A Straightforward Conversion of Activated Amides and Haloalkanes into Esters under Transition-Metal-Free Cs 2 CO 3 /DMAP Conditions

Article abstract of DOI:10.1055/s-0039-1690178

The esterification of activated amides, N -acylsaccharins, under transition-metal-free conditions with good functional group tolerance has been developed, resulting in C-N cleavage leading to efficient synthesis of a variety of esters in moderate to good yields. This work demonstrates that esterification may proceed by using simple N -acylsaccharins, haloalkanes, and Cs ₂ CO ₃ as oxygen source.

Full text of DOI:10.1055/s-0039-1690178

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–G
paper
A
en
J. Jian et al.
Paper
Synthesis
A Straightforward Conversion of Activated Amides and Haloalkanes
into Esters under Transition-Metal-Free Cs2CO3/DMAP Conditions
Junsheng Jian
Zijia Wang*
Liuqing Chen
Ying Gu
O
R2
X
(6 equiv)
R2
O
R1
O
O
DMAP (8 mol%)
Cs2CO3 (1 equiv)
X = Cl, Br, I
O
S
R1
N
O
O
CH3CN, 110 °C, 12 h
Cl
Cl
Liqiong Miao
Yueping Liu
Zhuo Zeng*
O
O
n O
n
n = 2,4
C–N bond cleavage
1 = aryl, alkenyl, alkyl, benzyl
Transition-metal-free
Wide substrate scope
Commercially available
28 examples
up to 88%
R
School of Chemistry and Environment, South China Normal
University, Guangzhou, P. R. of China
wslnwzj@foxmail.com
zhuoz@scnu.edu.cn
Received: 03.04.2019
Accepted after revision: 24.07.2019
Published online: 14.08.2019
ing Ni-catalyzed synthesis of esters (Scheme 1a).8a Since
this work, it has been rapidly followed by Danoun and co-
workers who described the first Co-catalyzed conversion of
N-Boc-amides into esters (Scheme 1b).8h In 2018, Szostak
and co-works presented an excellent metal-free protocol
for esterification of amides with broad substrate scope and
functional group tolerance under exceedingly mild condi-
tions (Scheme 1c).9 In the previous work, the oxygen atom
attached to the carbonyl groups of the ester groups is al-
ways derived from hydroxyl groups, oxidants, or carboxylic
DOI: 10.1055/s-0039-1690178; Art ID: ss-2019-h0204-op
Abstract The esterification of activated amides, N-acylsaccharins, un-
der transition-metal-free conditions with good functional group toler-
ance has been developed, resulting in C–N cleavage leading to efficient
synthesis of a variety of esters in moderate to good yields. This work
demonstrates that esterification may proceed by using simple N-acyl-
saccharins, haloalkanes, and Cs2CO3 as oxygen source.
Key words esterification, amides, metal-free, haloalkanes, C–N cleav-
age
a) Garg's work
O
O
Cat. Ni
HO R2
HO R2
HO R2
Esters are ubiquitously present in most of the natural
products and synthetic organic molecules. The construction
of esters is an important aspect for organic chemists. Al-
though compared to traditional methods of esterification or
transesterification, Baeyer–Villiger oxidation does not need
strong acid or base; a mixture of regioisomers was always
observed due to the poor regioselectivity.1 Therefore, the
oxidative esterification of alcohols or aldehydes with alco-
hols has been a widespread concern and is an alternative to
traditional methods of synthesis of esters. For example, Pa-
tel,2 Rovis,3 Yokayama,4 and Konakahara5 achieved oxidative
esterification of aldehydes with alcohols by using H2O2,
NHC, Ir complex, or iodine as oxidants or catalysts, respec-
tively. Beyond that transition-metal-catalyzed C–H esterifi-
cation provide a novel method that reduces synthetic steps
and energy consumption, which is in line with green chem-
istry.6
+
R2
R1
NR'R''
R1
O
b) Danoun's work
O
O
Me
Cat.Co
Ar
N
+
R2
Ar
O
Boc
c) Szostak's work
O
K3PO4
O
R1
NR'R''
+
R2
R1
O
THF, RT
d) This work
O
O
O
S
R1
N
O
Cs2CO3, DMAP
R2
+
R1
O
R2
Cl
O
CH3CN, 110 °C, 12 h
Likewise, amides are readily available starting materials
or intermediates in organic synthesis. However, the trans-
formation of the amides to other functional groups is still a
longstanding challenge due to the high activation energy of
the C–N bond.7 A pioneered strategy of cleavage of C–N
bonds in amides was reported by Garg and co-workers us-
R1 = Ar, benzyl, alkyl
Low price
New method to synthesize esters
Transition-metal-free
Air/moisture-stable
Selective C–N cleavage
Wide substrate scope
Scheme 1 Previous studies on esterification of amides
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
J. Jian et al.
Paper
Synthesis
acids. In 2015, Gao and co-workers reported a novel meth-
od for the construction of esters between acyl chloride and
halohydrocarbon by using Cs2CO3 as oxygen source with a
wide scope of substrates and gram-scale.10 Mechanistic
studies suggest that the alcohol O atom rather than carbon-
yl O atom in the products come from Cs2CO3 via a free radi-
cal pathway. However, in this reaction, acyl chloride is high-
ly active and air/moisture-unstable. Furthermore, inactive
sp3 carbons on N-acyl chloride are not suitable for esterifi-
cation. Because of these shortcomings, acyl chlorides are in-
capable of synthesizing a variety of esters containing sensi-
tive functional groups, such as epoxy and nitrile groups. Al-
though recently the use of transition-metal-catalyzed
conversions was found, these conversions require expen-
sive catalysts and ligands.11 According to the experience of
our group,12 we designed conversion of activated amides
and haloalkanes into esters under transition-metal-free
Cs2CO3/DMAP condition.
We initiated to investigate the esterification between N-
benzoylsaccharin (1a) and chlorobutane (2a) in CH3CN at
100 °C. After the investigation of the carbonate bases,
Li2CO3, Na2CO3, K2CO3, and Cs2CO3, the optimal carbonate
base was found to be Cs2CO3 (Table 1, entries 1–4). Decreas-
ing the amount of DMAP results in the formation of ester
3aa in 74% yield (entry 5). Without DMAP, only 60% of 3aa
was observed (entry 6). Obviously, DMAP promotes the
transformation for acylation reaction and plays a role for
activation of C–N bond in this transformation. Several sol-
vents were then examined for this esterification (entries 7–
10). Obviously, the carbonate base is crucial to the esterifi-
cation of N-benzoylsaccharin with chloroalkane (entry 11).
When the reaction was conducted under nitrogen atmo-
sphere, the corresponding product 3aa was obtained in 86%
yield. This result clearly shows that oxygen does not partic-
ipate in the esterification (entry 12) and the ester 18O was
not found in GC/MS analysis by addition of H218O to the re-
action. When 1–2 equivalents of water were added to this
reaction, it was found that the yield of the final product de-
creased to 33% (entry 13). Although increasing the solubili-
ty of Cs2CO3, the water may decompose intermediate A (vi-
de infra) to benzoic acid and carbonic acid. Furthermore,
carbonic acid releases water and carbon dioxide.
Table 1 Optimization the Reaction Conditionsa
O
O
DMAP (X mol%)
M2CO3 (1 equiv)
O
O
S
n-Bu
N
O
+
n-BuCl
solvent
110 ºC, 12 h
(6 equiv)
O
1a
2a
3aa
Entry
Base
DMAP
Solvent
Yield (%)b
1
Li2CO3
8
8
8
4
5
–
8
8
8
8
8
8
8
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
0
2
Na2CO3
K2CO3
0
3
<5
86
74
60
<5
43
59
0
4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
5
6
7
8
DMF
9
DMAc
10
11
12c
13d
1,4-dioxane
CH3CN
CH3CN
CH3CN
0
86
33
a Reaction conditions: 1a (0.3 mmol), base (1 equiv), DMAP (x mol%), n-
BuCl (6 equiv), CH3CN (2.0 mL), 100 °C, 12 h.
b Isolated yields.
c Under N2 atmosphere.
d In the presence of H2O (2 equiv).
ing group delivered the corresponding ester in 76% yield.
Particularly, naphthalene, heterocycle, and N-cinnamoyl
containing N-acylsaccharins were compatible with this re-
action system to give the products 3ka, 3la, and 3ma in
52%, 40% and 88% yield, respectively. It is especially worth
nothing that the acyl groups of inactive sp3 carbons 3na,
3oa, and 3pa could also couple with 2a. The previous reac-
tion has not been involved in the esterification of inactive
sp3 carbons.10
The scope of haloalkane derivatives was also investigat-
ed (Scheme 3). The reactions of 1a with dichloroethane and
dichlorobutane under 1 equivalent of Cs2CO3 gave the single
product 3ab and 3ac, respectively. The disubstituted esters
3ak and 3al (vide infra) were not detected. The functional
groups, ether, epoxide, nitrile, and benzyl, could be assem-
bled in the products 3ad, 3ae, 3af, and 3ag in moderate
yields. No matter whether terminal or internal alkenes, es-
terification happened to provide both 3ah and 3ai. The
product 3aj was obtained by using phenyl N-benzoylsac-
charin in 74% yield. Finally, bromobutane and iodobutane
could also react as well as chlorobutane to give the corre-
sponding ester 3aa in 75% and 73% yield, respectively.
With the optimized reaction conditions in hand, the
scope of N-acylsaccharins 1 was checked (Scheme 2). The
yield of the ester 3ba is slightly decreased because of the
steric effect. The substituted N-acylsaccharins 1c–f bearing
a methoxy group at ortho-, meta-, and para-position of N-
acylsaccharins were smoothly converted to esters in 60%,
80%, and 85% yield, respectively. Halogen atoms, fluorine,
chlorine, and bromine are tolerated under our reaction con-
ditions to give products 3ga, 3ha, and 3ia in yields 90%,
76%, and 60%. N-Acylsaccharin with an electron-withdraw-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–G

C
J. Jian et al.
Paper
Synthesis
O
O
DMAP (8 mol%)
Cs2CO3 (1 equiv)
O
O
S
R1
N
n-Bu
R2 Cl
R1
O
+
CH3CN, 110 °C, 12 h
O
(6 equiv)
R1 = Ar, alkyl
R2 = n-Bu, CH2CH2Ph
1
2a
3
O
O
O
Me
O
O
OMe
O
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
O
O
O
O
O
O
MeO
Me
80%
85%
86%
71%
88%
3ca
O
60%
OMe
3ea
3fa
3aa
3ba
3da
O
O
O
O
O
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
O
O
O
O
O
O
S
F
Cl
Br
F3C
90%
3ga
76%
60%
3ia
76%
52%
40%
3ha
3ja
3ka
3la
O
O
O
O
O
n-Bu
n-Bu
Ph
Ph
O
O
O
8
88%
72%
56%
38%
3ma
3na
3oa
3pa
Scheme 2 Scope of esterification reaction using N-acylsaccharins
O
O
DMAP (8 mol%)
Cs2CO3 (1 equiv)
O
O
When 2 equivalents of Cs2CO3 were added to the reac-
S
R
N
O
+
R Cl
tion of 1a with 2b or 2c, the disubstituted esters 3ak and
3al were found without formation of the expected mono-
substituted ester (Scheme 4).
CH3CN, 110 °C, 12 h
(6 equiv)
O
1a
2
3
O
O
O
DMAP
(8 mol%)
Cs2CO3
(2 equiv)
Cl
Cl
O
O
O
O
O
O
O
O
O
S
Cl
Cl
N
O
nO
+
60%
3ab
80%
3ac
45%
n
CH3CN
110 °C, 12 h
n = 2,4
O
(6 equiv)
3ad
O
O
O
1a
2
3
O
O
CN
O
Ph
Ph
O
O
O
45%
3ae
O
74%
65%
O
O
O
O
3af
3ag
O
O
O
O
51%
78%
O
3ak
3al
O
O
Scheme 4 Synthesis of disubstituted esters
72%
70%
74%
3aj
3ah
3ai
Four amides 1q, 1r, 1s, and 1t were checked in this reac-
tion system for comparing reactivity with N-benzoylsac-
charin (1a) under the same conditions (Scheme 5). No reac-
tion occurred when 1q and 1r were mixed with 2a. Howev-
er, the results showed that the yield of esters from other
amides 1s and 1t was lower than N-benzoylsaccharin.
To get some insights into the reaction mechanism, we
carried out the reaction in the presence of 4 equivalents of
TEMPO or 1,1-diphenylethylene as a radical scavenger.
Accordingly, only 10% product 3aa was observed (Scheme 6,
eq 1) and the product with m/z = 300 [M]+ trapped by
O
n-Bu
O
75%
73%
n-BuBr:
n-BuI:
3aa
Scheme 3 Scope of esterification reaction using haloalkanes
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–G

D
J. Jian et al.
Paper
Synthesis
lapses to release CO gas and form the radical intermediate
B. Finally, the radical B reacts with butylsaccharin coming
from saccharincesium and chlorobutane to generate prod-
uct 3aa.
O
DMAP (8 mol%)
Cs2CO3 (1 equiv)
O
N
n-Bu
R1
O
+
n-BuCl
R2
CH3CN, 110 °C, 12 h
(6 equiv)
In conclusion, we have developed the transition-metal-
free esterification of amides by the cleavage of the amide C–
N bond. This method is achieved under mild conditions
with highly functional group tolerance and can be strategi-
cally employed in the synthesis of esters in moderate to
good yields. Given the importance of esters, this work pro-
vides an example of the use of N-acylsaccharins with
haloalkanes as a method for synthesis of esters.
1
2a
3aa
O
R1
CH3
Boc
Ph
N
N
N
N
N
R2
=
CH3
Boc
Ts
O
1r
1q
1s
23%
1t
Yield
0%
0%
48%
Scheme 5 Scope of esterification reaction using other amides
1,1-diphenylethylene was found (Scheme 6, eq 2), suggest-
ing that the reaction proceed via the formation of radical
species.
All reactions were conducted in a sealed tube under N2 atmosphere.
All reactants reported are commercially available and have been pre-
pared by the method reported previously. N-Acylsaccharins were pre-
pared by the general method (see Supporting Information). All sol-
vents were purchased from suppliers of China and used without any
purification. Et3N was purified by distillation with CaH2. Flash chro-
matography was performed using 200–300 mesh silica gel. All prod-
ucts are known compounds. 1H and 13C and 19F NMR data were re-
corded with Varian (400 MHz) spectrometers in CDCl3 with TMS as an
internal standard.
DMAP
(8 mol%)
Cs2CO3
(2 equiv)
TEMPO
(4 equiv)
O
O
O
O
n-Bu
S
O
N
+
n-BuCl
(1)
CH3CN
110 °C, 12 h
O
( 6 equiv)
1a
2a
3aa
10%
Butyl Benzoate (3aa); Typical Procedure
To a 10 mL round-bottomed flask was added N-benzoylsaccharin (1a;
86.1 mg, 0.30 mmol), DMAP (2.9 mg, 0.024 mmol), Cs2CO3(96.9 mg,
0.30 mmol), n-BuCl (2a; 166.7 mg, 1.80 mmol), CH3CN (2 mL). Then,
the mixture was stirred at 100 °C for 12 h. After cooling to RT, the
mixture was filtered through a short pad of silica gel, and the silica
gel was washed with CH2Cl2 (3 × 10 mL). The organic phases were
combined and concentrated in vacuo. The residue was purified by col-
umn chromatography on silica gel (PE/EtOAc 20:1) as eluent to afford-
ed butyl benzoate 3aa as a colorless oil; yield: 45.9 mg (86%).
DMAP
(8 mol%)
Cs2CO3
(2 equiv)
O
O
O
Ph
O
Ph
(2)
1,1-Diphenylethylene
(4 equiv)
O
O
S
N
n-BuCl
( 6 equiv)
2a
+
CH3CN
110 °C, 12 h
1a
m/z = 300 [M]+
Scheme 6 Control reactions
1H NMR (400 MHz, CDCl3):  = 8.05 (d, J = 7.2 Hz, 2 H), 7.58–7.51 (m, 1
H), 7.47–7.40 (m, 2 H), 4.33 (t, J = 6.6 Hz, 2 H), 1.79–1.71 (m, 2 H),
1.53–1.43 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H).
The proposed mechanism for the esterification of N-
acylsaccharin derivatives using haloalkanes is shown in
Scheme 7. Based on the previous report,10 nucleophilic sub-
stitution of N-benzoylsaccharin (1a) with Cs2CO3 gives sac-
charincesium and the unstable intermediate A, which col-
Butyl 2-Methylbenzoate (3ba)
Following the typical procedure, 3ba was isolated as a colorless oil;
yield: 40.9 mg (71%).
O
O
O
O
O
O
O
S
O
N
S
DMAP
2
O
O
CsN
+
2
O
1a
Cs2CO3
A
O
n-BuCl
2
CO
O
S
O
O
O
O
O
O
n-Bu
S
O
N
N
O
2 CsCl
2
2
n-Bu
N
+
+
+
2
S
O
O
O
O
3aa
B
Scheme 7 Proposed mechanism for esterification of N-acylsaccharins with haloalkanes
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–G

E
J. Jian et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 7.91 (d, J = 7.8 Hz, 1 H), 7.42–7.35 (m, 1
H), 7.24 (dd, J = 7.2, 5.6 Hz, 2 H), 4.30 (t, J = 6.6 Hz, 2 H), 2.60 (s, 3 H),
1.82–1.69 (m, 2 H), 1.55–1.40 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3):  = 8.16 (d, J = 8.2 Hz, 2 H), 7.70 (d, J = 8.2
Hz, 2 H), 4.36 (t, J = 6.6 Hz, 2 H), 1.83–1.73 (m, 2 H), 1.55–1.44 (m, 2
H), 0.99 (t, J = 7.4 Hz, 3 H).
19F NMR (376 MHz, CDCl3):  = –63.15.
Butyl 4-Methylbenzoate (3ca)
Following the typical procedure, 3ca was isolated as a colorless oil;
Butyl 2-Naphthoate (3ka)
yield: 50.7 mg (88%).
Following the typical procedure, 3ka was isolated as a colorless oil;
yield: 35.6 mg (52%).
1H NMR (400 MHz, CDCl3):  = 8.61 (s, 1 H), 8.07 (d, J = 8.4 Hz, 1 H),
7.96 (d, J = 7.6 Hz, 1 H), 7.88 (d, J = 8.4 Hz, 2 H), 7.63–7.50 (m, 2 H),
4.39 (t, J = 6.6 Hz, 2 H), 1.88–1.74 (m, 2 H), 1.58–1.47 (m, 2 H), 1.01 (t,
J = 7.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3):  = 7.93 (d, J = 8.0 Hz, 2 H), 7.23 (d, J = 8.0
Hz, 2 H), 4.31 (t, J = 6.6 Hz, 2 H), 2.40 (s, 3 H), 1.80–1.70 (m, 2 H),
1.53–1.42 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H).
Butyl 2-Methoxybenzoate (3da)
Following the typical procedure, 3da was isolated as a colorless oil;
yield: 37.4 mg (60%).
Butyl Thiophene-2-carboxylate (3la)
1H NMR (400 MHz, CDCl3):  = 7.78 (d, J = 7.6 Hz, 1 H), 7.50–7.41 (m, 1
H), 6.97 (dd, J = 7.4, 5.1 Hz, 2 H), 4.30 (t, J = 6.6 Hz, 2 H), 3.89 (s, 3 H),
1.77–1.70 (m, 2 H), 1.53–1.42 (m, 2 H), 0.97 (t, J = 7.4 Hz, 3 H).
Following the typical procedure, 3la was isolated as a colorless oil;
yield: 22.1 mg (40%).
1H NMR (400 MHz, CDCl3):  = 7.80 (d, J = 3.6 Hz, 1 H), 7.54 (d, J = 4.8
Hz, 1 H), 7.13–7.06 (m, 1 H), 4.30 (t, J = 6.6 Hz, 2 H), 1.79–1.66 (m, 2
H), 1.54–1.39 (m, 2 H), 0.97 (t, J = 7.4 Hz, 3 H).
Butyl 3-Methoxybenzoate (3ea)
Following the typical procedure, 3ea was isolated as a colorless oil;
yield: 49.9 mg (80%).
Butyl Cinnamate (3ma)
1H NMR (400 MHz, CDCl3):  = 7.64 (d, J = 7.6 Hz, 1 H), 7.57 (s, 1 H),
7.38–7.30 (m, 1 H), 7.12–7.07 (m, 1 H), 4.32 (t, J = 6.6 Hz, 2 H), 3.85 (s,
3 H), 1.81–1.70 (m, 2 H), 1.54–1.40 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H).
Following the typical procedure, 3ma was isolated as a colorless oil;
yield: 53.9 mg (88%).
1H NMR (400 MHz, CDCl3):  = 7.68 (d, J = 16.0 Hz, 1 H), 7.54–7.49 (m,
2 H), 7.40–7.35 (m, 3 H), 6.44 (d, J = 16.0 Hz, 1 H), 4.21 (t, J = 6.6 Hz, 2
H), 1.73–1.65 (m, 2 H), 1.49–1.40 (m, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
Butyl 4-Methoxybenzoate (3fa)
Following the typical procedure, 3fa was isolated as a colorless oil:
yield: 53.0 mg (85%).
Butyl 3-Phenylpropanoate (3na)
1H NMR (400 MHz, CDCl3):  = 8.00 (d, J = 8.8 Hz, 2 H), 6.91 (d, J = 8.8
Hz, 2 H), 4.29 (t, J = 6.6 Hz, 2 H), 3.86 (s, 3 H), 1.80–1.69 (m, 2 H),
1.53–1.42 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H).
Following the typical procedure, 3na was isolated as a colorless oil;
yield: 44.5 mg (72%).
1H NMR (400 MHz, CDCl3):  = 7.28 (d, J = 7.4 Hz, 2 H), 7.23–7.16 (m, 3
H), 4.07 (t, J = 6.6 Hz, 2 H), 2.95 (t, J = 7.8 Hz, 2 H), 2.62 (t, J = 7.8 Hz, 2
H), 1.62–1.54 (m, 2 H), 1.39–1.29 (m, 2 H), 0.91 (t, J = 7.4 Hz, 3 H).
Butyl 4-Fluorobenzoate (3ga)
Following the typical procedure, 3ga was isolated as a colorless oil;
yield: 52.9 mg (90%).
Phenethyl Decanoate (3oa)
1H NMR (400 MHz, CDCl3):  = 8.09–8.03 (m, 2 H), 7.15–7.05 (m, 2 H),
4.32 (t, J = 6.6 Hz, 2 H), 1.80–1.70 (m, 2 H), 1.53–1.42 (m, 2 H), 0.98 (t,
J = 7.4 Hz, 3 H).
Following the typical procedure, 3oa was isolated as a colorless oil;
yield: 46.4 mg (56%).
1H NMR (400 MHz, CDCl3):  = 7.33–7.26 (m, 2 H), 7.25–7.19 (m, 3 H),
4.28 (t, J = 7.2 Hz, 2 H), 2.93 (t, J = 7.0 Hz, 2 H), 2.28 (t, J = 7.6 Hz, 2 H),
1.63–1.55 (m, 2 H), 1.29–1.23 (m, 12 H), 0.88 (t, J = 6.8 Hz, 3 H).
19F NMR (376 MHz, CDCl3):  = –106.10.
Butyl 4-Chlorobenzoate (3ha)
Phenethyl Cyclohexanecarboxylate (3pa)
Following the typical procedure, 3ha was isolated as a colorless oil;
yield: 48.3 mg (76%).
Following the typical procedure, 3pa was isolated as a colorless oil;
yield: 26.4 mg (38%).
1H NMR (400 MHz, CDCl3):  = 7.98 (d, J = 8.4 Hz, 2 H), 7.41 (d, J = 8.4
Hz, 2 H), 4.32 (t, J = 6.6 Hz, 2 H), 1.79–1.71 (m, 2 H), 1.52–1.43 (m, 2
H), 0.98 (t, J = 7.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3):  = 7.33–7.27 (m, 2 H), 7.25–7.18 (m, 3 H),
4.28 (t, J = 7.0 Hz, 2 H), 2.93 (t, J = 7.0 Hz, 2 H), 2.27 (tt, J = 11.2, 1.8 Hz,
1 H), 1.86 (d, J = 13.2 Hz, 2 H), 1.72 (d, J = 11.6 Hz, 2 H), 1.65–1.60 (m,
1 H), 1.45–1.35 (m, 2 H), 1.29–1.20 (m, 3 H).
Butyl 4-Bromobenzoate (3ia)
Following the typical procedure, 3ia was isolated as a colorless oil;
yield: 46.3 mg (60%).
2-Chloroethyl Benzoate (3ab)
Following the typical procedure, 3ab was isolated as a colorless oil;
yield: 33.1 mg (60%).
1H NMR (400 MHz, CDCl3):  = 8.07 (d, J = 8.4 Hz, 2 H), 7.62–7.55 (m, 1
H), 7.49–7.42 (m, 2 H), 4.57 (t, J = 5.8 Hz, 2 H), 3.82 (t, J = 5.8 Hz, 2 H).
1H NMR (400 MHz, CDCl3):  = 7.90 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.4
Hz, 2 H), 4.32 (t, J = 6.6 Hz, 2 H), 1.81–1.69 (m, 2 H), 1.54–1.41 (m, 2
H), 0.98 (t, J = 7.4 Hz, 3 H).
Butyl 4-(Trifluoromethyl)benzoate (3ja)
Following the typical procedure, 3ja was isolated as a colorless oil;
yield: 56.1 mg (76%).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–G

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J. Jian et al.
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Synthesis
4-Chlorobutyl Benzoate (3ac)
Ethane-1,2-diyl Dibenzoate (3ak)
Following the typical procedure, 3ac was isolated as a colorless oil;
Following the typical procedure, 3aj was isolated as a colorless oil;
yield: 51.0 mg (80%).
yield: 20.7 mg (51%).
1H NMR (400 MHz, CDCl3):  = 8.04 (d, J = 7.2 Hz, 2 H), 7.59–7.52 (m, 1
H), 7.48–7.41 (m, 2 H), 4.36 (t, J = 5.8 Hz, 1 H), 3.61 (t, J = 6.0 Hz, 2 H),
1.99–1.90 (m, 4 H).
1H NMR (400 MHz, CDCl3):  = 8.07 (d, J = 7.6 Hz, 4 H), 7.62–7.54 (m, 2
H), 7.47–7.42 (m, 4 H), 4.67 (s, 4 H).
Butane-1,4-diyl Dibenzoate (3al)
2-Methoxyethyl Benzoate (3ad)
Following the typical procedure, 3al was isolated as a colorless oil;
Following the typical procedure, 3ad was isolated as a colorless oil;
yield: 34.9 mg (78%).
yield: 24.3 mg (45%).
1H NMR (400 MHz, CDCl3):  = 8.04 (d, J = 7.2 Hz, 4 H), 7.63–7.51 (m, 2
H), 7.51–7.38 (m, 4 H), 4.36 (t, J = 5.8 Hz, 4 H), 3.61 (t, J = 5.8 Hz, 4 H).
1H NMR (400 MHz, CDCl3):  = 8.07 (d, J = 7.2 Hz, 2 H), 7.60–7.53 (m, 1
H), 7.48–7.40 (m, 2 H), 4.48 (t, J = 4.8 Hz, 2 H), 3.74 (t, J = 4.8 Hz, 2 H),
3.44 (s, 3 H).
Funding Information
Oxiran-2-ylmethyl Benzoate (3ae)
The authors gratefully acknowledge the support of Science and Tech-
nology Planning Project of Guangdong Province (2017A010103017),
Special Innovation Projects of Common Universities in Guangdong
Province (20178S0182), National Natural Science Foundation of China
Following the typical procedure, 3ae was isolated as a colorless oil;
yield: 24.0 mg (45%).
1H NMR (400 MHz, CDCl3):  = 8.07 (d, J = 8.0 Hz, 2 H), 7.60–7.56 (m, 1
H), 7.48–7.43 (m, 2 H), 4.66 (dd, J = 12.4, 3.2 Hz, 1 H), 4.18 (dd, J =
12.4, 6.4 Hz, 1 H), 3.41–3.29 (m, 1 H), 2.90 (t, J = 4.6 Hz, 1 H), 2.74 (dd,
J = 4.8, 2.4 Hz, 1 H).
(21272080).
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Supporting Information
3-Cyanopropyl Benzoate (3af)
Supporting information for this article is available online at
Following the typical procedure, 3af was isolated as a colorless oil;
yield: 42.0 mg (74%).
https://doi.org/10.1055/s-0039-1690178.
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1H NMR (400 MHz, CDCl3):  = 8.04 (d, J = 7.6 Hz, 2 H), 7.61–7.53 (m, 1
H), 7.48–7.41 (m, 2 H), 4.43 (t, J = 6.0 Hz, 2 H), 2.53 (t, J = 7.0 Hz, 2 H),
2.18–2.10 (m, 2 H).
References
(1) (a) Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A. Chem. Rev. 2004,
104, 4105. (b) Yang, N.; Su, Z.; Feng, X.; Hu, C. Chem. Eur. J. 2015,
21, 7264. (c) Shimizu, N.; Sakata, D.; Schmelz, E. A.; Mori, N.;
Kuwahara, Y. Proc. Natl. Acad. Sci. U.S.A. 2017, 11, 2616.
Benzyl Benzoate (3ag)
Following the typical, 3ag was isolated as a colorless oil; yield: 41.3
mg (65%).
1H NMR (400 MHz, CDCl3):  = 8.14–8.09 (m, 2 H), 7.61–7.54 (m, 1 H),
7.50–7.34 (m, 7 H), 5.39 (s, 2 H).
(2) Gopinath, R.; Patel, B. K. Org. Lett. 2000, 2, 577.
(3) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534.
(4) Kiyooka, S.; Wada, Y.; Ueno, M.; Yokoyama, T.; Yokoyama, R. Tet-
rahedron 2007, 63, 12695.
2-Methylallyl Benzoate (3ah)
(5) Konakahara, T.; Kiran, Y.; Ikeda, R.; Sakai, N. Synthesis 2010, 276.
(6) (a) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004,
126, 2300. (b) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2004, 126, 9542. (c) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu,
J.-Q. J. Am. Chem. Soc. 2006, 128, 6790. (d) Kano, T.; Mii, H.;
Maruoka, K. J. Am. Chem. Soc. 2009, 131, 3450. (e) Wang, Z.;
Kuninobu, Y.; Kanai, M. Org. Lett. 2014, 16, 4790.
(f) Raghuvanshi, K.; Rauch, K.; Ackermann, L. Chem. Eur. J. 2015,
21, 1790.
Following the typical procedure, 3ag was isolated as a colorless oil;
yield: 38.0 mg (72%).
1H NMR (400 MHz, CDCl3):  = 8.08 (d, J = 7.2 Hz, 2 H), 7.60–7.53 (m, 1
H), 7.49–7.42 (m, 2 H), 5.08 (s, 1 H), 4.99 (s, 1 H), 4.75 (s, 2 H), 1.84 (s,
3 H ).
(E)-But-2-en-1-yl Benzoate (3ai)
Following the typical procedure, 3ai was isolated as a colorless oil;
(7) (a) Ouyang, K.; Hao, W.; Zhang, W. X.; Xi, Z. Chem. Rev. 2015,
115, 12045. (b) Takise, R.; Muto, K.; Yamaguchi, J. Chem. Soc. Rev.
2017, 46, 5864. (c) Shi, S.; Nolan, S. P.; Szostak, M. Acc. Chem.
Res. 2018, 51, 2589. (d) Meng, G.; Szostak, M. Eur. J. Org. Chem.
2018, 2352. (e) Buchspies, J.; Szostak, M. Catalysts 2019, 9, 53.
(8) (a) Hie, L.; Nathel, N. F. F.; Shah, T. K.; Baker, E. L.; Hong, X.; Yang,
Y.-F.; Liu, P.; Houk, K. N.; Garg, N. K. Nature 2015, 524, 79.
(b) Baker, E. L.; Yamano, M. M.; Zhou, Y.; Anthony, S. M.; Garg,
N. K. Nat. Commun. 2016, 7, 11554. (c) Dander, J. E.; Weires, N.
A.; Garg, N. K. Org. Lett. 2016, 18, 3934. (d) Hie, L. E.; Baker, L.;
Anthony, S. M.; Desrosiers, J. N.; Senanayake, C.; Garg, N. K.
Angew. Chem. Int. Ed. 2016, 55, 15129. (e) Weires, N. A.; Baker, E.
L.; Garg, N. K. Nat. Chem. 2016, 8, 75. (f) Dander, J. E.; Baker, E. L.;
Garg, N. K. Chem. Sci. 2017, 8, 6433. (g) Meng, G.; Lalancette, R.;
Szostak, R.; Szostak, M. Org. Lett. 2017, 19, 4656. (h) Branchu, Y.;
yield: 37.0 mg (70%).
1H NMR (400 MHz, CDCl3):  = 8.09–8.02 (m, 2 H), 7.58–7.51 (m, 1 H),
7.46–7.39 (m, 2 H), 5.94–5.65 (m, 2 H), 4.90–4.75 (m, 2 H), 4.82 (dd,
J = 55.4, 6.8 Hz, 1 H), 1.81–1.71 (m, 3 H).
Phenethyl Benzoate (3aj)
Following the typical procedure, 3aj was isolated as a colorless oil;
yield: 50.2 mg (74%).
1H NMR (400 MHz, CDCl3):  = 8.01 (d, J = 7.2 Hz, 2 H), 7.58–7.50 (m, 1
H), 7.46–7.38 (m, 2 H), 7.35–7.20 (m, 5 H), 4.53 (t, J = 7.0 Hz, 2 H), 3.02
(t, J = 7.0 Hz, 2 H).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–G

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J. Jian et al.
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Synthesis
Gosmini, C.; Danoun, G. Chem. Eur. J. 2017, 23, 10043. (i) Liu, Y.;
Shi, S.; Achtenhagen, M.; Liu, R.; Szostak, M. Org. Lett. 2017, 19,
1614. (j) Li, G.; Szostak, M. Nat. Commun. 2018, 9, 4165. (k) Liu,
Y.; Achtenhagen, M.; Liu, R.; Szostak, M. Org. Biomol. Chem.
2018, 16, 1322. (l) Boit, T. B.; Weires, N. A.; Kim, J.; Garg, N. K.
ACS Catal. 2018, 8, 1003. (m) Chen, C.; Liu, P.; Luo, M.; Zeng, X.
ACS Catal. 2018, 8, 5864.
Meng, G.; Szostak, M. Angew. Chem. Int. Ed. 2016, 55, 6959.
(f) Liu, Y.; Liu, R.; Szostak, M. Org. Biomol. Chem. 2017, 15, 1780.
(g) Cong, X.; Fan, F.; Ma, P.; Luo, M.; Chen, H.; Zeng, X. J. Am.
Chem. Soc. 2017, 139, 15182. (h) Szostak, R.; Liu, C.; Lalancette,
R.; Szostak, M. J. Org. Chem. 2018, 83, 14676.
(12) (a) Cui, M.; Wu, H.; Jian, J.; Wang, H.; Liu, C.; Daniel, S.; Zeng, Z.
Chem. Commun. 2016, 52, 2076. (b) Wu, H.; Li, Y.; Cui, M.; Jian,
J.; Zeng, Z. Adv. Synth. Catal. 2016, 358, 3876. (c) Wu, H.; Liu, T.;
Cui, M.; Li, Y.; Jian, J.; Wang, H.; Zeng, Z. Org. Biomol. Chem.
2017, 15, 536. (d) Cui, M.; Chen, Z.; Liu, T.; Wang, H.; Zeng, Z.
Tetrahedron Lett. 2017, 58, 3819. (e) Wu, H.; Guo, W.; Daniel, S.;
Li, Y.; Liu, C.; Zeng, Z. Chem. Eur. J. 2018, 24, 3444. (f) Luo, Z.; Liu,
T.; Guo, W.; Wang, Z.; Huang, J.; Zhu, Y.; Zeng, Z. Org. Process
Res. Dev. 2018, 22, 1188. (g) Guo, W.; Huang, J.; Wu, H.; Liu, T.;
Luo, Z.; Jian, J.; Zeng, Z. Org. Chem. Front. 2018, 5, 2950.
(9) Li, G.; Lei, P.; Szostak, M. Org. Lett. 2018, 20, 5622.
(10) (a) Ren, L.; Wang, L.; Lv, Y.; Li, G.; Gao, S. Org. Lett. 2015, 17,
5172. (b) Wang, L.; Li, J.; Dai, W.; Lv, Y.; Zhang, Y.; Gao, S. Green
Chem. 2014, 16, 2164.
(11) (a) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2007, 129,
6098. (b) Tobisu, M.; Nakamura, K.; Chatani, N. J. Am. Chem. Soc.
2014, 136, 5587. (c) Liu, C.; Meng, G.; Szostak, M. J. Org. Chem.
2016, 81, 12023. (d) Liu, C.; Meng, G.; Liu, Y.; Liu, R.; Lalancette,
R.; Szostak, R.; Szostak, M. Org. Lett. 2016, 18, 4194. (e) Shi, S.;
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–G