Catalytic C-O bond cleavage of 2-aryloxy-1-arylethanols and its application to the depolymerization of lignin-related polymers

Article abstract of DOI:10.1021/ja106101f

A ruthenium-catalyzed, redox neutral C-O bond cleavage of 2-aryloxy-1-arylethanols was developed that yields cleavage products in 62-98% isolated yield. This reaction is applicable to breaking the key ethereal bond found in lignin-related polymers. The bond transformation proceeds by a tandem dehydrogenation/reductive ether cleavage. Initial mechanistic investigations indicate that the ether cleavage is most likely an organometallic C-O activation. A catalytic depolymerization of a lignin-related polymer quantitatively yields the corresponding monomer with no added reagent.

Full text of DOI:10.1021/ja106101f

Published on Web 08/23/2010
Catalytic C-O Bond Cleavage of 2-Aryloxy-1-arylethanols and Its Application
to the Depolymerization of Lignin-Related Polymers
Jason M. Nichols, Lee M. Bishop, Robert G. Bergman,* and Jonathan A. Ellman*
Department of Chemistry, UniVersity of California, Berkeley, California 94720
Received July 9, 2010; E-mail: jonathan.ellman@yale.edu; rbergman@berkeley.edu
C-O bond. To be successful, however, this strategy requires a
catalyst that can perform the requisite hydrogen shuttling and the
novel C-O bond activation processes in tandem. The ruthenium
Abstract: A ruthenium-catalyzed, redox neutral C-O bond cleav-
age of 2-aryloxy-1-arylethanols was developed that yields cleav-
age products in 62-98% isolated yield. This reaction is applicable
to breaking the key ethereal bond found in lignin-related polymers.
The bond transformation proceeds by a tandem dehydrogenation/
reductive ether cleavage. Initial mechanistic investigations indicate
that the ether cleavage is most likely an organometallic C-O
activation. A catalytic depolymerization of a lignin-related polymer
complex RuH2(CO)(PPh3)3 is known to be competent for both
dehydrogenation8 and C-O activation chemistry and was chosen
as the starting point for catalyst development.9
Table 1 summarizes the results of a screen of phosphine ligands
using catalytic amounts of RuH2(CO)(PPh3)3 with 2-phenoxy-1-
phenethanol (2a). In the absence of added ligand, little product was
obtained (entry 1). Adding monodentate phosphines resulted in
quantitatively yields the corresponding monomer with no added
reagent.
lower conversion (entries 2 and 3). Bidentate ligands (entries 4-7)
with a range of phosphine bite-angles effected dehydrogenation to
yield R-phenoxyacetophenone but were not able to promote the
Lignin depolymerization is one of the most significant barriers
to reaching the full potential of lignocellulosic biofuels as fossil
fuel replacements.1 The problem stems from the fact that lignin
comprises 15-25% of the mass found in lignocellulose and up to
40% of the energy content.2 For lignocellulosic biofuels to be
sustainable, chemistry must be developed to convert lignin into
small molecules that can be upgraded into a fuel stream.3
Homogeneous and heterogeneous catalytic processes for both
oxidative and reductive lignin depolymerizations are known.4 Here
we describe a tandem catalytic dehydrogenation/C-O bond cleav-
age that enables a redox neutral approach for lignin depolymeri-
zation. This approach is noteworthy both as a novel C-O bond-
cleavage reaction and as a process for depolymerization that requires
no added reagent.
The chemical structure of lignin is highly variable; therefore,
choosing a small-molecule system and targeting a bond transforma-
tion is challenging.5 The ꢀ-[O]-4′-glycerolaryl ether linkages (1)
are ubiquitous in lignin found across many species including
Miscanthus giganteus, a species of particular interest for industrial
lignocellulosic biofuels production (Figure 1).6 2-Aryloxy-1-
arylethanols (2), or “ꢀ-[O]-4′-ethanolaryl ethers”, are often used
to model the ꢀ-[O]-4′-glycerolaryl ether linkages and were chosen
for the purpose of reaction development.7
reductive ether cleavage. However, a quantitative yield was attained
with the wide bite-angle ligand, 9,9-dimethyl-bis(diphenylphos-
phino)xanthene (Ph-xantphos), providing proof-of-principle for the
tandem catalysis strategy (entry 8).
Table 1. Ligand Screening for C-O Bond Cleavage of 2a
yield (%)c,d
entrya
ligand
conv.,d (%)
PhCOMe
PhOH
1
2
3
4
5
6
7
8
none
PPh3
PCy3
dppm
dppp
dppbz
dppf
Ph-xantphos
45
39
27
11
32
32
37
>99
5
<1
4
0
0
0
5
>99
6
5
5
0
<1
0
b
b
6
>99
a Reactions were run in sealed tubes under nitrogen. b 2 equiv relative
to Ru. c Yields and conversions were determined by GC/MS relative to
an internal standard. d Average of two duplicate experiments.
Additional reaction optimization yielded a set of general condi-
tions for 2-aryloxy-1-arylethanols. The substrates in Table 2 model
the substitution patterns found in lignin. Increased methoxyl
substitution of the O-terminus aryl ring resulted in diminished yields
(2a-c), while methoxylation of the C-terminus aryl ring had
comparatively little effect on the reaction outcome (2d). The
conditions also worked well for the highly substituted substrate 2e.
The next challenge came in applying the small-molecule
chemistry to an actual polymer of 2-aryloxy-1-arylethanol. Scheme
1 shows the quantitative depolymerization of poly(4′-hydroxy-1-
phenethanol)10 (3) to 4′-hydroxyacetophenone. Solvent, temperature,
and catalyst loading were modified to ameliorate the poor solubility
and reactivity of 3 under the conditions developed for the 2-aryloxy-
1-arylethanols (Scheme 1). Complete conversion of polymer to
Figure 1. 2-Aryloxy-1-arylethanols approximate the functionality in ꢀ-[O]-
4′-glycerolaryl ethers.
Structural analysis of polymer 1 suggested a redox neutral set
of transformations that would result in depolymerization. In the
desired reaction, catalytic dehydrogenation of the R-carbinol
provides the reducing equivalents needed to cleave the ꢀ-arylether
9
12554 J. AM. CHEM. SOC. 2010, 132, 12554–12555
10.1021/ja106101f  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. C-O Bond Cleavage of Various 2-Aryloxy-1-arylethanols
Scheme 2. (a) Blocking Formation of 4a Prevents C-O Cleavage;
(b) Hydrosilylation of 4a Yields C-O Cleavage
substrate
Ar
Ar′
yield (%)a
2a
2b
2c
2d
2e
C6H5
C6H5
C6H5
4-(CH3O)-C6H4
3,4-(CH3O) -C6H3
C6H5
98
88
62
98
89
2-(CH3O)-C6H4
2,6-(CH3O)2-C6H3
C6H5
2-(CH3O)-C6H4
a Average isolated yield of the corresponding ketone based on two
duplicate experiments.
radical inhibitor 2,6-di-(tert-butyl)-4-methylphenol (BHT) has no
effect on the apparent half-life, or yield, for the disproportionation
of 2b (t1/2 ) 2 h, 135 °C, [2b] ) 0.1 M). Finally, hydrosilylation
of ketone 4a with Et3SiD forms acetophenone with 55% deuterium
incorporation at the R-keto position as confirmed by 2H NMR. The
selective deuteration result is consistent with a mechanism in which
a ruthenium enolate (6) is formed and trapped by the deuterated
silane.13 These experiments indicate that radical and elimination
mechanisms are not likely responsible for the observed transforma-
tion and support the proposed model outlined in Figure 2.7b,12
Future work will be directed toward the investigation of the
elementary steps of the organometallic C-O activation process as
well as applications to natural lignin and other model systems.
monomer in 99% isolated yield demonstrates the utility of the
catalytic system for depolymerizing polyethers that are in the
molecular weight range of isolated lignin.
Scheme 1. Depolymerization of Lignin-Related Polymer
The proposed mechanism for the transformation is shown in
Figure 2. It begins with a well-known Ru-catalyzed dehydrogenative
equilibrium between a benzylic alcohol and the corresponding aryl
ketone.10 This is followed by loss of HX from the catalyst precursor
and formation of Ru(0) complex 5. C-O activation in 5 leads to
Ru-enolate (6). Hydrogenation of 6 yields a Ru-alkoxide (7)
followed by reductive elimination of phenol and association with
4 to close the cycle.
Acknowledgment. We gratefully acknowledge the Energy
Biosciences Institute (Grant No. OO7J37) for financial support.
J.M.N. thanks the National Institutes of Health for support through
the Ruth L. Kirschstein Postdoctoral Fellowship (F32GM084597).
Supporting Information Available: Substrate syntheses and ex-
perimental procedures. This material is available free of charge via the
Internet at http://pubs.acs.org.
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Figure 2. Mechanistic rationale for C-O bond cleavage.
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Alternate mechanisms that do not proceed through the R-aryloxy
ketone are not consistent with the experimental observations
summarized in Scheme 2. These mechanisms include a free-radical
mechanism initiated by the formation of a benzyl radical11 or the
elimination of phenol to yield styryl enol ethers. Compound 8 is
theoretically able to participate in both mechanisms and yet is not
converted to product under the reaction conditions. Moreover, the
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