2,6-Lutidine (10 equiv.) in Toluene
2
1
7
.24, 7.07 (d, 1H, J=7.5 Hz, pyridyl), 7.71, 7.56 (tr, 1H, J=
.5 Hz, pyridyl), 5.5 (s, 2H, CH ), 2.65, 2.54 (s, 3H, CH );
This reaction was performed as above except replacing
7
2
3
1
1 mg of CuCl with 2 mg (0.02 mmol) and 9 mg of TEMPO
13
1
C{ H} NMR (CDCl , 100 MHz): d=165.13 (s), 159.28 (s),
3
with 3.75 mg (0.024 mmol). The red reaction mixture was
heated at 1008C. After 18 h, oxygen was bubbled into the
reaction mixture for 2 min the reactor was sealed again and
heated at 1008C. After 40 h, the reaction was cooled to
room temperature, the solvent was removed under vacuum
and the products analyzed as above. Conversion and prod-
158.22 (s), 155.05 (s), 147.34 (s), 137.02 (s), 126.87 (s), 122.65
(
s), 122.48 (s), 118.67 (s), 67.97 (s), 24.68 (s), 24.43 (s); IR:
n=3445 (w), 2726 (w), 2927 (s), 2981 (m), 1727 (s), 1591 (s),
456 (s), 1299 (s), 1232 (s), 1173 (s), 921 (m), 784 (s), 761
s); GC/MS (CH CN): m/z=214.0, 197, 122, 106, 93 65, 53;
1
(
3
+
ESI/MS: m/z=215.20, calcd. for C H N O [M+H] :
1
1
3
14
2
uct yields are shown in Table 1. H NMR resonances not as-
1
215.68 (consistent with H,H COSY).
signed to products 2–4, 7–10: d=6.62 (br), 6.60 (br), 6.58
6
,6’-Oxybis(2-methylpyridine) (6): pale yellow oil; isolated
(
br), 5.82 (d, J=2 Hz), 5.51 (d, J=2 Hz), 4.47 (br), 4.04 (br),
1
yield: 12%; H NMR: d=7.54, 7.47 (t, 1H, J=7.8 Hz, pyrid-
yl), 7.29, 6.95 (d, 1H, J=7.8 Hz, pyridyl), 7.02 (ov d, 2H,
J=7.8 Hz, pyridyl), 5.14 (dd, 1H, J=9.3, 3.0 Hz, CHOH),
1
.69 (br), 1.58 (br), 1.32 (br), 1.23 (s), 1.19 (br).
Formyl esters 7 and 10 were isolated from a large-scale re-
action (400 mg 1a in 1.4 mL of 2,6-lutidine) by column chro-
matography with silica gel using 80:20 mixture of hexanes:
ethyl acetate.
3
9
1
.27 (dd, 1H, J=14, 3 Hz, CH ), 3.01 (dd, 1H, J=14,
2
1
1
3
.3 Hz, CH ), 2.53 (s, 6H); C{ H} NMR: d=162.13 (s),
59.09 (s), 157.21 (s), 157.20 (s), 136.90 (s), 136.86 (s), 121.30
2
3
-(3,5-Dimethoxyphenyl)-3-hydroxy-2-(2-methoxyphenox-
(
(
s), 121.28 (s), 120.89 (s), 117.15 (s), 73.7 (s), 44.5 (s), 24.41
s), 24.39 (s); IR: n=3310 (br), 1594 (s), 1576 (s), 1458 (s),
y)propyl formate (7): colorless oil; isolated yield: 11%;
1
H NMR: d=8.05 (s, 1H, CHO), 7.23 (d, 2H,=2.64 Hz,
1
264 (m), 1154 (m), 1072 (m), 791 (s), 761 (s); ESI/MS:
aryl), 7.06 (d, 1H, J=7.5 Hz, aryl), 6.93 (d, 1H, J=7.5 Hz,
aryl), 6.67 (t, 1H, J=2.6 Hz, aryl), 6.56 (d, 1H, J=2.6 Hz,
aryl), 6.34 (t, 1H, J=2.6 Hz, aryl), 4.89 (d, 1H, J=3.5 Hz,
+
m/z=229.20, calcd, for C H N O [M+H] : 229.29 (consis-
tent with H,H COSY).
1
4
16
2
1
CHOH), 4.52 (dd, 1H, J=12, 8 Hz, CH CH), 4.42 (ddd, 1H,
2
Oxidation of Non-Phenolic b-O-4 Lignin Model 1a
using Cu(OTf) /TEMPO in 2,6-Lutidine
J=8, 3.5, 3 Hz, CH CH), 4.14 (dd, 1H, J=12, 3 Hz,
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
CH CH), 3.82 (s, 6H, OCH ), 3.76 (s, 3H, OCH );
2
2
3
3
1
3
1
C{ H} NMR: d=161.08 (s), 151.84 (s), 146.40 (s), 140.94
s), 131.06 (s), 124.50 (s), 121.57 (s), 121.16 (s), 112.37 (s),
This experiment was performed in the similar fashion as
above except using 39 mg of Cu(OTf) (0.109 mmol) instead
(
AHCTUNGTRENNUNG
2
1
07.64 (s), 106.73 (s), 103.88 (s), 99.72 (s), 84.51 (s), 71.91
of CuCl. After 18 h, oxygen was bubbled into the reaction
mixture for 2 min the reactor was sealed again and heated
at 1008C. Conversion and product yields after 40 h are
(
s), 62.23 (s), 55.90 (s), 55.62 (s), 55.22 (s); HR-MS (EI):
+
m/z=362.1370, calcd. for C H O [M] : 362.1366.
1
9
22
7
3
-(3,5-Dimethoxyphenyl)-2-(2-methoxyphenoxy)-3-oxo-
1
shown in Table 1. H NMR resonances not assigned to prod-
propyl formate (10): colorless oil; isolated yield: 3%;
ucts 2–7: d=9.83 (s), 4.60 (s), 1.70 (s), 1.43 (s), 1.40 (br),
1
H NMR: d=8.08 (s, CHO), 7.23 (d, 2H, J=2.5 Hz, aryl),
1.19 (br).
6
.996.78 (m, 4H, aryl), 6.66 (t, 1H, J=2.5 Hz, aryl), 5.63
(
1
dd, 1H, J=3.70, 6.70 Hz, CH CH), 4.75 (dd, J=3.7,
2
Oxidation of Non-Phenolic b-O-4 Lignin Model 1a
1.8 Hz, CH ), 4.56 (dd, 1H, J=6.7, 11.8 Hz, CH ), 3.80 (s,
2 2
13 1
using CuSO /TEMPO in 2,6-Lutidine
6H, OCH ), 3.74 (s, 3H, OCH ); C{ H} NMR (CDCl ,
4
3
3
3
1
1
00 MHz): d=194.88 (s), 160.95 (s), 160.65 (s), 150.38 (s),
46.56 (s), 140.1 (s), 136.55 (s), 123.73 (s), 121.00 (s), 118.65
This experiment was performed in the similar fashion as
above except using 29 mg of CuSO (0.116 mmol) instead of
4
(
s), 112.58 (s), 106.56 (s), 106.43 (s), 105.1 (s), 80.07 (s),
CuCl. After 18 h, oxygen was bubbled into the reaction mix-
ture for 2 min the reactor was sealed again and heated at
6
3
3.79 (s), 55.79 (s), 55.71 (s), 55.39 (s); HR-MS (EI): m/z=
+
60.1239, calcd. for C H O [M+H] : 360.1209.
1
9
20
7
1
008C. Conversion and product yields after 40 h are shown
1
in Table 1. H NMR resonances not assigned to products 2–
: d=2.50 (s), 1.34 (s), 1.23 (s).
7
Oxidation of 1a using Cu
in Toluene
ACHTUNGTNERNUNG( OTf)/TEMPO/2,6-Lutidine
Oxidation of 1a using CuCl/TEMPO with 2,6-
Lutidine (10 equiv.) in Toluene
This experiment was performed as for the stoichiometric
CuCl one above except using 61 mg of [Cu(OTf)] ·toluene
AHCTUNGTRENNUNG
2
This reaction was performed as above except replacing
(0.12 mmol). The orange-red reaction mixture was dark red
4
mL of 2,6-lutidine with 0.14 mL of 2,6-lutidine
after 18 h at 1008C. Conversion and product yields are
shown in Table 1. H NMR resonances not assigned to prod-
1
(
1.19 mmol) in 6 mL of toluene. After 18 h, oxygen was bub-
bled into the reaction mixture for 2 min the reactor was
ucts 2–4 or 7–10: d=6.65 (br), 6.62 (br), 6.40 (br), 5.82 (d,
J=2 Hz), 5.51 (d, J=2 Hz), 4.43(br), 4.19 (m), 2.15 (s), 1.68
(br), 1.44 (s), 1.23 (s).
sealed again and heated at 1008C. Conversion and product
1
yields after 40 h are shown in Table 1. H NMR resonances
8
asc.wiley-vch.de
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ÝÝ
These are not the final page numbers!

FULL PAPERS
Copper Catalysts for Selective CÀC Bond Cleavage of b-O-4 Lignin
Oxidation of 1a using Cu
in DMF
A
T
N
T
E
N
N
(OTf)/TEMPO/2,6-Lutidine
red reaction mixture was dark red after 18 h at 1008C. After
8 h, oxygen was bubbled into the reaction mixture again
1
for 2 min and the reactor was sealed again. After 40 h, the
reaction was cooled to room temperature, the solvent was
removed under vacuum and the products analyzed as above.
Conversion and product yields are shown in Table 1.
This experiment was performed as for the stoichiometric
Cu(OTf) one above except the toluene was replaced by
mL of dimethylformamide. The orange mixture was dark
ACHTUNGTRENNUNG
6
red after 18 h at 1108C. Conversion and product yields are
1
H NMR resonances not assigned to products 2–4, 7–10: d=
1
shown in Table 1. H NMR resonances not assigned to prod-
6
.65 (br), 6.60 (br), 6.40 (br), 5.82 (d, J=2 Hz), 5.51 (d, J=
ucts 2–4 or 7–10: d=6.60 (br), 6.65 (br), 6.45 (br), 5.82 (br),
2
Hz), 4.44 (br), 1.67 (br), 1.44 (s), 1.23 (s).
5.50 (br), 4.44 (br), 3.89 (s), 3.88 (s), 1.67 (br), 1.44 (br), 1.23
(
s).
Oxidation of 1a using Cu ACHNTUGRNENUG( OTf)/TEMPO/N,N’-
Dimesityl-1,4-diazabutadiene (5 equiv.) in Toluene
Oxidation of 1a using Cu
in DMF/Water
ACHTUNGTNERNUNG( OTf)/TEMPO/2,6-Lutidine
This experiment was performed as for the stoichiometric
Cu ACHUTNGRNENGU( OTf) one above except the 2,6-lutidine was replaced by
This experiment was performed as for the stoichiometric
Cu(OTf) one above except the DMF (3 mL) was replaced
5
0
equiv. of N,N’-dimesityl-1,4-diazabutadiene (0.19 g,
.59 mmol). The purple-yellow reaction mixture was dark
ACHTUNGTRENNUNG
by 3 mL of water. The greenish mixture was reddish green
red after 18 h at 1008C. Conversion and product yields are
1
after 18 h at 1008C. Conversion and product yields are
shown in Table 1. H NMR resonances not assigned to prod-
1
shown in Table 1. H NMR resonances not assigned to prod-
ucts 2–4 or 7–10: d=10.4 (br), 8.82 (s), 8.25 (s), 8.10 (br),
ucts 2–4 or 7–10: d=2.85 (s), 2.63 (s), 1.67 (s), 1.57 (s), 1.23
7
.71 (br), 1.66 (s), 1.44 (br), 1.23 (s).
(
s).
Oxidation of 1a using Cu ACHNTUGRNENUG( OTf)/TEMPO/2,2’-
Bipyridine (5 equiv.) in Toluene
Oxidation of 1a using C
in Acetonitrile
ACHTUNGTNERNUNG( uOTf)/TEMPO/2,6-Lutidine
This experiment was performed as for the stoichiometric
This experiment was performed as for the stoichiometric
Cu(OTf) one above except the toluene was replaced by
mL of acetonitrile. The orange-red reaction mixture was
Cu
ACHTUNGTRENNU(GN OTf) one above except the 2,6-lutidine was replaced by
ACHTUNGTRENNUNG
5
equiv. of 2,2’-bipyridine (92 mg, 0.59 mmol). The purple-
6
red reaction mixture was dirty green after 18 h at 1008C.
dark red after 18 h at 808C. Conversion and product yields
Conversion and product yields are shown in Table 1.
1
1
are shown in Table 1. H NMR resonances not assigned to
H NMR resonances not assigned to products 2–4 or 7–10:
products 2–4 or 7–10: d=6.65 (br), 4.44 (br), 3.61(br), 1.66
d=8.25 (s), 7.81 (m), 6.60 (br), 6.12 (br), 5.12 (s), 4.44 (br),
(
br), 1.41 (s), 1.34 (s).
3
.89 (s), 1.63 (br), 1.43 (br), 1.23 (s).
Oxidation of 1a using Cu
Toluene (no TEMPO)
A
H
U
G
R
N
N
(OTf)/2,6-Lutidine in
Oxidation of 1a using Cu AHCUTNGTERNNUNG( OTf)/TEMPO/
Bis(oxazoline) (5 equiv.) in Toluene
This experiment was performed as for the stoichiometric
Cu(OTf) one above except without TEMPO. The orange-
This experiment was performed as for the stoichiometric
Cu AHCTUNGTERNNNU(G OTf) one above except the 2,6-lutidine was replaced by
5 equiv. of bis(oxazoline) (0.16 g, 0.59 mmol). The reaction
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
red reaction mixture was red after 18 h at 1008C. Conver-
1
sion and product yields are shown in Table 1. H NMR reso-
mixture was light green after 18 h at 1008C. Conversion and
1
nances not assigned to products 2–4 or 7–10: d=6.63 (br),
product yields are shown in Table 1. H NMR resonances
6.60 (br), 6.56 (br), 5.82 (d, J=2 Hz), 5.51 (br), 4.44 (br),
not assigned to products 2–4 or 7–10: d=7.49 (br), 6.60 (br),
6.00 (br), 3.89 (s), 1.70 (br), 1.46 (br), 1.22 (s).
1.23 (s).
Oxidation of 1a using Cu
with 2-Methoxyphenol (1 equiv.) in Toluene
A
H
U
G
R
N
N
(OTf)/TEMPO/2,6-Lutidine
Oxidation of 1a using Cu
(5 equiv.) in Toluene
ACHTUNGERTNNUNG( OTf)/TEMPO/Neocuproine
This experiment was performed as for the stoichiometric
This experiment was performed as for the stoichiometric
Cu(OTf) one above except the 2,6-lutidine was replaced by
Cu
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OTf) one above except with equimolar mixture of 1a
ACHTUNGTRENNUNG
and 2-methoxyphenol (14 mg, 0.11 mmol). The orange-red
5 equiv. of neocuproine (0.12 g, 0.60 mmol). The reaction
reaction mixture was dark red after 18 h at 1008C. Conver-
sion and product yields are shown in Table 1. H NMR reso-
mixture turned dark red after 18 h at 1008C. Conversion
and product yields are shown in Table 1. H NMR resonan-
1
1
nances not assigned to products 2–4 or 7–10: d=6.65 (br),
ces not assigned to products 2–4 or 7–10: d=9.20 (br), 6.81
(br), 3.89 (s), 3.63 (s), 1.66 (s), 1.44 (br), 1.23 (s).
6.60 (br), 5.82 (d, J=2 Hz), 5.50 (d, J=2 Hz), 3.89 (s), 1.66
(
s), 1.44 (br), 1.23 (s).
Oxidation of 2-Methoxyphenol using Cu
TEMPO/2,6-Lutidine in Toluene
ACHTUNGTRNENUNG( OTf)/
Catalytic Oxidation of 1a using Cu
,6-Lutidine in Toluene
ACHTUNGTRENNGNU( OTf)/TEMPO/
2
This experiment was performed as for the stoichiometric
Cu(OTf) one above except substrate 1a was replaced by 2-
This experiment was performed as for the catalytic CuCl
one above except using 12 mg of [Cu(OTf)] ·toluene
ACHTUNGTRENNUNG
A
H
U
G
R
N
N
methoxyphenol (20 mg, 0.161 mmol). The orange-red reac-
2
(
0.02 mmol) and 4 mg of TEMPO (0.02 mmol). The orange-
tion mixture was black after 18 h at 1008C. Approximately
Adv. Synth. Catal. 0000, 000, 0 – 0
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asc.wiley-vch.de
9
ÞÞ
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Baburam Sedai and R. Tom Baker
FULL PAPERS
75% of 2-methoxyphenol had been consumed, with the
Table 2.
products consisting of quinone products consistent with the
[20d,e] 1
Time [h]
6
Conv. [%]
11
12
13
14
13+14
literature.
H NMR: d=8.14 (t, J=7.5 Hz), 7.50 (d, J=
7
6
.5 Hz), 7.07 (m), 7.05 (br), 6.99 (br), 6.97 (br), 6.95 (br),
.93 (br), 6.70 (s), 5.82 (d, J=2 Hz), 5.50 (d, J=2 Hz), 3.83
98
100
100
20
23
22
6
10
12
55
48
44
0
5
7
55
53
51
1
1
2
8
(
s), 3.87 (s), 2.86 (s), 1.98 (s), 1.68 (br), 1.44 (s), 1.23 (s).
Control Experiment: Aerobic Thermolysis of 1a with
,6-Lutidine (10 equiv.) in Toluene
2
1
1
H NMR. H NMR resonances not assigned to products 11–
1
4: d=8.25 (s), 7.94 (t, J=7.5 Hz), 7.39 (br), 7.31 (d,
In an NMR tube, 1a (20 mg, 0.059 mmol) was dissolved in
CDCl3 (1 mL) containing dimethylsulfone (1.39 mg,
7
.5 Hz), 3.96 (s), 2.79 (s), 1.67 (br), 1.44 (s), 1.23 (s).
0
.015 mmol) as an internal standard. An initial spectrum
was recorded and solvent was removed. The reaction mix- Control Experiment: Aerobic Thermolysis of
ture was transferred to a thick-walled 50 mL Schlenk tube Phenolic b-O-4 Lignin Model 1b with 2,6-Lutidine
equipped with Teflon stopcock containing 2,6-lutidine (10 equiv.) in Toluene
(
0.07 mL, 0.59 mmol) in toluene (4 mL) under air. Oxygen
In an NMR tube, phenolic lignin model 1b (20 mg,
.06 mmol) was dissolved in CDCl (1 mL) containing dime-
was bubbled into the mixture for 2 min and the reactor
sealed. After heating at 1008C for 18 h with constant stirring
the solvent was removed under vacuum and the residue ana-
lyzed by H NMR spectroscopy; no conversion or products
were detected.
0
3
thylsulfone (1.3 mg, 0.01 mmol) as an internal standard. An
initial spectrum was recorded and solvent was removed. The
reaction mixture was transferred to a thick-walled 50 mL
Schlenk tube equipped with Teflon stopcock containing 2,6-
lutidine (0.07 mL, 0.57 mmol) in toluene (4 mL) under air.
Oxygen was bubbled into the reaction mixture for 2 min
and the reactor sealed. The reaction mixture was heated at
1008C with constant stirring. After 18 h, approximately 6%
starting material had been consumed and the yield of 2,6-di-
methoxy-1,4-benzoquinone 11 (4%) was determined by
1
Representative LC/MS Data for Copper Complex-
Catalyzed Oxidation of 1a
+
2
-Methoxyphenol (4) [M+H]+ (7.86 min, m/z=125.06,
calcd.: 125.06); TEMPO [M] (22.61 min, m/z=156.14,
calcd.: 156.14); 1-(3,5-dimethoxyphenyl)-2-(2-methoxyphe-
noxy)propane-1,3-diol (1a) [M+H] (26.60 min, m/z=
1
+
H NMR spectroscopy.
3
35.13, calcd.: 335.16); 3,5-dimethoxybenzaldehyde (2) [M+
+
H] (30.76 min, m/z=167.16, calcd.: 167.07); 1-(3,5-dime- Representative LC/MS Data for Oxidation of 1b
thoxyphenyl)-3-hydroxy-2-(2-methoxyphenoxy)propan-1-
one (8) [M+H] (33.78 min, m/z=333.05, calcd.: 333.13); 1-
using Cu AHCTUNTGERNNUN(G OTf)/TEMPO/2,6-Lutidine in Toluene
+
+
2
-(2-Methoxyphenoxy)acrylaldehyde
(12)
[M+H]
(
3,5-dimethoxyyphenyl)-2-(2-methoxyphenoxy)-prop-2-en-1-
+
(1.58 min, m/z=179.20, calcd.: 179.19); 2,6-dimethoxy-1,4-
one (9) [M+H] (36.76 min, m/z=315.05, calcd.: 315.13); 3-
3,5-dimethoxyphenyl)-2-(2-methoxyphenoxy)-3-oxopropyl
+
benzoquinone (11) [M+H] (1.83 min, m/z=169.20, calcd.:
(
+
169.15), 3-hydroxy-1-(4-hydroxy-3,5-dimetho-xyphenyl)-2-(2-
formate (10)
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
[M+H]
(41.97 min, m/z=361.10, calcd.:
+
methoxyphenoxy)propan-1-one (13) [M+H] (2.25 min, m/
361.37); 3-(3,5-dimethoxyphenyl)-3-hydroxy-2-(2-methoxy-
+
z=349.30, calcd. 349.36), unidentified compounds: * (2.62,
phenoxy)propyl formate (7) [M+H] (47.14 min, m/z=
2
.88, 3.85 min, unknown compounds).
363.20; calcd.: 363.38); unidentified compounds: * (17.61,
40.67, 44.06, 49.74, 44.06 min, unknown compounds)
Oxidation of Phenolic b-O-4 Lignin Model 1b using
Cu(OTf)/TEMPO/2,6-Lutidine in Toluene
Acknowledgements
ACHTUNGTRENNUNG
We thank the NSERC Biomaterials and Chemicals strategic
research network (Lignoworks) for support of this work and
the Canada Foundation for Innovation, Ontario Ministry of
Economic Development and Innovation, Canada Research
Chairs and the University of Ottawa for provision of ena-
bling infrastructure. Thanks are also due to Dr. Ammar
Saleem, Dr. Sharon Curtis and Christian Dꢀaz-Urrutia for as-
sistance with the LC/MS and ESI-MS and Dr. Susan Hanson
This experiment was performed as for the stoichiometric
Cu(OTf) one above except substrate 1a was replaced by 1b
40 mg, 0.11 mmol). The orange-red reaction mixture was
ACHTUNGTRENNUNG
(
dark red after 18 h at 1008C. Conversion and product yields
1
are shown in Figure 4. H NMR resonances not assigned to
products 11–13: d=7.96 (t, J=7.5 Hz), 7.33 (d, 7.5 Hz), 3.86
(
s)„ 2.79 (s), 1.68 (br), 1.45 (s).
(
Los Alamos National Lab Chemistry Division) for helpful
Catalytic Oxidation of 1b using Cu
,6-Lutidine in Toluene
ACHTUNGTRENNGNU( OTf)/TEMPO/
discussions.
2
This experiment was performed as for the catalytic Cu
one above except substrate 1a was replaced by 1b (40 mg, References
.11 mmol). The orange-red reaction mixture was dark red
after 6 h at 1008C. Conversion and product yields after 6,
2, and 18 h are shown in Table 2. After the 6 h run ca. 3%
of 4-hydroxy-3,5-dimethoxybenzaldehyde was identified by
ACHTUNGTNERNUNG( OTf)
0
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showed that the 3,5-dimethoxylated aryl ring
model used here gave similar oxidation products. We
1
3
employed a C-labeled version of 1a in previous
[16a]
work
and wanted to compare our results here with
4
318–4327.
the analogous substrate.
12
asc.wiley-vch.de
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These are not the final page numbers!

FULL PAPERS
Copper Catalysts for Selective CÀC Bond Cleavage of b-O-
13
4
Lignin Model Compounds
Adv. Synth. Catal. 2014, 356, 1 – 13
Baburam Sedai, R. Tom Baker*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
13
ÞÞ
These are not the final page numbers!