The Ru-catalyzed alkylative dearyloxylation of L-type 2-Aryloxyethanols

Full text of DOI:10.1002/cctc.201300177

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DOI: 10.1002/cctc.201300177
The Ru-Catalyzed Alkylative Dearyloxylation of L-type
2-Aryloxyethanols
Daniel Weickmann and Bernd Plietker*[a]
Lignin is a natural occurring biopolymer, which, along with cel-
lulose and hemicellulose, is a major component of wooden
plants. Cellulose is an important feedstock for the production
of paper, whereas lignin accumulates in large amounts as side
product during this process. To date, lignin has received only
little attention as a starting material for the production of bulk
chemicals and fuels.[1] A small amount of the produced lignin
is used for the synthesis of dispersing agents or is burned for
the generation of energy and syngas (CO/H2). Owing to its
unique structure, as the only biomaterial consisting mostly of
aromatic subunits (Figure 1), lignin is considered to play an im-
portant role as a renewable resource for the sustainable pro-
duction of fuels and chemicals containing aromatic groups in
the future.[2]
bonds[5–9] remains one of the challenging tasks of transition
metal catalysis. Recently, Bergman and Ellman,[9a] and later on
Leitner and Klankermayer[9b] described the ruthenium-catalyzed
C-O cleavage of 2-aryloxy-1-arylethanol derivatives which
mimic the b-O-4 linkage within the lignin framework. This type
of linkage represents the most present junction of the single
monomers within the lignin structure (Figure 1). The cleavage
of 2-phenoxy-1-phenylethanol proceeded in the presence of
a combination of RuH2CO(PPh3)3 and Ph-XANTPHOS or Ru-
(cod)(methallyl)2 and TRIPHOS under redox neutral conditions
and might be regarded as an intramolecular version of a so
called “hydrogen autotransfer” process (Figure 2).[10–12]
Herein, we present the use of a range of simple and readily
available ruthenium catalysts which are not only able to cleave
the b-C-O linkage in different lignin model compounds but
also allow for a direct sequential alkylation of the resulting ace-
tophenone derivatives using alcohols as alkylating agents
(Figure 2).[13] The combination of two independent catalytic hy-
drogen-autotransfer steps generates new structural motifs with
formation of water as the only byproduct.
The activation and functionalization of intrinsically non-reac-
tive chemical bonds like CÀH,[3] but also CÀC[4] and CÀO
Figure 1. Substructures found in lignin.
[a] D. Weickmann, Prof. Dr. B. Plietker
Institut fꢀr Organische Chemie
Universitꢁt Stuttgart
Pfaffenwaldring 55d-70569 Stuttgart (Germany)
Fax: (+49)711-685 64285
E-mail: bernd.pliekter@oc.uni-stuttgart.de
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201300177.
Figure 2. Ru-catalyzed dearyloxylation and Ru-catalyzed alkylative dearyloxy-
lation.
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During our investigation regarding the use of (NNNN)(P)Ru
complexes as catalyst for reactions based on ruthenium hy-
dride mechanisms,[14] we found that the simple ruthenium
complex (Ph3P)3RuCl2 efficiently cleaves the b-CÀO bond in
2-phenoxy-1-phenylethanol 1 after activation of the precatalyst
with Ktamylate (entry 2, Table 1). The presence of a catalytic
amount of ethyl acetate proved to be essential for an efficient
catalytic turn over (entry 3, Table 1). In the absence of a catalyst
Table 2. Ru-catalyzed C-O cleavage of 2-phenoxy-1-phenylethanol 1 -
phosphine effect.
Entry[a]
Phosphine R3P
Yield 2
[%][b]
Yield 3
[%][b]
1
2
3
4
5
Ph3P
68
78
72
26
47
74
85
84
20
47
Table 1. Ru-catalyzed C-O cleavage of 2-phenoxy-1-phenylethanol 1.
(p-MeC6H4)3P
(p-MeOC6H4)3P
(p-FC6H4)3P
Ph2CyP
[a] All reactions were carried out in a closed Schlenk tube under N2 at-
mosphere with 2-phenoxy-1-phenylethanol (0.125 mmol), catalyst
(5 mol%), Ktamylate (25 mol%) and EtOAc (25 mol%) in toluene
(0.25 mL). [b] Determined by GC analysis using dodecane as internal stan-
dard.
1
Entry[a]
Catalyst
Yield 2
Yield 3
[%][b]
[%][b]
1
2
3
4
5
6
7
8
9
10
–
2
13
94
27
70
81
89
47
58
99
75
(PPh3)3RuCl2
(PPh3)3RuCl2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2/PPh3
(Ph3P)3Ru(OAc)2
(Ph3P)3Ru(OAc)2
(dmso)4RuCl2
(PPh3)4RuH2
94
23
70
80
80
53
52
80
79
[c]
ered as chemoselective as the b-alkyl-aryl-ether bond is
cleaved in the presence of one or more methyl-aryl-ether
bonds.
[c]
With this system in hand, we were wondering whether the
coupling of two H2-autotransfer processes would be possible.
(Ph3P)3RuCl2 is known to catalyze the direct alkylation of ke-
RuHCl(CO)(PPh3)3
[a] All reactions were carried out in a closed Schlenk tube under N2 at-
mosphere with 2-phenoxy-1-phenylethanol (0.125 mmol), catalyst
1
(5 mol%), Ktamylate (25 mol%) and EtOAc (25 mol%) in toluene
(0.25 mL). [b] Determined by GC analysis using dodecane as internal stan-
dard. [c] Without EtOAc.
Table 3. Ru-catalyzed cleavage of different lignin model compounds.
the C-O cleavage did not take place under thermal conditions
Entry[a]
Substrate
Yield A
[%][b]
Yield B
[%][b]
and only a small of amount of phenol 2 and trace amounts of
acetophenone
3 were formed (entry 1, Table 1). Besides
(Ph3P)3RuCl2 a range of other ruthenium complexes gave the
cleavage products in good to high yields (entries 4–10,
Table 1).
1
2
2 59
9 53
3 82
Based on (Ph3P)3RuCl2, which showed the highest catalytic
activity in the CÀO cleavage of 2-phenoxy-1-phenylethanol 1,
the influence of monodentate phosphine ligands in complexes
of the kind (R3P)3RuCl2 was further investigated. Complexes
containing more electron donating phosphines showed im-
proved reactivity (entries 2 and 3, Table 2), whereas the use of
a more electron deficient phosphine ligand lead to a decrease
of the yield of the cleavage products (entry 4, Table 2). The
presence of mixed aryl-alkyl-phosphines proved to be less ef-
fective than the presence triaryl-substituted phosphines
(entry 5, Table 2).
10 62
3
4
5
11 98[c]
11 81[c]
12 68[c]
3 98
9 62
3 65
With (Ph3P)3RuCl2, as one of the most reactive and most
readily available catalysts containing the cheapest phosphine
ligand, a range of lignin model compounds were subjected to
the established reaction conditions. Substrates 4–8 derived
from the three monolignols coumaryl-, coniferyl-, and sinapyl-
alcohol underwent clean CÀO cleavage reactions and the cor-
responding products could be obtained in good to excellent
yields (Table 3). The reaction of these substrates can be consid-
[a] All reactions were carried out in a closed Schlenk tube under N2 at-
mosphere with substrate 4–8 (0.25 mmol), (Ph3P)3RuCl2 (5 mol%), Ktamy-
late (25 mol%), EtOAc (25 mol%) in toluene (0.5 mL) at 1408C for 18 h.
[b] Determined by GC analysis using dodecane as internal standard.
[c] Isolated yield.
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tones with alcohols.[13a] Hence, after the dearyloxylation of
1 was completed benzyl alcohol and a stoichiometric amount
of KOH was added to the reaction mixture. Gratifyingly, after
heating for another 16 h the benzylated acetophenone 13
could be obtained in 71% overall yield (entry 1, Table 4). In this
type of ruthenium catalyzed sequential C-O cleavage/a-alkyla-
tion reaction we were able to convert different lignin model
compounds to the corresponding alkylated acteophenone de-
rivatives with a range of benzylic-, heterobenzylic-, and aliphat-
ic alcohols (Table 4).
Table 4. Ru-catalyzed
sequential
C-O
cleavage/a-alkylation.
The selective cleavage of b-aryloxy groups is one of the
most promising strategies in lignin chemistry. Herein, we dis-
closed a study in which (Ph3P)3RuCl2 was employed as a com-
mercially available catalyst for the selective CÀO-bond cleav-
age in different 2-aryloxy-1-phenylethanols. The corresponding
acetophenones were obtained in good to excellent yields. The
coupling of two hydrogen-autotransfer processes of dearyloxy-
lation and subsequent dehydrative a-alkylation using primary
alcohols allowed for the alkylative dearyloxylation of various
lignin-type model compounds. Future work along these lines is
currently underway.
Entry[a]
Substrate
Product
Yield
[%][b]
1
Ar=C6H5 1
Ar=C6H5 1
71
Experimental Section
2
3
R=OMe 14
Cl 15
43
51
General procedure for the Ru-catalyzed C-O cleavage of lignin
model compounds
KOtAm (36 mL, 0.063 mmol) was added to a solution of (Ph3P)3RuCl2
(12 mg, 0.013 mmol) in toluene (0.5 mL). Then ethyl acetate (6.2 mL,
0.063) and substrate 1 or 4–8 (0.250 mmol) were added. The
Schlenk tube was sealed and the reaction mixture was stirred at
1408C for 18 h. After cooling to room temperature dodecane
(30 mL, 0.125 mmol) was added and an aliquot of the reaction mix-
ture was filtered over silica and analyzed by gas chromatography.
Products were identified by comparison with an original sample.
Acetophenones 11 and 12 were isolated by flash column
chromatography.
4
5
Ar=C6H5 1
58
47
Ar=C6H5 1
Ar=C6H5 1
6
7
X=O 18
S 19
40
40
8
9
Ar=C6H5 1
Ar=C6H5 1
47
53
General procedure for the Ru-catalyzed sequential C-O
cleavage/a-alkylation of lignin model compounds
KOtAm (36 mL, 0.063 mmol) was added to a solution of (Ph3P)3RuCl2
(12 mg, 0.013 mmol) in toluene (0.5 mL). Then ethyl acetate (6.2 mL,
0.063) and substrate 1, 5, 6 or 8 (0.250 mmol) were added. The
Schlenk tube was sealed and the reaction mixture was stirred at
1408C for 8 h. After cooling to room temperature KOH (14 mg,
0.25 mmol) and the corresponding alcohol (0.25 mmol) was added.
The reaction mixture was stirred for another 16 h at 1408C. Prod-
ucts were isolated by flash column chromatography.
10
11
Ar=4-MeO-C6H5 5
Ar =3,4-MeO-C6H5 6
44
53
Acknowledgements
12
13
Ar=3,4-MeO-C6H5 6
Ar=3,4,5-MeO-C6H5 8
53
37
Financial support by the Deutsche Forschungsgemeinschaft (SFB
706) is gratefully acknowledged.
Keywords: catalysis · CÀO-bond · hydrogenation · lignin ·
ruthenium
[a] All reactions were carried out in a closed Schlenk tube under N2 at-
mosphere with substrate 1, 5, 6 or 8 (0.25 mmol), (Ph3P)3RuCl2 (5 mol%),
Ktamylate (25 mol%), EtOAc (25 mol%) in toluene (0.5 mL) at 1408C for
8 h, then KOH (0.25 mmol) and alcohol (0.25 mmol) for another 16 h.
[b] Isolated yield.
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Received: March 12, 2013
Published online on May 21, 2013
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