Mn(OAc)3-Mediated Hydrotrifluoromethylation of Unactivated Alkenes Using CF3SO2Na as the Trifluoromethyl Source

Article abstract of DOI:10.1021/acs.joc.8b00633

A simple and efficient method for hydrotrifluoromethylation of unactivated alkenes was reported. The reaction relied on the single electron oxidation of a commercially available sodium trifluoromethanesulfinate (CF₃SO₂Na, Langlois' reagent) using Mn(OAc)₃·2H₂O as the oxidant and the subsequent addition of trifluoromethyl radical to C=C double bonds. The reaction proceeded readily under mild conditions with good tolerance of a variety of functional groups in the substrates. The preliminary reaction mechanism was studied with deuteration, radical clock, and TEMPO inhibition experiments.

Full text of DOI:10.1021/acs.joc.8b00633

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Article
Mn(OAc)3-Mediated Hydrotrifluoromethylation of Unactivated
Alkenes Using CF3SO2Na as the Trifluoromethyl Source
Bin Cui, Hui Sun, Yibo Xu, Lin Li, Lili Duan, and Yue-Ming Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00633 • Publication Date (Web): 07 May 2018
Downloaded from http://pubs.acs.org on May 7, 2018
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Mn(OAc)3-Mediated Hydrotrifluoromethylation of Unactivated Alkenes Using
CF3SO2Na as the Trifluoromethyl Source
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9
Bin Cui, Hui Sun, Yibo, Xu,† Lin Li, Lili Duan,* YueꢀMing Li*
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin
Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People’s
Republic of China
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Email: ymli@nankai.edu.cn
ABSTRACT
CF3SO2Na (2 equiv)
Mn(OAc)3—2H2O (2 euiv)
R1
R2
R3
CF3
R4
R1
R2
R3
R4
AcOH, Ar, rt, 24 h
mild conditions
monoꢀ,diꢀ and triꢀsubstituted alkenes
wide substrate scope
36 examples, up to 78 % isolated yields
A simple and efficient method for hydrotrifluoromethylation of unactivated alkenes was
reported. The reaction relied on the single electron oxidation of a commercially available
sodium trifluoromethanesulfinate (CF3SO2Na, Langlois’ reagent) using Mn(OAc)3·2H2O as
the oxidant, and the subsequent addition of trifluoromethyl radical to C=C double bonds. The
reaction proceeded readily under mild conditions with good tolerance of a variety of
functional groups in the substrates. Preliminary reaction mechanism was studied with
deuteration, radical clock and TEMPO inhibition experiments.
INTRODUCTION
Trifluoromethyl group has been well recognized in medicinal chemistry due to its strong
electronꢀwithdrawing and lipophilic properties. The lipophilicity, bioavailability, binding
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selectivity and metabolic stability of a compound can be significantly improved by the
incorporation of trifluoromethyl group,1 and significant efforts have been made to develop
new and efficient methods for trifluoromethylation of different substrates. Among the variety
of methods developed, direct trifluoromethylation of C=C double bonds has been proved to
be one of the most straightforward methods for the incorporation of trifluoromethyl group.2
In this connection, Togni’s reagents,3 Umemoto’s reagents,4 Langlois’ reagents
(trifluoromethanesulfinate, CF3SO2Na),5 Ruppert’s and related reagents,6 fluoroalkyl halides7
and fluoroform derived trifluoromethyl agents8 have all been studied for their potential of
trifluoromethylation of different unactivated alkenes. Among the trifluoromethylating agents
studied, Langlois’ reagent has attracted considerable attention as the trifluoromethyl radical
precursor and found numerous applications in a variety of trifluoromethylation reactions such
as photoredox systemꢀpromoted9 or visibleꢀlightꢀinduced photocatalytic reactions.10
We have shown that trifluoromethylation of ketones and esters/lactones could be realized
using Ruppert’s reagent as the trifluoromethylating agent and 10 mol% of MgCl2 as the
catalyst.11 Herein we wish to report our recent results on Mn(OAc)3·2H2Oꢀmediated free
radical hydrotrifluoromethylation of unactivated alkenes as a continuation of our program on
trifluoromethylation and manganeseꢀcatalyzed reactions.
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RESULTS AND DISCUSSION
Manganeseꢀmediated oxidative radical reactions have been proved to be simple and efficient
methods for the functionalization of CꢀH and CꢀC bonds.12 Vicic et al. reported the
Mn(II)ꢀcatalyzed aerobic oxytrifluoromethylation of styrene derivatives using CF3SO2Na as
the trifluoromethyl source.13 Zou et al. reported an Mn(III)ꢀmediated direct Csp2ꢀH radical
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trifluoromethylation of coumarins using CF3SO2Na as the trifluoromethylation agent.5a The
reaction involved the addition of trifluoromethyl radical to 3ꢀposition of coumarins A and
subsequent oxidation of the intermediate radical B by Mn(OAc)3. Deprotonation of the
resulted carbenium cation intermediate C gave the desired 3ꢀtrifluoromethylcoumarins D as
the final products (Scheme 1).5a
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Scheme 1. Csp2-H radical trifluoromethylation of coumarins
—
+
CF3
O
CF3
O
CF3
O
ꢀH+
CF3—
O
O
O
O
O
B
D
C
A
We anticipated that the formation of carbenium cation may be avoided if the reactions were
carried out under inert atmosphere with reduced amount of Mn(OAc)3, and a
hydrotrifluoromethylation reaction should be possible under carefully controlled conditions.
To verify this assumption, hydrotrifluoromethylation of model substrate hexꢀ5ꢀenꢀ1ꢀyl
benzoate (1a) was carried out using Mn(OAc)3·2H2O as the oxidant in the presence of a
variety of trifluoromethylating agents. To our delight, 77% of the substrate was converted to
the desired 2a when a solution of 1a, CF3SO2Na (2 equiv) and Mn(OAc)3·2H2O (3 equiv) in
AcOH was stirred at room temperature for 24 h under argon atmosphere (entry 1, Table 1).
Further studies indicated that AcOH was superior to other solvents such as MeOH, DMF,
DCE or acetone (Table 1, entry 1 vs entries 2ꢀ5). Reaction with other trifluoromethylating
agent such as Ruppert’s reagent TMSCF3 was not successful (Table 1, entry 6). Similar
substrate conversion was observed when the amount of Mn(OAc)3·2H2O was reduced from 3
equiv to 2 equiv (Table 1, entry 7), and further reducing the amount of Mn(OAc)3·2H2O or
CF3SO2Na led to drops of substrate conversions (Table 1, entries 8ꢀ10). Reactions without
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argon protection were also tested.13 However, complex mixtures were obtained under
otherwise identical conditions. The desired hydrotrifluoromethylation product 2a was
obtained in 57% isolated yield after careful separation and purification (Table 1, entry 11).
Therefore, the hydrotrifluoromethylation reaction was finally carried out for 24 h in AcOH in
the present of 2 equiv of Mn(OAc)3·2H2O and 2 equiv of CF3SO2Na under argon
atmosphere.
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Table 1. Optimization of reaction conditionsa
CF3 Source
Mn(OAc)3—2H2O
O
O
CF3
O
O
Solvent, rt, Ar, 24 h
2a
1a
Mn(OAc)3·2H2O
(equiv)
entry
CF3SO2Na (equiv)
solvent
yield (%)b
1
2
3
3
2
2
AcOH
MeOH
DMF
77
ꢀ
3
3
2
ꢀ
4
3
2
DCE
ꢀ
5
3
2
Actone
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
ꢀ
6c
7
3
ꢀ
ꢀ
2
2
75
69
61
53
57
8
1.5
1.2
1.1
2
1.5
1.2
1.1
2
9
10
11d
aAll reactions were carried out with 0.25 mmol of 1a, 0.50 mmol of Mn(OAc)3·2H2O and
b
0.50 mmol of CF3 source in 10 mL of solvent, rt = room temperature. Isolated yield.
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cTMSCF3 was used. dReaction without argon protection.
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With the optimized reaction conditions in hand, the scope and limitations of this reaction
were studied. Different esters and ethers were first tested. The results are summarized in
Table 2. The use of chromophoreꢀcontaining substrates is to increase the molecular weight of
products, and to facilitate the workꢀup process. As these results showed, a variety of isolated
unactivated C=C double bonds could be hydrotrifluoromethylated in good yields, and a wide
array of functional groups such as halogen atoms and alkyl groups could be tolerated (Table 2,
entries 1ꢀ10, entry 14). Electronic properties of the substituents on the arene rings generally
showed less effect on the reactions (Table 2, entry 1 vs entries 3ꢀ10). The effect of carbon
chain length in the substrates was investigated, and this also showed little impact on the
course of the reactions (Table 2, entries 1 and 2, entries 7ꢀ9). Other substrates such as
heteroaromatic carboxylates (Table 2, entries 11 and 12 ), naphthyl carboxylate (Table 2,
entry 13), aliphatic carboxylate (Table 2, entry 14) and sulfonate (Table 2, entry 15) could
also be converted to the hydrotrifluoromethylation products in acceptable isolated yields. In
addition, ethers 1p/1q and alcohol 1r were also viable substrates for the
hydrotrifluoromethylation reaction (Table 2, entries 16ꢀ18).
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Table 2. Hydrotrifluoromethylation of ester and ether substratesa
Mn(OAc)3—2H2O (2 equiv)
R
R
CF3
( )n
( )n
O
O
CF3SO2Na (2 equiv), AcOH
Ar, 24 h, rt
1
2
entry
product
2a
R
n
yield (%)b
1
2
PhCO
PhCO
3
2
77
69
2b
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3
4
4ꢀMePhCO
4ꢀFPhCO
3
3
3
3
3
2
0
0
3
3
3
3
3
3
3
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2c
2d
2e
2f
5
4ꢀBrPhCO
4ꢀIPhCO
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7
2ꢀMeOPhCO
2ꢀMeOPhCO
2ꢀMeOPhCO
4ꢀNCPhCO
(3ꢀpyridyl)CO
(4ꢀpyridyl)CO
(2ꢀnaphthyl)CO
(Cyclohexyl)CO
4ꢀMePhSO2
Bn
2g
2h
2i
8
9
10
11
12
13
14
15
16
17
2j
2k
2l
2m
2n
2o
2p
2q
Ph
HO
HO
CF3
18
2r, 53%
1r
aAll reactions were carried out with 0.25 mmol of 1, 0.50 mmol of Mn(OAc)3·2H2O and 0.50
mmol of CF3SO2Na in 10 mL of solvent, rt = room temperature. bIsolated yield.
After trifluoromethylation of ester, ether and alcohol substrates, amide substrates were also
subjected to the same reaction. The results are summarized in Table 3. As could be expected,
a variety of substitutents such as alkoxyl groups, alkyl group and halogens were tolerated,
and the desired products could be obtained in satisfactory isolated yields (Table 3, entries 2ꢀ4,
entries 7ꢀ8). The presence of halogen atoms on arene rings would allow additional functional
group transformation reactions (Table 2, entries 4ꢀ6. Table 3, entry 8). The effect of carbon
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chain length in the substrates also showed little impact on the course of the reactions (Table 3,
entries 1 and 5, entries 10 and 11). Substrates without aryl group such as 3i and 3l could also
be transformed into the desired products (Table 3, entries 9 and 12).
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Table 3. Hydrotrifluoromethylation of amide substratesa
entry
1
product
R
n
0
yield (%)b
72
PhCO
4a
2
3
4
5
6
7
8
9
4ꢀMeOPhCO
3ꢀMeOPhCO
2ꢀMeOPhCO
PhCO
0
0
0
3
3
3
3
3
73
62
71
73
69
71
63
52
68
4b
4c
4d
4e
4f
PhSO2
4ꢀMePhSO2
2ꢀClPhSO2
4g
4h
4i
MeSO2
O
n = 1, 4j
n = 3, 4k
10
11
12
N
( )n
CF3
O
76
77
NC
CF3
CO2Et
4l
aAll reactions were carried out with 0.25 mmol of 3, 0.50 mmol of Mn(OAc)3·2H2O and 0.50
mmol of CF3SO2Na in 10 mL of solvent, rt = room temperature. bIsolated yield.
After the hydrotrifluoromethylation of terminal unactivated alkenes, the substrates were
extended to internal olefins bearing different substituents and the results are summarized in
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Table 4. Results showed that gemꢀdisubstituted terminal alkenes were viable substrates for
the current reaction system, and Markovnikov product 6a was obtained in 71% yield (Table 4,
entry 1). It is remarkable that 1,2ꢀdisubstituted cyclic and acyclic internal alkenes could be
hydrotrifluoromethylated under optimized conditions, furnishing products 6b and 6c in
moderate yields (Table 4, entries 2 and 3). Markovnikov products 6d and 6e were obtained in
good yields when trisubstituted internal alkenes were subjected to the reaction (Table 4,
entries 4 and 5).
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Table 4. Hydrotrifluoromethylation of ester and ether substratesa
entry
1
product
yield (%)b
76
O
O
CF3
6a
CF3
O
2
3
56
47
H
6b
O
CF3
O
O
H
O
6c
O
CF3
N
4
5
76
69
O
6d
O
O
CF3
6e
aAll reactions were carried out with 0.25 mmol of 5, 0.50 mmol of Mn(OAc)3·2H2O and 0.50
mmol of CF3SO2Na in 10 mL of solvent, rt = room temperature. bIsolated yield.
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After hydrotrifluoromethylation of different unactivated alkene substrates, reaction of quinine
was carried out under optimized conditions. Again, quinine could be
hydrotrifluoromethylated with 69% isolated yield with intact of both the functional groups
and the quinoline ring (Scheme 2).
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Scheme 2. Hydrotrifluoromethylation of quinine
F3C
N
N
HO
Mn(OAc)3—2H2O (2 equiv)
HO
MeO
CF3SO2Na (2 equiv), AcOH
Ar, 24 h, rt
MeO
N
N
7
8
63% isolated yield
Compound 4b was subjected to Xꢀray diffraction experiment to further determine the
skeleton of the product. The ORTEP drawing clearly confirmed the
hydrotrifluoromethylation structure (Figure 1).14
Figure 1. ORTEP drawing of 4b at 30% probability displacement ellipsoid (the
hydrogen atoms are omitted for clarity)
Hydrotrifluoromethylation of substrate 3a was also carried out on gram scale under the
optimized conditions, and the desired product 4a was obtained in 63% isolated yield (Scheme
3).
Scheme 3. Gram-scale hydrotrifluoromethylation of substrate 3a
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O
O
Mn(OAc)3—2H2O (2.0 equiv)
N
H
CF3
N
H
3a
CF3SO2Na (2.0 equiv), AcOH
Ar, 24 h, rt
4a
1.61 g
0.90 g
63 % isolated yield
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Mn(III) was known to promote oxidative radical reactions. In the current study, clean
reactions were observed in argon atmosphere, and reactions carried out in open air gave
complex mixtures. These results indicated that the current reaction may also proceed via a
free radical pathway. Trifluoromethyl free radical may be generated in situ via reaction
between Mn(OAc)3·2H2O and CF3SO2Na, Markovnikov addition of trifluoromethyl radical
to C=C double bond and subsequent hydrogen abstraction afforded the desired
hydrotrifluoromethylation product.
To prove the free radical pathway of the reaction, control experiments in the presence of 3
equiv of free radical capturer TEMPO was carried out under otherwise identical conditions.
Complete suppression of the reaction was observed and free radical capture product 9 was
detected by 19F NMR (Scheme 4a). Further, a radical clock reaction of 10 under the standard
reaction conditions gave the trifluoromethylated pyrrolidine 11 in 74% yield (Scheme 4b).15
These results supported a CF3 free radical pathway under the optimized reaction conditions.
Scheme 4. Mechanistic studies involving (a) the use of TEMPO and (b) a radical clock
reaction.
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F3C
O
N
Mn(OAc)3—2H2O (2 equiv)
1a
2a,
+
(a)
CF3SO2Na (2 equiv), AcOH
TEMPO, Ar, 24 h, rt
not observed
7
8
9
9
confirmed by 19F NMR
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F3C
Mn(OAc)3—2H2O (2 equiv)
(b)
N
Ts N
CF3SO2Na (2.0 equiv)
AcOH, Ar, 24 h, rt
Ts
10
11
74% isolated yield
To get detailed insights into the proton abstraction process, control experiments were carried
out by replacing the reaction medium CH3COOH with CH3COOD and CD3COOD (Table 5).
Hydrotrifluoromethylation of alkene 3g in CH3COOH proceeded smoothly under standard
condition. When the reaction was carried out in CH3COOD, no deuterated product 4gꢀ[D]
was observed (Table 5, entry 2). This result suggested that the proton was not from the
carboxyl group of the solvent. When the reaction was carried out in CD3COOD (Table 5,
entry 3), 71% of the product was deuterated. When the reaction was run in a 1:1 mixture of
CD3COOD and CH3COOH (Table 5, entry 4), the product distribution revealed a normal
kinetic isotope effect (kH/kD = 2.4). These results implied that the αꢀH of CH3COOꢀ served as
the hydrogen source during the reaction.16
Table 5. Trifluoromethylation of 3g in different deuterated acetic acidsa
Mn(OAc)3—2H2O (2 equiv)
H/D
CF3SO2Na (2 equiv)
CF3
TsHN
TsHN
solvent, Ar, rt, 24 h
4g:4g-[D]
3g
entry
1
solvent
4g:4gꢀ[D]b
CH3COOH
100:0
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CH3COOD
CD3COOD
100:0
29:71
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4
CD3COOD:CH3COOH=1:1
71:29
aReaction conditions: 3g (0.25 mmol), solvent (5 mL). bdetermined by 1H NMR analysis. The
deuterated product was verified by HRMS.14
On the basis of these results, a preliminary reaction mechanism was proposed in Scheme 5.
At first, CF3 radical was generated from CF3SO2Na in the presence of Mn(OAc)3·2H2O.
Markovnikov addition of trifluoromethyl radical to C=C double bond of the substrate led to
formation of the radical species E. Finally, species E underwent hydrogen abstraction from
CH3COOꢀ to afford the desired hydrotrifluoromethylation product. 4a,6a,9a
Scheme 5. Proposed mechanism for hydrotrifluoromethylation of alkenes
Mn(OAc)3—2H2O
—CF3
—CF3
CF3SO2Na
O
O
CF3
O
O
E
1a
O
O
hydrogen abstraction
CF3
2a
CONCLUSION
In summary, a simple and efficient method for hydrotrifluoromethylation of unactivated
alkenes was explored using CF3SO2Na as the trifluoromethyl source in the presence of
Mn(OAc)3·2H2O. The mild reaction conditions allowed efficient access to a variety of
trifluoromethylꢀcontaining products bearing a wide range of functional groups. Deuteration,
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radical clock and TEMPO trapping experiments revealed the mechanism of this reaction.
Further studies on synthetic application of hydrotrifluoromethylation of unactivated alkenes
and the understanding of Mn(OAc)3ꢀmediated oxidative radical reactions are underway.
EXPERIMENTAL SECTION
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General experimental information. All reactions were carried out at room temperature and
using dry solvents under anhydrous conditions unless otherwise stated. Mn(OAc)3·2H2O,
CF3SO2Na were purchased at the highest commercial quality and were used without further
purification. Thin layer chromatography (TLC) was performed on silica gel plates (silica gel
GF254) and visualized with iodine or UV light. Column chromatography was performed on
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silica gel (200–300 mesh). H NMR (400 MHz), 13C NMR (101 MHz) and 19F NMR (376
MHz) were recorded at 298 K using deuterated chloroform as solvent. Infrared (IR) spectra
were reported as wavenumber (cm–1). HRMS analyses were carried out with Varian
FTICRꢀMS 7.0T.
General procedure for the hydrotrifluoromethylation of unactivated alkenes. Alkenes
(0.25 mmol), Mn(OAc)3·2H2O (0.5 mmol), and CF3SO2Na (0.5 mmol) were placed in a 25
mL roundꢀbottom flask. The flask was evacuated and backfilled with argon for 3 times.
CH3COOH (10 mL) was added with syringe under argon protection and the mixture was
stirred vigorously at room temperature for 24 h. After the reaction was complete (TLC
analysis), the reaction mixture was poured into a beaker (500 mL) containing H2O (200 mL)
and Na2S2O4 (3 g). Then the beaker was added slowly with Na2CO3 until no bubbles of CO2
were formed. The mixture in the beaker was poured into a separating funnel (1 L) and was
extracted with CH2Cl2 (3 × 400 mL). The combined organic layers were dried over
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anhydrous MgSO4 and concentrated in vacuo. The crude product was purified by column
chromatography (using 100:1 hexane/ethyl acetate solvent system) to afford the desired
product.
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Gram-scale procedure for the hydrotrifluoromethylation of 3a. Substrate 3a (1.61 g),
Mn(OAc)3·2H2O (5.36 g), and CF3SO2Na (3.12 g) were placed in a 25 mL roundꢀbottom
flask. The flask was evacuated and backfilled with argon for 3 times. CH3COOH (50 mL)
was added with syringe under argon gas protection and the mixture was stirred vigorously at
room temperature for 24 h. After the reaction was complete (TLC analysis), the reaction
mixture was poured into a beaker (500 mL) containing H2O (300 mL) and Na2S2O4 (15 g).
Then the beaker was added slowly with Na2CO3 until no bubbles of CO2 were formed. The
mixture in the beaker was poured into a separating funnel (1 L) and was extracted with
CH2Cl2 (3 × 600 mL). The combined organic layers were dried over anhydrous MgSO4 and
concentrated in vacuo. The crude product was purified by column chromatography (using
100:1 hexane/ethyl acetate solvent system) to afford the desired product 4a (0.90 g, 63 %).
7,7,7-trifluoroheptylbenzoate (2a)
According to the general procedure, 1a (0.25 mmol, 51.1 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2a (53.0 mg,
77% yield) which was isolated as a colorless oil after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 100:1). 1H NMR (400 MHz, CDCl3) δ 7.97
(d, J = 7.7 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.7 Hz, 2H), 4.25 (t, J = 6.5 Hz, 2H),
2.11 – 1.91 (m, 2H), 1.77 – 1.62 (m, 2H), 1.62 – 1.45 (m, 2H), 1.46 – 1.27 (m, 4H). 13C NMR
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(101 MHz, CDCl3) δ 165.6, 131.9, 129.3, 128.5, 127.3, 126.2 (q, J(C, F)= 276.0 Hz), 63.8,
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32.6 (q, J(C, F) = 28.4 Hz), 27.5, 27.3, 24.7, 20.8 (q, J(C, F) = 2.7 Hz). 19F NMR (376
MHz, CDCl3) δ ꢀ66.4 (t, 3J(F, H) = 10.2 Hz). The NMR data were in agreement with reported
results.17
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6,6,6-trifluorohexyl benzoate (2b)
According to the general procedure, 1b (0.25 mmol, 47.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2b (44.8 mg,
69% yield) which was isolated as a colorless oil after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 100:1). 1H NMR (400 MHz, CDCl3) δ 7.97
(d, J = 7.6 Hz, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 4.27 (t, J = 6.5 Hz, 2H),
2.16 – 1.93 (m, 2H), 1.80 – 1.68 (m, 2H), 1.65 – 1.53 (m, 2H), 1.53 – 1.40 (m, 2H). 13C NMR
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(101 MHz, CDCl3) δ 165.6, 131.9, 129.3, 128.5, 127.3, 126.2 (q, J(C, F)= 276.1 Hz), 63.8,
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32.6 (q, J(C, F) = 28.4 Hz), 27.5, 24.7, 20.8 (q, J(C, F) = 2.7 Hz). 19F NMR (376 MHz,
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CDCl3) δꢀ66.4 (t, J(F, H) = 10.2 Hz). The NMR data were in agreement with reported
results.18
7,7,7-trifluoroheptyl 4-methylbenzoate (2c)
According to the general procedure, 1c (0.25 mmol, 54.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2c (53.5 mg,
74% yield) which was isolated as a colorless oil after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 100:1). 1H NMR (400 MHz, CDCl3) δ 7.85
(d, J = 8.2 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 4.23 (t, J = 6.6 Hz, 2H), 2.33 (s, 3H), 2.10 –
1.90 (m, 2H), 1.78 – 1.60 (m, 2H), 1.59 – 1.45 (m, 2H), 1.45 – 1.28 (m, 4H). 13C NMR (101
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MHz, CDCl3) δ 165.7, 142.5, 128.5, 128.0, 126.6, 126.2 (q, J(C, F)= 276.3 Hz), 63.6, 32.6
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(q, J(C, F) = 28.4 Hz), 27.5, 27.3, 24.7, 20.8 (q, J(C, F) = 2.7 Hz).19F NMR (376 MHz,
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CDCl3) δ ꢀ66.4 (t, J(F, H) = 10.6 Hz). IR (KBr): 2946, 1718, 1613, 1275, 1109, 1021, 842,
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755 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C15H20F3O2: 289.1415; Found:
289.1416.
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7,7,7-trifluoroheptyl 4-fluorobenzoate (2d)
According to the general procedure, 1d (0.25 mmol, 55.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2d (47.7 mg,
65% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 8.08
– 7.86 (m, 2H), 7.03 (t, J = 8.7 Hz, 2H), 4.24 (t, J = 6.6 Hz, 2H), 2.08 – 1.89 (m, 2H), 1.77 –
1.62 (m, 2H), 1.51 (dt, J = 15.3, 7.6 Hz, 2H), 1.47 – 1.22 (m, 4H). 13C NMR (101 MHz,
CDCl3) δ 165.7, 165.7 (d, 1J(C, F) = 253.7 Hz), 132.1 (d, J(C, F) = 9.3 Hz), 127.2 (q, J(C,
3
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F) = 276.3 Hz), 126.6 (d, 4J(C, F) = 2.8 Hz), 115.5(d, 2J(C, F) = 21.9 Hz), 64.9, 33.6 (q, 2J(C,
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F) = 28.4 Hz), 28.5, 28.4, 25.7, 21.8 (d, J(C, F) = 2.8 Hz). 19F NMR (376 MHz, CDCl3) δ
ꢀ66.4 (t, 3J(F, H) = 11.0 Hz), ꢀ105.9. IR (KBr): 2946, 1730, 1283, 1129, 1064, 852, 759 cmꢀ1.
HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C14H17F4O2: 293.1165; Found: 293.1163.
7,7,7-trifluoroheptyl 4-bromobenzoate (2e)
According to the general procedure, 1e (0.25 mmol, 70.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2e (68.6 mg,
78% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.82
(d, J = 8.5 Hz, 2H), 7.51 (d, J = 8.6 Hz, 2H), 4.24 (t, J = 6.6 Hz, 2H), 2.10 – 1.92 (m, 2H),
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δ 164.9, 130.7, 130.0, 128.2, 127.0, 126.1 (q, J(C, F)= 276.5 Hz), 64.0, 32.6 (q, J(C, F) =
28.4 Hz), 27.4, 27.3, 24.7, 20.8 (d, 3J(C, F) = 2.7 Hz). 19F NMR (376 MHz, CDCl3) δꢀ66.4 (t,
3J(F, H) = 10.9 Hz). The NMR data were in agreement with reported results.9b
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7,7,7-trifluoroheptyl 4-iodobenzoate (2f)
According to the general procedure, 1f (0.25 mmol, 82.5 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2f (64.0 mg,
64% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR 400 MHz, CDCl3) δ 7.71
(d, J = 7.6 Hz, 2H), 7.65 (d, J = 7.4 Hz, 2H), 4.23 (t, J = 6.3 Hz, 2H), 2.10 – 1.90 (m, 2H),
1.79 – 1.63 (m, 2H), 1.57 – 1.44 (m, 2H), 1.44 – 1.29 (m, 4H). 13C NMR (101 MHz, CDCl3)
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δ 165.1, 136.7, 130.0, 128.9, 126.17 (q, J(C, F)= 276.4 Hz), 99.6, 64.0, 32.6 (q, 2J(C, F) =
28.4 Hz) 27.4, 27.3, 24.7, 20.8 (q, 3J(C, F) = 2.7 Hz). 19F NMR (376 MHz, CDCl3) δꢀ66.4 (t,
3J(F, H) = 10.2 Hz). IR (KBr): 2947, 1721, 1605, 1270, 1118, 1015, 856, 769 cmꢀ1. HRMS
(ESIꢀTOF) m/z: [M + H]+ Calcd for C14H17F3IO2: 401.0225; Found: 401.0221.
7,7,7-trifluoroheptyl 2-methoxybenzoate (2g)
According to the general procedure, 1g (0.25 mmol, 58.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2g (55.7 mg,
73% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.86
– 7.62 (m, 1H), 7.51 – 7.32 (m, 1H), 7.10 – 6.72 (m, 2H), 4.23 (t, J = 6.5 Hz, 2H), 3.83 (s,
3H), 2.11 – 1.92 (m, 2H), 1.75 – 1.63 (m, 2H), 1.52 (s, 2H), 1.47 – 1.31 (m, 4H). 13C NMR
(101 MHz, CDCl3) δ 166.3, 159.1, 133.5, 131.6, 131.5, 127.2 (q, 1J (C, F)= 276.3 Hz), 120.1,
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112.0, 64.6, 55.9, 33.65 (q, J (C, F)= 28.3 Hz), 28.5, 28.3, 25.7, 21.8 (q, J (C, F)= 2.8
Hz).19F NMR (376 MHz, CDCl3) δ ꢀ66.3 (t, 3J (H, F)= 10.2 Hz). IR (KBr): 3546, 2946, 1727,
1602, 1254, 1135, 1083, 757 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C15H20F3O3:
305.1365; Found: 305.1356.
6,6,6-trifluorohexyl 2-methoxybenzoate (2h)
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According to the general procedure, 1h (0.25 mmol, 55.1 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2h (46.6 mg,
64% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.71
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(dd, J = 7.9, 1.8 Hz, 1H), 7.43 – 7.36 (m, 1H), 6.96 – 6.84 (m, 2H), 4.23 (t, J = 6.5 Hz, 2H),
3.83 (s, 3H), 2.13 – 1.89 (m, 2H), 1.80 – 1.64 (m, 2H), 1.63 – 1.52 (m, 2H), 1.53 – 1.36 (m,
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2H). 13C NMR (101 MHz, CDCl3) δ 166.3, 159.1, 133.5, 131.5, 127.2 (q, J(C, F)= 276.2
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Hz), 120.2, 120.1, 112.0, 64.4, 55.9, 33.7 (q, J (C, F)= 28.5 Hz), 28.4, 25.3, 21.7 (q, J (C,
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F)= 2.8 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ64.0 (t, J(H, F)= 10.9 Hz) . IR (KBr): 3546,
2951, 1727, 1602, 1255, 1134, 1084, 757 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for
C14H18F3O3: 291.1208; Found: 291.1208.
4,4,4-trifluorobutyl 2-methoxybenzoate (2i)
According to the general procedure, 1i (0.25 mmol, 48.1 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2i (40.0 mg,
61% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.78
(d, J = 7.9 Hz, 1H), 7.58 – 7.39 (m, 1H), 7.13 – 6.91 (m, 2H), 4.31 (t, J = 6.5 Hz, 2H), 3.90 (s,
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3H), 2.22 – 2.01 (m, 2H), 1.87 – 1.71 (m, 2H). C NMR (101 MHz, CDCl3) δ 164.5, 156.4,
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F)= 28.9 Hz) , 21.4 (q, J(C, F)= 2.6 Hz).19F NMR (376 MHz, CDCl3) δ ꢀ66.1 (t, 3J(H, F)=
10.9 Hz). IR (KBr): 3402, 2948, 1650, 1537, 1253, 1150, 1023, 757 cmꢀ1. HRMS (ESIꢀTOF)
m/z: [M + H]+ Calcd for C12H14F3O3: 263.0895; Found: 263.0892.
4,4,4-trifluorobutyl 4-cyanobenzoate (2j)
According to the general procedure, 1j (0.25 mmol, 46.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2j (28.5 mg,
44% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 8.06
(d, J = 8.2 Hz, 2H), 7.69 (d, J = 8.2 Hz, 2H), 4.36 (t, J = 6.3 Hz, 2H), 2.36 – 2.10 (m, 2H),
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2.14 – 1.88 (m, 2H).13C NMR (101 MHz, CDCl3) δ 163.7, 132.7, 131.3, 128.2 (q, J(C, F)=
210.0 Hz), 129.1, 116.9, 115.7, 63.0, 29.8 (q, 2J(C, F)= 29.4 Hz) , 20.6 (q, 3J(C, F)= 2.9 Hz).
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19F NMR (376 MHz, CDCl3) δ ꢀ66.3 (t, 3J(H, F)= 10.9 Hz). IR (KBr): 3552, 2964, 2233,
1728, 1280, 1108, 1008, 862, 768 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for
C12H11F3NO2: 258.0742; Found: 258.0738.
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7,7,7-trifluoroheptyl nicotinate (2k)
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According to the general procedure, 1k (0.25 mmol, 51.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2k (40.8 mg,
59% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 9.16
(s, 1H), 8.71 (s, 1H), 8.23 (d, J = 5.8 Hz, 1H), 7.33 (d, J = 2.8 Hz, 1H), 4.29 (t, J = 6.6 Hz,
2H), 2.14 – 1.90 (m, 2H), 1.83 – 1.65 (m, 2H), 1.64 – 1.47 (m, 2H), 1.48 – 1.30 (m, 4H). 13C
NMR (101 MHz, CDCl3) δ 165.3, 153.4, 150.9, 137.0, 127.2 (q, 1J(C, F)= 276.4 Hz), 126.2,
123.3, 65.3, 33.6 (q, 2J(C, F)= 28.5 Hz), 28.4, 28.4, 25.7, 21.8 (q, 3J(C, F)= 2.7 Hz). 19F NMR
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(376 MHz, CDCl3) δ ꢀ66.4 (t, J(H, F)= 10.8 Hz). IR (KBr): 2946, 1730, 1284, 1129, 1064,
852, 759, 708 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C13H17F3NO2, 276,1211;
Found: 276.1205.
7,7,7-trifluoroheptyl isonicotinate (2l)
According to the general procedure, 1l (0.25 mmol, 51.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2l (44.1 mg,
64% yield) which was isolated as a white solid after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 100:1). M.P. 35 ꢀ 36 °C. 1H NMR (400 MHz,
CDCl3) δ 8.75 – 8.68 (m, 2H), 7.83 – 7.70 (m, 2H), 4.29 (t, J = 6.6 Hz, 2H), 2.12 – 1.92 (m,
2H), 1.81 – 1.66 (m, 2H), 1.60 – 1.47 (m, 2H), 1.46 – 1.31 (m, 4H). 13C NMR (101 MHz,
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CDCl3) δ 165.2, 150.6, 137.5, 127.2 (q, J(C, F)= 276.4 Hz), 122.8, 65.6, 33.6 (q, J(C, F)=
28.4 Hz), 28.4, 28.3, 25.7, 21.8 (q, 3J(C, F)= 2.8 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.4 (t,
3J(H, F)= 10.0 Hz). IR (KBr): 3566, 2947, 1726, 1286, 1136, 1025, 803, 743 cmꢀ1. HRMS
(ESIꢀTOF) m/z: [M + H]+ Calcd for C13H17F3NO2: 276,1211; Found: 276.1202.
7,7,7-trifluoroheptyl 2-naphthoate (2m)
According to the general procedure, 1m (0.25 mmol, 63.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2m (54.9 mg,
68% yield) which was isolated as a white solid after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). M.P. 47 ꢀ 48 °C. 1H NMR (400 MHz,
CDCl3) δ 8.53 (s, 1H), 8.04 – 7.95 (m, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 8.5 Hz, 2H),
7.57 – 7.42 (m, 2H), 4.32 (t, J = 6.6 Hz, 2H), 2.13 – 1.90 (m, 2H), 1.81 – 1.69 (m, 2H), 1.61
– 1.48 (m, 2H), 1.47 – 1.32 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 166.8, 135.5, 132.5,
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131.0, 129.4, 128.3, 128.2, 127.8, 127.6, 127.2 (q, J(C, F)= 282.8 Hz), 126.7, 125.2, 65.0,
33.7(q, 2J(C, F)= 28.3 Hz), 28.6, 28.4, 25.8, 21.9 (q, 3J(C, F)= 2.8 Hz). 19F NMR (376 MHz,
CDCl3) δ ꢀ66.4 (t, 3J(H, F)= 10.1 Hz). IR (KBr): 3611, 2959, 1712, 1279, 1137, 1047, 779,
762 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C18H20F3O2: 325.1415; Found:
325.1413.
7,7,7-trifluoroheptyl cyclohexanecarboxylate (2n)
According to the general procedure, 1n (0.25 mmol, 52.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2n (40.0 mg,
57% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 3.99
(t, J = 6.2 Hz, 2H), 2.73 – 2.57 (m, 1H), 2.10 – 1.91 (m, 2H), 1.92 – 1.76 (m, 2H), 1.79 –
1.68 (m, 2H), 1.68 – 1.60 (m, 2H), 1.61 – 1.54 (m, 2H), 1.54 – 1.42 (m, 4H), 1.40 – 1.24 (m,
4H). 13C NMR (101 MHz, CDCl3) δ 175.8, 126.2 (q, 1J(C, F)= 276.3 Hz), 63.0, 42.9, 32.6 (q,
2J(C, F)= 28.4 Hz), 29.0, 27.4, 27.3, 24.8, 24.6, 20.8 (q, J(C, F)= 2.8 Hz). 19F NMR (376
3
MHz, CDCl3) δ ꢀ66.4 (t, 3J(H, F)= 10.9 Hz). IR (KBr): 3685, 2954, 1733, 1256, 1146, 1051
cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C13H22F3O2: 267.1572; Found: 267.1568.
7,7,7-trifluoroheptyl 4-methylbenzenesulfonate (2o)
According to the general procedure, 1o (0.25 mmol, 63.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2o (54.1 mg,
67% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.72
(d, J = 7.8 Hz, 2H), 7.28 (d, J = 7.8 Hz, 2H), 3.95 (t, J = 6.2 Hz, 2H), 2.38 (s, 3H), 2.03 –
1.84 (m, 2H), 1.63 – 1.52 (m, 2H), 1.47 – 1.36 (m, 2H), 1.30 – 1.19 (m, 4H). 13C NMR (101
MHz, CDCl3) δ 144.8, 133.1, 129.8, 127.9, 127.1 (q, 1J(C, F)= 276.4 Hz), 70.3, 33.5 (q, 2J(C,
F)= 28.4 Hz), 28.5, 28.0, 25.0, 21.7 (q, 3J(C, F)= 2.9 Hz), 21.6. 19F NMR (376 MHz, CDCl3)
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δ ꢀ66.4 (t, 3J(H, F)= 10.9 Hz). IR (KBr): 3406, 2947, 2362, 1600, 1361, 1141, 959, 818 cmꢀ1.
HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C14H20F3O3S: 325.1085; Found: 325.1079.
(((7,7,7-trifluoroheptyl)oxy)methyl)benzene (2p)
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According to the general procedure, 1p (0.25 mmol, 47.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2p (48.0 mg,
74% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.44
– 7.18 (m, 5H), 4.56 (s, 2H), 3.55 (t, J = 6.2 Hz, 2H), 2.32 – 2.03 (m, 2H), 1.78 – 1.60 (m,
4H), 1.60 – 1.44 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 138.6, 128.4, 127.8, 127.7, 127.4 (q,
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1J(C, F)= 276.4 Hz), 72.9, 70.1, 32.6 (q, 2J(C, F)= 28.4 Hz), 27.5, 27.4, 24.7, 20.8 (q, J(C,
F)= 2.8 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.4 (t, 3J(H, F)= 10.0 Hz). The NMR data were
in agreement with reported results.9b
((7,7,7-trifluoroheptyl)oxy)benzene (2q)
According to the general procedure, 1q (0.25 mmol, 44.1 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2q (39.5 mg,
64% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.21
(t, J = 7.6 Hz, 2H), 6.93 – 6.73 (m, 3H), 3.88 (t, J = 6.2 Hz, 2H), 2.15 – 1.98 (m, 2H), 1.85 –
1.71 (m, 2H), 1.69 – 1.55 (m, 2H), 1.53 – 1.37 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 159.0,
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129.41, 127.2 (q, 1J(C, F)= 274.6 Hz), 120.5, 114.4, 67.5, 33.6 (q, J(C, F)= 28.2 Hz), 29.0,
28.4, 25.7, 21.8 (q, 3J(C, F)= 2.7 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.4 (t, 3J(H, F)= 10.9
Hz). The NMR data were in agreement with reported results.9b
7,7,7-trifluoroheptan-1-ol (2r)
According to the general procedure, 1r (0.25 mmol, 28.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 2r (24.5 mg,
53% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 3.64
(t, J = 6.6 Hz, 2H), 2.79 (s, 1H), 2.23 – 1.97 (m, 2H), 1.68 – 1.52 (m, 4H), 1.49 – 1.32 (m,
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4H). 13C NMR (101 MHz, CDCl3) δ 127.2 (q, J(C, F)= 273.6 Hz), 62.0, 36.5 (q, J(C, F)=
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28.4 Hz), 35.4, 31.6, 29.9, 23.8 (q, 3J(C, F)= 2.8 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.4 (t,
3J(H, F)= 10.8 Hz). The NMR data were in agreement with reported results.6a
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N-(4,4,4-trifluorobutyl)benzamide (4a)
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According to the general procedure, 3a (0.25 mmol, 40.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4a (41.7 mg,
72% yield) which was isolated as a white solid after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). M.P. 47 ꢀ 48 °C. 1H NMR (400 MHz,
CDCl3) δ 7.69 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 7.3 Hz, 1H), 7.35 (t, J = 7.5 Hz, 2H), 6.40 (s,
1H), 3.44 (t, J = 10.0 Hz, 2H), 2.19 – 2.03 (m, 2H), 1.87 – 1.75 (m, 2H). 13C NMR (101 MHz,
CDCl3) δ 167.9, 134.3, 131.7, 128.6, 126.9, 126.7 (q, 1J(C, F)= 276.1 Hz), 38.8, 31.3 (q, 2J(C,
F)= 29.1 Hz), 22.5 (q, 3J(C, F)= 2.6 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.1 (t, 3J(H, F)=
10.8 Hz, 3F). IR (KBr): 3334, 3065, 2954, 1636, 1541, 1309, 1152, 692, 667 cmꢀ1. HRMS
(ESIꢀTOF) m/z: [M + H]+ Calcd for C11H13F3NO: 232.0949; Found: 232.0943.
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4-methoxy-N-(4,4,4-trifluorobutyl)benzamide (4b)
According to the general procedure, 3b (0.25 mmol, 47.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4b (47.5 mg,
73% yield) which was isolated as a white solid after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). M.P. 82 ꢀ 83 °C. 1H NMR (400 MHz,
CDCl3) δ 7.66 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.19 (s, 1H), 3.78 (s, 3H), 3.45 (q,
J = 6.7 Hz, 2H), 2.22 – 2.01 (m, 2H), 1.92 – 1.70 (m, 2H). 13C NMR (101 MHz, CDCl3) δ
167.3, 162.3, 128.7, 127.0 (q, 1J(C, F)= 276.1 Hz), 126.5, 113.9, 54.4, 37.6, 30.3 (q, 2J(C, F)=
29.0 Hz), 21.6 (q, 3J(C, F)= 2.6 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.1 (t, 3J(H, F)= 10.8
Hz). IR (KBr): 3327, 2944, 1635, 1540, 1254, 1145, 848 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M +
H]+ Calcd for C12H15F3NO2: 262.1055; Found: 262.1055.
Crystal data for 4b: C24H28F6N2O4, M = 522.48, orthorhombic, a = 5.1273(14) Å, b =
7.9444(19) Å, c = 30.291(7) Å, α = 90.00°, β = 90.00°, γ = 90.00°, V = 1233.9(5) Å3, T =
113(2) K, space group P2(1)2(1)2(1), Z = 2, 13501 reflections measured, 2179 independent
reflections (Rint = 0.0486). The final R1 values were 0.0778 (I > 2σ(I)). The final wR(F2)
values were 0.2407 (I > 2σ(I)). The final R1 values were 0.0823 (all data). The final wR(F2)
values were 0.2446 (all data). The goodness of fit on F2 was 1.028. Flack parameter = 1(2).
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According to the general procedure, 3c (0.25 mmol, 47.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4c (40.6 mg,
62% yield) which was isolated as a colorless oil after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). 1H NMR (400 MHz, CDCl3 δ 7.28 (s,
1H), 7.27 – 7.23 (m, 1H), 7.22 – 7.18 (m, 1H), 6.97 (d, J = 7.8 Hz, 1H), 6.37 (s, 1H), 3.77 (s,
3H), 3.56 – 3.35 (m, 2H), 2.26 – 2.00 (m, 2H), 1.96 – 1.75 (m, 2H). 13C NMR (101 MHz,
CDCl3) δ 167.6, 159.9, 135.7, 129.6, 118.5, 117.8, 114.7 (q, 1J(C, F)= 276.2 Hz), 112.3, 55.5,
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38.8, 31.3 (q, J(C, F)= 29.1 Hz) , 22.6 (q, J(C, F)= 2.6 Hz). 19F NMR (376 MHz, CDCl3) δ
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ꢀ66.1 (t, J(H, F)= 10.9 Hz). IR (KBr): 3303, 2945, 1641, 1544, 1308, 1150, 788, 690 cmꢀ1.
HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C12H15F3NO2: 262.1055; Found: 262.1055.
2-methoxy-N-(4,4,4-trifluorobutyl)benzamide (4d)
According to the general procedure, 3d (0.25 mmol, 47.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4d (46.5 mg,
71% yield) which was isolated as a colorless oil after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). 1H NMR (400 MHz, CDCl3) δ 8.20 –
8.04 (m, 1H), 7.88 (s, 1H), 7.43 – 7.35 (m, 1H), 7.02 (t, J = 7.5 Hz, 1H), 6.92 (d, J = 8.3 Hz,
1H), 3.90 (s, 3H), 3.47 (q, J = 6.7 Hz, 2H), 2.21 – 2.04 (m, 2H), 1.89 – 1.78 (m, 2H). 13C
NMR (101 MHz, CDCl3) δ 165.6, 157.4, 132.9, 132.3, 127.1 (q, 1J(C, F)= 276.3 Hz), 121.4,
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121.2, 111.3, 55.9, 38.3, 31.4 (q, J(C, F)= 29.0 Hz), 22.5 (q, J(C, F)= 2.6 Hz). 19F NMR
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(376 MHz, CDCl3) δ ꢀ66.1(t, J(H, F)= 10.9 Hz). IR (KBr): 3401, 2948, 1649, 1537, 1254,
1150, 758 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C12H15F3NO2: 262.1055; Found:
262.1055.
N-(7,7,7-trifluoroheptyl)benzamide (4e)
According to the general procedure, 3e (0.25 mmol, 50.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4e (50.1 mg,
73% yield) which was isolated as a white solid after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). M.P. 43 ꢀ 44 °C. 1H NMR (400 MHz,
CDCl3) δ 7.69 (d, J = 7.2 Hz, 2H), 7.43 (t, J = 7.3 Hz, 1H), 7.36 (t, J = 7.4 Hz, 2H), 6.07 (s,
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1H), 3.39 (q, J = 6.9 Hz, 2H), 2.13 – 1.89 (m, 2H), 1.64 – 1.43 (m, 6H), 1.41 – 1.24 (m, 2H).
13C NMR (101 MHz, CDCl3) δ 167.6, 134.8, 131.4, 128.6, 126.8, 126.6 (q, 1J(C, F)= 152.4
Hz), 39.9, 33.6 (q, 2J(C, F)= 28.4 Hz), 29.5, 28.4, 26.6, 21.8 (q, 3J(C, F)= 2.8 Hz). 19F NMR
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(376 MHz, CDCl3) δ ꢀ66.4 (t, J(H, F)= 10.9 Hz). IR (KBr): 3326, 2943, 2362, 1637, 1535,
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1255, 1138, 803, 714 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C14H19F3NO:
274.1419; Found: 274.1410.
N-(7,7,7-trifluoroheptyl)benzenesulfonamide (4f)
According to the general procedure, 3f (0.25 mmol, 59.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4f (53.5 mg,
69% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 10:1). H NMR (400 MHz, CDCl3) δ 7.81
(d, J = 7.4 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 4.64 (s, 1H), 2.88 (q, J
= 6.7 Hz, 2H), 2.04 – 1.85 (m, 2H), 1.51 – 1.32 (m, 4H), 1.29 – 1.12 (m, 4H). 13C NMR (101
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MHz, CDCl3) δ 138.9, 131.6, 128.1, 126.1 (q, J(C, F)= 276.4 Hz), 126.0, 42.0, 32.51 (q,
3
2J(C, F)= 28.3 Hz), 28.3, 27.1, 25.0, 20.7 (q, J(C, F)= 2.8 Hz). 19F NMR (376 MHz, CDCl3)
δ ꢀ66.4 (t, 3J(H, F)= 11.0 Hz). IR (KBr): 3286, 2943, 2867, 1596, 1325, 1158, 755, 724 cmꢀ1.
HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C13H19F3NO2S: 310.1089; Found: 310.1081.
4-methyl-N-(7,7,7-trifluoroheptyl)benzenesulfonamide (4g)
According to the general procedure, 3g (0.25 mmol, 63.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4g (57.2 mg,
71% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 10:1). H NMR (400 MHz, CDCl3) δ 7.72
(d, J = 7.8 Hz, 2H), 7.28 (d, J = 7.8 Hz, 2H), 3.95 (t, J = 6.2 Hz, 2H), 2.38 (s, 3H), 2.03 –
1.84 (m, 2H), 1.63 – 1.36 (m, 4H), 1.30 – 1.19 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 142.4,
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135.8, 128.7, 127.9, 126.1, 126.1 (q, J(C, F)= 282.8 Hz), 42.0, 32.5 (q, J(C, F)= 28.4 Hz),
28.2, 27.1, 25.0, 20.7 (q, 3J(C, F)= 2.8 Hz), 20.6. 19F NMR (376 MHz, CDCl3) δ ꢀ66.4 (t, 3J(H,
F)= 10.9 Hz). The NMR data were in agreement with reported results.9b
2-chloro-N-(7,7,7-trifluoroheptyl)benzenesulfonamide (4h)
According to the general procedure, 3h (0.25 mmol, 68.4 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4h (54.2 mg,
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63% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 10:1). H NMR (400 MHz, CDCl3) δ 8.10
(d, J = 8.0 Hz, 1H), 7.57 – 7.47 (m, 2H), 7.47 – 7.38 (m, 1H), 4.96 (t, J = 6.0 Hz, 1H), 2.98 –
2.87 (m, 2H), 2.09 – 1.94 (m, 2H), 1.53 – 1.40 (m, 4H), 1.36 – 1.23 (m, 4H). 13C NMR (101
MHz, CDCl3) δ 137.2, 133.7, 131.5, 131.3, 131.2, 127.3, 127.1 (d, 1J(C, F)= 276.3 Hz), 43.1,
33.5 (q, 2J(C, F)= 28.5 Hz), 29.2, 28.0, 26.0, 21.6 (q, 3J(C, F)= 2.8 Hz). 19F NMR (376 MHz,
CDCl3) δ ꢀ66.4 (t, 3J(H, F)= 10.9 Hz). IR (KBr): 3314, 2944, 1577, 1334, 1165, 759 cmꢀ1.
HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C13H18ClF3NO2S: 344.0699; Found: 344.0693.
N-(7,7,7-trifluoroheptyl)methanesulfonamide (4i)
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According to the general procedure, 3i (0.25 mmol, 44.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4i (32.3 mg,
52% yield) which was isolated as a white solid after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). M.P. 35 ꢀ 36 °C. 1H NMR (400 MHz,
CDCl3) δ 4.52 (s, 1H), 3.12 – 3.00 (m, 2H), 2.89 (s, 3H), 2.07 – 1.93 (m, 2H), 1.56 – 1.45 (m,
4H), 1.37 – 1.29 (m, 4H). 13C NMR (101 MHz, CDCl3) δ127.2 (q, 1J(C, F)= 276.3 Hz), 43.1,
3
40.2, 33.6 (q, 2J(C, F)= 28.3 Hz), 29.9, 28.2, 26.1, 21.8 (q, J(C, F)= 2.8 Hz). 19F NMR (376
3
MHz, CDCl3) δ ꢀ66.4 (t, J(H, F)= 10.6 Hz). IR (KBr): 3268, 2940, 2362, 1439, 1309, 1143
cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C8H17F3NO2S: 248.0932; Found: 248.0927.
2-(5,5,5-trifluoropentyl)isoindoline-1,3-dione (4j)
According to the general procedure, 3j (0.25 mmol, 50.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4j (46.1 mg,
68% yield) which was isolated as a white solid after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). M.P. 74 ꢀ 75 °C. 1H NMR (400 MHz,
CDCl3) δ 7.82 – 7.74 (m, 2H), 7.71 – 7.61 (m, 2H), 3.64 (t, J = 7.0 Hz, 2H), 2.14 – 1.99 (m,
13
2H), 1.76 – 1.64 (m, 2H), 1.59 – 1.47 (m, 2H). C NMR (101 MHz, CDCl3) δ 168.3, 134.0,
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132.0, 127.0 (q, J(C, F)= 276.4 Hz), 123.3, 37.3, 33.2 (q, J(C, F)= 28.7 Hz), 27.7, 19.3 (q,
3J(C, F)= 2.8 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.3 (t, 3J(H, F)= 10.8 Hz). The NMR data
were in agreement with reported results.19
2-(7,7,7-trifluoroheptyl)isoindoline-1,3-dione (4k)
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According to the general procedure, 3k (0.25 mmol, 57.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4k (57.1 mg,
76% yield) which was isolated as a white solid after purification on silica gel
chromatography (petroleum ether:ethyl acetate = 10:1). M.P. 54 ꢀ 55 °C. 1H NMR (400 MHz,
CDCl3) δ 7.81 – 7.74 (m, 2H), 7.68 – 7.62 (m, 2H), 3.62 (t, J = 7.0 Hz, 2H), 2.07 – 1.90 (m,
2H), 1.68 – 1.57 (m, 2H), 1.53 – 1.41 (m, 2H), 1.40 – 1.24 (m, 4H). 13C NMR (101 MHz,
CDCl3) δ 167.4, 132.9, 131.1, 126.1 (q, 1J(C, F)= 276.3 Hz), 122.2, 36.8, 32.6 (q, 2J(C, F)=
28.3 Hz), 27.3, 27.2, 25.4, 20.7 (q, 3J(C, F)= 2.6 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.4 (t,
3J(H, F)= 10.9 Hz). The NMR data were in agreement with reported results.6a
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ethyl 2-cyano-6,6,6-trifluorohexanoate (4l)
According to the general procedure, 3l (0.25 mmol, 38.3 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 4l (42.8 mg,
77% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 4.29
(q, J = 7.1 Hz, 2H), 3.54 (t, J = 6.8 Hz, 1H), 2.28 – 2.10 (m, 2H), 2.10 – 1.99 (m, 2H), 1.88 –
13
1.72 (m, 2H), 1.34 (t, J = 7.1 Hz, 3H). C NMR (101 MHz, CDCl3) δ 165.5, 126.6 (q, 1J(C,
F)= 276.5 Hz), 116.0, 63.1, 37.2, 33.0 (q, 2J(C, F)= 29.2 Hz), 28.6, 19.5 (q, 3J(C, F)= 3.0 Hz),
14.0. 19F NMR (376 MHz, CDCl3) δ ꢀ66.2 (t, 3J(H, F)= 10.6 Hz). IR (KBr): 3567, 2962, 1747,
1260, 1140, 1022 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C9H13F3NO2: 224.0898;
Found: 224.0891.
4,4,4-trifluoro-2-methylbutyl benzoate (6a)
According to the general procedure, 5a (0.25 mmol, 44.1 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 6a (47.0 mg,
76% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 8.03
– 7.95 (m, 2H), 7.55 – 7.47 (m, 1H), 7.41 – 7.35 (m, 2H), 4.24 – 4.08 (m, 2H), 2.40 – 2.21 (m,
2H), 2.10 – 1.88 (m, 1H), 1.10 (d, J = 6.5 Hz, 3H).. 13C NMR (101 MHz, CDCl3) δ 165.3,
132.1, 128.6, 128.5, 127.4, 126.1 (q, 1J(C, F)= 275.3 Hz), 67.3, 36.1 (q, 2J(C, F) = 28.2 Hz),
26.9 (q, 3J(C, F) = 2.4 Hz), 16.0. 19F NMR (376 MHz, CDCl3) δꢀ63.6 (t, 3J(F, H) = 11.4 Hz).
The NMR data were in agreement with reported results.9a
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2-(trifluoromethyl)-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (6b)
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According to the general procedure, 5b (0.25 mmol, 36.0 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 6b (30.1 mg,
56% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.33
– 7.27 (m, 2H), 7.23 – 7.19 (m, 2H), 5.53 – 5.48 (m, 2H), 2.46 – 2.34 (m, 1H), 2.19 (dt, J =
12.1, 4.8 Hz, 1H), 1.77 (dd, J = 12.1, 8.8 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 149.0,
147.5, 128.9, 128.8 (q, 1J(C, F)= 272.7 Hz), 128.6, 120.3, 119.9, 78.7, 78.6, 44.8 (q, J(C, F)
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= 28.1 Hz), 29.4. 19F NMR (376 MHz, CDCl3) δꢀ68.7 (t, 3J(F, H) = 10.0 Hz). The NMR data
were in agreement with reported results.6a
2-(trifluoromethyl)butane-1,4-diyl dibenzoate (6c)
According to the general procedure, 5c (0.25 mmol, 74.1 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 6c (43.3 mg,
47% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 8.07
– 7.94 (m, 4H), 7.59 – 7.48 (m, 2H), 7.45 – 7.33 (m, 4H), 4.82 – 4.62 (m, 2H), 4.60 – 4.40 (m,
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2H), 3.36 – 3.24 (m, 1H), 2.09 – 1.91 (m, 2H). C NMR (101 MHz, CDCl3) δ 165.0, 162.1,
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132.9, 132.4, 129.1, 128.7, 128.6, 127.6, 127.5, 127.5, 127.1 (q, J(C, F)= 242.4 Hz), 64.6,
60.7 (q, J(C, F) = 2.4 Hz), 44.8 (q, J(C, F) = 31.2 Hz), 28.7. 19F NMR (376 MHz, CDCl3)
δꢀ69.4 (t, 3J(F, H) = 8.2 Hz). IR (KBr): 2962, 1729, 1262, 1107, 1025, 801, 709 cmꢀ1. HRMS
(ESIꢀTOF) m/z: [M + H]+ Calcd for C19H18F3O4: 367.1157; Found: 367.1159.
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2-(3-methyl-2-(trifluoromethyl)butyl)isoindoline-1,3-dione (6d)
According to the general procedure, 5d (0.25 mmol, 53.8 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 6d (54.1 mg,
76% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ 7.80
– 7.77 (m, 2H), 7.68 – 7.65 (m, 2H), 4.01 – 3.92 (m, 1H), 3.72 – 3.61 (m, 1H), 2.74 – 2.57 (m,
1H), 2.13 – 1.98 (m, 1H), 1.09 (d, J = 7.1 Hz, 3H), 1.01 (d, J = 7.0 Hz, 3H). 13C NMR (101
MHz, CDCl3) δ 166.9, 133.1, 130.8, 126.4 (q, 1J(C, F)= 281.9 Hz), 122.4, 45.0 (q, J(C, F)=
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23.8 Hz), 32.9 (q, J(C, F)= 2.8 Hz), 25.1(d, J(C, F)= 1.1 Hz), 18.7, 17.7. 19F NMR (376
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MHz, CDCl3) δ ꢀ66.4 (d, 3J(H, F)= 6.6 Hz). The NMR data were in agreement with reported
results.9a
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3-methyl-2-(trifluoromethyl)butyl benzoate (6e)
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According to the general procedure, 5e (0.25 mmol, 47.6 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 6e (45.0 mg,
69% yield) which was isolated as a colorless oil after purification on silica gel
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chromatography (petroleum ether:ethyl acetate = 100:1). H NMR (400 MHz, CDCl3) δ H
NMR (400 MHz, ) δ 8.22 – 8.04 (m, 2H), 7.74 – 7.59 (m, 1H), 7.53 (t, J = 7.6 Hz, 2H), 4.81
– 4.57 (m, 2H), 2.63ꢀ2.47 (m, 1H), 2.43ꢀ2.26 (m, 1H), 1.17 (d, J = 7.1 Hz, 3H), 1.08 (d, J =
7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 165.6, 132.4, 129.9, 129.1, 127.9, 126.7 (q, 1J(C,
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F)= 282.1 Hz), 59.9 (q, J(C, F)= 3.0 Hz), 48.1 (q, J(C, F)= 24.5 Hz), 25.6, 20.9, 19.0. 19F
NMR (376 MHz, CDCl3) δ ꢀ66.0 (d, 3J(H, F)= 9.6 Hz). The NMR data were in agreement
with reported results.9a
(1R)-(6-methoxyquinolin-4-yl)((1S,4S,5R)-5-(3,3,3-trifluoropropyl)quinuclidin-2-yl)meth
anol (8)
According to the general procedure, 7 (0.25 mmol, 81.1 mg), Mn(OAc)3·2H2O (0.5 mmol,
134.1 mg) and CF3SO2Na (0.5 mmol, 78.0 mg) in CH3COOH (10 mL) afforded 8 (62.0 mg,
63% yield) which was isolated as a yellow solid after purification on silica gel
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chromatography (ethyl acetate:methanol = 10:1). H NMR (400 MHz, CDCl3) δ 8.64 (d, J =
4.5 Hz, 1H), 7.79 (d, J = 9.2 Hz, 1H), 7.58 (d, J = 4.5 Hz, 1H), 7.12 (dd, J = 9.2, 2.3 Hz, 1H),
6.88 (d, J = 2.1 Hz, 1H), 6.12 (s, 1H), 3.87 – 3.71 (m, 4H), 3.22 – 3.11 (m, 2H), 2.81 – 2.70
(m, 1H), 2.41 (d, J = 13.6 Hz, 1H), 2.04 – 1.75 (m, 6H), 1.64 (s, 1H), 1.45 – 1.23 (m, 4H).13C
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NMR (101 MHz, CDCl3) δ 157.6, 147.3, 146.7, 143.9, 131.2, 126.8 (q, J(C, F)= 274.8 Hz),
126.6, 121.4, 118.5, 101.4, 71.9, 60.0, 57.1, 55.7, 43.2, 34.1, 31.7(q, 2J(C, F)= 28.6 Hz), 27.0,
26.3 (q, 3J(C, F)= 2.0 Hz), 25.3, 21.8. 19F NMR (376 MHz, CDCl3) δ ꢀ66.4 (t, 3J(H, F)= 10.8
Hz). The NMR data were in agreement with reported results.20
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ASSOCIATED CONTENT
Supporting information
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The Supporting Information is available free of charge on the ACS Publications website at
DOI: 10.1021/XXXXXXXX.
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Optimization of reaction conditions, copies of NMR spectra, and Xꢀray diffraction data for
compound 4b (pdf)
Crystallographic data for compound 4b (CIF).
AUTHOR INFORMATION
Corresponding Authors
*Eꢀmail: lduan@nankai.edu.cn.
*Eꢀmail: ymli@nankai.edu.cn.
ORCID ID
YueꢀMing Li: 0000ꢀ0003ꢀ2632ꢀ9253
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
We acknowledge financial support from the National Natural Science Foundation of China
(NSFC 21672106, NSFC 21272121) and Tianjin Municipal Commission of Science and
Technology (15JCZDJC33300). YML acknowledges the support from “The Fundamental
Research Funds for the Central Universities (63171337)”.
REFERENCES
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