Iron-catalyzed cross-dehydrogenative coupling esterification of unactive C(sp3)-H bonds with carboxylic acids for the synthesis of α-acyloxy ethers

Article abstract of DOI:10.1021/jo500192h

An iron-catalyzed oxidative esterification reaction between unactivated C(sp³)-H bonds from symmetric and asymmetric ethers and carboxylic acids using di-tert-butyl peroxide (DTBP) as the oxidant via a cross dehydrogenative coupling (CDC) react

Full text of DOI:10.1021/jo500192h

Article
pubs.acs.org/joc
Iron-Catalyzed Cross-Dehydrogenative Coupling Esterification of
Unactive C(sp3)−H Bonds with Carboxylic Acids for the Synthesis of
α‑Acyloxy Ethers
Jincan Zhao,† Hong Fang,† Wei Zhou,† Jianlin Han,*,†,‡ and Yi Pan†,‡
†School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People’s Republic of China
‡Institute for Chemistry & BioMedical Sciences, Nanjing University, Nanjing 210093, People’s Republic of China
S
* Supporting Information
ABSTRACT: An iron-catalyzed oxidative esterification reaction between
unactivated C(sp3)−H bonds from symmetric and asymmetric ethers and
carboxylic acids using di-tert-butyl peroxide (DTBP) as the oxidant via a
cross dehydrogenative coupling (CDC) reaction was established, which
tolerates a wide range of cyclic ether substrates to react with aromatic
acids and phenylacetic acid, providing an efficient method for the
preparation of α-acyloxy ethers with good to excellent yields.
Intermolecular competing kinetic isotope effect (KIE) experiments were
also carried out, which indicate that C(sp3)−H bond cleavage may be the rate-determining step of this CDC reaction.
C−H activating esterification has also attracted attentions in
the past few years, which proceeds through oxidative coupling
reactions from common starting materials with high atom
economy. Several transition-metal catalysts, including palla-
dium,10 copper,11 rhodium,12 and platinum,13 have been
developed for this new C−H activating esterification reaction.
In addition, a metal-free methodology using Bu4NI as a catalyst
has also been employed for C−H activating esterification.14
However, to the best of our knowledge, no reports of iron-
catalyzed oxidative C(sp3)−H activating esterification of ethers
are known. The readily available and nontoxic iron catalysts are
highly attractive for chemical synthesis from environmental and
economic points of view.15 Therefore, the development of iron-
catalyzed C−O cross-coupling methods would be of a great
value. Herein, we report an iron-catalyzed dehydrogenative
cross-coupling reaction for C−O bond formation to construct
α-acyloxy ethers using DTBP as the oxidant.
INTRODUCTION
■
Direct C−H functionalization for the formation of C−C and
C−X (X = O, S, N, P, etc.) bonds catalyzed by transition metals
has become one of the most useful tools in organic chemistry
owing to its remarkable potential for step economy, atom
economy, and environmental sustainability.1 In the past years,
oxidative C(sp)−H and C(sp2)−H cross couplings for various
C−C bond-forming reactions have received special research
attention and made great progress.2 However, oxidative
couplings involving C(sp3)−H bonds remain challenging due
to their low reactivity and the lack of a coordination site for the
transition-metal catalyst.3
Functionalization of C(sp3)−H bonds adjacent to the oxygen
of ethers represents one of the hot topics in the research of
C(sp3)−H bond activation, and some developments have taken
place recently.4 The Li group developed Fe-catalyzed N-
alkylation of azoles via oxidation of unactivated C(sp3)−H
bonds of ethers in 2010.5 Later, the Wang group demonstrated
a Cu-catalyzed cross-dehydrogenative coupling reactions of
(benzo)thiazoles with cyclic ethers using K2S2O8 as an oxidant.6
Very recently, the Lei group reported oxidative arylation of
cyclic ethers catalyzed by nickel.7 Our group also developed an
iron-catalyzed decarboxylative alkenylation of cyclic ethers with
cinnamic acids via a radical process.8 Encouraged by these
results, we then tried to realize the oxidative arylation of cyclic
ethers with more easily available aromatic carboxylic acids with
iron as catalyst (Scheme 1). Surprisingly, the expected product
2-(4-methoxyphenyl)-1,4-dioxane was not observed. Instead,
we found that 4-methoxybenzoic acid reacted with 1,4-dioxane
directly through a cross dehydrogenative coupling (CDC)
process,9 giving an unexpected α-acyloxy ether product of 1,4-
dioxan-2-yl 4-methoxybenzoate with 89% isolated chemical
yield.
RESULTS AND DISCUSSION
■
The initial choice of reaction conditions was focused on using
4-methoxybenzoic acid (1a) and 1,4-dioxane as substrates with
Fe(acac)3 as catalyst. Among a wide range of oxidant
candidates, such as TBHP (5−6 M in decane), K2S2O8, H2O2
(30% aqueous solution), and TBPB (Table 1, entries 2−5),
DTBP was found to be the most effective oxidant, giving 89%
chemical yield (entry 1). The iron(III) acetylacetonate was
found to be the best choice of catalyst, and the other tested iron
compounds, such as Fe2O3 and FeCl3, did not give any
improvement (entries 6 and 7). No significant increase in the
yield of 5a was observed with the use of more than 2 equiv of
Received: January 25, 2014
Published: April 11, 2014
© 2014 American Chemical Society
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Scheme 1. Decarboxylative and Dehydrogenative Cross-Coupling Reactions
a
zoic acid, afforded the corresponding α-acyloxy ethers in the
highest yield (96% 5u) .
Table 1. Optimization of Typical Reaction Conditions
To prove the synthetic utility of the methodology, heteroaryl
carboxylic acids and fused aryl carboxylic acids were subjected
to the reaction under the optimized conditions (Scheme 3). As
shown in Scheme 3, these reactions proceeded smoothly, giving
the desired products in good to excellent yields (73−98%).
Thiophene-2-carboxylic acid afforded a better yield than 1-
methyl-1H-pyrrole-2-carboxylic acid (97% for 6a and 89% for
6d). Notably, a double-heteroatom aryl carboxylic acid, 2,4-
dimethylthiazole-5-carboxylic acid, also gave the desired
product in excellent yield (94%, 6e). In addition, 1-naphthoic
acid, 2-naphthoic acid, and 4-methyl-1-naphthoic acid were also
good reaction partners, providing the corresponding products
in 82%, 85%, and 86% yields, respectively (6f−h). Furthermore,
it is also noteworthy that 1-methyl-1H-indole-3-carboxylic acid
and benzo[b]thiophene-2-carboxylic acid could provide the
corresponding products in good yields (6i,j).
b
entry
1
catalyst (amt, mol %)
oxidant
yield, %
g
Fe(acac)3 (20)
Fe(acac)3 (20)
Fe(acac)3 (20)
Fe(acac)3 (20)
Fe(acac)3 (20)
Fe2O3 (20)
DTBP
89
c
h
2
TBHP
46
3
4
5
6
7
K2S2O8
N.D.
trace
21
d
H2O2
TBPB
DTBP
DTBP
DTBP
34
FeCl3 (20)
23
e
8
Fe(acac)3 (20)
Fe(acac)3 (10)
Fe(acac)3 (20)
85
f
9
DTBP
67
10
11
N.D.
N.D.
DTBP
After testing the coupling reaction with a symmetric ether,
1,4-dioxane, we then tried to extend the reaction substrate
scope to an asymmetric ether as substrate, to investigate the
reactivity and regioselectivity of this system. 1,3-Dioxolane, an
asymmetric ether, was then used in this oxidative esterification
reaction which has not been thus far achieved under CDC
reactions (Scheme 4). We began our investigation by
examining the coupling of 4-methoxybenzoic acid and 1,3-
dioxolane under the optimized conditions. Surprisingly, the
expected product 1,3-dioxolan-2-yl 4-methoxybenzoate was not
observed. Instead, we obtained 1,3-dioxolan-4-yl 4-methox-
a
Catalytic conditions: 4-methoxybenzoic acid (2 mmol), 1,4-dioxane
(4 mL), iron catalyst (20 mol %), oxidant (2.0 equiv), 120 °C, 24 h.
b
c
Isolated yield based on carboxylic acid. TBHP (5−6 M in decane).
d
e
f
g
30% aqueous solution. 130 °C. 3.0 equiv. DTBP = di-tert-butyl
h
peroxide. TBHP = tert-butyl hydroperoxide.
DTBP (entry 8). Finally, an examination of the loading amount
of Fe(acac)3 catalyst demonstrated that 20 mol % was needed
for this reaction (67% yield, entry 9). Furthermore, the reaction
did not proceed without the use of iron catalyst or DTBP
(entries 10 and 11).
1
ybenzoate (7a) in 86% yield, which was identified by its H
NMR and 13C NMR spectra. As illustrated in Scheme 4,
benzoic acids containing methoxy, methyl, ethyl, tert-butyl,
phenyl, and phenoxy groups could all react well with 1,3-
dioxolane to afford the corresponding α-acyloxy ethers in good
yields (7a−e). In addition, thiophene-2-carboxylic and
thiophene-3-carboxylic acids were also good reaction partners,
providing the corresponding products in 90% and 87% yields,
respectively (7f,g). Furthermore, the reactions have excellent
regioselectivities, and only one regioisomer is detected for all
cases.
With the optimized reaction conditions in hand, we next
explored the benzoic acid scope of this iron-catalyzed oxidative
esterification reaction (Scheme 2). As shown in Scheme 2, the
process has a broad scope, with groups such as methoxy,
methyl, ethyl, tert-butyl, n-propoxy, phenyl, phenoxy, bromo,
and ethoxy, giving good to excellent yields of 62−96% (5a−
m,o−x). Ortho-, meta-, and para-substituted benzoic acids
could all work in this system. Slightly lower yields were
observed in the cases of ortho-substituted benzoic acids in
comparison to their para or meta analogues, possibly due to
steric hindrance (5a−c,p−r,u−v). Variation of substituents on
the aromatic ring showed obvious effects on the reaction
efficiency. The reaction with benzoic acids substituted with an
electron-donating group afforded the expected product with
excellent yields (5u, 96% yield). However, benzoic acids
substituted with an electron-withdrawing group, such as 4-
bromobenzoic acid, afforded the corresponding product in only
62% yield (5m). Even more, the reaction did not work when
benzoic acid contained a nitro substituent group (5n). Notably,
disubstituted and trisubstituted benzoic acids also worked well
in the reaction and gave the desired products (5o−x). In
addition, a highly electron-rich substrate, 3,4,5-trimethoxyben-
Thereafter, the scope of this protocol was evaluated using
other C(sp3)−H bonds as the cross-coupling partners with
thiophene-2-carboxylic acid (Scheme 5). The substrate
methoxybenzene coupled well with thiophene-2-carboxylic
acid under our optimized conditions to give the corresponding
product in 82% yield (8a). Remarkably, the protocol was also
successfully utilized for the esterification of cyclohexene in 42%
yield (8b). Disappointingly, tetrahydrofuran, 2,5-dihydrofuran,
toluene, and benzyl ether could not react with thiophene-2-
carboxylic acid under the current conditions (8c−f).
Finally, we examined whether other types of acids were
suitable substrates for this oxidative esterification reaction.
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a
Scheme 2. Coupling of 1,4-Dioxane with Substituted Benzoic Acids
a
Catalytic conditions: 1 (2.0 mmol), 1,4-dioxane 2a (4.0 mL), DTBP (2.0 equiv), 120 °C, 24 h. Isolated yield based on 1.
Phenylacetic acid (4) was used in this system to react with 1,4-
dioxane under the typical reaction conditions. We were pleased
to find that the reaction proceeded well and gave the
corresponding product 9 in 62% yield (Scheme 6).
On the basis of the above results and the literature
reports,8,16 a plausible radical oxidative coupling mechanism
containing a μ-oxo, μ-carboxylate diiron(III) intermediate is
illustrated in Scheme 8. At the beginning, the iron catalyst
reacts with carboxylic acid and the oxidant DTBP, forming the
μ-oxo, μ-carboxylate diiron(III) intermediate A (methane
monooxygenase model system).17 The intermediate A is
further oxidized to give the Fe(IV) intermediate B. Then,
intermediate B reacts with a cyclic ether to generate
intermediate C.17b,18 Subsequently, the intermediate C under-
goes a cross-coupling process, giving the final product 5a and
catalyst Fe(III) intermediate A.
To investigate the details of the mechanism for this iron-
catalyzed oxidative esterification of ethers with carboxylic acids,
a series of controlled experiments were carried out. No desired
product was observed by addition of TEMPO as a radical
inhibitor. In addition, an intermolecular competing kinetic
isotope effect (KIE) experiment was carried out (Scheme 7). As
a result, a significant KIE was observed with kH/kD = 3 (the KIE
1
was determined by H NMR spectroscopy by analyzing the
According to a previous report on the stereoelectronic effects
in hydrogen atom abstraction from ethers19 and the mechanism
proposed above (Scheme 8), the abnormal regioselectivity of
the reaction on the substrate 1,3-dioxolane could be explained.
ratio of 6a and [D]6a). This indicates that C(sp3)−H bond
cleavage may be one of the rate-determining steps of this
procedure.
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Scheme 3. Coupling of 1,4-Dioxane to Heteroaryl Carboxylic
Acids and Fused Aryl Carboxylic Acids
Scheme 5. Substrate Scope for the Iron-Catalyzed Oxidative
a
Esterification of Other C(sp3)−H Bonds with Thiophene-2-
a
carboxylic Acid
a
Catalytic conditions: thiophene-2-carboxylic acid (2.0 mmol), 2 (4.0
mL), DTBP (2.0 equiv), 120 °C, 24 h. Isolated yield based on
thiophene-2-carboxylic acid.
a
Scheme 6. Coupling of 1,4-Dioxane with Phenylacetic Acid
a
Catalytic conditions: 3 (2.0 mmol), 1,4-dioxane (4.0 mL), DTBP (2.0
equiv), 120 °C, 24 h. Isolated yield based on 3.
a
Catalytic conditions: phenylacetic acid (2.0 mmol), 2a (4.0 mL),
If the radical forms at the Ha position (path b, Scheme 9), it
will be a bridgehead radical, which is notoriously very difficult
to form.19 Thus, for the Fe-catalyzed radical reaction of this
substrate containing two oxygen atoms, the regioselectivity is
abnormal, and the reaction happens selectively at the Hb
position and proceeds through path a to give the final products
7.
DTBP (2.0 equiv), 120 °C, 24 h. Isolated yield based on phenylacetic
acid.
Finally, the different pathways for the current cross-
dehydrogenative coupling of benzoic acid and our previous
cross-decarboxylative coupling of cinnamic acids8 have been
a
Scheme 4. Coupling of 1,3-Dioxolane with Aromatic Carboxylic Acids
a
Catalytic conditions: aromatic carboxylic acids (2.0 mmol), 1,3-dioxolane (2b; 4.0 mL), DTBP (2.0 equiv), 120 °C, 24 h. Isolated yield based on
aromatic carboxylic acids.
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Scheme 7. KIE Studies
Scheme 8. Possible Mechanism
Scheme 10. Different Pathways for Reactions of Benzoates
and Cinnamic Acids
catalyst via a CDC reaction. Furthermore, this reaction provides
a useful strategy for the synthesis of substituted α-acyloxy
ethers. Various carboxylic acids and several symmetric and
asymmetric ethers were well tolerated in this catalytic system
with moderate to excellent chemical yields and completely
controlled regioselectivities. The mechanism of this reaction
has also been studied through an intermolecular competing
kinetic isotope effect (KIE) experiment. Further studies on
iron-catalyzed C−O bond formation reactions are currently
being investigated in our laboratory.
Scheme 9. Regioselectivity of the Reaction on 1,3-Dioxolane
EXPERIMENTAL SECTION
■
General Procedure of the Fe-Catalyzed Oxidative Ester-
ification Reaction. In a Schlenk tube equipped with a magnetic stir
bar were added Fe(acac)3 (141 mg, 0.4 mmol) and 4-methoxybenzoic
acid (304 mg, 2.0 mmol). 1,4-Dioxane (4.0 mL, 30−50 mmol) and
DTBP (di-tert-butyl peroxide, 4 mmol, 753 μL) were added. The
resulting reaction mixture was stirred at 120 °C for 24 h. After the
required reaction time, the mixture was cooled to room temperature.
The reaction mixture was extracted with dichloromethane. The
organic phases were evaporated under reduced pressure. The crude
product was purified by column chromatography on silica gel
(petroleum ether/dichloromethane 2/1) to afford the corresponding
product.
investigated (Scheme 10). For the current reaction with
benzoates and phenylacetate as substrates, the cyclic ether
radical intermediate reacts with the Fe(IV) carboxylate
intermediate through either a single electron transfer process
(SET) or a ligand transfer process (LT), giving the final cross
dehydrogenative coupling products without decarboxylation
(Scheme 10a).11d,20 However, for our previous system with
cinnamic acids as substrates, the reaction goes through a
different pathway, which consists of the addition of the cyclic
ether radical intermediate to a C−C double bond. Then,
releasing CO2 gives the final cross decarboxylative coupling
products (Scheme 10b).8
1,4-Dioxan-2-yl 4-Methoxybenzoate (5a).21 Colorless oil. Yield:
1
424 mg (89%). H NMR (400 MHz, CDCl3): δ 8.10−8.04 (m, 2H),
6.94−6.88 (m, 2H), 6.05 (s, 1H), 4.21−4.15 (m, 1H), 3.87−3.81 (m,
5H), 3.79 (dd, J = 4.1, 1.9 Hz, 2H), 3.68−3.61 (m, 1H). 13C NMR
(100 MHz, CDCl3): δ 164.7, 163.6, 131.8, 121.8, 113.5, 89.3, 67.7,
66.0, 61.6, 55.3.
CONCLUSION
■
In conclusion, an efficient procedure for the Fe(acac)3-
catalyzed direct esterification of unactivated C(sp3)−H bonds
with DTBP as an oxidant has been reported. This is a novel
method for the construction of C−O bonds using iron as
1,4-Dioxan-2-yl 3-Methoxybenzoate (5b). Colorless oil. Yield: 405
1
mg (85%). H NMR (400 MHz, CDCl3): δ 7.74−7.66 (m, 1H), 7.61
(dd, J = 2.6, 1.5 Hz, 1H), 7.34 (dd, J = 9.1, 6.9 Hz, 1H), 7.10 (ddd, J =
8.3, 2.7, 0.9 Hz, 1H), 6.08 (t, J = 1.8 Hz, 1H), 4.20 (ddd, J = 11.9, 7.5,
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5.6 Hz, 1H), 3.86 (d, J = 1.9 Hz, 2H), 3.83 (d, J = 5.2 Hz, 3H), 3.81−
3.76 (m, 2H), 3.65 (dt, J = 11.7, 2.6 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 164.6, 159.2, 130.7, 129.1, 121.8, 119.2, 114.0, 89.5, 67.38,
65.6, 61.4, 54.9. HRMS (TOF MS EI+): m/z calcd for [C12H14O5]
238.0841, found 238.0845.
7.34−7.27 (m, 2H), 7.10 (t, J = 7.4 Hz, 1H), 6.99 (d, J = 7.7 Hz, 2H),
6.96−6.87 (m, 2H), 6.01 (s, 1H), 4.19−4.06 (m, 1H), 3.79 (d, J = 1.7
Hz, 2H), 3.73−3.68 (m, 2H), 3.59−3.53 (m, 1H). 13C NMR (100
MHz, CDCl3): δ 164.0, 161.7, 155.0, 131.6, 129.6, 124.1, 123.5, 119.6,
116.8, 89.2, 67.3, 65.6, 61.2. HRMS (TOF MS EI+): m/z calcd for
[C17H16O5] 300.0998, found 300.0995.
1,4-Dioxan-2-yl 2-Methoxybenzoate (5c). White solid, mp 63−64
°C. Yield: 376 mg (79%). H NMR (400 MHz, CDCl3): δ 7.85−7.79
1,4-Dioxan-2-yl Benzoate (5l).14d Colorless oil. Yield: 304 mg
1
1
(m, 1H), 7.45−7.39 (m, 1H), 6.95−6.89 (m, 2H), 6.02 (d, J = 1.6 Hz,
1H), 4.20−4.10 (m, 1H), 3.87−3.82 (m, 3H), 3.80 (d, J = 2.0 Hz,
2H), 3.76−3.70 (m, 2H), 3.65−3.55 (m, 1H). 13C NMR (100 MHz,
CDCl3): δ 164.2, 159.3, 133.7, 131.5, 119.8, 119.1, 111.8, 89.3, 67.5,
65.8, 61.4, 55.7. HRMS (TOF MS EI+): m/z calcd for [C12H14O5]
238.0841, found 238.0843.
(73%). H NMR (400 MHz, CDCl3): δ 8.05−7.99 (m, 2H), 7.50−
7.43 (m, 1H), 7.38−7.32 (m, 2H), 5.99 (t, J = 2.0 Hz, 1H), 4.12−4.06
(m, 1H), 3.80−3.74 (m, 2H), 3.74−3.66 (m, 2H), 3.61−3.49 (m, 1H).
13C NMR (100 MHz, CDCl3): δ 164.9, 133.1, 129.6, 129.5, 128.2,
89.6, 67.5, 65.8, 61.5.
1,4-Dioxan-2-yl 4-Bromobenzoate (5m).14d White solid, mp 98−
1
1,4-Dioxan-2-yl 3-Methylbenzoate (5d). Colorless oil. Yield: 355
100 °C. Yield: 353 mg (62%). H NMR (400 MHz, CDCl3): δ 7.92
1
mg (80%). H NMR (400 MHz, CDCl3): δ 7.78 (dd, J = 4.1, 1.4 Hz,
(d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 6.03 (s, 1H), 4.21−4.09
(m, 1H), 3.83 (d, J = 1.6 Hz, 2H), 3.80−3.74 (m, 2H), 3.68−3.57 (m,
1H). 13C NMR (100 MHz, CDCl3): δ 164.2, 131.5, 131.1, 128.4,
128.3, 89.8, 67.5, 65.8, 61.5.
2H), 7.24−7.13 (m, 2H), 5.94 (t, J = 1.8 Hz, 1H), 4.10−4.02 (m, 1H),
3.72 (d, J = 1.7 Hz, 2H), 3.70−3.61 (m, 2H), 3.50 (dt, J = 11.8, 2.6 Hz,
1H), 2.24 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 164.7, 137.7,
133.6, 129.8, 129.3, 127.9, 126.6, 89.3, 67.3, 65.6, 61.3, 20.7. HRMS
(TOF MS EI+): m/z calcd for [C12H14O4] 222.0892, found 222.0895.
1,4-Dioxan-2-yl 4-Ethylbenzoate (5e). Colorless oil. Yield: 382 mg
(81%). 1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 8.2 Hz, 2H), 7.27
(d, J = 8.2 Hz, 2H), 6.08 (s, 1H), 4.24−4.18 (m, 1H), 3.88 (d, J = 1.9
Hz, 2H), 3.81 (dd, J = 6.6, 2.5 Hz, 2H), 3.71−3.60 (m, 1H), 2.70 (q, J
= 7.6 Hz, 2H), 1.28−1.25 (m, 3H). 13C NMR (100 MHz, CDCl3): δ
165.0, 150.1, 129.8, 127.7, 127.0, 89.4, 67.6, 65.9, 61.5, 28.7, 15.0.
HRMS (TOF MS EI+): m/z calcd for [C13H16O4] 236.1049, found
236.1052.
1,4-Dioxan-2-yl 3,5-Dimethylbenzoate (5o). Colorless oil. Yield:
401 mg (85%). 1H NMR (400 MHz, CDCl3): δ 7.61 (s, 2H), 7.07 (s,
1H), 5.96 (t, J = 1.9 Hz, 1H), 4.10 (ddd, J = 12.0, 7.8, 5.3 Hz, 1H),
3.76 (d, J = 2.0 Hz, 2H), 3.74−3.65 (m, 2H), 3.54 (dt, J = 11.8, 2.6 Hz,
1H), 2.24 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 165.1, 137.7,
134.7, 129.3, 127.2, 89.3, 67.5, 65.8, 61.4, 20.8. HRMS (TOF MS EI+):
m/z calcd for [C13H16O4] 236.1049, found 236.1051.
1,4-Dioxan-2-yl 3,5-Dimethoxybenzoate (5p). White solid, mp
51−53 °C. Yield: 466 mg (87%). 1H NMR (400 MHz, CDCl3): δ 7.23
(d, J = 1.8 Hz, 2H), 6.65 (d, J = 2.0 Hz, 1H), 6.05 (s, 1H), 4.25−4.14
(m, 1H), 3.86 (d, J = 1.3 Hz, 2H), 3.84−3.76 (m, 8H), 3.72−3.61 (m,
1H). 13C NMR (100 MHz, CDCl3): δ 164.9, 160.5, 131.4, 107.4,
105.7, 89.9, 67.6, 65.9, 61.7, 55.4. HRMS (TOF MS EI+): m/z calcd
for [C13H16O6] 268.0947, found 268.0952.
1,4-Dioxan-2-yl 3,4-Dimethoxybenzoate (5q). Colorless oil. Yield:
499 mg (93%). 1H NMR (400 MHz, CDCl3): δ 7.78 (dd, J = 8.4, 2.0
Hz, 1H), 7.59 (d, J = 2.0 Hz, 1H), 6.90 (d, J = 8.5 Hz, 1H), 6.07 (t, J =
1.9 Hz, 1H), 4.24−4.16 (m, 1H), 3.94 (s, 6H), 3.88 (d, J = 2.1 Hz,
2H), 3.83−3.75 (m, 2H), 3.67 (dt, J = 11.7, 2.6 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 164.4, 152.9, 148.2, 123.6, 121.6, 111.6, 109.8,
89.2, 67.4, 65.6, 61.4, 55.6, 55.54. HRMS (TOF MS EI+): m/z calcd
for [C13H16O6] 268.0947, found 268.0949.
1,4-Dioxan-2-yl 4-(tert-Butyl)benzoate (5f).14a Colorless oil. Yield:
1
438 mg (83%). H NMR (400 MHz, CDCl3): δ 8.10−8.04 (m, 2H),
7.49−7.45(m, 2H), 6.09 (t, J = 1.8 Hz, 1H), 4.21 (dt, J = 12.1, 6.5 Hz,
1H), 3.87 (d, J = 2.0 Hz, 2H), 3.80 (dd, J = 6.9, 2.5 Hz, 2H), 3.65 (dt,
J = 11.7, 2.6 Hz, 1H), 1.33 (s, 9H). 13C NMR (100 MHz, CDCl3): δ
164.8, 156.8, 129.5, 126.7, 125.1, 89.3, 67.6, 65.8, 61.4, 34.8, 30.8.
1,4-Dioxan-2-yl 4-Propoxybenzoate (5g). White solid, mp 37−39
1
°C. Yield: 484 mg (91%). H NMR (400 MHz, CDCl3): δ 8.05−7.95
(m, 2H), 6.90−6.84 (m, 2H), 6.02 (t, J = 1.9 Hz, 1H), 4.20−4.10 (m,
1H), 3.91 (t, J = 6.6 Hz, 2H), 3.82 (d, J = 1.9 Hz, 2H), 3.75 (dd, J =
6.6, 2.6 Hz, 2H), 3.61 (dt, J = 11.8, 2.7 Hz, 1H), 1.82−1.72 (m, 2H),
0.99 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 164.6, 163.1,
131.7, 121.5, 113.9, 89.2, 69.4, 67.6, 65.8, 61.5, 22.1, 10.2. HRMS
(TOF MS EI+): m/z calcd for [C14H18O5] 266.1154, found 266.1159.
1,4-Dioxan-2-yl 2,3-Dihydrobenzo[b][1,4]dioxine-6-carboxylate
1,4-Dioxan-2-yl 2,4-Dimethoxybenzoate (5r). White solid, mp
1
102−103 °C. Yield: 445 mg (83%). H NMR (400 MHz, CDCl3): δ
7.97 (d, J = 8.5 Hz, 1H), 6.54−6.46 (m, 2H), 6.06 (d, J = 1.7 Hz, 1H),
4.28−4.18 (m, 1H), 3.90 (s, 3H), 3.88−3.84 (m, 5H), 3.81 (dd, J =
7.0, 2.6 Hz, 2H), 3.67 (dt, J = 11.6, 2.6 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 164.6, 163.7, 161.8, 134.0, 111.4, 104.5, 98.8, 89.1, 67.8,
66.0, 61.7, 55.8, 55.3. HRMS (TOF MS EI+): m/z calcd for
[C13H16O6] 268.0947, found 268.0951.
1
(5h). White solid, mp 98−100 °C. Yield: 495 mg (93%). H NMR
(400 MHz, CDCl3): δ 7.62 (d, J = 6.7 Hz, 2H), 6.89 (d, J = 8.9 Hz,
1H), 6.04 (s, 1H), 4.28 (d, J = 9.0 Hz, 4H), 4.23−4.14 (m, 1H), 3.86
(s, 2H), 3.80 (d, J = 4.7 Hz, 2H), 3.65 (d, J = 11.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 164.3, 147.9, 142.9, 123.4, 122.5, 118.9, 116.9,
89.3, 67.5, 65.8, 64.3, 63.7, 61.4. HRMS (TOF MS EI+): m/z calcd for
[C13H14O6] 266.0790, found 266.0791.
1,4-Dioxan-2-yl 3,4-Diethoxybenzoate (5s). Colorless oil. Yield:
1
562 mg (95%). H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.4 Hz,
1,4-Dioxan-2-yl [1,1′-Biphenyl]-4-carboxylate (5i). White solid,
mp 83−84 °C. Yield: 495 mg (92%). 1H NMR (400 MHz, CDCl3): δ
8.16 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.60−7.52 (m, 2H),
7.41 (t, J = 7.4 Hz, 2H), 7.38−7.31 (m, 1H), 6.10 (s, 1H), 4.27−4.15
(m, 1H), 3.92−3.81 (m, 2H), 3.80−3.73 (m, 2H), 3.64−3.60 (m, 1H).
13C NMR (100 MHz, CDCl3): δ 164.5, 145.5, 139.3, 130.0, 128.5,
128.1, 127.8, 126.8, 126.6, 89.4, 67.4, 65.6, 61.3. HRMS (TOF MS
EI+): m/z calcd for [C17H16O4] 284.1049, found 284.1044.
1,4-Dioxan-2-yl [1,1′-Biphenyl]-3-carboxylate (5j). Colorless oil.
Yield: 488 mg (86%). 1H NMR (400 MHz, CDCl3): δ 8.36 (t, J = 1.6
Hz, 1H), 8.15−8.09 (m, 1H), 7.85−7.79 (m, 1H), 7.69−7.60 (m, 2H),
7.55 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 10.3, 4.7 Hz, 2H), 7.40 (dd, J =
8.3, 6.4 Hz, 1H), 6.14 (t, J = 1.7 Hz, 1H), 4.33−4.20 (m, 1H), 3.93 (d,
J = 1.9 Hz, 2H), 3.85 (dd, J = 6.7, 2.5 Hz, 2H), 3.70 (dt, J = 11.7, 2.6
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 165.1, 141.6, 139.9, 132.0,
130.2, 128.8, 128.8, 128.6, 128.4, 127.7, 127.1, 89.9, 67.7, 66.0, 61.8.
HRMS (TOF MS EI+): m/z calcd for [C17H16O4] 284.1049, found
284.1043.
1H), 7.57 (s, 1H), 6.86 (d, J = 8.5 Hz, 1H), 6.04 (s, 1H), 4.22−4.08
(m, 5H), 3.85 (s, 2H), 3.79 (d, J = 6.2 Hz, 2H), 3.65 (d, J = 11.8 Hz,
1H), 1.50−1.42 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 164.9,
153.1, 148.0, 123.9, 121.7, 113.9, 111.4, 89.4, 67.7, 66.0, 64.5, 64.3,
61.7, 14.5, 14.4. HRMS (TOF MS EI+): m/z calcd for [C15H20O6]
296.1260, found 296.1263.
1,4-Dioxan-2-yl 4-Methoxy-3-methylbenzoate (5t). White solid,
mp 64−66 °C. Yield: 459 mg (91%). 1H NMR (400 MHz, CDCl3): δ
7.88 (dd, J = 8.6, 2.1 Hz, 1H), 7.80 (d, J = 1.4 Hz, 1H), 6.74 (d, J = 8.6
Hz, 1H), 5.97 (t, J = 1.9 Hz, 1H), 4.17−4.06 (m, 1H), 3.78 (d, J = 2.1
Hz, 2H), 3.77 (s, 3H), 3.74−3.69 (m, 2H), 3.57 (dt, J = 11.8, 2.7 Hz,
1H), 2.15 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 164.6, 161.5,
131.7, 129.4, 126.2, 121.0, 108.8, 89.0, 67.5, 65.7, 61.4, 55.0, 15.71.
HRMS (TOF MS EI+): m/z calcd for [C13H16O5] 252.0998, found
252.0993.
1,4-Dioxan-2-yl 3,4,5-Trimethoxybenzoate (5u). White solid, mp
1
104−105 °C. Yield: 572 mg (96%). H NMR (400 MHz, CDCl3): δ
7.37 (s, 2H), 6.08 (t, J = 2.0 Hz, 1H), 4.25−4.15 (m, 1H), 3.93 (s,
6H), 3.92 (s, 3H), 3.92−3.89 (m, 2H), 3.84 (dd, J = 6.6, 2.7 Hz, 2H),
3.70 (dt, J = 11.8, 2.7 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 164.8,
1,4-Dioxan-2-yl 4-Phenoxybenzoate (5k). Light yellow oil. Yield:
1
564 mg (94%). H NMR (400 MHz, CDCl3): δ 8.09−7.98 (m, 2H),
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152.8, 142.5, 124.5, 107.0, 89.9, 67.7, 65.9, 61.8, 60.8, 56.2. HRMS
(TOF MS EI+): m/z calcd for [C14H18O7] 298.1053, found 298.1050.
1,4-Dioxan-2-yl 2,4,5-Trimethoxybenzoate (5v). White solid, mp
92−94 °C. Yield: 536 mg (90%). 1H NMR (400 MHz, CDCl3): δ 7.45
(s, 1H), 6.55 (s, 1H), 6.06 (s, 1H), 4.27−4.15 (m, 1H), 3.93 (s, 3H),
3.91 (s, 3H), 3.87 (s, 3H), 3.86 (d, J = 1.8 Hz, 2H), 3.81−3.76 (m,
2H), 3.66 (dt, J = 11.6, 2.5 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
163.4, 155.6, 153.4, 141.8, 113.8, 109.3, 97.1, 88.8, 67.2, 65.4, 61.2,
56.3, 55.7, 55.3. HRMS (TOF MS EI+): m/z calcd for [C14H18O7]
298.1053, found 298.1052.
8.10 (dd, J = 8.6, 1.7 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.80 (t, J = 8.5
Hz, 2H), 7.49 (tdd, J = 14.8, 7.0, 1.3 Hz, 2H), 6.15 (s, 1H), 4.27−4.21
(m, 1H), 3.94−3.85 (m, 2H), 3.83−3.73 (m, 2H), 3.64 (dt, J = 11.7,
2.5 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 164.9, 135.3, 132.0,
131.1, 129.0, 128.1, 127.9, 127.4, 126.6, 126.3, 124.9, 89.6, 67.5, 65.7,
61.4.
1,4-Dioxan-2-yl 4-Methyl-1-naphthoate (6h). White solid, mp
59−61 °C. Yield: 468 mg (86%). 1H NMR (400 MHz, CDCl3): δ 9.13
(d, J = 8.6 Hz, 1H), 8.25 (d, J = 7.4 Hz, 1H), 7.99 (d, J = 8.3 Hz, 1H),
7.67−7.60 (m, 1H), 7.56−7.50 (m, 1H), 7.30 (d, J = 7.5 Hz, 1H), 6.20
(s, 1H), 4.30−4.19 (m, 1H), 3.97−3.88 (m, 2H), 3.83−3.76 (m, 2H),
3.68 (dt, J = 11.7, 2.5 Hz, 1H), 2.67 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 165.5, 140.7, 132.5, 131.3, 130.5, 127.2, 126.0, 125.7, 125.1,
124.1, 124.1, 89.4, 67.6, 65.8, 61.5, 19.7. HRMS (TOF MS EI+): m/z
calcd for [C16H16O4] 272.1049, found 272.1044.
1,4-Dioxan-2-yl 3,4-Dimethoxy-2-methylbenzoate (5w). White
1
solid, mp 39−41 °C. Yield: 519 mg (92%). H NMR (400 MHz,
CDCl3): δ 7.78 (d, J = 8.7 Hz, 1H), 6.69 (d, J = 8.7 Hz, 1H), 5.95 (s,
1H), 4.08 (dd, J = 11.6, 6.0 Hz, 1H), 3.80 (s, 3H), 3.77 (s, 2H), 3.70
(d, J = 5.8 Hz, 2H), 3.67 (s, 3H), 3.57 (d, J = 11.5 Hz, 1H), 2.48 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 165.2, 156.0, 147.2, 135.3,
127.9, 121.7, 108.4, 89.1, 67.7, 65.8, 61.6, 60.0, 55.4, 13.1. HRMS
(TOF MS EI+): m/z calcd for [C14H18O6] 282.1103, found 282.1101.
1,4-Dioxan-2-yl 4-Methoxy-3,5-dimethylbenzoate (5x). White
1,4-Dioxan-2-yl 1-Methyl-1H-indole-3-carboxylate (6i).21 Yellow
1
solid, mp 94−96 °C. Yield: 459 mg (88%). H NMR (400 MHz,
CDCl3): δ 8.25−8.19 (m, 1H), 7.79 (s, 1H), 7.32−7.22 (m, 3H), 6.10
(t, J = 2.0 Hz, 1H), 4.23−4.17 (m, 1H), 3.87 (d, J = 2.0 Hz, 2H),
3.81−3.76 (m, 2H), 3.70 (s, 3H), 3.63 (dt, J = 11.8, 2.7 Hz, 1H). 13C
NMR (100 MHz, CDCl3): δ 162.9, 136.9, 135.6, 126.3, 122.6, 121.8,
121.3, 109.6, 105.8, 88.2, 67.9, 65.9, 61.5, 33.0.
1
solid, mp 101−102 °C. Yield: 495 mg (93%). H NMR (400 MHz,
CDCl3): δ 7.72 (s, 2H), 5.99 (s, 1H), 4.22−4.10 (m, 1H), 3.80 (d, J =
2.0 Hz, 2H), 3.77−3.70 (m, 2H), 3.68 (s, 3H), 3.59 (dt, J = 11.7, 2.5
Hz, 1H), 2.25 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 164.6, 161.1,
130.8, 130.4, 124.6, 89.2, 67.5, 65.7, 61.4, 59.2, 15.7. HRMS (TOF MS
EI+): m/z calcd for [C14H18O5] 266.1154, found 266.1152.
1,4-Dioxan-2-yl Benzo[b]thiophene-2-carboxylate (6j). White
1
solid, mp 67−68 °C. Yield: 385 mg (73%). H NMR (400 MHz,
CDCl3): δ 8.16 (s, 1H), 7.87 (t, J = 7.8 Hz, 2H), 7.46−7.39 (m, 2H),
6.10 (s, 1H), 4.30−4.22 (m, 1H), 3.90 (d, J = 1.9 Hz, 2H), 3.86−3.80
(m, 2H), 3.69 (dd, J = 11.8, 1.3 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 161.4, 142.4, 138.5, 132.9, 131.2, 127.1, 125.5, 124.9, 122.6,
90.1, 67.6, 66.0, 61.6. HRMS (TOF MS EI+): m/z calcd for
[C13H12O4S] 264.0456, found 264.0459.
1,4-Dioxan-2-yl Thiophene-2-carboxylate (6a).14d White solid,
mp 48−49 °C. Yield: 415 mg (97%). 1H NMR (400 MHz, CDCl3): δ
7.90−7.80 (m, 1H), 7.62−7.52 (m, 1H), 7.09 (dt, J = 8.7, 4.8 Hz, 1H),
6.02 (s, 1H), 4.19−4.13 (m, 1H), 3.86−3.82(m, 2H), 3.80−3.74 (m,
2H), 3.68−3.58 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 160.6,
133.9, 133.0, 133.0, 127.7, 89.7, 67.5, 65.8, 61.5.
1,3-Dioxolan-4-yl 4-Methoxybenzoate (7a). Light yellow oil.
1
1,4-Dioxan-2-yl Thiophene-3-carboxylate (6b). Colorless oil.
Yield: 385 mg (86%). H NMR (400 MHz, CDCl3): δ 7.98 (d, J =
1
Yield: 407 mg (95%). H NMR (400 MHz, CDCl3): δ 8.23 (dd, J =
8.9 Hz, 2H), 6.90 (d, J = 8.9 Hz, 2H), 6.55 (dd, J = 4.1, 1.9 Hz, 1H),
5.14 (d, J = 18.1 Hz, 2H), 4.11 (ddd, J = 11.3, 9.5, 3.0 Hz, 2H), 3.83
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 165.1, 163.5, 131.5, 121.4,
113.4, 95.4, 94.1, 70.3, 55.1. HRMS (TOF MS EI+): m/z calcd for
[C11H12O5] 224.0685, found 224.0684.
3.0, 1.0 Hz, 1H), 7.59 (dd, J = 5.1, 1.0 Hz, 1H), 7.33 (dd, J = 5.1, 3.1
Hz, 1H), 6.04 (s, 1H), 4.24−4.12 (m, 1H), 3.86 (d, J = 1.9 Hz, 2H),
3.79 (dd, J = 6.7, 2.5 Hz, 2H), 3.65 (dt, J = 11.7, 2.5 Hz, 1H). 13C
NMR (100 MHz, CDCl3): δ 160.8, 133.3, 132.8, 127.7, 125.9, 89.2,
67.4, 65.7, 61.4. HRMS (TOF MS EI+): m/z calcd for [C9H10O4S]
214.0300, found 214.0296.
1,3-Dioxolan-4-yl 3-Methylbenzoate (7b). Light yellow oil. Yield:
1
333 mg (80%). H NMR (400 MHz, CDCl3): δ 7.86−7.80 (m, 2H),
1,4-Dioxan-2-yl 5-Methylthiophene-2-carboxylate (6c). Colorless
oil. Yield: 467 mg (98%). 1H NMR (400 MHz, CDCl3): δ 7.60 (d, J =
3.7 Hz, 1H), 6.69 (dd, J = 3.7, 1.0 Hz, 1H), 5.91 (t, J = 1.8 Hz, 1H),
4.11−4.06 (m, 1H), 3.74 (d, J = 2.0 Hz, 2H), 3.71−3.66 (m, 2H), 3.54
(dt, J = 11.6, 2.5 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 160.2,
148.4, 134.2, 130.1, 126.1, 89.2, 67.3, 65.6, 61.30, 15.3. HRMS (TOF
MS EI+): m/z calcd for [C10H12O4S] 228.0456, found 228.0461.
1,4-Dioxan-2-yl 1-Methyl-1H-pyrrole-2-carboxylate (6d).21 White
7.40−7.30 (m, 2H), 6.57 (dd, J = 4.1, 2.0 Hz, 1H), 5.16 (d, J = 20.6
Hz, 2H), 4.13 (qd, J = 9.5, 3.1 Hz, 2H), 2.38 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 165.8, 138.1, 134.1, 130.1, 129.2, 128.2, 126.8, 95.7,
94.5, 70.5, 21.0. HRMS (TOF MS EI+): m/z calcd for [C11H12O4]
208.0736, found 208.0731.
1,3-Dioxolan-4-yl 4-Ethylbenzoate (7c). Light yellow oil. Yield:
1
364 mg (82%). H NMR (400 MHz, CDCl3): δ 8.03−7.89 (m, 2H),
7.25 (d, J = 8.3 Hz, 2H), 6.58 (dd, J = 4.2, 1.9 Hz, 1H), 5.16 (d, J =
16.6 Hz, 2H), 4.13 (ddd, J = 11.4, 9.5, 3.1 Hz, 2H), 2.69 (q, J = 7.6 Hz,
2H), 1.24 (t, J = 7.7 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 165.6,
150.2, 129.7, 127.8, 126.7, 95.6, 94.3, 70.5, 28.8, 15.0. HRMS (TOF
MS EI+): m/z calcd for [C12H14O4] 222.0892, found 222.0895.
1,3-Dioxolan-4-yl 4-(tert-Butyl)benzoate (7d). Light yellow oil.
Yield: 415 mg (83%). 1H NMR (400 MHz, CDCl3): δ 8.11−7.85 (m,
2H), 7.44 (d, J = 8.5 Hz, 2H), 6.58 (dd, J = 4.1, 1.9 Hz, 1H), 5.15 (d, J
= 17.0 Hz, 2H), 4.18−4.08 (m, 2H), 1.32 (s, 9H). 13C NMR (100
MHz, CDCl3): δ 165.3, 156.8, 129.4, 126.4, 125.1, 95.4, 94.2, 70.3,
34.7, 30.7. HRMS (TOF MS EI+): m/z calcd for [C14H18O4]
250.1205, found 250.1208.
1
solid, mp 48−49 °C. Yield: 376 mg (89%). H NMR (400 MHz,
CDCl3): δ 7.03 (dd, J = 4.0, 1.8 Hz, 1H), 6.76 (t, J = 2.0 Hz, 1H), 6.06
(dd, J = 4.0, 2.5 Hz, 1H), 5.93 (t, J = 2.0 Hz, 1H), 4.15−4.03 (m, 1H),
3.86 (s, 3H), 3.81−3.74 (m, 2H), 3.74−3.69 (m, 2H), 3.56 (dt, J =
11.9, 2.7 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 159.1, 129.9,
121.3, 118.4, 107.6, 88.2, 67.4, 65.6, 61.3, 36.3.
1,4-Dioxan-2-yl 2,4-Dimethylthiazole-5-carboxylate (6e). Light
yellow oil. Yield: 457 mg (94%). 1H NMR (400 MHz, CDCl3): δ 5.87
(s, 1H), 4.04−3.98 (m, 1H), 3.72−3.70 (m, 2H), 3.68−3.63 (m, 2H),
3.52 (dt, J = 11.8, 2.5 Hz, 1H), 2.58 (s, 3H), 2.55 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 169.4, 160.6, 160.2, 120.8, 89.5, 67.3, 65.6, 61.3,
19.0, 17.0. HRMS (TOF MS EI+): m/z calcd for [C10H13NO4S]
243.0565, found 243.0568.
1,3-Dioxolan-4-yl [1,1′-Biphenyl]-4-carboxylate (7e). White solid,
mp 86−87 °C. Yield: 475 mg (88%). 1H NMR (400 MHz, CDCl3): δ
8.12 (d, J = 8.3 Hz, 2H), 7.64 (dd, J = 18.5, 7.8 Hz, 4H), 7.43 (dt, J =
26.0, 7.2 Hz, 3H), 6.63 (dd, J = 3.8, 2.0 Hz, 1H), 5.20 (d, J = 22.7 Hz,
2H), 4.22−4.12 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 165.4,
145.9, 139.5, 130.1, 128.7, 128.1, 127.9, 127.0, 126.9, 95.7, 94.5, 70.5.
HRMS (TOF MS EI+): m/z calcd for [C16H14O4] 270.0892, found
270.0894.
1,4-Dioxan-2-yl 1-Naphthoate (6f).15 Light yellow oil. Yield: 423
1
mg (82%). H NMR (400 MHz, CDCl3): δ 9.03 (d, J = 8.7 Hz, 1H),
8.36 (dd, J = 7.3, 1.2 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 8.1
Hz, 1H), 7.64 (ddd, J = 8.5, 6.9, 1.4 Hz, 1H), 7.58−7.49 (m, 2H), 6.22
(t, J = 1.8 Hz, 1H), 4.32−4.22 (m, 1H), 4.01−3.90 (m, 2H), 3.90−
3.82 (m, 2H), 3.72 (dt, J = 11.8, 2.5 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 165.8, 134.0, 133.8, 131.5, 130.9, 128.5, 127.9, 126.2, 126.0,
125.7, 124.4, 89.8, 67.9, 66.1, 61.8.
1,3-Dioxolan-4-yl Thiophene-2-carboxylate (7f). Light yellow oil.
1
Yield: 360 mg (90%). H NMR (400 MHz, CDCl3): δ 7.83 (dd, J =
1,4-Dioxan-2-yl 2-Naphthoate (6g).14d White solid, mp 88−89 °C.
3.7, 1.1 Hz, 1H), 7.59 (dd, J = 5.0, 1.1 Hz, 1H), 7.10 (dd, J = 4.9, 3.9
Hz, 1H), 6.54 (dd, J = 4.1, 1.9 Hz, 1H), 5.15 (d, J = 15.8 Hz, 2H), 4.12
1
Yield: 439 mg (85%). H NMR (400 MHz, CDCl3): δ 8.66 (s, 1H),
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(qd, J = 9.5, 3.0 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 161.2,
134.1, 133.2, 132.8, 127.8, 95.8, 94.6, 70.5. HRMS (TOF MS EI+): m/
z calcd for [C8H8O4S] 200.0143, found 200.0144.
(3) (a) Chatani, N.; Asaumi, T.; Yorimitsu, S.; Ikeda, T.; Kakiuchi, F.;
Murai, S. J. Am. Chem. Soc. 2001, 123, 10935−10941. (b) DeBoef, B.;
Pastine, S. J.; Sames, D. J. Am. Chem. Soc. 2004, 126, 6556−6557.
(c) Song, C. X.; Cai, G. X.; Farrell, T. R.; Jiang, Z. P.; Li, H.; Gan, L.
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1,3-Dioxolan-4-yl Thiophene-3-carboxylate (7g). Light yellow oil.
1
Yield: 348 mg (87%). H NMR (400 MHz, CDCl3): δ 8.14 (dd, J =
3.0, 1.2 Hz, 1H), 7.52 (dd, J = 5.1, 1.2 Hz, 1H), 7.31 (dd, J = 5.1, 3.1
Hz, 1H), 6.54 (dd, J = 4.1, 2.0 Hz, 1H), 5.15 (d, J = 18.9 Hz, 2H), 4.11
(qd, J = 9.5, 3.0 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 161.4,
133.4, 132.6, 127.6, 126.0, 95.5, 94.1, 70.3. HRMS (TOF MS EI+): m/
z calcd for [C8H8O4S] 200.0143, found 200.0141.
Phenoxymethyl Thiophene-2-carboxylate (8a). Yellow solid, mp
45−47 °C. Yield: 384 mg (82%). 1H NMR (400 MHz, CDCl3): δ 7.86
(dd, J = 3.8, 1.2 Hz, 1H), 7.60 (dd, J = 5.0, 1.2 Hz, 1H), 7.40−7.30 (m,
2H), 7.14−7.06 (m, 4H), 5.98 (s, 2H). 13C NMR (100 MHz, CDCl3):
δ 160.9, 156.9, 134.3, 133.3, 132.8, 129.6, 127.9, 122.8, 116.2, 86.2.
HRMS (TOF MS EI+): m/z calcd for [C12H10O3S] 234.0351, found
234.0354.
Cyclohex-2-en-1-yl Thiophene-2-carboxylate (8b).14e Colorless
oil. Yield: 175 mg (42%). 1H NMR (400 MHz, CDCl3): δ 7.79 (dd, J
= 3.7, 1.2 Hz, 1H), 7.53 (dd, J = 5.0, 1.2 Hz, 1H), 7.10−7.06 (m, 1H),
6.04−5.96 (m, 1H), 5.85−5.78 (m, 1H), 5.49−5.43 (m, 1H), 2.10−
1.65 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 161.9, 134.4, 133.1,
132.9, 132.1, 127.6, 125.4, 68.9, 28.3, 24.8, 18.8.
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1,4-Dioxan-2-yl 2-Phenylacetate (9). White solid, mp 48−49 °C.
Yield: 275 mg (62%). 1H NMR (400 MHz, CDCl3): δ 7.33−7.21 (m,
5H), 5.83 (t, J = 1.7 Hz, 1H), 4.03−3.93 (m, 1H), 3.76−3.65 (m, 6H),
3.52 (dt, J = 11.7, 2.5 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 170.0,
133.3, 129.0, 128.3, 126.9, 89.3, 67.3, 65.7, 61.3, 41.0. HRMS (TOF
MS EI+): m/z calcd for [C12H14O4] 222.0892, found 222.0890.
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3567−3571. (b) Tan, Q.; Hayashi, M. Adv. Synth. Catal. 2008, 350,
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ASSOCIATED CONTENT
■
S
* Supporting Information
Spectra of the KIE experiment and H and 13C NMR spectra
1
for compounds 5−9. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for J.H.: hanjl@nju.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(12) Ye, Z.; Wang, W.; Luo, F.; Zhang, S.; Cheng, J. Org. Lett. 2009,
11, 3974−3977.
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 21102071) and the
Fundamental Research Funds for the Central Universities (No.
1107020522 and No. 1082020502). The Jiangsu 333 program
(for Y.P.) and Changzhou Jin-Feng-Huang program (for J.H.)
are also acknowledged.
(13) Lee, J. M.; Chang, S. Tetrahedron Lett. 2006, 47, 1375−1379.
(14) (a) Chen, L.; Shi, E.; Liu, Z.; Chen, S.; Wei, W.; Li, H.; Xu, K.;
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3384−3387.
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