Chemical conversion of β-O-4 lignin linkage models through Cu-catalyzed aerobic amide bond formation

Article abstract of DOI:10.1039/c3cc46912c

Methods for conversion of the lignin β-O-4 models into amide derivatives and phenols have been developed, which is achieved via chemo-selective oxidation of the secondary benzylic alcohol and subsequent Cu-catalyzed aerobic amide bond formation.

Full text of DOI:10.1039/c3cc46912c

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Chemical conversion of b-O-4 lignin linkage models
through Cu-catalyzed aerobic amide bond formation†
Cite this: Chem. Commun., 2013,
49, 11439
a
a
Jian Zhang,z Yu Liu,z Shunsuke Chiba*a and Teck-Peng Loh*ab
Received 10th September 2013,
Accepted 15th October 2013
DOI: 10.1039/c3cc46912c
www.rsc.org/chemcomm
Methods for conversion of the lignin b-O-4 models into amide
derivatives and phenols have been developed, which is achieved
via chemo-selective oxidation of the secondary benzylic alcohol
and subsequent Cu-catalyzed aerobic amide bond formation.
Scheme 1 Oxidative conversion of lignin b-O-4 linkage models.
With the possible depletion of fossil fuels in the near future,
lignocellulosic biomass has recently emerged as a possible alternative Ni-catalyzed hydrogenolysis of aryl ether bonds,4 Ru-catalyzed C–O
renewable source of energy. Therefore, many efforts have been bond cleavage by a sequence of hydrogenation–reductive ether
directed towards chemical conversion of all the components in cleavage,5 and V-catalyzed aerobic C–C/C–O bond fission.6,7 While
biomass into useful chemicals, drugs, fuels, functional materials, these methods are efficient in only C–C/C–O bond cleavage they do
etc.1 In this context, chemical conversion of cellulose and hemi- not include formation of any new bond except for C–H and C–O bond
cellulose has extensively been studied, while that of lignin remains formation in hydrogenation and oxidation to carboxylic acids, respec-
scarce albeit lignin is the second most abundant biopolymer, con- tively, which can limit their synthetic applications. Therefore there
stituting up to 15–30% of the weight and 40% of the energy content of still remain challenges to develop new methods to convert the lignin
lignocellulosic biomass.2 This is probably due to its rigid cross-linked models to valuable chemicals through new bond forming processes.
structure that renders lignin resistant to chemical degradation. The Herein, we report conversion of the b-O-4 lignin models into amides
most abundant unit of lignin is the b-O-4 linkage (Fig. 1). 1-Aryl- and phenols based on Cu-catalyzed aerobic amide bond formation.
2-aryloxy propane-1,3-diol derivatives are often utilized for the lignin
model to mimick the b-O-4 linkage to explore methods for chemical (Scheme 1) would commence with chemoselective oxidation
conversion. of the secondary benzylic alcohol of model 1 to b-hydroxy
Our tactics for conversion of the lignin b-O-4 models
While the robust nature of this biopolymer hinders the develop- ketones 2,8 which might undergo the retro-aldol reaction to
ment of efficient processes to convert lignin to useful platform afford a-phenoxy ketones 3. Further oxidative conversion of 3
chemicals, several recent studies have shown the potential of transi- was envisioned via new bond forming processes associated
tion-metal catalysts that enable selective cleavage of certain chemical with C–C or C–O bond cleavage in a one-pot fashion.
bonds in the lignin models.3 Some representative approaches are
First of all, the possibility of the oxidative conversion of ketones 3
was explored. It was envisaged that the corresponding enamines
derived from ketones 3 and secondary amines 4 might undergo
oxidative molecular transformation under transition-metal catalyzed
aerobic reaction conditions.9 With this hypothesis as well as our
recent studies on Cu-catalyzed aerobic reactions including enamine
intermediates,10 we embarked on our investigation of the reactions of
2-phenoxyacetophenone (3aa) with piperidine (4a) under Cu-catalyzed
aerobic reaction conditions (Table 1). It was found that treatment of
the mixture of 3aa and 4a (5 equiv.) with 10 mol% of CuCl under an
O2 atmosphere in toluene at 70 1C afforded a-keto amide 5aa11 and
phenol (6a) in 69% and 54% yields, respectively (entry 1). Screening of
the copper catalysts revealed that CuI performs best for this transfor-
mation (entry 3). It is worthy of note that this process also proceeded
smoothly under an air atmosphere (0.21 atm of O2) (Table 1, entry 4).
Fig. 1 The structure of lignin and the model of b-O-4 linkage.
a Division of Chemistry and Biological Chemistry, School of Physical and
Mathematical Sciences, Nanyang Technological University, Singapore 637616.
E-mail: teckpeng@ntu.edu.sg; Fax: +65 6515 8229; Tel: +65 6513 8475
b Department of Chemistry, University of Science and Technology of China, Hefei,
Anhui 230026, P. R. China
† Electronic supplementary information (ESI) available: Detailed experimental
procedures and analytical data. See DOI: 10.1039/c3cc46912c
‡ J. Z. and Y. L. contributed equally to this work.
c
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Table 1 Optimization of reaction conditions of aerobic reactions of 3aa with
amines 4a
Table 2 Substrate scopea,b
Model 3/2 with
Entry amines 4
Products, yields
1
2
3
Yieldb (%)
Catalyst
(10 mol%)
Amine 4
(equiv.)
Entry
Solvents
5
6a
1
2
CuCl
CuBr
CuI
CuI
CuI
CuI
CuI
CuI
CuI
4a (5)
4a (5)
4a (5)
4a (5)
4a (3)
4a (5)
4a (5)
4a (5)
4a (5)
4a (5)
4a (5)
4a (5)
4b (5)
4c (5)
4d (5)
4e (5)
4f (5)
Toluene
Toluene
Toluene
Toluene
Toluene
DCE
MeCN
DMF
DMSO
MeOH
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
5aa: 69
5aa: 78
5aa: 88
5aa: 84
5aa: 76
5aa: 85
5aa: 81
5aa: 67
5aa: 71
5aa: 9
5aa: 21
5aa: 29
5ab: 79
5ac: 73
5ad: 63
5ae: 62
5af: 56
54
56
63
71
74
70
65
60
59
0
12
14
66
69
57
55
56
3
4c
5
4
6
7
8
9
10
11
12
13
14
15
16
17
5
6
CuI
FeCl3
RuCl3
CuI
CuI
CuI
CuI
CuI
5aa, 81% + 6a, 65%
7
8
2aa with 4b
2aa with 4e
5ab, 76% + 6a, 69%
5ae, 61% + 6a, 58%
a
Unless otherwise noted, the reactions were carried out using
2-phenoxyacetophenone (3aa) (0.1 mmol), amine 4 (0.5 mmol), and
catalyst (10 mol%) in solvents (0.25 M, 0.4 mL) at 70 1C for 8 h under an
9
5da, 56% + 6d, 59%
b
c
oxygen atmosphere (1 atm). Isolated yields. The reaction was per-
formed under an air atmosphere (0.21 atom of O2).
10
5ea, 58% + 7ea, 24% + 6c, 56%
a
Unless otherwise noted, the reactions were carried out using model
The reaction in 1,2-dichloroethane (DCE) as well as polar solvents
ketones 2 or 3 (0.1–0.2 mmol), amines 4 (5 equiv.), and CuI (10 mol%)
such as MeCN, DMF, and DMSO also resulted in good yields of 5aa in toluene (0.25 M) at 70 1C for 6–8 h under an oxygen atmosphere
b
(1 atm). Isolated yields were noted as the average of the two runs.
and 6a (entries 6–9), while polar protic solvents such as MeOH render
the process sluggish (entry 10). No remarkable effect of various
nitrogen ligands screened was observed [see the ESI† for more details].
Other metal complexes such as RuCl3 and FeCl3 exhibited lower
catalytic activities (entries 11 and 12). Under the conditions in entry 3,
the reactions with various secondary amines 4b–f including cyclic,
acyclic, and alkenyl amines were next examined (entries 13–17),
affording the corresponding b-ketoamides 5 and phenol 6a in good
to moderate yields.
Having optimized the reaction conditions (Table 1, entry 3), the
compatibility of the methoxy substituent on aryloxy-acetophenones
3 for the reactions with piperidine (4a) was investigated (Table 2).
The corresponding a-keto amides 5 were obtained in good yields
along with formation of phenols 6, while installation of the methoxy
group on the C-terminal benzene ring resulted in the concurrent
formation of amides 712 (up to 27% yields, entries 2, 3 and 5) except
for the reaction of 3dd (entry 4). We then turned our attention to
the transformation of lignin models 2 bearing the hydroxymethyl
Scheme 2 Proposed reaction mechanisms.
unit (Table 2, entries 6–10). It is worthy of note that the present
CuI-catalyzed aerobic reaction conditions allowed direct conversion
of lignin model 2aa into a-keto amides 5 and phenol (6a) in good
yields by the reactions with amines 4a, 4b and 4e (entries 6–8).
On the basis of these results as well as several control experiments
Similarly, the reaction of model 2ec bearing methoxy groups onto (see the ESI† for the detailed control experiments) and isotope-labeling
the C-terminal benzene rings resulted in the formation of not only reactions using 18O2,13 proposed mechanistic possibilities of the
a-keto amide 5ea (58% yield) but also amide 7ea (24% yield) along formation of a-keto amides 5 and amides 7 as well as phenols 6 from
with phenol 6c (56% yield) (entry 10).
oxidized lignin models 2 (or 3) are illustrated in Scheme 2. The present
c
11440 Chem. Commun., 2013, 49, 11439--11441
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for SC), the National Environment Agency (NEA-ETRP Project Ref.
No. 1002 111), and University of Science and Technology of China.
Notes and references
1 (a) A. Corma, S. Iborra and A. Velty, Chem. Rev., 2007, 107, 2411;
(b) D. R. Dodds and R. A. Gross, Science, 2007, 318, 1250.
2 (a) J. Zakzeski, P. C. A. Bruijnincx, A. L. Jongerius and B. M.
Weckhuysen, Chem. Rev., 2010, 110, 3552; (b) Lignin and Lignans:
Advances in Chemistry, ed. C. Heitner, D. Dimmel and J. A. Schmidt,
CRC Press, Boca Raton, FL, 2010.
3 For a recent review, see: S. R. Collinson and W. Thielemans, Coord.
Chem. Rev., 2010, 254, 1854.
4 A. G. Sergeev and J. F. Hartwig, Science, 2011, 332, 439.
5 J. M. Nichols, L. M. Bishop, R. G. Bergman and J. A. Ellman, J. Am.
Chem. Soc., 2010, 132, 12554.
Scheme 3 One-pot conversion of lignin b-O-4 models 1ec/11ec.
6 S. Son and F. D. Toste, Angew. Chem., Int. Ed., 2010, 49, 3791.
7 (a) G. Zhang, B. L. Scott, R. Wu, L. A. Silks and S. A. Hanson, Inorg.
Chem., 2012, 51, 7354; (b) S. K. Hanson, R. Wu and L. A. Silks, Angew.
Chem., Int. Ed., 2012, 51, 3410; (c) S. K. Hanson, R. T. Baker,
J. C. Gordon, B. L. Scott and D. L. Thorn, Inorg. Chem., 2010, 49, 5611.
8 During the course of our study, Stahl reported chemoselective
oxidation of the secondary benzylic alcohol in lignin by metal-free
aerobic oxidation, see: A. Rahimi, A. Azarpira, H. Kim, J. Ralph and
S. S. Stahl, J. Am. Chem. Soc., 2013, 115, 6415.
9 For recent reviews on transition-metal catalyzed aerobic molecular
transformation, see: (a) Z. Shi, C. Zhang, C. Tang and N. Jiao, Chem.
Soc. Rev., 2012, 41, 3381; (b) C. Zhang, C. Tang and N. Jiao, Chem.
Soc. Rev., 2012, 41, 3464; (c) A. E. Wendlandt, A. M. Suess and
S. S. Stahl, Angew. Chem., Int. Ed., 2011, 50, 11062.
10 (a) K. K. Toh, Y.-F. Wang, E. P. J. Ng and S. Chiba, J. Am. Chem. Soc., 2011,
133, 13942;(b)J.-S.TianandT.-P. Loh,Angew. Chem., Int. Ed., 2010, 49, 8417.
11 For recent report on Cu-catalyzed aerobic synthesis of a-keto amides,
see: (a) C. Zhang, X. Zong, L. Zhang and N. Jiao, Org. Lett., 2012,
14, 3280; (b) F.-T. Du and J.-X. Ji, Chem. Sci., 2012, 3, 460; (c) C. Zhang,
Z. Xu, L. Zhang and N. Jiao, Angew. Chem., Int. Ed., 2011, 50, 11088;
(d) C. Zhang and N. Jiao, J. Am. Chem. Soc., 2010, 132, 28.
12 For Cu-catalyzed aerobic synthesis of amides from enamines, see:
(a) K. Kaneda, T. Itoh, N. Kii, K. Jitsukawa and S. Teranishi, J. Mol.
Catal., 1982, 15, 349; (b) V. V. Rheenen, Chem. Commun., 1969, 314.
13 To investigate the possible reaction mechanism, isotope-labeling
experiments using 18O2 were conducted under the standard reaction
conditions (below). The reaction of 3aa with 4a under 18O2 provided
5aa in 85% yield, which constituted (18O–18O)-5aa, (18O–16O)-5aa,
and (16O/16O)-5aa in the ratio of 54 : 46 : 0. Similarly, the reaction of
2aa with 4a afforded (18O–18O)-5aa, (18O–16O)-5aa, and (16O/16O)-5aa
in the ratio of 72 : 28 : 0 (in 79% yield). Considering that the keto-
carbonyl oxygen could be easily exchanged with present H2O, there
still remain possibilities of both paths I and II (Scheme 2)
CuI-catalyzed aerobic conditions with secondary amines 4 readily
induce the retro-aldol reaction of 2 probably via the corresponding
iminium cations A to afford enamines B, which are also generated
from models 3 with amines 4. Subsequently, single-electron-oxidation
of enamines B with the transient higher valent Cu(II)–oxygen species14
followed by trapping the resulting cation-radicals of B with O2 produce
a-imino copper peroxides C, which cyclizes to afford aminodioxetanes
D. Subsequent fragmentation of D via O–O bond cleavage leads to
arylglyoxylic acid aryl esters E,11b–d which further react with amines 4
to form a-keto amides 5 and phenols (6) (path-I). Another possibility
for the formation of a-keto amides 5 includes Fenton-like fragmenta-
tion of copper peroxides C to form hemiacetals F, which eliminate
phenols 6 to provide arylglyoxals G (path-II). Arylglyoxals G are
converted into a-keto amides 5 under the present reaction conditions
with amines 4,11a which could be experimentally confirmed (see the
ESI†). The pathway for the formation of amides 7 could be rationalized
by concurrent O–O and C–C bond cleavages of aminodioxetanes D
(path-III). Formyl esters I concurrently formed with amides 7 are
hydrolyzed under the present reaction conditions to give phenols 6.
Stimulated by promising conversion of oxidized lignin models 2
into amide derivatives, we explored methods for chemo-selective
oxidation of the secondary benzylic alcohol of lignin model 1ec (see
the ESI† for more details). Finally, one-pot direct conversion of
lignin model 1ec was challenged (Scheme 3). It is of remarkable
15,16
´
significance that combination of the Marko-oxidation
and the
Cu-catalyzed aerobic reaction with piperidine (4a) afforded a-keto
amide 5ea, amide 7ea, and phenol 6c in 48%, 28% and 41% yields,
respectively (Scheme 3a). Similarly, the NHPI–TBHP oxidation8,17,18
could be associated with the CuI-catalyzed amide formation, while
phenol 6c could not be detected (Scheme 3b). It was of great
significance that this one-pot strategy was applicable to trimeric
lignin b-O-4 model 11ec, affording a-keto amide 5ea, amide 7ea, and
phenol 6c in 43%, 22% and 55% yields, respectively (Scheme 3c),
although the formation of amide derivatives derived from the
middle benzene ring fragment could not be detected.
In summary, we have developed a method for the chemical
conversion of lignin b-O-4 linkage models through Cu-catalyzed
aerobic amide bond formation with secondary amines. Further
efforts will be made to apply the present strategy to the
chemical conversion of the natural lignin.
14 For recent reviews of dioxygen–copper systems, see: (a) M. Rolff and
F. Tuczek, Angew. Chem., Int. Ed., 2008, 47, 2344; (b) E. A. Lewis and
W. B. Tolman, Chem. Rev., 2004, 104, 1047; (c) P. Gamez, P. G. Aubel,
W. L. Driessen and J. Reedijk, Chem. Soc. Rev., 2001, 30, 376.
´
15 (a) I. E. Masko, M. Tsukazaki, P. R. Giles, S. M. Brown and C. J. Urch,
´
Angew. Chem., Int. Ed., 1997, 36, 2208; (b) I. E. Masko, P. R. Giles,
M. Tsukazaki, S. M. Brown and C. J. Urch, Science, 1996, 274, 2044.
16 The reaction of 2-phenoxy-1-phenylprop-2-en-1-one with piperidine
(4) under the present CuI-catalyzed aerobic reaction conditions also
affords a-keto amide 5aa and phenol (6a) in 81% and 76% yields,
respectively. See the ESI† for more details .
17 For reviews, see: (a) F. Recupero and C. Punta, Chem. Rev., 2007, 107, 3800;
(b) Y. Ishii, S. Sakaguchi and T. Iwahama, Adv. Synth. Catal., 2001, 343, 393.
18 For a review on oxidation with PhI(OAc)2, see: V. V. Zhdankin,
ARKIVOC, 2009, (i), 1.
This work was supported by funding from Nanyang Technological
University, the Singapore Ministry of Education (Academic Research
Fund Tier 2: MOE2011-T2-1-013 for TPL and MOE2012-T2-1-014
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 11439--11441 11441