A photochemical strategy for lignin degradation at room temperature

Article abstract of DOI:10.1021/ja4113462

The development of a room-temperature lignin degradation strategy consisting of a chemoselective benzylic oxidation with a recyclable oxidant ([4-AcNH-TEMPO]BF₄) and a catalytic reductive C-O bond cleavage utilizing the photocatalyst [Ir(ppy)₂(dtbbpy)]PF₆ is described. This system was tested on relevant lignin model substrates containing β-O-4 linkages to generate fragmentation products in good to excellent yields.

Full text of DOI:10.1021/ja4113462

Communication
pubs.acs.org/JACS
A Photochemical Strategy for Lignin Degradation at Room
Temperature
John D. Nguyen,‡ Bryan S. Matsuura,‡ and Corey R. J. Stephenson*
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
S
* Supporting Information
Scheme 1. Two-Step Redox-Neutral Lignin Degradation
Strategy
a
ABSTRACT: The development of a room-temperature
lignin degradation strategy consisting of a chemoselective
benzylic oxidation with a recyclable oxidant ([4-AcNH-
TEMPO]BF4) and a catalytic reductive C−O bond
cleavage utilizing the photocatalyst [Ir(ppy)2(dtbbpy)]PF6
is described. This system was tested on relevant lignin
model substrates containing β-O-4 linkages to generate
fragmentation products in good to excellent yields.
ignin, an important aromatic biopolymer responsible for the
Lstrength and shape of plants, constitutes 30% of non-fossil
organic carbon.1 The primary structure of lignin is composed of a
diversely linked network of electron-rich phenylpropanols:
coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol (Scheme
1).2 Its abundance in nature, as well as its potential for providing
high-value low-molecular weight aromatics,3 has made the
controlled depolymerization of lignin an intense focus for both
industrial and academic research. In industry, biomass is
processed using the traditional kraft, sulfite, or soda pulping
methods.4 Although these processes have yielded some market-
able substances, the harsh and energy-intensive conditions do
not allow for the production of useful quantities of commodity
compounds from lignin. Several environmentally benign pulping
processes have been investigated, such as the organosolv
process,5 but they have yet to be widely implemented.
Furthermore, although oxidative,6 reductive,7 and redox-neutral8
lignin degradation protocols have been demonstrated on
processed lignin, native lignin, and lignin model systems, the
development of a reliable procedure for the production of fine
and specialty compounds from lignin remains underdeveloped.9
Several of the most promising catalytic lignin degradation
methods to date have been recently developed by Baker, Hanson,
Silks,6g,h,k Hartwig,7f,h Bergman, Ellman,8a and Toste.8b,d These
methods represent diverse strategies toward lignin degradation
utilizing transition-metal catalysis; however, these approaches
also reveal significant challenges that have yet to be addressed.
Specifically, catalytic lignin degradation typically requires
elevated temperatures (>80 °C) and functional groups such as
free phenols and γ-alcohols are not well tolerated. Therefore, we
sought to address these issues by developing a room temperature
lignin degradation method that could be performed efficiently in
the presence of functional groups found in native and processed
lignin. Herein we report a lignin degradation strategy that
involves a two-step redox-neutral method. In the first step,
Bobbitt’s salt ([4-AcNH-TEMPO]BF4)10 mediates a benzylic
oxidation, which is followed by a chemoselective visible-light-
a
Representation of the structure of lignin. Bond dissociation
enthalpies, calculated with M06-2X functional and 6-311++G(d,p)
basis set, indicate that alcohol oxidation can significantly weaken β-O-4
linkages.12
mediated reductive C−O bond cleavage promoted by the
photocatalyst [Ir(ppy)2(dtbbpy)]PF6.11
Although many types of C−O bonds are found in the lignin
biopolymer, the most common type is the β-O-4 linkage (see
Scheme 1), comprising >50% of all linkages found in
lignocelluloses.9a DFT calculations have indicated that the C−
O bond of the β-O-4 linkage is significantly weakened (∼14 kcal/
mol) upon the oxidation of the α- or γ-carbon.12 Based upon
these calculations, we postulated that it would be possible to
chemoselectively cleave the C−O bond of the β-O-4 linkage after
selective oxidation (benzylic or primary) followed by a single
electron-transfer event to allow access to complementary
fragmentation partners. The cleavage of C−O bonds utilizing
visible-light-active photocatalysts has been reported by Hasega-
wa,13 Ollivier,14 and our group.15 In particular, the groups of
Hasegawa and Ollivier studied the reductive cleavage of strained
C−O bonds of ketoepoxides with the photocatalyst Ru(bpy)3Cl2
to generate β-hydroxy ketones. However, a generalized visible-
light-mediated reductive cleavage of Cα−O bonds (Cβ in lignin is
the equivalent to Cα for a carbonyl) has not yet been reported.
We identified this opportunity to develop such a method in the
Received: November 6, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja4113462 | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
context of our goal toward a mild and chemoselective lignin
degradation.
strongly influenced by the pKa of the leaving group. The reaction
is also influenced by the reactivity of the carbonyl portion of the
molecule, as illustrated by the absence of fragmentation products
upon substitution of the phenyl ketone with a methyl ketone (3),
presumably due to the larger reduction potential of methyl
ketones in comparison to phenyl ketones.25 On the contrary,
commercially available 2-(benzyloxy)acetaldehyde (4) under-
went efficient fragmentation, cleaving the much stronger C−O
bond, to give benzyl alcohol in high yield. Substrates 5−8 were
selected to test the generality of the catalytic C−O bond cleavage
reaction on relevant lignin model systems. Specifically, substrates
5−7 represent products of a benzylic oxidation on each of the
different phenylpropanol monomers, whereas substrate 8
represents a lignin model system of coniferyl alcohol that has
been oxidized at the primary alcohol (see Scheme 1). As
expected, lignin model systems 5−8 all underwent efficient
fragmentation. However, although the fragmentation of
substrate 8 gave good yields of guaiacol, the complementary
aldehyde fragment could not be isolated (Table 1, entry 8),
possibly due to polymerization of the expected cinnamaldehyde
product. Instead, we were able to isolate ethyl 3,4-dimethox-
ybenzoate in 30% isolated yield, which represents a unique
oxidative cleavage of the α−β linkage.24
Overall, the mild reaction conditions allow for the atom-
economical reductive fragmentation of the lignin model systems
to generate guaiacol and β-hydroxy phenyl ketones. No evidence
of undesired oxidation26 or further fragmentation of the
guaiacol7f was observed, and the β-hydroxy phenyl ketones did
not undergo retro-aldol or elimination reactions under our
conditions.8b The ability to generate these fragmentation
products under mild conditions and in high yields highlights
the potential ability of this method to assist in the production of
commodity compounds.9 In addition, the successful fragmenta-
tion of substrate 8 highlights the versatility of this lignin
degradation strategy because γ-alcohols typically survive lignin
pulping methods, whereas benzylic alcohols are known to
undergo substitution to form benzylic thiols (kraft), benzylic
sulfones (sulfite), and benzylic ethers (organosolv).9a Further-
more, the β-hydroxy phenyl ketone fragments produced from
substrates 5−7 have not been generated by any other lignin
degradation method in high yields, particularly 7, which is a
difficult substrate due to the free phenol.6a,b,h,i,7g,8a−d
We began our investigation by exploring Cα−O bond cleavage
of ketones and aldehydes. Based on our previous success with
cleaving C−X bonds,16 we hypothesized that we could apply
photoredox catalysis17,18 toward the Cα−O bond cleavage of
lignin model substrate 1. Evaluation of a series of common
photoredox catalysts including Ru(bpy)3Cl2,19 fac-Ir(ppy)3,20
[Ir(ppy)2(dtbbpy)]PF6,11 [Ir{dF(CF3)ppy}2(dtbbpy)]PF6,21
Cu(dap)2Cl,22 and eosin Y23 revealed that fac-Ir(ppy)3 and
[Ir(ppy)2(dtbbpy)]PF6 could effectively promote the Cα−O
bond cleavage of 1 to give 4′-methoxyacetophenone and guaiacol
in high conversions.24 Upon discovering that [Ir(ppy)2-
(dtbbpy)]PF6 could be employed without degassing, we were
able to develop optimized reaction conditions capable of fully
fragmenting 1 in 12 h to generate 4′-methoxyacetophenone and
guaiacol in 88% and 89% yield, respectively (Table 1, entry 1).
We next examined the Cα−O bond cleavage in more detail by
varying the ether substituents (Table 1). A substrate bearing an
α-acetoxy group instead of guaiacol (2) reached full conversion
in significantly less time, indicating that the reaction rate is
Table 1. Substrate Scope of Visible-Light-Mediated Cα−O
Bond Cleavage
Native lignin, as well as processed lignin, is not typically
obtained in an oxidized form,9a and therefore an efficient method
for oxidation, prior to any C−O bond reduction, is necessary.
Thus, we next examined the development of an oxidation
method that could be used to oxidize either the α- or γ-carbon of
β-O-4 lignin model systems. Such an oxidation would give α-
alkoxyketones or α-alkoxyaldehydes that could undergo
reductive fragmentation, as described above. During our
investigation of oxidation conditions,24 the Stahl group reported
an elegant catalytic aerobic benzylic alcohol oxidation of lignin
model systems utilizing 4-AcNH-TEMPO (5 mol%), HNO3 (10
mol%), and HCl (10 mol%).26 This set of conditions can be
applied to produce ketones such as 1 and 5−7, which can
subsequently be used as substrates in our reductive Cα−O bond
cleavage reaction to give the fragmentation products in high
yields. Unfortunately, we have not yet been able to successfully
implement Stahl’s oxidation in sequence with the photocatalytic
reductive fragmentation without purification, precluding a one-
pot procedure. It is possible that the presence of 4-AcNH-
TEMPO may be interfering with photocatalyst turnover.
Consequently, we turned to [4-AcNH-TEMPO]BF4 for three
a
Yields of products isolated via column chromatography and based on
an average of two runs.
B
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Journal of the American Chemical Society
Communication
main reasons. First, [4-AcNH-TEMPO]BF4 has been shown to
selectively oxidize benzylic alcohols at room temperature.
Second, the hydroxylamine byproduct can be removed from
the reaction mixture by adsorption onto silica. Third, the spent
oxidant can be recycled using hydrogen peroxide and fluoroboric
acid.10a,c As predicted, substrates 9−11 were efficiently oxidized
to benzylic ketones with [4-AcNH-TEMPO]BF4, and simple
filtration provided the products in high purity.27
Scheme 2. Improving Lignin Degradation Strategy Utilizing
Continuous Flow and Lower Catalyst Loading
By combining the chemoselective benzylic oxidation utilizing
[4-AcNH-TEMPO]BF4 and our visible-light-mediated Cα−O
bond cleavage, we successfully developed a lignin degradation
method that can be performed at ambient temperature.
Substrates 9−11 were cleanly oxidized to benzylic ketones by
mixing with a slight excess of [4-AcNH-TEMPO]BF4 and silica.
Upon completion of the oxidation, the mixture was filtered, and
dichloromethane was removed in vacuo. Next, DIPEA, formic
acid, [Ir(ppy)2(dtbbpy)]PF6, and MeCN were added, and the
reaction mixture was irradiated with blue LEDs to produce the
fragmentation products in high yields (Table 2). This system is
particularly amenable to a batch-to-flow28,29 reaction setup in
which the oxidation is performed in batch and the reductive
cleavage is performed in flow. Utilizing an easily assembled flow
reactor,24 the rate of substrate consumption for 10 could be
increased to 1.8 mmol/h in flow from 0.050 mmol/h in batch,
even when the catalyst loading is reduced from 1.0 to 0.030 mol%
(Scheme 2, top). The ability to perform the reductive Cα−O
bond cleavage reaction at lower catalyst loading is not exclusive
to flow reactions, as is demonstrated by the gram-scale batch
fragmentation of substrate 11 with only 0.030 mol% catalyst
loading (not shown). Surprisingly, in both of these cases the use
of 0.030 mol% catalyst loading gave slightly improved yields for
both fragmentation products as compared to 1.0 mol%.
no conversion after 48 h. However, when the same reaction was
carried out in flow, we observed full consumption of 1, providing
a high yield of both guaiacol and 4′-methoxyacetophenone,
despite reduced light transmittance (Scheme 2). This clearly
demonstrates the ability of our reaction to operate in the
presence of sulfonate groups, solvent quantities of water, and
dark colored impurities found in lignosulfonate.
We propose that the mechanism of the reductive Cα−O bond
cleavage is based on the well-established reductive quenching
cycle of [Ir(ppy)2(dtbbpy)]PF6 and is analogous to the reductive
dehalogenation mechanism previously studied by our group.16
Visible light absorption by the photocatalyst initiates a metal-to-
ligand charge transfer to generate the excited state [Ir]3+*. This
excited state accepts an electron from the amine or amine−
formate complex to generate [Ir]2+, a strong reductant (−1.51 V
vs SCE). The [Ir]2+ complex performs a single electron transfer
to the benzylic ketone or aliphatic aldehyde to generate a radical
anion, which undergoes a fragmentation to generate an alkoxy
anion and the corresponding Cα-radical. Protonation of the
alkoxy anion and H-atom abstraction by Cα-radical produces the
fragmentation products.
At the outset, we were aware of the potential difficulty of
irradiating darkly colored solutions of lignin. Therefore, we
performed the photocatalytic reduction of 1 (0.4 mmol) in the
presence of an equivalent weight of lignosulfonate. The dark
brown color of the resulting solution prevented efficient
irradiation of the reaction medium in batch, which resulted in
Table 2. Two-Step Degradation of Lignin Model Systems
In conclusion, we have described a potential mild and efficient
two-stage lignin degradation strategy that proceeds through a
selective [4-AcNH-TEMPO]BF4-mediated oxidation and a
photoredox-catalyzed reductive C−O bond cleavage. The
separation of the oxidation and reduction steps, as well as the
mild nature of the reaction conditions, allows for greater control
of bond construction and cleavage to ultimately maintain the
integrity of the fragmentation products. This proof-of-principle
approach addresses many of the challenges in the chemoselective
degradation of lignin, which include functional group tolerance
and mild reaction conditions; however, aspects of scalability,
stoichiometric waste, and cost remain to be addressed. Further
development of a photocatalytic depolymerization that obviates
the need for superstoichiometric additives is currently ongoing in
our laboratory and will be reported in due course.
ASSOCIATED CONTENT
■
S
* Supporting Information
a
Experimental details and characterization data. This material is
available free of charge via the Internet at http://pubs.acs.org.
Yields of products isolated via column chromatography and based on
an average of two runs.
C
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AUTHOR INFORMATION
Corresponding Author
crjsteph@umich.edu
■
Author Contributions
‡J.D.N. and B.S.M. contributed equally.
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the University of Michigan, the Alfred P.
Sloan Foundation, and the Camille and Henry Dreyfus
Foundation is gratefully acknowledged. J.D.N. thanks The
American Chemical Society Division of Organic Chemistry
and Amgen for a graduate fellowship. B.S.M. thanks Vertex for a
graduate fellowship.
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