Synthesis of thioethers, arenes and arylated benzoxazoles by transformation of the C(aryl)-C bond of aryl alcohols

Article abstract of DOI:10.1039/d0sc01229g

Transformation of aryl alcohols into high-value functionalized aromatic compounds by selective cleavage and functionalization of the C(aryl)-C(OH) bond is of crucial importance, but very challenging by far. Herein, for the first time, we report a novel and versatile strategy for activation and functionalization of C(aryl)-C(OH) bonds by the cooperation of oxygenation and decarboxylative functionalization. A diverse range of aryl alcohol substrates were employed as arylation reagents via the cleavage of C(aryl)-C(OH) bonds and effectively converted into corresponding thioether, arene, and arylated benzoxazole products in excellent yields, in a Cu based catalytic system using O2 as the oxidant. This study offers a new way for aryl alcohol conversion and potentially offers a new opportunity to produce high-value functionalized aromatics from renewable feedstocks such as lignin which features abundant C(aryl)-C(OH) bonds in its linkages.

Full text of DOI:10.1039/d0sc01229g

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DOI: 10.1039/D0SC01229G
ARTICLE
Synthesis of Thioethers, Arenes and Arylated Benzoxazoles by
Transformation of C(aryl)−C Bond of Aryl Alcohols
Mingyang Liu,[a,b,c] Zhanrong Zhang,*[a,c] Bingfeng Chen, [a,c] Qinglei Meng, [a,c] Pei Zhang, [a,c] Jinliang
Received 00th January 20xx,
Accepted 00th January 20xx
Song, [a,c] Buxing Han*[a,b,c]
DOI: 10.1039/x0xx00000x
Transformation of aryl alcohols into high-value functionalized aromatic compounds by selective cleavage and
functionalization of C(aryl)−C(OH) bond is of crucial importance, but very challenging by far. Herein, for the first time, we
report a novel and versatile strategy for activation and functionalization of C(aryl)−C(OH) bonds by the cooperation of
oxygenation and decarboxylative functionalization. A diverse range of aryl alcohol substrates were employed as arylation
reagents via cleavage of C(aryl)−C(OH) bonds and effectively converted into corresponding thioether, arene, and arylated
benzoxazole products in excellent yields, in a Cu based catalytic system using O2 as the oxidant. This study offers a new way
for aryl alcohols conversion and potentially offers a new opportunity to produce high-value functionalized aromatics from
renewable feedstocks such as lignin which features abundant C(aryl)−C(OH) bonds in its linkages.
economy for cross-coupling reactions. On the other hand, it is
important to divert the current fossil-based feedstocks to
naturally renewable biomass resources.
Introduction
Functionalized aromatic compounds are ubiquitously involved
in and of significant importance in medicinal chemistry,
biological chemistry and chemical industry. Selective
production of aromatic compounds represents one of the most
attractive and imperative topics in organic and synthetic
chemistry.1 In this regard, research advances on cross-coupling
reactions have significantly promoted this area and these
methods are now routinely employed in both fundamental
research and industry.2-5 Notably, significant efforts have been
devoted to constructing aryl/alkyl-metal intermediates (Fig. 1a)
for cross-coupling reactions to produce aromatic compounds
with diverse functionalities. However, there are still many
challenges need to be addressed in this field. For instance,
expensive pre-functionalized aromatic substrates originated
from finite and depleting fossil resources, such as aryl halides,6
a. Fossil resource-derived substrates as
arylation reagents.
Fossil fuels
Aryl metal
Aromatics
based substrates
intermediates
b. Lignin as arylation reagent via C(aryl)−C bond
activation.
Native lignin with
Aryl metal
Aromatics
rich β−O−4 linkage intermediates
aniline/thiophenol/phenol
derivatives7-15
and
aroyl
c. This work for C(aryl)−C bond activation.
compounds16-25, are almost exclusively used as feedstocks.
Meanwhile, the cross-coupling reactions suffer from some
drawbacks such as low atom economy, requirement for
sophisticated catalysts or catalytic systems, generation and
inevitably handling of toxic and corrosive halide-containing
wastes etc. To address these issues, on one hand, it is crucial to
develop more efficient catalytic systems with improved atom
BDE: ~99 kcal mol–1
Aryl alcohols
Aromatics
1. C(alkyl)−C
2. C(aryl)−C
Bond activation
Bond activation
Cooperation of oxygenation and
decarboxylative functionalization
Figure 1. Research background and design. (a) Traditional
a.Beijing National Laboratory for Molecular Science, CAS Key Laboratory of Colloid
and Interface and Thermodynamics, CAS Research/Education Center for
Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of
Sciences, Beijing 100190, China.
arylation reaction by using fossil fuels-based substrates. (
b)
Envisioned strategy for using lignin as arylating reagent. ( ) Our
c
proposed Cu catalyzed arylation by using aryl alcohol as
arylating agent mediated with acid intermediates.
b.School of Chemistry and Chemical Engineering, University of Chinese Academy of
Sciences, Beijing 100049, China.
c. Physical Science Laboratory, Huairou National Comprehensive Science Center,
Beijing 101400, China.
Electronic Supplementary Information (ESI) available: [details of any supplementary
Lignin represents the only naturally renewable aromatic
resource and features abundant C(aryl)−C(OH) structures in its
information available should be included here]. See DOI: 10.1039/x0xx00000x
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Journal Name
linkage motifs (occurrence values of β−O−4 type linkages: 45- 10), indicating that a high ratio of metal to ligand (VCieuw:Aprtihclee nOn=lin2e
84%),26-29 the activation of C(aryl)−C(OH) bond to construct aryl- : 1) was crucial to this chemical transformation.
DOI: 10.1039/D0SC01229G
metal intermediates of phenyl ethanol-based compounds offers
an attractive strategy for both lignin depolymerization and
Table 1. Optimization of reaction conditions.
functionalization to produce fine functionalized aromatic
chemicals (Fig. 1b). Among the various types of ubiquitous C−C
bonds, C(aryl)−C bonds are relatively less polar and possess
higher stability (bond dissociation energy: ~99 kcal mol–1).30
Their direct activation and functionalization are kinetic inert. In
this regard, very limited research advances have been achieved
by far and wide application of developed methods are often
[Cu]
Phen
Base
K2CO3
K2CO3
K2CO3
Solvent Yield
Entry
hindered, owing to the requirement of indispensable directing
1
2
30% CuSO4 40%
30% CuSO4 40%
30% CuSO4 40%
DMSO
DMF
Tol
33%
6%
group modified substrates,31-34 highly toxic reagents and strong
35
oxidants.30,
The development of a versatile and robust
strategy for the activation and functionalization of C(aryl)−C
bonds that allows aryl alcohols to be used as latent arylating
agents is highly desirable, but very challenging. Notably, in the
pursuit of a sustainable future and biobased economy, this also
represents a very interesting topic in terms of effectively
transforming the only naturally renewable aromatic resource
lignin into high-value fine aromatic chemicals.
3
0%
4
30% CuSO4 40% Cs2CO3 DMSO
30% CuSO4 40% NaHCO3 DMSO
11%
17%
27%
4%
5
6
30% Cu(Ac)2 40%
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
7
30% CuCl
30% CuCl2
40%
40%
8
9%
9
40% CuSO4 40%
40% CuSO4 20%
43%
93%
Catalytic oxidation is an effective method for the cleavage
of C(alkyl)−C bonds to generate acid36, 37 or aldehyde products.38
Meanwhile, aryl acids could be used as arylating agents for
decarboxylative coupling reactions which is an effective
synthetic strategy for the activation of C(aryl)−C bond with less
toxic by-products.16-18, 23 Herein, we for the first time, report
activation and functionalization of C(aryl)−C(OH) bonds of aryl
alcohols to produce thioethers, arenes and arylated
benzoxazole products by the cooperation of oxygenation and
decarboxylative functionalization (Figure 1c). Using aryl
alcohols as substrates and arylation reagents via cleavage of
C(aryl)−C(OH) bonds, environmentally benign O2 as oxidant, a
diverse array of substrates were converted into the desired
products with excellent yields in a Cu based catalytic system.
10
Experiments were performed on 0.2 mmol scale unless
otherwise noted. Reaction conditions: 0.2 mmol 1-(2-
nitrophenyl)ethanol, 0.4 mmol diphenyldisulfane, 0.06 or 0.08
mmol [Cu] salt, 0.08 or 0.04 mmol anhydrous 1, 10-
phenanthroline (phen), 1 mmol base, 200 mg 4Å molecular
sieve (4Å), 2 mL solvent, 0.5 MPa O2, 140 °C, 12 h. Yield was
determined by gas chromatography (GC).
Next, the scope of this oxidative C(aryl)−C(OH) bond
thioetherification reaction was examined in detail under the
optimized reaction condition (Table 2). Benzyl alcohol 1b and
alkyl alcohol 1c were effectively converted into thioether
product in excellent yields (95%-97%). Secondary alcohols with
various alkyl carbon-chain length (1a
smoothly. 1-(2-Nitrophenyl)ethanol derivatives with electron-
donating or electron-withdrawing substituents on both the aryl
Results and discussion
We started our study about C(aryl)−C(OH) bond activation
and functionalization by oxidative thioetherification using a
secondary aryl alcohol 1-(2-Nitrophenyl)ethanol (1a) as a model
, 1d) also reacted
ring (1h-1k) and the methyl group (1l-1n) are also suitable
substrate, in
a catalytic reaction system consisting of
substrates, affording corresponding thioether products in
moderate to excellent yields (63%-95%). In addition, this
transformation could also tolerate heteroaryl alcohol
diphenyldisulfane (2a) as sulfur source, CuSO4 as catalyst, 1, 10-
phenanthroline as ligand, K2CO3 as a base additive, DMSO as
solvent and O2 as the environmentally benign oxidant (Table 1).
Initially, the targeted thioether product 3a was generated in
substrates (1o
obtained in satisfactory yields. Moreover, cellulosic biomass-
derived furan compounds (1r 1t) performed well, affording
-1q) and asymmetric thioether products were
o
only 33% yield at 140 C for 12 h reaction (entry 1). We then
-
conducted a series of experiments to optimize the reaction
conditions and improve the yield. For optimization details
please refer to Fig. S1-5. Notably, it was found that using other
polar aprotic solvent DMF (entry 2), nonpolar solvent toluene
(entry 3), base additives (entries 4-5) and Cu salts (entries 6-8)
resulted in lower yields of thioether product (0-27%), while
increasing the catalyst amount slightly improved the yield to
43% (entry 9). To our delight, when the amount of ligand was
corresponding thioether products in high yields (69%-89%). In
addition to using diphenyldisulfane as sulfur source, we also
explored other sulfur sources including diphenyldiselane (2b
and diphenyldisulfane derivatives with both electron-donating
2d) and electron-withdrawing substituent groups (2c) on the
)
(
aryl ring, under optimized reaction conditions (Fig. S6). These
sulfur sources were also tolerated and effectively transformed
into corresponding products. Other sulfur sources including
dibenzyldisulfane (2e) or aliphatic dihexyldisulfane (2f) are not
reduced, the yield of 3a significantly improved to 93% (entry
2 | J. Name., 2012, 00, 1-3
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satisfactory in this reaction, probably because of the weaker
coordination to Cu catalyst in comparison to that between Cu
View Article Online
DOI: 10.1039/D0SC01229G
catalyst and aryl disulphide we used (Fig. S6)
.
Table 2. Substrate scope for the oxidative transformation of aryl alcohols to thioethers.
Substrates
Products
Yield
Substrates
Products
Yield
97%
79%*
95%
93%
95%
63%
87%
22%
88%
72%*
86%*
80%*
89%*
87%*
69%*
32%
5%*
90%*
93%*
79%*
Experiments were performed on 0.2 mmol scale unless otherwise noted. Optimized conditions: 0.2 mmol alcohols, 0.4 mmol
diphenyldisulfane, 0.08 mmol CuSO4, 0.04 mmol phen, 0.8 mmol K2CO3, 200 mg 4Å, 2 mL DMSO, 0.5 MPa O2, 140 °C, 12 h. *24 h.
Yield was determined by GC.
Having thoroughly investigated the oxidative cleavage and C(aryl)−C(OH) bonds hydrogenation and carbonization of aryl
thioetherification reaction, we further investigated the alcohols (Fig. 2). By adding Ag salts into the standard catalytic
This journal is © The Royal Society of Chemistry 20xx
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system, the C(aryl)−C bonds of a diverse range of primary and of alcohol to ketone, C(C=O)-C bond cleavage of ketone to
View Article Online
DOI: 10.1039/D0SC01229G
secondary benzyl alcohols, as well as alkyl alcohols were aldehyde, oxidation of aldehyde to acid, together with
selectively cleaved and functionalized to C(aryl)−H bonds, decarboxylative thioetherification of acid intermediates. Since
producing arenes in moderate to excellent yields ranging from acid intermediate was not detected in the out-situ experiments,
48% to 97% (Fig. 2a). Furthermore, for the first time, we the oxidation of aldehyde to acid intermediate, rather than
employed aryl alcohols as aryl agents for regiospecific decarboxylation step, represents the rate-determining step.
construction of aryl–heteroaryl bonds via C(aryl)−C(OH) bond This effect is also verified by supplementary experiments (Fig.
carbonization (Fig. 2b). Under given conditions, the C(aryl)−C S17).
bonds and C−H bonds were simultaneously activated, affording
a. Out-situ experiments.
aryl-benzothiazole products that possess important
40
applications.39,
For detailed information about the
Optimized
condition
optimization of C(aryl)−C(OH) bonds hydrogenation and
carbonization reaction conditions, please refer to Fig. S7-16.
100
80
60
40
20
0
a. C(aryl)−C(OH) bonds hydrogenation.
OH
COC
CHO
COOH
Thioether
3
6
9
12
Reaction time (h)
b. Possible intermediates used as substrates.
Optimized
condition
Yield: 89%
Optimized
condition
b. C(aryl)−C(OH) bonds carbonization.
Yield: 88%
Optimized
condition
Yield: 95%
Figure 3. Mechanism study. (
a
) Out-situ experiments recorded
the evolution of intermediates of oxidative C(aryl)−C(OH) bond
thioetherification reaction. OH: (1-(2-nitrophenyl)ethanol, COC:
1-(2-nitrophenyl)ethenone, CHO: 2-nitrobenzaldehyde, COOH:
2-nitrobenzoic acid. (b) Potential intermediates were tested
under the optimized conditions (same to table 2).
Figure 2. Universality of C(aryl)−C(OH) bonds functionalization.
(a
) C(aryl)−C(OH) bonds hydrogenation of aryl alcohols. (
b)
C(aryl)−C(OH) bonds carbonization of aryl alcohols.
Based on the above results, we propose a plausible
reaction mechanism for the oxidative C(aryl)−C(OH) bonds
thioetherification reaction using aryl alcohols as arylating
agents (Fig. 4). The reaction is initiated by Cu/phenanthroline
catalyzed dehydrogenation of alcohol substrate under alkaline
condition. Deprotonation followed by hydride transfer of
alcohol substrate generates ketone intermediate (R = H,
As an effort to explore the reaction mechanism, we then
probed the potential intermediates during the oxidative
thioetherification reaction (Fig. 3). Out-situ kinetic study
revealed that ketone intermediate was generated at very
beginning of the reaction (1 h) and consumed quickly. Aldehyde
was identified as the major intermediate and presented for
several hours of reaction (Fig. 3a). To get further in-depth
details, possible intermediates including ketone, aldehyde and
acid were tested under optimized conditions. In this case, these
possible intermediates were all effectively converted into the
thioether product in excellent yields (Fig. 3b). These control
experiments indicate that the oxidative C(aryl)−C(OH) bond
thioetherification reaction was mediated by dehydrogenation
aldehyde intermediate). Simultaneously, CuII species
reduced to CuI
which then reacts with dioxygen to generate
CuII intermediate. Under alkaline condition, CuII species
is
regenerated from the CuII with consumption of OH-.41 Then,
1 is
2
3
1
3
according to our previous research,42, 43 Cu catalyzed successive
C(CO)−C bond cleavage of the ketone intermediate leads to aryl
aldehyde intermediate via hydroxylation of β-H and 1,2-hydride
4 | J. Name., 2012, 00, 1-3
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shift. The β-carbon of alkyl substituent would transfer into
formic acid and decomposed to CO2 and H2. For the substrates generates a bifunctional aryl metal species
containing phenoxy groups on the β-carbon (1n), the leaving species
part would be converted into phenyl formate followed by by oxidation of
ARTICLE
5
via decarboxylation. Transmetalation betweeVniew5ArtaicnledOnl1in1e
II
DOI: 170.1a0n39d/Da0cStCiv0e122C9uG
6
. Thereafter, the final thioether product is generated
and reductive elimination of in the
7
8
decomposition into benzoquinone, CO2 and H2 according to thioetherificative cycle. It is noteworthy that aryl alcohol
previous reports.38, 42-44 In the presence of Cu catalyst and under substrates serve as electrophilic synthetic equivalents for the
alkaline condition, the aryl aldehyde is oxidized to aryl acid C(aryl)−C(OH) bonds thioetherification reaction. Notably, all the
which represents the key intermediate for thioetherification three reactions are mediated with acid intermediate, and
reaction.45-47 Subsequently, in the decarboxylation cycle, acid- probable reaction pathway for hydrogenation and
base reaction between aryl acid and Cu salts generates metal carbonization of C(aryl)−C(OH) bonds are illustrated in Fig. S18
carboxylate
4
, which is further converted to aryl metal species and S19, respectively.
Dehydrogenation
Alcohol
substrates
Decarboxylation
Thioetherification
Products
Figure 4. Plausible reaction pathway for the oxidative C(aryl)−C(OH) bonds thioetherification reaction.
Experimental
Chemicals
Conclusions
In summary, we have achieved functionalization including
Commercially available Cu salts (CuSO4, Cu(Ac)2, CuCl, CuCl2), Ag
salts (Ag2O, Ag2CO3, AgCl, AgAc), bases (K2CO3, Cs2CO3, Na2CO3,
NaOH, KOH, NaHCO3), 4Å molecular sieve (4Å), anhydrous 1,10-
phenanthroline (phen), were purchased from Acros, J&K, or Alfa
thioetherification, hydrogenation and carbonization of the
C(aryl)−C(OH) bonds of aryl alcohols, using cheap copper salts
as catalysts and oxygen as the environmentally benign oxidant.
A diverse range of aryl alcohol substrates were used as arylation Aesar. Diphenyldisulfanes, diphenyldiselane, benzoxazole, and
solvents were purchased from Sigma-Aldrich. Alcohols
substrates including 1-(2-nitrophenyl)ethanol 1a), (2-
nitrophenyl)methanol (1b), 2-(2-nitrophenyl)ethanol (1c), 1-(2-
nitrophenyl)propan-2-ol 1d), 1-(2-methoxyphenyl)ethanol
1e), 1-(2-chlorophenyl)ethanol (1f), 1-(3-nitro-[1,1'-biphenyl]-
4-yl)ethanol (1i), 1-(2-nitrophenyl)propan-1-ol (1l 1-(furan-2-
yl)ethanol (1o), 1-(pyridin-2-yl)ethanol (1q), furan-2-ylmethanol
1r), furan-2-carbaldehyde 1s), 5-(hydroxymethyl)furan-2-
carbaldehyde (1t) were obtained from Sigma-Aldrich or Acros.
Other alcohol substrates including 1p 1h 1k 1m 1n 1j, and 1g
reagents and effectively converted into corresponding
thioethers, arenes and arylated benzoxazole products in
excellent yields. Detailed mechanism study indicated that this
transformation was achieved by a well-ordered cooperation of
oxygenation and decarboxylative functionalization that both
catalyzed by the same Cu catalyst. In the process, oxidative
cleavage of C(alkyl)−C(OH) bond of alcohol substrates leads to
aryl acid intermediates. Then decarboxylative functionalization
is achieved via C(aryl)−C activation. Although at present this
transformation is limited to ortho-substituted substrates (e.g.,
ortho-nitroaryl alcohols), the current work provides a new route
for oxidative cleavage and functionalization of C(aryl)−C bond,
and potentially offers a new way to produce functionalized
aromatic compounds from renewable resources such as lignin.
In this regard, further work is currently ongoing.
(
(
(
)
，
(
(
,
,
,
,
,
were synthesized according to the following procedure.
Synthesis of alcohol substrates48
Aryl alcohols were synthesized by reduction of corresponding
ketones with NaBH4 in MeOH. Typically, ketone (15 mmol) was
dissolved in 100 mL MeOH and the solution was cooled to 0 °C
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in ice bath for 10 min. NaBH4 (5 mmol) powder was added in solvent. The resonance band of TMS or solvents or was used as
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several portions. The reaction was stirred at 0 °C for 10 min and the internal standard. The spectra was reDcOorI:d1e0d.10a3t93/D003SCK0. 1229G
warmed to room temperature. Thin layer chromatography (TLC)
was used to record the transformation. Then the reaction was
fully concentrated in vacuo, before adding 100 mL saturated
aqueous NH4Cl. The organic products were extracted from
aqueous phase using ethyl acetate for three times (3×100 mL).
Conflicts of interest
There are no conflicts to declare.
Finally, the organic phase was washed with brine, dried with
anhydrous Na2SO4, and fully concentrated in vacuo to generate
the corresponding alcohols. Further purification process was
performed using gel column chromatography if necessary.
Acknowledgements
The authors thank the National Natural Science Foundation of
China (21972146, 21890761,), National Key Research and
Development Program of China (2017YFA0403103), Beijing
Thioetherification reaction
0.2 mmol alcohol substrate, 0.4 mmol diphenyldisulfane, 0.08
Municipal
Science
&
Technology
Commission
mmol CuSO4, 0.04 mmol phen, 1 mmol K2CO3, 200 mg 4Å, 0.2
mmol n-decane as internal standard, and 2 mL DMSO were
added into a Teflon-lined stainless-steel reactor, followed by
charging 0.5 MPa O2 and heated at 140 °C for 12 h. After
reaction, the reactor was quenched in ice-water bath. Then, the
reaction mixture was extracted using ethyl acetate and
saturated aqueous NH4Cl to separate the products.
Subsequently, the organic matter was further extracted using
ethyl acetate twice and combined for qualitative and
quantitative analysis.
(Z191100007219009), and the Chinese Academy of Sciences
(QYZDY-SSW-SLH013).
Notes and references
1. L. Ackermann, in Modern Arylation Methods, 2009, DOI:
10.1002/9783527627325.ch1, pp. 1-23.
2. N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457-2483.
3. T. W. Lyons and M. S. Sanford, Chem. Rev., 2010, 110, 1147-1169.
4. X. Chen, K. M. Engle, D.-H. Wang and J.-Q. Yu, Angew. Chem. Int.
Ed., 2009, 48, 5094-5115.
Hydrogenation reaction
5. C. S. Yeung and V. M. Dong, Chem. Rev., 2011, 111, 1215-1292.
6. A. F. Littke and G. C. Fu, Angew. Chem. Int. Ed., 2002, 41, 4176-
4211.
7. M. R. Yadav, M. Nagaoka, M. Kashihara, R.-L. Zhong, T. Miyazaki,
S. Sakaki and Y. Nakao, J. Am. Chem. Soc., 2017, 139, 9423-9426.
8. F. Inoue, M. Kashihara, M. R. Yadav and Y. Nakao, Angew. Chem.
Int. Ed., 2017, 56, 13307-13309.
9. A. Roglans, A. Pla-Quintana and M. Moreno-Mañas, Chem. Rev.,
2006, 106, 4622-4643.
10. S. B. Blakey and D. W. C. MacMillan, J. Am. Chem. Soc., 2003, 125,
6046-6047.
11. D.-G. Yu, M. Yu, B.-T. Guan, B.-J. Li, Y. Zheng, Z.-H. Wu and Z.-J.
Shi, Org. Lett., 2009, 11, 3374-3377.
12. S. G. Modha, V. P. Mehta and E. V. Van der Eycken, Chem. Soc.
Rev., 2013, 42, 5042-5055.
13. B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N. Zhang, A.-M.
Resmerita, N. K. Garg and V. Percec, Chem. Rev., 2011, 111, 1346-
1416.
14. D.-G. Yu, B.-J. Li and Z.-J. Shi, Acc. Chem. Res., 2010, 43, 1486-
1495.
0.2 mmol alcohol substrate, 0.12 mmol Cu(Ac)2, 0.08 mmol
AgNO3, 0.08 mmol phen, 0.8 mmol NaOH, 0.2 mmol n-decane
as internal standard, and 2 mL DMSO were added into a Teflon-
lined stainless-steel reactor, followed by charging 0.5 MPa O2
and heated at 140 °C for 12 h. After reaction, the reactor was
quenched in ice-water bath. Then, the reaction mixture was
extracted using ethyl acetate and saturated aqueous NH4Cl to
separate the products. Subsequently, the organic matter was
further extracted using ethyl acetate twice and combined for
qualitative and quantitative analysis.
Carbonization reaction
0.2 mmol alcohol substrate, 0.5 mmol benzothiazole, 0.15
mmol CuCl, 0.25 mmol Ag2O, 0.1 mmol phen, 100 mg 4Å, 0.2
mmol Cs2CO3, 0.2 mmol n-decane as internal standard, and 2
mL DMSO were added into a Teflon-lined stainless-steel
reactor, followed by charging 0.5 MPa O2 and heated at 140 °C
for 12 h. After reaction, the reactor was quenched in ice-water
bath. Then, the reaction mixture was extracted using ethyl
acetate and saturated aqueous NH4Cl to separate the products.
Subsequently, the organic matter was further extracted with
ethyl acetate twice and combined for qualitative and
quantitative analysis.
15. J. Cornella, C. Zarate and R. Martin, Chem. Soc. Rev., 2014, 43,
8081-8097.
16. L. J. Gooßen, G. Deng and L. M. Levy, Science, 2006, 313, 662.
17. L. J. Gooßen, N. Rodríguez and K. Gooßen, Angew. Chem. Int. Ed.,
2008, 47, 3100-3120.
Characterization methods
18. W. I. Dzik, P. P. Lange and L. J. Gooßen, Chem. Sci., 2012, 3, 2671-
2678.
19. K. Muto, J. Yamaguchi, D. G. Musaev and K. Itami, Nat. Commun.,
2015, 6, 7508.
20. J. A. Kautzky, T. Wang, R. W. Evans and D. W. C. MacMillan, J. Am.
Chem. Soc., 2018, 140, 6522-6526.
21. Y. Liang, X. Zhang and D. W. C. MacMillan, Nature, 2018, 559, 83-
88.
GC-MS (Agilent 5975C-7890A, equipped with a electron
ionization mass spectrometry detector, EI-MS) was used for
qualitative analysis of products and other intermediates. The
conversion of substrates and yield of products were
quantitatively analyzed using GC (Agilent 7820, equipped with a
hydrogen flame-ionization detector, HP-5 non-polar columns)
based on internal standard curves and areas of integrated peak
area of corresponding species. NMR spectra was recorded on a
Bruker Avance 400 spectrometer equipped with 5 mm pulsed-
field-gradient (PFG) probes. DMSO-d6 or CDCl3 was used as
22. C. P. Johnston, R. T. Smith, S. Allmendinger and D. W. C.
MacMillan, Nature, 2016, 536, 322-325.
23. T. Patra and D. Maiti, Chem. Eur. J., 2017, 23, 7382-7401.
6 | J. Name., 2012, 00, 1-3
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Page 7 of 7
Chemical Science
Please do not adjust margins
Journal Name
ARTICLE
24. A. Fawcett, J. Pradeilles, Y. Wang, T. Mutsuga, E. L. Myers and V. 37. M. Wang, J. Lu, L. Li, H. Li, H. Liu and F. Wang, J. Catal., 2017, 348,
View Article Online
K. Aggarwal, Science, 2017, 357, 283.
160-167.
DOI: 10.1039/D0SC01229G
25. C. Li, J. Wang, L. M. Barton, S. Yu, M. Tian, D. S. Peters, M. Kumar, 38. M. Liu, Z. Zhang, X. Shen, H. Liu, P. Zhang, B. Chen and B. Han,
A. W. Yu, K. A. Johnson, A. K. Chatterjee, M. Yan and P. S. Baran,
Science, 2017, 356, eaam7355.
26. R. Rinaldi, R. Jastrzebski, M. T. Clough, J. Ralph, M. Kennema, P.
Chem. Commun., 2019, 55, 925-928.
39. T. Patra, S. Nandi, S. K. Sahoo and D. Maiti, Chem. Commun.,
2016, 52, 1432-1435.
C. A. Bruijnincx and B. M. Weckhuysen, Angew. Chem. Int. Ed., 40. L. Chen, L. Ju, K. A. Bustin and J. M. Hoover, Chem. Commun.,
2016, 55, 8164-8215. 2015, 51, 15059-15062.
27. W. Schutyser, T. Renders, S. Van den Bosch, S. F. Koelewijn, G. T. 41. S. E. Allen, R. R. Walvoord, R. Padilla-Salinas and M. C. Kozlowski,
Beckham and B. F. Sels, Chem. Soc. Rev., 2018, 47, 852-908.
28. Z. Zhang, J. Song and B. Han, Chem. Rev., 2017, 117, 6834-6880.
29. A. J. Ragauskas, G. T. Beckham, M. J. Biddy, R. Chandra, F. Chen,
Chem. Rev., 2013, 113, 6234-6458.
42. L. Zhang, X. Bi, X. Guan, X. Li, Q. Liu, B.-D. Barry and P. Liao,
Angew. Chem. Int. Ed., 2013, 52, 11303-11307.
M. F. Davis, B. H. Davison, R. A. Dixon, P. Gilna, M. Keller, P. 43. Y.-Y. Jiang, G. Li, D. Yang, Z. Zhang, L. Zhu, X. Fan and S. Bi, ACS
Langan, A. K. Naskar, J. N. Saddler, T. J. Tschaplinski, G. A. Tuskan
and C. E. Wyman, Science, 2014, 344, 1246843.
30. J. Liu, X. Qiu, X. Huang, X. Luo, C. Zhang, J. Wei, J. Pan, Y. Liang, Y.
Zhu, Q. Qin, S. Song and N. Jiao, Nat. Chem., 2019, 11, 71-77.
31. H. Li, Y. Li, X.-S. Zhang, K. Chen, X. Wang and Z.-J. Shi, J. Am. Chem.
Soc., 2011, 133, 15244-15247.
Catal., 2019, 9, 1066-1080.
44. M. Liu, Z. Zhang, J. Song, S. Liu, H. Liu and B. Han, Angew. Chem.
Int. Ed., 2019, 58, 17393-17398.
45. Z. Duan, S. Ranjit, P. Zhang and X. Liu, Chem. Eur. J., 2009, 15,
3666-3669.
46. M. Li and J. M. Hoover, Chem. Commun., 2016, 52, 8733-8736.
32. E. Ozkal, B. Cacherat and B. Morandi, ACS Catal., 2015, 5, 6458- 47. J. Wang, H. Li, T. Leng, M. Liu, J. Ding, X. Huang, H. Wu, W. Gao
6462.
and G. Wu, Organic & Biomolecular Chemistry, 2017, 15, 9718-
9726.
48. R. M. Haak, F. Berthiol, T. Jerphagnon, A. J. A. Gayet, C.
Tarabiono, C. P. Postema, V. Ritleng, M. Pfeffer, D. B. Janssen, A.
J. Minnaard, B. L. Feringa and J. G. de Vries, J. Am. Chem. Soc.,
2008, 130, 13508-13509.
33. H. Wang, I. Choi, T. Rogge, N. Kaplaneris and L. Ackermann, Nat.
Catal., 2018, 1, 993-1001.
34. Y. Qiu, A. Scheremetjew and L. Ackermann, J. Am. Chem. Soc.,
2019, 141, 2731-2738.
35. P.-F. Dai, X.-S. Ning, H. Wang, X.-C. Cui, J. Liu, J.-P. Qu and Y.-B.
Kang, Angew. Chem. Int. Ed., 2019, 58, 5392-5395.
36. A. Xia, X. Qi, X. Mao, X. Wu, X. Yang, R. Zhang, Z. Xiang, Z. Lian, Y.
Chen and S. Yang, Org. Lett., 2019, 21, 3028-3033.
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