Synthesis of Esters from Stable and Convenient Sulfoxonium Precursors under Catalyst- And Additive-Free Conditions

Article abstract of DOI:10.1055/s-0039-1690157

A convenient and efficient procedure for the construction of esters from stable sulfoxonium ylides and alcohols has been developed. This protocol presents a broad substrate scope and good yields of the desired esters can be isolated. Notably, no catalyst, oxidant, base or any other additive is required.

Full text of DOI:10.1055/s-0039-1690157

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
letter
A
en
Synlett
Y. Yuan, X.-F. Wu
Letter
Synthesis of Esters from Stable and Convenient Sulfoxonium Pre-
cursors under Catalyst- and Additive-Free Conditions
Yang Yuan
O
O
O
2
R2
Xiao-Feng Wu*
S
R OH
R1
120 °C
R1
O
2
6
5 examples
0–97%
Leibniz-Institut für Katalyse e.V. an der Universität Rostock,
Albert-Einstein-Straße 29a, 18059 Rostock, Germany
xiao-feng.wu@catalysis.de
Catalyst-free
Additive-free
Broad substrate scope
Stable acyl source
Received: 16.07.2019
Accepted after revision: 25.07.2019
Published online: 13.08.2019
ganic compounds has been established as an efficient
methodology for the synthesis of esters (Scheme 1d). Nev-
ertheless, some deficiencies still exist, including the re-
DOI: 10.1055/s-0039-1690157; Art ID: st-2019-k0368-l
7
quirement for toxic CO gas, metal catalyst, and bases.
Abstract A convenient and efficient procedure for the construction of
esters from stable sulfoxonium ylides and alcohols has been developed.
This protocol presents a broad substrate scope and good yields of the
desired esters can be isolated. Notably, no catalyst, oxidant, base or any
other additive is required.
Previous work
O
O
R
R1
ROH
O
a)
Additive
R1 = OH, OOCR', Cl
Key words sulfoxonium, ester synthesis, alcohols, catalyst-free, acyl
source, green chemistry
O
O
Oxidant
b)
c)
O
Esterification is one of the most important transforma-
tions both in organic synthesis and in the chemical indus-
Aldehydes
1
Catalyst
Oxidant
try. The product esters are widely used in the synthesis of
or
+
R
OH
Esters
Alcohols
pharmaceuticals and natural compounds as well as numer-
2
ous other fine chemicals. Given their importance, various
O
X
methods have been developed for the synthesis of esters.
Traditionally, esters can be obtained by reacting activated
carboxylic acid derivatives with alcohols or transesterifica-
tion reactions (Scheme 1a). However, besides the low sta-
bility of those compounds, the presence of strong acid or
base produces large amounts of undesired by-products and
Catalyst
Base
R
d)
+
CO
+
ROH
O
X = I, Br, Cl, OTf
This work
O
O
O
ROH
3
also limits the reaction scope. Alternatively, Baeyer–Villiger
S
R1
R
e)
R1
120 °C
O
oxidation reaction is a useful approach for the synthesis of
esters (Scheme 1b). However, in addition to the high costs
and hazards associated with peracids, the use of an organic
peracid would result in the formation of one equivalent of
Catalyst-free
Additive-free
Broad substrate scope
Stable acyl source
Scheme 1 Approaches for the synthesis of esters
4
the corresponding carboxylic acid salt as waste. In recent
years, considerable effort has been devoted to oxidative es-
terification of aldehydes or alcohols with alcohols for the
synthesis of esters (Scheme 1c). Most of these protocols
On the other hand, sulfoxonium ylides have been exten-
sively studied and applied in modern organic chemistry. In
general, according to the reported procedures, sulfoxonium
8
5
9
proceed in the presence of various catalysts or require stoi-
chiometric amounts of reagents such as peroxides, Oxone,
MnO or PhI(OAc) , and thus a large amount of toxic waste
ylides are usually used as RCOCH sources, or carbon nu-
2
cleophiles.10 Various functionalized ketones and heterocy-
cles can be prepared easily. However, to our surprise, the
use of sulfoxonium ylides for the preparation of esters has
2
2
6
is generated. Additionally, the alkoxycarbonylation of or-
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synlett
Y. Yuan, X.-F. Wu
Letter
not been systematically studied to date.11 Given this back-
ground, herein we report our finding on the application of
sulfoxonium ylides in esters synthesis (Scheme 1e). In the
presence of alcohols, various esters can be produced in
good to excellent yields without the need for catalyst, oxi-
dant, base or any other additive.
suggested that when a mixed solvent system of MeOH and
t-BuOH (v/v = 2:3) was used, the yield of 3a greatly improve
to 96% (entry 15). Notably, the reaction time could also be
shortened to 24 hours. Therefore, the optimal reaction con-
ditions were defined as 1a stirring in either neat MeOH or
MeOH/t-BuOH (2:3) at 120 °C for 24–40 hours.
To test our hypothesis, systematic studies were carried
out with sulfoxonium ylide 1a and methanol as the model
substrates (Table 1). To begin, the following conditions were
selected: in the absence of catalyst, 1a (0.2 mmol, 1.0 equiv)
was stirred in MeOH (0.5 mL) at 120 °C for 40 hours. To our
delight, the desired product methyl benzoate (3a) was
formed in 97% GC yield (entry 1). Under lower reaction
temperature, the desired product 3a was formed in 21% and
Having determined the best conditions, we next evalu-
ated the substrate scope of this reaction with a range of
sulfoxonium ylides 1 with n-butanol.12 Generally, sulfoxoni-
um ylides containing a diverse range of substituents on the
phenyl ring were all easily converted into the correspond-
ing products in good to excellent yields (Table 2). More spe-
cifically, sulfoxonium ylides 1a–f with either electron-do-
nating (Me, OMe) or electron-withdrawing (F, Cl, CF3)
groups on the phenyl ring provided the corresponding es-
ters 2a–k in 78–93% yields. A disubstituted phenyl ring and
a naphthyl group also reacted smoothly to furnish the de-
sired products 2g and 2h in 90% and 92% yields, respective-
ly. Remarkably, the aromatic heterocycles of furan and thio-
phene were well tolerated in the reaction, yielding the
products 2i and 2j in good yields. Moreover, aliphatic sub-
stituted sulfoxonium ylide 1k was also successfully em-
ployed as the substrate to give the corresponding product
6
0% yields at room temperature and 80 °C, respectively (en-
tries 2 and 3). Then we investigated the reaction of 1a with
.0 equivalents of methanol in different solvents, such as
THF, toluene, 1,4-dioxane, CH Cl , 1,2-dichloroethane (DCE)
5
2
2
and MeCN but found that the yield of 3a decreased to 38–
5% (entries 4–10). Interestingly, when t-BuOH was used as
5
the solvent, 58% yield of 3a was formed and no tert-butyl
benzoate was detected (entry 11). Further optimization
Table 1 Optimization of Reaction Conditionsa
2k in 89% yield. However, no reaction occurred when tert-
butyl substituted 1l was applied, presumably due to the
steric hindrance. It should be noted that transesterification
also occurred when sulfoxonium ylides contained an ester
group (2m, 2n).
O
O
O
S
T °C
O
+
MeOH
solvent
1a
3a
Table 2 Scope of the Reaction with Respect to Sulfoxonium Ylidesa
Entry
Temp (°C)
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
9
120
RT
MeOH
MeOH
MeOH
THF
97
21
60
53
38
55
50
40
45
42
58
66
72
78
96
96
O
O
O
2
R OH
R2
S
R1
R1
120 °C
O
1
2
80
120
120
120
120
120
120
120
120
120
120
120
120
120
Entry
1
1
Esters
Yield
b
(
%)
toluene
CH
2
Cl
2
O
O
O
S
DCE
O
O
93
MeCN
1
1
a
2a
2b
1,4-dioxane
2-Me-THF
t-BuOH
O
1
1
1
1
1
1
0
O
S
1
2
3
4
O
89
81
83
2c
3d
4
t-BuOH
b
t-BuOH
O
O
O
MeOH/t-BuOH (1:4)
MeOH/t-BuOH (2:3)
MeOH/t-BuOH (1:1)
S
S
O
5
OMe
O
OMe
16
1
1
c
2c
a
Reaction conditions: Sulfoxonium ylide 1a (0.15 mmol, 1 equiv), metha-
O
O
F
nol (0.75 mmol, 5.0 equiv) in solvent (0.5 mL) for 40 hours at indicated
temperature in sealed tubes under air.
O
b
Yields were determined by GC using n-hexadecane as the internal stan-
dard.
F
c
Methanol (1.5 mmol, 10.0 equiv).
d
2d
d
Methanol (3.0 mmol, 20.0 equiv).
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

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Synlett
Y. Yuan, X.-F. Wu
Letter
responding esters were obtained in good to high yields. For
example, primary alcohols such as methanol, ethanol, pro-
pan-1-ol, octan-1-ol, cyclopropylmethanol, and cyclohexyl-
methanol, all gave the desired products 3a–f in 67–97%
yields. Similarly, reaction with less reactive secondary alco-
hols, for instance propan-2-ol and cyclopentanol, proceed-
ed smoothly, providing the corresponding products 3g and
Entry
5
1
Esters
Yield
b
(
%)
O
O
O
S
O
85
Cl
Cl
2e
1
e
O
O
3h in good yields. Furthermore, benzyl alcohol, 5-hexen-1-
O
S
ol, 2-chloroethanol and 3-thiopheneethanol also reacted
well and gave the corresponding esters 3i–l in 65–91%
yields. However, when 1,2-diol was tested in this reaction,
only a trace amount of the target ester product could be de-
tected.
O
6
7
78
F3C
F3C
1
f
2f
O
O
O
Cl
S
Cl
O
90
92
Table 3 Synthesis of Esters from Alcoholsa
Cl
Cl
1
g
2g
O
O
O
S
O
O
OR
ROH
O
S
120 °C
O
8
9
1a
3
1
1
h
i
2h
2i
Entry ROH
Ester
Yield
b
(
%)
O
O
O
O
S
O
O
O
O
68
97
O
S
O
S
1
2
MeOH
97
3
a
O
O
S
10
O
O
1
1
1
j
2j
EtOH
87
O
O
O
3b
S
1
1
2
O
89c
5
O
k
l
2k
2l
O
3
4
5
6
7
n-PrOH
90
O
O
O
S
3c
1
O
0
O
O
HO
O
90c
5
O
5
O
n
S
O Bu
3
d
13
nBuO
94
63
MeO2C
O
O
O
1
m
2
m
HO
HO
O
67
91
68
O
O
nBuO
3e
O
n
14
S
O Bu
MeO2C
O
1
n
2
n
O
a
Reaction conditions: Sulfoxonium ylide 1 (0.2 mmol, 1 equiv) in neat
n-butanol (0.5 mL) for 40 hours at 120 °C in sealed tubes under air.
b
3f
Isolated yield.
Using octan-1-ol/t-BuOH (2:3) as solvent.
c
O
O
i-PrOH
Subsequently, under the optimized conditions, the
scope of the reaction with different alcohols with sulfoxo-
nium ylide 1a was examined (Table 3). Gratifyingly, the cor-
3g
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

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Y. Yuan, X.-F. Wu
Letter
Entry ROH
Ester
Yield
O
O
b
(
%)
O
O
S
S
O
O
ROH
ROH
A
8
70
1
HO
O
3h
OR
O
ROH
HO
O
O
S
O
S
9
91c
+
ROMe
B
3i
C
H
Scheme 3 Possible reaction mechanism
O
O
87c
86c
65c
1
1
0
1
2
HO
HO
In summary, the use of sulfoxonium ylides for the pro-
duction of esters has been systematically studied. In the
presence of alcohol, a broad range of esters were produced
in good to excellent yields. Notably, no catalyst, oxidant,
base or any other additive is required. This method also fea-
tured broad substrate scope, operational simplicity, and
easy scale-up.
3
j
O
O
Cl
Cl
O
3k
S
1
S
O
HO
Funding Information
3l
Y.Y. thanks the China Scholarship Council for financial support.()
a
Reaction conditions: Sulfoxonium ylide 1a (0.2 mmol, 1 equiv) in neat
ROH (0.5 mL) for 40 hours at 120 °C in sealed tubes under air.
b
Isolated yield.
Using ROH/t-BuOH (2:3) as solvent.
c
Acknowledgment
We thank the analytical team of LIKAT for their kind support. We also
appreciate the generous support from Professor Matthias Beller in
LIKAT.
To demonstrate the applicability of this procedure, the
reaction between 1h and butan-1-ol was also performed on
a 5 mmol scale (Scheme 2). To our delight, the correspond-
ing product 2h was produced in 90% isolated yield (1.03
gram).
Supporting Information
Supporting information for this article is available online at
O
O
O
https://doi.org/10.1055/s-0039-1690157.
S
u
p
p
orti
n
g Inform ati
o
n
S
u
p
p
orti
n
g Inform ati
o
n
S
nBuOH (5 mL)
20 °C, 40 h
O
1
References and Notes
1
9
.03 g, 2h
0% yield
5
mmol, 1h
(
(
(
1) Otera, J.; Nishikido, J. Esterification: Methods, Reactions, and
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Scheme 3. Initially, sulfoxonium ylide 1 undergoes nucleop-
hilic attack by alcohol, leading to the formation of interme-
diate A. The desired ester product then formed with the re-
lease of intermediate B (dimethylsulfoxonium methylide).
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13
ether C and DMSO.
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

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Synlett
Y. Yuan, X.-F. Wu
Letter
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to neat alcohol (0.5 mL) or to alcohol/tBuOH (2:3, 0.5 mL), and
the solution was stirred in a 20 mL sealed tube under an atmo-
sphere of air at 120 °C for 40 h. After cooling the mixture to
room temperature, the solvent was evaporated under vacuum,
and the crude product was purified by column chromatography
(
2017, 56, 4277. (b) Vaitla, J.; Bayer, A.; Hopmann, K. H. Angew.
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1
(g) Barday, M.; Janot, C.; Halcovitch, N.; Muir, J.; Aïssa, C. Angew.
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3
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2 H), 7.54–7.45 (m, 1 H), 7.43–7.32 (m, 2 H), 4.30 (t, J = 6.6 Hz,
2 H), 1.87–1.58 (m, 2 H), 1.58–1.26 (m, 2 H), 0.96 (t, J = 7.4 Hz,
13
3 H). C NMR (75 MHz, CDCl ):  = 166.5, 132.7, 130.5, 129.5,
3
128.2, 64.7, 30.8, 19.2, 13.7.
(
k) Xie, H.; Lan, J.; Gui, J.; Chen, F.; Jiang, H.; Zeng, W. Adv. Synth.
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©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E