Selective Oxidative Esterification from Two Different Alcohols via Photoredox Catalysis

Article abstract of DOI:10.1002/cssc.201601113

Esters functionalities are important building blocks that are extensively used in the chemical industry and academic laboratories. Direct oxidative esterification from easy-available alcohols to esters would be a much more appealing approach, especially using O₂as terminal oxidant. Inputting external energy by photocatalysis for dioxygen activation, a mild and simple method for ester synthesis from two different alcohols has been achieved in this work. This reaction is performed under neutral conditions using O₂as the terminal oxidant. A variety of primary alcohols, especially long chain alcohols and secondary alcohols are tolerated in this system.

Full text of DOI:10.1002/cssc.201601113

DOI: 10.1002/cssc.201601113
Communications
Selective Oxidative Esterification from Two Different
Alcohols via Photoredox Catalysis
Hong Yi+,[a] Xia Hu+,[a] Changliang Bian,[a] and Aiwen Lei*[a, b]
Esters functionalities are important building blocks that are ex-
tensively used in the chemical industry and academic laborato-
ries. Direct oxidative esterification from easy-available alcohols
to esters would be a much more appealing approach, especial-
ly using O2 as terminal oxidant. Inputting external energy by
photocatalysis for dioxygen activation, a mild and simple
method for ester synthesis from two different alcohols has
been achieved in this work. This reaction is performed under
neutral conditions using O2 as the terminal oxidant. A variety
of primary alcohols, especially long chain alcohols and secon-
dary alcohols are tolerated in this system.
ysis for dioxygen activation to synthesize useful compounds
will be a challenging but highly desirable task.
Esters are important building blocks and widely found in
natural products, bulk chemicals, and polymers.[7] Direct oxida-
tive esterification from easy-available alcohols to esters would
be a much more appealing approach. Although several report-
ed methods with stoichiometric amounts of oxidants, such as
metal salts, molecular iodine, and H2O2, can achieve this trans-
formation,[8] large amounts of toxic waste are formed. In the
search for a more sustainable chemical production, researchers
have put considerable effort into the development of catalytic
oxidations using air or molecular dioxygen as the stoichiomet-
ric oxidant. In 2012, Beller’s group and our group independent-
ly realized the palladium-catalyzed direct oxidative esterifica-
tion reactions between two different alcohols using molecular
oxygen.[9] Later, other groups successfully realized direct oxida-
tive esterification reactions from alcohols under homogeneous
or heterogeneous conditions.[10] These methods provided gen-
eral routes to a variety of esters through dioxygen activation.
Despite notable recent efforts, transition metal catalysts, base,
or special ligands are always needed and the alcohols are
always limited to primary alcohols with short chains. Owing to
the importance of the esters, seeking a mild and simple way to
oxidative esterification from alcohols is always under operation
in our lab. In this communication, we present a simple and effi-
cient method for the direct esterification of alcohols through
dioxygen activation promoted by visible light (Scheme 1). This
protocol can tolerate a variety of primary and secondary alco-
hols, especially long chain alcohols.
Oxidation using dioxygen has been of long-standing interest
and has fascinated chemists owing to its tremendous potential
usage.[1] Although a variety of oxidation processes have been
developed, direct oxidation of organic substrates using molec-
ular oxygen under mild conditions still remains difficult.[2] Visi-
ble light, as a clean source of energy, has received increasing
attention from the chemistry community.[3] The application of
light-induced processes can avoid the need for further external
energy supply, as the molecule takes up sufficient energy
upon photochemical excitation for immediate product forma-
tion.[4] Over the years, various useful and unique organic reac-
tions that are initiated by visible light irradiation have been
well-developed.[5] The unique mode of “activating” molecule
through photocatalysis carries great potential towards inven-
tion of novel chemical reactivity and mediating efficient trans-
formation under mild and environmentally benign conditions.
The molecular oxygen was also used as the oxidant in many
visible-light mediated oxidative reactions.[6] On behalf of green
and sustainable chemistry, using visible-light photoredox catal-
Scheme 1. Oxidative esterification between two alcohols via photoredox cat-
alysis.
[a] H. Yi,+ X. Hu,+ C. Bian, Prof. A. Lei
College of Chemistry and Molecular Sciences, The Institute for Advanced
Studies (IAS)
Wuhan University
Wuhan 430072, Hubei (P.R. China)
E-mail: aiwenlei@whu.edu.cn
We started our evaluation of oxidative esterification reaction
parameters using benzylic alcohol and methanol as model sub-
strates (Table 1). The desired ester product 3a could be ach-
ieved in 76% yield in the presence of 3 mol% photocatalyst 9-
[b] Prof. A. Lei
National Research Center for Carbohydrate Synthesis
Jiangxi Normal University
Nanchang 330022 (China)
mesityl-10-methylacridinium perchlorate (Acr+-Mes ClO4 )
À
[+] These two authors contributed equally to this work.
using methanol (2a) as both the nucleophile and solvent
under O2 atmosphere. The data in Table 1 illustrates the impact
of different conditions on the efficiency of this reaction. Other
tested photocatalysts, such as tris(bipyridine)ruthenium(II)
chloride [Ru(bpy)3Cl2] or 2’,4’,5’,7’-tetrabromofluorescein (Eosin
Y) did not promote this reaction and could not get desired
Supporting Information and the ORCID identification number(s) for the
author(s) of this article can be found under http://dx.doi.org/10.1002/
cssc.201601113.
This publication is part of a Special Issue celebrating “10 Years of Chem-
SusChem”. A link to the issue’s Table of Contents will appear here once
it is complete.
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Table 1. Reaction optimization of visible light mediated aerobic oxidative
direct esterification.[a]
Table 2. Visible light mediated aerobic oxidative direct esterification be-
tween benzylic alcohol derivatives and methanol.[a]
Entry
1
1
3
Yield
Entry
Photocatalyst
Yield[b] [%]
1
2
Acr+-Mes ClO4
Ru(bpy)3(PF6)2
Eosin Y
Acr+-Mes ClO4
Acr+-Mes ClO4
Acr+-Mes ClO4
none
76
n.d.
n.d.
29
n.d.
n.d.
n.d.
3a, 76%
3[c]
4[d]
5[e]
6[f]
7
2
3
4
3b, 74%
3c, 72%
3d, 57%
[a] Reaction conditions: 1a (0.5 mmol), photocatalyst (3.0 mol%) in
CH3OH (1.0 mL) at room temperature in O2 using 3 W blue LEDs for 24 h.
[b] Isolated product. n.d.=not detected. [c] Under 3 W green LEDs.
[d] Under an air atmosphere. [e] Without light. [f] Under N2 atmosphere.
product (Table 1, entries 2 and 3). The desired ester product
could be obtained in 29% yield under air atmosphere (Table 1,
entry 4). In the control experiments, no desired product was
observed with neither photoredox catalyst nor light, indicating
that the photoredox catalysis is essential to this oxidative pro-
cess (Table 1, entries 5–7).
5
6
7
3e, 70%
3f, 71%
3g, 80%
With the optimal conditions established, various substituted
benzylic alcohols were employed in this aerobic oxidative
esterification reaction (Table 2). The benzylic alcohols substitut-
ed with a methyl group in the para- and meta- positions could
get the desired ester products in good yield (3b and 3c). In
addition, the sterically hindered benzylic alcohol substituted
with methyl group in the ortho- position could also get 57%
yield of ester product (3d). An electron-donating group, such
as a tert-butyl group, was well tolerated and afforded the de-
sired product in 70% yield (3e). Interestingly, the benzylic alco-
hols substituted with Cl and Br could also be smoothly con-
verted into ester products in high yields, which can be used
for further transformation (3 f and 3g). There was no reaction
when testing benzylic alcohols substituted with other electron-
withdrawing groups, such as CN and NO2.
[a] Reaction conditions: 1 (0.5 mmol), Acr+-Mer ClO4 (3.0 mol%) in CH3OH
(1.0 mL) at room temperature in O2 using 3 W Blue LEDs for 24 h. Isolated
yield.
Table 3. Visible light mediated aerobic oxidative direct esterification be-
tween benzylic alcohol and alkyl alcohols.
Entry
R2OH
3
Yield[a] [%]
Yield[b] [%]
Next we applied the optimized reaction conditions to exam-
ine different alkyl alcohols using 4-bromobenzyl alcohol as the
model substrate (Table 3). Reactions of 1g with primary alco-
hols, such as EtOH, n-BuOH, and iso-BuOH (3h–3j) could afford
the desired ester products in moderate yields. The long chain
primary alcohols such as n-C6H13OH and n-C12H25OH were suita-
ble for this reaction and could also obtained corresponding
ester products (3k and 3l). Especially, the secondary alcohol
was also tested for this ester transformation. The isopropanol
and heptan-2-ol could also be transformed into the ester prod-
ucts. However, the sterically hindered tertiary alcohol did not
afford the product (3o).
Although the yield is not high, this provides a method for
the synthesis of esters from two different alcohols using pho-
toredox catalysis. We proposed this is because of low reactivity
of the long-chain alcohols and secondary alcohols. Therefore,
several Lewis acids have been screened to promote this oxida-
1
2
3
MeOH
EtOH
nBuOH
3g
3h
3i
80
65
50
–
67
70
4
3j
34
60
5
6
CH3(CH2)5OH
CH3(CH2)11OH
3k
3l
43
32
65
63
7
8
9
3m
3n
3o
30
59
15
42
n.d.
n.d.
[a] Reaction conditions: 1g (0.5 mmol), Acr+-Mer ClO4 (3.0 mol%) in sol-
vent (R2OH/CH3CN=0.5 mL/1.0 mL) at room temperature in O2 using 3 W
blue LEDs for 24 h. Isolated yield. [b] Reaction conditions: 1g (0.5 mmol),
Acr+-Mer ClO4 (3.0 mol%), Cu(OTf)2 (10 mol%) in solvent (R2OH/CH3CN=
0.5 mL/1.0 mL) at room temperature in O2 under 3 W blue LEDs for 24 h.
Isolated yield.
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tive esterification reaction (see the Supporting Information for
details). Using 4-bromobenzyl alcohol and isopropanol as
model substrates, we found that 10 mol% copper(II) trifluoro-
methanesulfonate [Cu(OTf)2] can promote the reaction and
lead to the ester product up to 59% yield. Under the modified
reaction conditions established using Cu(OTf)2 as the additive,
several primary and secondary alcohols, for which the yields
are relatively low, were further tested. Reactions of 1g with pri-
mary alcohols, such as EtOH, n-BuOH and iso-BuOH (3h–3j)
can afford the desired ester product in good yields. The long
chain primary alcohols, such as C6H13OH and n-C12H25OH, could
get the product in good yields (3k and 3l). Isopropanol and
heptan-2-ol can be transformed into the ester products in
moderate yields under new reaction conditions (3m and 3n).
These results revealed the copper catalyst can promote this
photo-induced oxidative esterification.
Figure 1. Time profile of photocatalytic reaction with and without visible
light.
To gain some insights into this transformation, some mecha-
nistic studies were demonstrated. Using the 4-bromobenzyl al-
dehyde 4 as the model substrate under photocatalytic condi-
tions, almost quantitative yield of the ester product was
formed, which reveals that benzyl aldehyde may be an inter-
mediate in this oxidation esterification reaction (Scheme 2).
The radical-inhibiting experiment indicated that a radical
mechanism was involved in this transformation (Scheme 3).
Scheme 2. Oxidative esterification using benzyl aldehyde via photocatalysis.
Figure 2. Kinetic studies using in situ IR. Oxidative esterification between (4-
bromophenyl)methanol 1g and MeOH.
Scheme 3. Radical inhibiting experiment using TEMPO.
The time profile of photocatalytic reaction shown in Figure 1
revealed that the reaction was totally inhibited in the absence
of light. This result indicated that continuous irradiation of visi-
ble light is essential to this photocatalytic transformation. Fur-
thermore, operando IR was also used to probe this oxidative
reaction process. Figure 2 clearly shows an obvious decrease in
the substrate (1g) and increase of product (3g). Based on this
figure, an inductive period existed in this reaction for the form-
ing of ester product.
Based on the previous report[6f] and experimental results,
a plausible mechanism is proposed in Scheme 4. Firstly, the
Scheme 4. Proposed mechanism.
À
photocatalyst Acr+-Mes ClO4 is excited by visible-light irradia-
tion (3 W blue LEDs) to generate the excited species [Acr+-
MesClO4À]*, which then undergoes a single electron transfer
dized by O2 to recycle the photocatalytic reaction. The generat-
ed benzyl aldehyde can react with alcohol to form the hemia-
cetal intermediate 5. This hemiacetal could be under further
oxidation and transformed to ester 3. The copper catalyst may
(SET) process with benzylic alcohol to generate benzyl alde-
À CÀ
À CÀ
+
hyde 4, and [Acr+-Mes ClO4 ] . [Acr -Mes ClO4
] can be oxi-
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Acknowledgements
This work was supported by the 973 Program (2012CB725302),
the National Natural Science Foundation of China (21390400,
21520102003, 21272180 and 21302148), the Hubei Province Nat-
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Fund for the Doctoral Program of Higher Education of China
(20120141130002), and the Ministry of Science and Technology of
China (2012YQ120060). The Program of Introducing Talents of
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Keywords: alcohol oxidation
esterfication · oxidative coupling · photoredox catalysis
·
dioxygen activation
·
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Received: August 14, 2016
Published online on && &&, 0000
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COMMUNICATIONS
H. Yi, X. Hu, C. Bian, A. Lei*
&& – &&
Selective Oxidative Esterification from
Two Different Alcohols via Photoredox
Catalysis
Photo for energy: Inputting energy by
photocatalysis for dioxygen activation,
a mild and simple method for ester syn-
thesis from two different alcohols, is de-
scribed. This reaction is performed
under neutral conditions using O2 as
the terminal oxidant. A variety of pri-
mary alcohols, especially long chain al-
cohols and secondary alcohols are toler-
ated in this system.
ChemSusChem 2016, 9, 1 – 5
www.chemsuschem.org
5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ