A facile and mild Pd-catalyzed one-pot process for direct hydrodeoxygenation (HDO) phenols to arenes through a ArOSO2F intermediates transformation

Article abstract of DOI:10.1016/j.tetlet.2017.04.070

A practical one-pot process for hydrodeoxygenation (HDO) of phenolic derivatives to their corresponding arenes was developed. This method provided a facile route to upgrading bio-oil. The substrate scope of this protocol was wide, complicated and multi-phenolic compounds were also smoothly hydrodeoxygenated to their corresponding arenes.

Full text of DOI:10.1016/j.tetlet.2017.04.070

Accepted Manuscript
A facile and mild Pd-catalyzed one-pot process for direct hydrodeoxygenation
(
HDO) phenols to arenes through a ArOSO F intermediates transformation
2
Xiao-Yan Wang, Jing Leng, Shi-Meng Wang, Abdullah M. Asiri, Hadi M.
Marwani, Hua-Li Qin
PII:
S0040-4039(17)30523-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.04.070
TETL 48862
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
25 March 2017
19 April 2017
24 April 2017
Please cite this article as: Wang, X-Y., Leng, J., Wang, S-M., Asiri, A.M., Marwani, H.M., Qin, H-L., A facile and
mild Pd-catalyzed one-pot process for direct hydrodeoxygenation (HDO) phenols to arenes through a ArOSO F
2
intermediates transformation, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.04.070
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A facile and mild Pd-catalyzed one-pot process for direct hydrodeoxygenation (HDO) phenols to
2
arenes through a ArOSO F intermediates transformation
a†
Xiao-Yan Wang, Jing Leng, Shi-Meng Wang, Abdullah M. Asiri, Hadi M. Marwani , Hua-Li Qin *
a†
a
b
b
a
H
OSO2F
OH
SO2F2 (balloon)
rt, Et3N
Pd(cat.)/ Et3N/ HCOOH
rt
R
R
R
1
2
3
throught a one-pot process

1
Tetrahedron Letters
journal homepage: www.els evier.com
A facile and mild Pd-catalyzed one-pot process for direct hydrodeoxygenation (HDO) phenols to
2
arenes through a ArOSO F intermediates transformation
a†
a†
a
b
b
Xiao-Yan Wang, Jing Leng, Shi-Meng Wang, Abdullah M. Asiri, Hadi M. Marwani , Hua-Li Qin *
a
a
State Key Laboratory of Silicate Materials for Architectures; and School of Chemistry, Chemical Engineering and Life Science,, Wuhan University of
Technology, No. 122, Luoshi Road, Wuhan,430070, P. R. China.
b
Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
†
The two authors contributed equally to this work
Fax: + 86 27 87749300, qinhuali@whut.edu.cn.
ARTICLE INFO
ABSTRACT
Article history:
Received
A practical one-pot process for hydrodeoxygenation (HDO) of phenolic derivatives to their
corresponding arenes was developed. This method provided a facile route to upgrading bio-oil.
The substrate scope of this protocol was wide, complicated and multi-phenolic compounds were
also smoothly hydrodeoxygenated to their corresponding arenes.
Received in revised form
Accepted
Available online
Keywords:
2
009 Elsevier Ltd. All rights reserved.
Phenols
one pot
aryl fluorosulfates
hydrodeoxygenation
Phenols are readily available from fuel and biomass and the
world annual production of phenols is up to millions of tons.
amount of HCO
hydrogenation process is considered to be much milder compared
to those under high pressure of H atmosphere. In addition, the
Holmes group described a perfluoroalkylsulfonyl (PFS) fluoride
mediated transformation of phenols to aryl sulfonates which were
2 2 2
H for in-situ eluting H and CO this
1
The development of efficient and practical methods for
hydrodeoxygenation (HDO) (or deoxygenation) of phenolic
compounds plays an important role in natural products and
pharmaceutical active molecules synthesis, which requires mild
2
subsequently cleaved to arenes under Pd(cat.)/ Et
hydrogenation condition. However, the availability of
3
N-HCO
2
H
2
7
conditions, selectivity, and functional group tolerance. On the
other hand, the utilization of biomass as a renewable and
sustainable resource for the production of liquid fuels as a
replacement for fossil fuels has attracted significant attention
perfluoroalkylsulfonyl (PFS) fluoride and the requirement of
isolation of aryl sulfonates intermediates limited the application
and scope of this hydrogenation methodology. SO F , a stable
2 2
3
world widely. However, unlike petroleum, plant dry matter is
mostly composed of hundreds of oxygenated bio-oil compounds
such as cellulose and lignin. These oxygen-containing
and readily accessible gas was recently reported to be utilized for
efficient converting of phenols to their corresponding aryl
fluorosulfates. Meanwhile, aryl fluorosulfates were also
8
compounds have significant negative effects on the application of
bio-oils as fuel because of their low heating value, poor stability,
low volatility and high viscosity properties. Therefore, before
described to have a similar functionality to aryl triflates or aryl
halides to participate in various transition metal catalyzed
reactions and other synthetic transformations. We envisioned
4
9
these bio-oils can be used as a fuel, the oils must be further
upgraded to remove the oxygen. Phenols and substituted phenols,
representative of a large fraction of those oxygenated compounds
from the thermal breakdown of lignin, are often used as model
substrates. Thus, the development of new methodologies for
hydrodeoxygenation (HDO) of phenolic compounds has been
identified as the most attractive field for the upgrading of bio-
that introducing commercially abundant SO
provide their activated aryl fluorosulfates partners, which could
subsequently undergo a Pd(cat.)/ Et N/HCO H mediated
hydrogenation without isolation of fluorosulfates intermediates to
furnish the arenes products (Scheme 1).
2 2
F to phenols would
3
2
5
oil. Herein, we report a mild and versatile one-pot Pd-catalyzed
hydrodeoxygenation (HDO) of phenolic derivatives to their
corresponding arenes under the atmosphere of SO
2 2
F by using
HCOOH/ Et N as the transfer hydrogen reductant.
3
We have demonstrated that Pd(cat.)/ Et N-HCO
3
2
H system
6
performed well as transfer hydrogenation reductant. With excess

2
Tetrahedron
Scheme 1. One-pot process for the preparation of arenes
from corresponding phenols.
2
Pd(OAc) to a significant low level (0.1%) made the
efficiency of this transformation much poor to provide a
yield of 16 %. Control reactions demonstrated that the
reaction proceeded slavishly when further decreasing dppp
loading (entry 12). Not surprisingly, there is no product was
observed without palladium catalyst loading ( entry 13).
In order to testify the feasibility of the one-pot process,
fluorosulfate 2a was synthesized from phenol 1a and was
subsequently isolated as pure starting material before subjecting
to hydrodeoxygenation to examine the formation of biphenyl 3a
a
Table 2. A one-pot process for the preparation of arenes .
(
Table 1). To our delight, after screening of a variety of ligands,
the corresponding biphenyl 3a was obtained in excellent yield
92%) when 1,3-bis(diphenylphosphino) propane (dppp) was
used as ligand (entry 6). The reaction proceeded smoothly at
(
room temperature with the Pd(cat.)/ Et
DMF under air atmosphere.
3 2
N-HCO H system in
Table 1. A two-step sequence reaction for the
a
preparation of arenes .
Pd(OAc)
mol%)
2
b
Entry 1)Et N (eq)
3
Solvent
Yield(3a, %)
(
1
2
3
4
5
6
2
2
2
2
2
2
5
5
5
5
5
5
DMF
DCM
75
57
65
<1
<1
<1
CH
THF
CH OH
1,4-
3
CN
3
dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
7
8
9
1
2
5
5
5
5
2
5
-
0.1
99
95
96
89
94
41
-
b
Entry
1
Ligand
Yield(3a, %)
1.5
1.2
1
1.2
1.2
1.2
1.2
1, 10-Phen
-
0
c
2
2, 2’-bpy
-
11
d
1
1
1
a
2
3
4
c
3
PPh
3
6
e
16
2
-(diphenylphosphino)-
c
4
2
Reaction conditions: a mixture of 1a (0.3 mmol), Et
mL) was stirred at room temperature with a SO balloon for 3 hours;
and then, Pd(OAc) dppp (6 mol%), Et N (1.2 mmol), HCOOH (1.2
3
N, solvent (1.0
biphenyl
2 2
F
tris(4-
c
5
3
2
，
3
methoxyphenyl)phosphine
dppp
mmol) were added into the reaction mixture to react 2 hours at room
b
temperature. The yield was determined by HPLC using 1-1'-biphenyl
6
92
a
Reaction conditions: a mixture of 2a (0.3 mmol), Pd(OAc)
ligand (6 mol%), Et N (1.2 mmol), HCOOH (1.2 mmol), DMF (1 mL)
was stirred at room temperature for 2 hours. The yield was determined
by HPLC using 1-1'-biphenyl (3a) (t = 6.713min, λmax = 247.0 nm,
2
(5 mol%),
(
R
3a) (t = 6.713min, λmax = 247.0 nm, water / methanol = 20 : 80 (v / v))
c
as the external standard. dppp (2.4 mol%) without dppp. dppp (0.12
3
d
e
b
mol%).
R
c
water / methanol = 20 : 80 (v / v)) as the external standard. ligand 12
mol%.
With the optimized hydrodeoxygenation condition in
hand (Table 2, entry 11), we further investigated the scope
and limitations of this method (Table 3). Generally, good to
excellent yields of hydrodeoxygenation products were
obtained among a range of electron-donating and electron-
Encouraged by the results, a one-pot process was then
examined through subjecting 1a to a fluorosulfatation and
hydrodeoxygenation sequence without isolation of
intermediate 2a. Delightingly, a good but lower yield of
withdrawing substituents in the ortho-, meta-, and para-
7
5 % was obtained (Table 2, entry 1), compared to the two
independent steps procedure in the same DMF solvent
92%). Further solvents screening showed that DCM and
positions. Aromatic groups (3a and 3f), alkyl groups (3c, 3k
and 3i), ether (3j, 3m, and 3n), formyl (3o), cyano (3p) were
all tolerated. Bis-substituted phenols were also suitable for
the reaction with slight lower yields compared with
(
9
CH
transformation provided the desired hydrodeoxygenation
product in moderate yields (57 and 65 %, entry 2 and 3).
Other solvents such as THF, CH OH and 1,4-dioxane failed
to give a desired result, all these reactions were halted in the
form of the stable intermediate 2a and unable to further
transfer into the ultimate product (entries 4-6). It is worth
noting that when DMSO was used, this one-pot procedure
provided the best yield ( 99 %) of the desired product (entry
3
CN, which were typically used for the first step
monosubstituted phenols (3h and 3n). Two phenolic
hydroxyl groups either on one or two benzene rings,
provided the desired hydrodeoxygenation products in good
yields (3v and 3w), which demonstrated the great advantage
of this developed protocol for the upgradation of bio-oils
with the existence of multi-phenolic hydroxyl groups.
3
To further prove that the developed method has the
potentiality for late stage synthesis of natural product or bio-
mass upgrading (Scheme 2), complicated natural product
resveratrol 1x which possesses three phenolic hydroxyl groups
and more complicated natural product 1y were also conducted
hydrodeoxygenation under the standard conditions. To our
8
) among all of the solvents examined. The examination of
the influence of the loading amount of the base and catalyst
for the efficiency of the transformation was also conducted.
Decreasing the loading of Et N from 2 equiv to 1.2 equiv
also gave an excellent yield of 3a (96 %, entry 9). A slight
decreasing of the loading Et N to 1.0 equiv (entry 10)
caused a lower yield of desired product. Decreasing the
loading of Pd(OAc) from 5 mol% to 2 mol% still provided
an excellent yield (94 %, entry 11). However, the loading of
3
3
delight, both of them generated their desired products 3x
, 3y in
2
moderate to excellent yield respectively (56 %, 93 %). What’s

3
more, the non-steroidal estrogens estrostilben 1y proceeded the
one-pot process smoothly even in grams scale, which further
suggests the potentiality of this developed protocol could be
used for research in process chemistry and fine chemical field
even though the TON of the catalysis process is relatively low
benzyl chloride, benzyl mesylate and benzyl tosylate only
provided trace amounts of benzene product under the same
condition. This finding suggests aryl fluorosulfates
performed much more effectively for the
hydrodeoxygenation transformation than their aryl halides,
aryl triflates, aryl mesylates and aryl tosylates counterparts
even though the exact reason is still unclear.
(
30-100).
Table 3. Screening of substrate scope of the one-pot
hydrodeoxygenation process.
Table 4. Comparing of hydrodeoxygenation capability of
various phenyl substituted leaving groups for benzene
a
formation .
b
Yield (%)
Entry
X
1
2
3
4
5
6
7
OSO
OTf
OTs
OMs
I
2
F
87
23
trace
trace
43
Br
13
Cl
trace
a
Reaction conditions: a mixture of aryl-X (0.3 mmol), Et
Pd(OAc) (2 mol%), dppp (2.4 mol%) DMSO (1.0 mL) was stirred at
room temperature for 2 hours; HPLC yield
3
N (1.2 mmol),
2
b
1
0
A plausible mechanism was proposed in Scheme 3. We
envisioned, firstly, intermediate was formed by the
reaction of starting material phenol and SO . The
intermediate subsequently reacted with Pd(0) catalyst to
form an oxidative addition species ArLnPdOSO II. Next,
2
1
2 2
F
a
HPLC yield (the reaction was operated with 1.0 mmol of phenol starting
2
materials, due to the high volatility property of the arenes products, the
isolated yields were lower than their corresponding HPLC counterparts,
b
especially for those with very low boiling point; isolated yield; 1) Et
2
F
by the displacement of fluorosulfonate with formate ion, a
ligand exchange process, the intermediate III was
c
3
N 2.4
eq; 2) Pd(OAc) 4 mol %, dppp 4.8 mol %, HCOOH 8 eq, Et N 8 eq.
3
2
subsequently generated, which then underwent a releasing of
carbon dioxide to provide intermediate IV. Finally, arene
was obtained by the reductive elimination of the
intermediate IV along with regeneration of the Pd(0)
3
complex. During this transformation, excess of amine was
required to neutralize the generated acid species and
accelerate the dissociation of HOSO
intermediate.
2 2
F from ArLnPdOSO F
Scheme 2. Hydrodeoxygenation of complicated and
muti-phenolic molecules.
Notably, to compare the hydrodeoxygenation of aryl
fluorosulfonates with other common aryl leaving groups
under the optimized reaction conditions (Table 4), it was
interesting to found that the fluorosulfonate provided the
desired benzene product 3b in 87 % after 2 h (entry 1).
However, surprisingly, hydrodeoxygenation of the benzyl
triflate, benzyl iodide and benzyl bromide only formed
benzene in 23 %, 43 % and 13 % yield respectively. While
Scheme 3. Proposed mechanism
In conclusion, we have developed a one-pot process for
hydrodeoxygenation of phenols to their corresponding
arenes under mild conditions. This methodology displayed a

4
Tetrahedron
wide scope compatibility and functional groups tolerance.
Furthermore, this protocol was also suitable for
hydrodeoxygenation of complicated molecules and multi-
phenolic compounds which demonstrated the potentiality of
this method for the synthesis of natural products or
upgrading of biomass in fundamental research manner.
Acknowledgments
This work was supported by Wuhan University of Technology,
we are grateful to professor K. B. Sharpless (the Scripps
Research Institute) for helpful discussion and advisory on
application of SO
2 2
F .
Notes and references
1
2
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ed.,Springer-Verlag: Berlin Heidelberg, 2010. (b) The Chemistry of
Phenols, Z. Rappoport, Ed., John Wiley & Sons Ltd.: Chichester,
2
003. (c) Granda, M.; Blanco, C.; Alvarez, P.; Patrick, J.; Merendez,
R. Chem. Rev 2014 114, 1608.
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Tuck, C. O.; Perez, E.; Horvath, I. T.; Sheldon, R. A.; Poliakoff, M.
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(a) Oasmaa, A.; Czernik, S. Energy Fuels 1999
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Maggi, R.; Delmon, B. Biomass Bioenergy, 1994, 7, 245−249.
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Chem. Int. Ed. 2014, 53, 9430–9448. (b) Sulfuryl fluoride (SO F )
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1
0
,
,

5
A one-pot mild process for direct
hydrodeoxygenation of phenols to arenes.
This method displays wide scope compatibility and
functional groups tolerability;
This protocol is applicable for hydrodeoxygenation
of complicated molecules and multi-phenolic
compounds.