Palladium-catalyzed intramolecular fluorooxylation of styrenes

Article abstract of DOI:10.1002/cjoc.201300437

A novel palladium-catalyzed intramolecular fluorooxylation of styrenes has been developed by using NFSI as fluorinating reagent. This reaction provides an efficient way for the synthesis of 2-aryl-3-fluorotetrahydrofuran derivatives. A palladium-catalyzed intramolecular oxidative fluorooxylation of styrenes has been developed by using NFSI as fluorinating reagent. This reaction provides an efficient way for the synthesis of 2-aryl-3-fluorotetrahydrofuran derivatives. Copyright

Full text of DOI:10.1002/cjoc.201300437

FULL PAPER
DOI: 10.1002/cjoc.201300437
Palladium-Catalyzed Intramolecular Fluorooxylation
of Styrenes
Zheliang Yuan, Haihui Peng, and Guosheng Liu*
State Key Laboratory of Organometallics Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
A novel palladium-catalyzed intramolecular fluorooxylation of styrenes has been developed by using NFSI as
fluorinating reagent. This reaction provides an efficient way for the synthesis of 2-aryl-3-fluorotetrahydrofuran de-
rivatives.
Keywords palladium, intramoleclular, fluorooxylation, fluorotetrahydrofuran
Introduction
When substrate Z-1a was treated with NFSI in the
presence of a catalytic amount of PdCl2/L1, the reaction
afforded a trace amount of fluorooxylation product 2a
with 1∶1 ratio of trans/cis value (Table 1, Entry 1). As
similar to our previous intermolecular fluoroesterifica-
tion, the reaction yield was dramatically increased to
38% with addition of CF3CO2H, and the reaction af-
forded diastereoisomer with 14.4∶1 trans/cis ratio (En-
try 2). And the best yield was obtained in the presence
of CCl3CO2H (Entry 3).
Based on this result, acids screening revealed that
CCl3CO2H was used as additive to afford best result
(Entry 3). However, the further optimization could not
improve the reaction yield. To our surprise, the reaction
yield was significantly affected by reaction time, and
the reaction for 5 h afforded the best yield (78% yield,
Entries 6－10). Meanwhile, the diastereoselectivity of
the reaction was also affected by the reaction time.
The poor selectivity was observed in the early stage
of reaction, while good diastereoisomer ratio was given
in the end of reaction with decreased yield. Those re-
sults indicated that product cis-2a was possibly ex-
hausted due to its instability under the reaction condi-
tion. During the study of this work, Serguchev and co-
workers also published an electrophilic fluorination of
alkenes in ionic liquid with a similar observation.[3f]
They found that cis-2a was facially transferred to re-
lated peroxide 3 at ambient temperature (Eq. 1). Com-
parison to this electrophilic fluorination process, how-
ever, the palladium-catalyzed fluorooxylation gave an
opposite diastereoselectivity.
Fluorinated hetero- and carbocycles are widely used
as pharmaceuticals and agrochemicals in recent dec-
ades.[1] Among them, some organic compounds with a
fluorinated furan ring show their unique properties, such
as anti-HIV (human immunodeficiency virus) and anti-
cancer activities.[2] Thus, the efficient syntheses of
fluorinated furan compounds have been investigated.[3,4]
Very recently, transition metal-catalyzed fluorina-
tions have been proven to be efficient strategies to pro-
vide fluorinated compounds.[5] For example, Sanford
and co-workers demonstrated that palladium catalyst
could be used to achieve C－F bond formation by using
＋
F
fluorinating reagent.[6] In addition, Ag- and
Au-catalyzed C－F bond formation had also been re-
ported.[7,8]
As the part of our ongoing program for the synthesis
of fluorinated heterocycles, our group had reported a
series of transition metal-catalyzed fluorination of un-
saturated C－C bond.[9] For example, Pd-catalyzed in-
termolecular fluoroamination of styrenes was reported
by using N-fluorobenzenesulfonimide (NFSI), in which
fluoropalladation of alkene was proposed as the key step
to construct C－F bond.[9b] Furthermore, this strategy
was expanded to intramolecular reaction to synthesize
fluorotetrahydropyrroles.[9e] Very recently, we explored
a Pd-catalyzed intermolecular fluoroesterification of
styrenes.[9f] Herein, we reported a related intramolecular
fluorooxylation of styrenes, which presents a good
strategy to synthesize fluorinated tetrahydrofuran.
The further investigation of palladium catalyst dem-
onstrated that Pd(OAc)2 and Pd(dba)2 could also cata-
lyze this reaction, and PdCl2 provided the best result
Results and Discussion
The initial study was focused on the reaction of Z-1a.
*
E-mail: gliu@mail.sioc.ac.cn; Tel.: 0086-021-54925346; Fax: 0086-021-64166128
Received May 30, 2013; accepted June 17, 2013; published online July 5, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300437 or from the author.
908
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Chin. J. Chem. 2013, 31, 908—914

Palladium-Catalyzed Intramolecular Fluorooxylation of Styrenes
Table 1 Screening results of fluorooxylation of Z-1aa
ent group position on the benzene ring did not signifi-
cantly influence the yields (2b－2g). The substrates
bearing electron-withdrawing group, such as nitro, al-
dehyde and halides on benzene ring, were also compati-
ble for this transformation albeit with slightly lower
reactivity (2h－2k).
[Pd] (5 mol%)
Ph
O
Ligand (7.5 mol%)
Ph
+
FN(SO2Ph)2
CCl3CO2H (0.4 equiv.)
solvent, r.t.
OH
F
(NFSI)
(3.0 equiv.)
Z-1a
2a
As for the diene substrate 4, we could get product 5a
and 5b in 46% yield with poor diastereoselectivity (1∶
1 ratio, Eq. 2). Furthermore, for the 1,1-disubstituted
substrate 6, the reaction also underwent tandem fluori-
nation and cyclization to give desired product 7a in 55%
yield, combined with small amount of difluorinated
product 7b (Eq. 3). The formation of 7b might involve a
fluorooxylation of 8, which was a side product gener-
ated from β-H elimination of palladium intermediate.
Yieldb/% (2a)
(trans/cis)c
6 (1.0∶1)
38 (14.4∶1)
53 (6.8∶1)
56 (4.4∶1)
78 (2.3∶1)
67 (2.3∶1)
22 (2.2∶1)
57 (2.0∶1)
60 (4.0∶1)
0
Entry [Pd]
Solvent
Ligand Time/h
1d
2e
3
PdCl2
PdCl2
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
9
L1
9
L1
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
9
7
5
3
1
5
5
5
5
5
5
5
L1
L1
L1
L1
L1
L1
L1
－
4
5
6
PdCl2 (10 mol%)
HO
7
L1 (15 mol%)
+
F-N(SO2Ph)2
8
Pd(OAc)2 1,4-dioxane
Pd(dba)2 1,4-dioxane
OH
(6.0 equiv.)
CCl3CO2H (0.8 equiv.)
1,4-dioxane, r.t.
46% (1:1)
4
9
10f
11
12
13
14
－
1,4-dioxane
1,4-dioxane
1,4-dioxane
CH3NO2
O
O
PdCl2
PdCl2
PdCl2
PdCl2
0
L2
L3
L1
L1
F
+
F
51 (1.7∶1)
44 (2.4∶1)
75 (2.3∶1)
(2)
(3)
O
O
F
F
THF
5a
5b
a All reactions were conducted in 0.2 mmol; b 19F NMR yield with
PhCF3 as internal standard; The ratio of trans-2a∶cis-2a;
d without CCl3CO2H; CCl3CO2H was replaced by CF3CO2H;
F
F
c
standard
condition
F
OH
e
O
O
Ph
+ F-N(SO2Ph)2
Ph
+
f with or without L1.
Ph
(3.0 equiv.)
6
7b
7a
O
O
Further
Ph
Ph
oxyfluori-
nation
F
F
OH
redu. elimin.
PdCl2/L1
OH
LnPd
Ph
N
N
O
N
N
N
N
NFSI
L2
β-H elimination
L1
L3
Ph
8
F
Ph
O
O
Based on our previous studies,[9b,9f] a proposed
Ph
F
O
air
(1)
O
mechanism was showed in Scheme 1. the reaction is
initiated by oxidation of Pd(0) by NFSI to give PdII-F
complex I, which coordinates with substrate 1 to give
complex II.[11] With the following fluoropalladation of
styrenes, the intermediate III is oxidized by NFSI to
deliver Pd(IV) complex, which undergoes SN2-type nu-
cleophilic attack[12] to afford the cyclic product 2 and
releases Pd(II) species. Due to the poor selectivity of
cis- and trans-fluoropalladation, the reaction presents a
poor diastereoselectivity.
Ph
cis-2a
3
F
(Entries 5, 8, 9). But no reaction occurred in the absence
of palladium catalyst (Entry 10). In contrast to ligand
L1, other ligands were proven to be less compatible for
this transformation (Entries 11, 12). Solvent screening
suggested that ether solvents were better than other sol-
vents, and 1,4-dioxane gave the best yield (Entries 5, 13,
14).
With the optimized condition in hand, the substrate
scope was investigated and the results were summarized
in the Table 2. A wide range of styrenes were suitable
for this reaction. As the same with Z-1a, the reaction of
E-1a could also proceed smoothly to give desired prod-
uct 2a but in slightly lower yield and poor diastereose-
lectivity.[10] In addition, the substrates with electron-
donating group on the benzene ring gave the corre-
sponding products in moderate yields, and the substitu-
Conclusions
In conclusion, we have developed a palladium-
catalyzed intramolecular fluorooxylation of styrenes to
give corresponding fluorinated tetrahydro-furan com-
pounds. The methodology provides alternative route to
synthesize 2-aryl-3-fluoro-tetrahydrofuran derivatives.
Further study focuses on the improvement of diastereo-
Chin. J. Chem. 2013, 31, 908—914
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Yuan, Peng & Liu
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Table 2 Substrate scopea,b
PdCl2 (5 mol%)
L1 (7.5 mol%)
Ar
O
Ar
+
F-N(SO2Ph)2
OH
CCl3CO2H (0.4 equiv.)
1,4-dioxane, r.t.
F
NFSI
(3.0 equiv.)
1
2
O
O
O
O
F
F
F
2a
F
2b
2c
2a
72% (2.2 : 1)
48% (1 : 1)c
72% (2.4 : 1)
62% (2.7 : 1)
Ph
t-Bu
O
O
O
O
F
2e
F
2g
F
F
2f
2d
71% (2.2 : 1)
67% (2.2 : 1)
71% (2.8 : 1)
60% (1.5 : 1)
Br
F
O2N
O
OHC
O
O
O
F
F
F
F
2h
53% (1.3 : 1)
2i
48% (2.1 : 1)
2j
2k
54% (2.4 : 1)
71% (2.2 : 1)
a All reactions were conducted in 0.5 mmol; b isolated yield (the data in parentheses is the ratio of trans/cis); c 2a was got from E-1a.
Scheme 1 Proposed mechanism
chased from Aldrich or Alfa Aesar. NMR spectrum was
1
recorded on a Varian Inova 400 (400 MHz for H; 376
N
N
MHz for 19F; 100 MHz for 13C) or Aglient 400 spec-
trometer. The chemical shifts (δ) are given in parts per
million relative to internal standard TMS (0 ppm for 1H)
and CDCl3 (77.0 ppm for 13C).
Pd(0)
NFSI = FNZ2
(Z = SO2Ph)
F
F
Ar
N
General procedure
PdII
O
1
OH
Ar
N
2
In a dried Schlenk tube, PdCl2 (4.5 mg, 0.025 mmol),
Ligand L1 (8 mg, 0.0375 mmol), NFSI (470 mg, 1.5
mmol) were dissolved in fresh dried 1,4-dioxane (2.5
mL). Then substrate 1 (0.5 mmol) and a solution of
CCl3COOH in 1,4-dioxane (0.2 mol/L, 1 mL) were
added. The mixtrue was stirred at room temperature,
and monitored by TLC. After reaction completed, water
(10 mL) was added, and the mixture was extracted with
diethyl ether (20 mL×3). The organic layer was dried
over MgSO4, and filtered. After evaporation of diethyl
ether, the residue was purified by column chromatogra-
phy on silica gel with ethyl acetate/petroleum ether (1∶
30).
NZ2
I
F
NZ2
NZ2
N
N
N
PdII
PdIV
NZ2
F
F
N
Ar
HO
Ar
OH
F-
II
IV
N
II
N
NZ2
F
Pd
Ar
OH
O
III
F
selectivity, and this work is under process in our group.
trans-2a
1H NMR (400 MHz, CDCl3) δ: 7.40－7.25 (m, 5H),
5.15 (d, J＝25.5 Hz, 1H), 5.06 (dd, J＝53.1, 6.1 Hz,
1H), 4.28 (td, J＝8.4, 2.1 Hz, 1H), 4.12 (ddd, J＝10.8,
Experimental
All commercially available compounds were pur-
910
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Chin. J. Chem. 2013, 31, 908—914

Palladium-Catalyzed Intramolecular Fluorooxylation of Styrenes
8.4, 6.1 Hz, 1H), 2.27－1.98 (m, 2H); 13C NMR (100
MHz, CDCl3) δ: 139.4 (d, J＝10.2 Hz), 128.5, 127.7,
125.4, 99.4 (d, J＝180.8 Hz), 85.8 (d, J＝25.1 Hz), 67.5,
32.1 (d, J＝21.0 Hz); 19F NMR (376 MHz, CDCl3) δ:
−173.1 (dddd, J＝54.6, 38.3, 25.6, 21.9 Hz).
5.05 (dd, J＝54.7, 4.5 Hz, 1H), 4.28 (td, J＝8.4, 2.1 Hz,
1H), 4.11 (ddd, J＝10.7, 8.3, 6.1 Hz, 1H), 2.35 (s, 3H),
2.25－1.98 (m, 2H); 13C NMR (100 MHz, CDCl3) δ:
139.3 (d, J＝10.4 Hz), 138.2, 128.48, 128.43, 126.0,
122.4, 99.4 (d, J＝180.6 Hz), 85.8 (d, J＝25.0 Hz), 67.4,
32.1 (d, J＝21.0 Hz), 21.4; 19F NMR (376 MHz, CDCl3)
δ: −172.9 (dddd, J＝54.7, 38.2, 25.8, 22.1 Hz). HRMS:
m/z (EI) calculated C11H13FO [M]＋: 180.0950, meas-
ured: 180.0951.
O
F
cis-2a
1H NMR (400 MHz, CDCl3) δ: 7.45－7.26 (m, 5H),
5.18 (dm, J＝53.2 Hz, 1H), 4.82 (dd, J＝28.6, 2.9 Hz,
1H), 4.29 (q, J＝8.0 Hz, 1H), 4.04 (td, J＝8.4, 4.2 Hz,
1H), 2.42－2.23 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ: 135.97 (d, J＝4.5 Hz), 128.1, 127.8, 127.0 (d, J＝1.2
Hz), 93.9 (d, J＝184.4 Hz), 84.3 (d, J＝19.4 Hz), 66.6,
33.8 (d, J＝22.1 Hz); 19F NMR (376 MHz, CDCl3) δ:
−187.0 (m).
O
F
cis-2c
1H NMR (400 MHz, CDCl3) δ: 7.28－7.20 (m, 2H),
7.18 (d, J＝7.6 Hz, 1H), 7.11 (d, J＝7.4 Hz, 1H), 5.17
(dm, J＝53.2 Hz, 1H), 4.78 (dd, J＝28.7, 2.8 Hz, 1H),
4.29 (q, J＝8.2 Hz, 1H), 2.36 (s, 3H), 2.44－2.22 (m,
2H); 13C NMR (100 MHz, CDCl3) δ: 137.7, 135.8 (d,
J＝4.6 Hz), 128.5, 127.9, 127.6 (d, J＝0.9 Hz), 124.0 (d,
J＝0.8 Hz), 93.9 (d, J＝185.2 Hz), 84.3 (d, J＝19.4 Hz),
66.6, 33.7 (d, J＝22.1 Hz), 21.4; 19F NMR (376 MHz,
CDCl3) δ: −186.1－−187.2 (m). HRMS: m/z (EI) calcu-
lated C11H13FO [M]＋: 180.0950, measured: 180.0948.
O
F
trans-2b
1H NMR (400 MHz, CDCl3) δ: 7.21 (d, J＝8.1 Hz,
2H), 7.16 (d, J＝8.1 Hz, 2H), 5.12 (d, J＝25.5 Hz, 1H),
5.04 (dd, J＝54.7, 4.5 Hz, 1H), 4.27 (td, J＝8.4, 2.1 Hz,
1H), 4.11 (ddd, J＝10.7, 8.3, 6.1 Hz, 1H), 2.34 (s, 3H),
2.26－1.98 (m, 2H); 13C NMR (100 MHz, CDCl3) δ:
137.4, 136.4 (d, J＝10.6 Hz), 129.2, 125.3, 99.4 (d, J＝
180.5 Hz), 85.8 (d, J＝25.0 Hz), 67.4, 32.1 (d, J＝21.0
Hz), 21.1; 19F NMR (376 MHz, CDCl3) δ: −173.0 (dddd,
J＝54.7, 38.2, 25.6, 22.1 Hz). HRMS: m/z (EI) calcu-
lated C11H13FO [M]＋: 180.0950, measured: 180.0945.
O
F
trans-2d
1H NMR (400 MHz, CDCl3) δ: 7.38－7.31 (m, 1H),
7.24－7.12 (m, 3H), 5.31 (d, J＝26.3 Hz, 1H), 4.99 (dd,
J＝54.8, 4.3 Hz, 1H), 4.36 (t, J＝8.4 Hz, 1H), 4.14 (ddd,
J＝11.5, 8.3, 5.5 Hz, 1H), 2.38 (s, 3H), 2.26－1.96 (m,
2H); 13C NMR (100 MHz, CDCl3) δ: 137.6 (d, J＝10.8
Hz), 134.5, 130.3, 127.5, 126.1, 124.8 (d, J＝1.2 Hz),
98.6 (d, J＝181.2 Hz), 83.8 (d, J＝25.2 Hz), 67.7, 32.1
(d, J＝20.9 Hz), 19.2; 19F NMR (376 MHz, CDCl3) δ:
−172.4 (dddd, J＝54.9, 40.3, 26.3, 20.9 Hz). HRMS:
m/z (EI) calculated C11H13FO [M]＋: 180.0950, meas-
ured: 180.0946.
O
F
cis-2b
1H NMR (400 MHz, CDCl3) δ: 7.28 (d, J＝8.0 Hz,
2H), 7.18 (d, J＝8.0 Hz, 2H), 5.16 (dm, J＝42.0 Hz,
1H), 4.80 (dd, J＝28.6, 2.9 Hz, 1H), 4.29 (q, J＝8.2 Hz,
1H), 4.07－4.00 (m, 1H), 2.43－2.23 (m, 2H), 2.35 (s,
3H); 13C NMR (100 MHz, CDCl3) δ: 137.5, 132.9 (d,
J＝4.5 Hz), 128.8, 126.9 (d, J＝1.1 Hz), 93.9 (d, J＝
185.1 Hz), 84.2 (d, J＝19.3 Hz), 66.6, 33.8 (d, J＝22.1
Hz), 21.2; 19F NMR (376 MHz, CDCl3) δ: −186.8－
−187.3 (m). HRMS: m/z (EI) calculated C11H13FO [M]＋:
180.0950, measured: 180.0954.
O
F
cis-2d
1H NMR (400 MHz, CDCl3) δ: 7.55 (d, J＝7.1 Hz,
1H), 7.27－7.11 (m, 3H), 5.29 (dm, J＝53.6 Hz, 1H),
5.01 (dd, J＝28.1, 3.1 Hz, 1H), 4.29 (q, J＝8.0 Hz, 1H),
4.02 (td, J＝8.2, 5.7 Hz, 1H), 2.50－2.27 (m, 2H), 2.32
(s, 3H); 13C NMR (100 MHz, CDCl3) δ: 134.2 (d, J＝
5.1 Hz), 134.1, 129.9, 127.5, 127.0 (d, J＝1.4 Hz),
125.8, 92.1 (d, J＝185.0 Hz), 81.5 (d, J＝20.0 Hz), 66.2,
34.1 (d, J＝22.2 Hz), 19.3; 19F NMR (376 MHz, CDCl3)
δ: −185.3－−185.7 (m). HRMS: m/z (EI) calculated
C11H13FO [M]＋: 180.0950, measured: 180.0949.
O
F
trans-2c
1H NMR (400 MHz, CDCl3) δ: 7.24 (t, J＝7.5 Hz,
1H), 7.15－7.06 (m, 3H), 5.11 (d, J＝25.7 Hz, 1H),
Chin. J. Chem. 2013, 31, 908—914
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Yuan, Peng & Liu
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t-Bu
(100 MHz, CDCl3) δ: 137.6, 135.7 (d, J＝4.5 Hz), 129.5,
124.6 (d, J＝0.8 Hz), 94.0 (d, J＝185.1 Hz), 84.3 (d,
J＝19.4 Hz), 66.6, 33.8 (d, J＝22.1 Hz), 21.3. 19F NMR
(376 MHz, CDCl3) δ: −186.6－−187.1 (m). HRMS: m/z
(EI) calculated C12H15FO [M]＋: 194.1107, measured:
194.1105.
O
F
trans-2e
1H NMR (400 MHz, CDCl3) δ: 7.37 (d, J＝8.3 Hz,
2H), 7.25 (d, J＝8.2 Hz, 2H), 5.12 (d, J＝25.5 Hz, 1H),
5.07 (dd, J＝54.7, 4.5 Hz, 1H), 4.27 (td, J＝8.3, 2.2 Hz,
1H), 4.10 (ddd, J＝10.5, 8.3, 6.2 Hz, 1H), 2.26－1.96
(m, 2H), 1.31 (s, 9H); 13C NMR (100 MHz, CDCl3) δ:
150.7, 136.4 (d, J＝10.5 Hz), 125.4, 125.2, 99.3 (d, J＝
180.4 Hz), 85.7 (d, J＝24.9 Hz), 67.3, 34.5, 32.2 (d, J＝
20.9 Hz), 31.3; 19F NMR (376 MHz, CDCl3) δ: −173.0
Ph
O
F
trans-2g
1H NMR (400 MHz, CDCl3) δ: 7.60－7.54 (m, 4H),
7.46－7.30 (m, 5H), 5.19 (d, J＝25.6 Hz, 1H), 5.09 (dd,
J＝55.2, 3.7 Hz, 1H), 4.30 (td, J＝8.4, 2.1 Hz, 1H),
4.13 (ddd, J＝10.7, 8.4, 6.1 Hz, 1H), 2.27－2.00 (m,
2H); 13C NMR (100 MHz, CDCl3) δ: 140.6, 140.6,
138.4 (d, J＝10.5 Hz), 128.7, 127.3, 127.2, 127.0, 125.8,
99.3 (d, J＝181.1 Hz), 85.6 (d, J＝25.2 Hz), 67.5, 32.1
(d, J＝20.9 Hz); 19F NMR (376 MHz, CDCl3) δ: −173.0
(dddd, J＝54.6, 38.1, 25.5, 22.0 Hz). HRMS: m/z (EI)
(dddd, J＝54.7, 38.0, 25.7, 22.3 Hz). HRMS: m/z (EI)
calculated C14H19FO [M] : 222.1420, measured:
＋
222.1423.
t-Bu
O
F
cis-2e
1H NMR (400 MHz, CDCl3) δ: 7.40 (d, J＝8.5 Hz,
2H), 7.32 (d, J＝8.5 Hz, 2H), 5.16 (dm, J＝54 Hz, 1H),
4.78 (dd, J＝28.8, 2.8 Hz, 1H), 4.28 (q, J＝8.1 Hz, 1H),
4.08－3.97 (m, 1H), 2.43－2.22 (m, 2H), 1.32 (s, 9H);
13C NMR (100 MHz, CDCl3) δ: 150.7, 132.9 (d, J＝4.3
Hz), 126.8 (d, J＝1.1 Hz), 125.0, 93.9 (d, J＝185.2 Hz),
84.2 (d, J＝19.2 Hz), 66.5, 34.5, 33.8 (d, J＝22.1 Hz),
31.3; 19F NMR (376 MHz, CDCl3) δ: −186.7－−187.2
(m). HRMS: m/z (EI) calculated C14H19FO [M] ＋ :
222.1420, measured: 222.1421.
＋
calculated C16H15FO [M] : 242.1107, measured:
242.1104.
Ph
O
F
cis-2g
1H NMR (400 MHz, CDCl3) δ: 7.62－7.56 (m, 4H),
7.49－7.39 (m, 4H), 7.37－7.29 (m, 1H), 5.21 (dm, J＝
53.7 Hz, 1H), 4.85 (dd, J＝28.6, 2.8 Hz, 1H), 4.31 (q,
J＝8.1 Hz, 1H), 4.05 (td, J＝8.5, 4.8 Hz, 1H), 2.47－
2.22 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 140.8 (d,
J＝18.9 Hz), 135.0 (d, J＝4.6 Hz), 128.7, 127.4, 127.4,
127.2, 127.1, 126.9, 94.0 (d, J＝185.1 Hz), 84.1 (d, J＝
19.2 Hz), 66.7, 33.8 (d, J＝22.0 Hz); 19F NMR (376
MHz, CDCl3) δ: −186.7－−187.2 (m). HRMS: m/z (EI)
O
F
trans-2f
1H NMR (400 MHz, CDCl3) δ: 6.93 (s, 2H), 6.92 (s,
1H), 5.07 (d, J＝26.4 Hz, 1H), 5.05 (dd, J＝54.8, 4.5
Hz, 1H), 4.28 (td, J＝8.3, 2.2 Hz, 1H), 4.10 (ddd, J＝
10.5, 8.3, 6.2 Hz, 1H), 2.31 (s, 6H), 2.25－1.99 (m, 2H);
13C NMR (100 MHz, CDCl3) δ: 139.3 (d, J＝10.3 Hz),
138.1, 129.3, 123.1, 99.5 (d, J＝180.6 Hz), 85.9 (d, J＝
25.0 Hz), 67.4, 32.2 (d, J＝20.9 Hz), 21.3; 19F NMR
(376 MHz, CDCl3) δ: −173.0 (dddd, J＝55.0, 37.9, 25.9,
22.5 Hz). HRMS: m/z (EI) calculated C12H15FO [M]＋:
194.1107, measured: 194.1110.
＋
calculated C16H15FO [M] : 242.1107, measured:
242.1109.
O2N
O
F
trans-2h
1H NMR (400 MHz, CDCl3) δ: 8.23 (s, 1H), 8.15 (d,
J＝8.1 Hz, 1H), 7.69 (d, J＝8.3 Hz, 1H), 7.55 (t, J＝7.9
Hz, 1H), 5.20 (d, J＝25.1 Hz, 1H), 5.07 (dd, J＝54.4,
4.9 Hz, 1H), 4.35 (td, J＝8.5, 1.9 Hz, 1H), 4.16 (ddd,
J＝11.0, 8.5, 5.9 Hz, 1H), 2.33－1.98 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ: 148.4, 141.7 (d, J＝10.5
Hz), 131.5, 129.5, 122.8, 120.4, 99.0 (d, J＝182.6 Hz),
84.8 (d, J＝26.4 Hz), 67.8, 32.1 (d, J＝21.0 Hz); 19F
NMR (376 MHz, CDCl3) δ: −173.7 (dddd, J＝54.4,
37.3, 25.1, 21.5 Hz). HRMS: m/z (EI) calculated
C10H10FNO3 [M]＋: 211.0645, measured: 211.0648.
O
F
cis-2f
1H NMR (400 MHz, CDCl3) δ: 7.01 (s, 2H), 6.93 (s,
1H), 5.28－5.08 (dm, J＝53.6 Hz, 1H), 4.76 (dd, J＝
28.8, 2.8 Hz, 1H), 4.29 (q, J＝8.1 Hz, 1H), 4.07－3.98
(m, 1H), 2.42－2.22 (m, 2H), 2.32 (s, 6H); 13C NMR
912
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Chin. J. Chem. 2013, 31, 908—914

Palladium-Catalyzed Intramolecular Fluorooxylation of Styrenes
5.01 (dd, J＝54.6, 4.8 Hz, 1H), 4.27 (td, J＝8.5, 1.9 Hz,
1H), 4.11 (ddd, J＝10.9, 8.4, 5.9 Hz, 1H), 2.28－1.94
(m, 2H); 13C NMR (100 MHz, CDCl3) δ: 138.4 (d, J＝
10.4 Hz), 131.6, 127.1, 121.6, 99.2 (d, J＝181.5 Hz),
85.2 (d, J＝25.4 Hz), 67.5, 32.1 (d, J＝21.0 Hz). 19F
NMR (376 MHz, CDCl3) δ: −173.4 (dddd, J＝54.5,
38.0, 25.3, 21.5 Hz). HRMS: m/z (EI) calculated
C10H10BrFO [M]＋: 243.9899, measured: 243.9898.
O2N
O
F
cis-2h
1H NMR (400 MHz, CDCl3) δ: 8.25 (d, J＝9.7 Hz,
1H), 8.16 (dd, J＝8.2, 1.1 Hz, 1H), 7.72 (d, J＝7.7 Hz,
1H), 7.54 (t, J＝7.9 Hz, 1H), 5.27 (d, J＝52.0 Hz, 1H),
4.95 (dd, J＝27.7, 2.8 Hz, 1H), 4.33 (q, J＝8.1 Hz, 1H),
4.11 (td, J＝8.4, 5.4 Hz, 1H), 2.48－2.28 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ: 148.1, 138.4 (d, J＝5.3 Hz),
133.1 (d, J＝1.0 Hz), 129.0, 122.8, 122.1 (d, J＝0.8 Hz),
93.7 (d, J＝185.8 Hz), 83.2 (d, J＝19.4 Hz), 67.0, 33.7
(d, J＝21.8 Hz); 19F NMR (376 MHz, CDCl3) δ: −187.0
－−187.5 (m). HRMS: m/z (EI) calculated C10H10FNO3
[M]＋: 211.0645, measured: 211.0646.
Br
O
F
cis-2j
1H NMR (400 MHz, CDCl3) δ: 7.49 (d, J＝8.5 Hz,
2H), 7.27 (d, J＝8.5 Hz, 2H), 5.16 (dm, J＝53.2 Hz,
1H), 4.78 (dd, J＝28.2, 2.8 Hz, 1H), 4.28 (q, J＝8.2 Hz,
1H), 4.08－4.00 (m, 1H), 2.43－2.24 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ: 135.1 (d, J＝4.7 Hz), 131.2,
128.7 (d, J＝1.0 Hz), 121.7, 93.7 (d, J＝185.5 Hz), 83.7
(d, J＝19.3 Hz), 66.7, 33.7 (d, J＝22.0 Hz). 19F NMR
(376 MHz, CDCl3) δ: −187.0－−187.5 (m). HRMS: m/z
(EI) calculated C10H10BrFO [M]＋: 243.9899, measured:
243.9904.
OHC
O
F
trans-2i
1H NMR (400 MHz, CDCl3) δ: 10.03 (s, 1H), 7.87 (s,
1H), 7.81 (d, J＝7.5 Hz, 1H), 7.62 (d, J＝7.8 Hz, 1H),
7.54 (t, J＝7.6 Hz, 1H), 5.20 (d, J＝25.4 Hz, 1H), 5.07
(dd, J＝54.5, 4.8 Hz, 1H), 4.33 (td, J＝8.5, 1.9 Hz, 1H),
4.15 (ddd, J＝10.9, 8.5, 5.9 Hz, 1H), 2.32－1.99 (m,
2H); 13C NMR (100 MHz, CDCl3) δ: 192.0, 140.7 (d,
J＝10.5 Hz), 136.5, 131.4, 129.2, 129.2, 126.4, 99.1 (d,
J＝181.8 Hz), 85.2 (d, J＝25.8 Hz), 67.6, 32.1 (d, J＝
21.0 Hz); 19F NMR (376 MHz, CDCl3) δ: −173.4 (dddd,
J＝54.5, 37.7, 25.3, 21.6 Hz). HRMS: m/z (EI) calcu-
lated C11H11FO2 [M]＋: 194.0743, measured: 194.0741.
F
O
F
trans-2k
1H NMR (400 MHz, CDCl3) δ: 7.33－7.27 (dd, J＝
8.7, 5.4 Hz, 2H), 7.08－7.01 (m, 2H), 5.11 (d, J＝25.0
Hz, 1H), 5.02 (dd, J＝53.4, 5.9 Hz, 1H), 4.28 (td, J＝
8.5, 2.0 Hz, 1H), 4.11 (ddd, J＝10.8, 8.4, 5.9 Hz, 1H),
2.28－1.97 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:
162.3 (d, J＝245.9 Hz), 135.1 (dd, J＝10.3, 3.1 Hz),
127.1 (d, J＝8.2 Hz), 115.4 (d, J＝21.5 Hz), 99.3 (dd,
J＝181.1, 1.1 Hz), 85.3 (d, J＝25.7 Hz), 67.5, 32.1 (d,
J＝21.0 Hz); 19F NMR (376 MHz, CDCl3) δ: −114.8－
−114.9 (m), −173.5 (dddd, J＝54.6, 37.8, 25.4, 21.8 Hz).
HRMS: m/z (EI) calculated C10H10F2O [M]＋: 187.0700,
measured: 187.0697.
OHC
O
F
cis-2i
1H NMR (400 MHz, CDCl3) δ: 10.03 (s, 1H), 7.91 (s,
1H), 7.83 (d, J＝7.6 Hz, 1H), 7.67 (d, J＝7.6 Hz, 1H),
7.54 (t, J＝7.6 Hz, 1H), 5.24 (dm, J＝53.4 Hz, 1H),
4.92 (dd, J＝28.1, 2.8 Hz, 1H), 4.32 (q, J＝8.0 Hz, 1H),
4.09 (td, J＝8.5, 5.0 Hz, 1H), 2.47－2.27 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ: 192.3, 137.4 (d, J＝4.9 Hz),
136.3, 133.1, 129.2, 128.8, 128.3, 93.8 (d, J＝185.5 Hz),
83.7 (d, J＝19.4 Hz), 66.9, 33.8 (d, J＝21.9 Hz); 19F
NMR (376 MHz, CDCl3) δ: −187.0 － −187.4 (m).
HRMS: m/z (EI) calculated C11H11FO2 [M]＋: 194.0743,
measured: 194.0741.
F
O
F
cis-2k
1H NMR (400 MHz, CDCl3) δ: 7.36 (dd, J＝8.5, 5.7
Hz, 2H), 7.09－7.00 (m, 2H), 5.25－5.05 (dm, J＝53.2
Hz 1H), 4.79 (dd, J＝28.3, 2.7 Hz, 1H), 4.28 (q, J＝8.1
Hz, 2H), 4.08－3.99 (m, 1H), 2.45－2.24 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ: 162.4 (d, J＝245.6 Hz),
131.7 (dd, J＝3.4, 4.9 Hz), 128.8 (dd, J＝8.1, 1.1 Hz),
115.0 (d, J＝21.5 Hz), 93.8 (dd, J＝186.2, 2.6 Hz), 83.7
(d, J＝19.3 Hz), 66.6, 33.7 (d, J＝22.1 Hz); 19F NMR
(376 MHz, CDCl3) δ: −114.7－−114.8 (m), −187.1－
Br
O
F
trans-2j
1H NMR (400 MHz, CDCl3) δ: 7.48 (d, J＝8.5 Hz,
2H), 7.21 (d, J＝8.3 Hz, 2H), 5.08 (d, J＝25.2 Hz, 1H),
Chin. J. Chem. 2013, 31, 908—914
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
913

Yuan, Peng & Liu
FULL PAPER
−187.6 (m). HRMS: m/z (EI) calculated C10H10F2O
National Basic Research Program of China (No.
973-2011CB808700), the National Natural Science
Foundation of China (Nos. 21225210, 21121062, and
20923005), the Science Technology Commission of the
Shanghai Municipality (No. 11JC1415000) and the
CAS/SAFEA International Partnership Program for
Creative Research Teams.
[M]＋: 187.0700, measured: 187.0696.
O
F
O
F
5a
1H NMR (400 MHz, CDCl3) δ: 7.32 (s, 4H), 5.13 (d,
J＝25.1 Hz, 2H), 5.04 (dd, J＝54.0, 5.0 Hz, 2H), 4.28
(td, J＝8.5, 1.9 Hz, 2H), 4.11 (ddd, J＝10.8, 8.4, 6.0 Hz,
2H), 2.28－1.96 (m, 4H); 13C NMR (100 MHz, CDCl3)
δ: 139.0 (dd, J＝10.4, 0.8 Hz), 125.6, 99.3 (d, J＝181.1
Hz), 85.6 (dd, J＝25.3, 2.0 Hz), 67.5, 32.1 (d, J＝21.0
Hz); 19F NMR (376 MHz, CDCl3) δ: −173.2 (ddddd,
J＝62.8, 38.0, 25.6, 21.8, 16.2 Hz). HRMS: m/z (EI)
calculated C14H16F2O2 [M] ＋ : 254.1118, measured:
254.1119.
References
[1] (a) Kirsch, P. Modern Fluoroorganic Chemistry, Wiley-VCH,
Weinheim, 2004; (b) Purser, S. P.; Moore, R.; Swallow, S.; Gou-
verneur, V. Chem. Soc. Rev. 2008, 37, 320.
[2] (a) Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic Chem-
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Takenoshita, H.; Ishiyama, T.; Iimura, S.; Hirota, Y.; Mitsui, I.;
Terasawa, H.; Soga, T. Chem. Pharm. Bull. 1997, 45, 1793; (c)
Arimitsu, S.; Hammond, G. B. J. Org. Chem. 2007, 72, 8559.
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waguchi, M.; Hara, S.; Fukuhara, T.; Yoneda, N. J. Fluorine Chem.
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T.; Taguchi, T. J. Fluorine Chem. 1997, 82, 157; (f) Lourie, L. F.;
Serguchev, Y. A.; Ponomarenko, M. V.; Rusanov, E. B.; Vovk, M.
V.; Ignat’ev, N. V. Tetrahedron 2013, 69, 833.
O
F
O
F
5b
1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J＝8.3 Hz,
2H), 7.32 (d, J＝8.2 Hz, 2H), 5.20 (dm, J＝52.8 Hz,
1H), 5.16 (d, J＝25.1 Hz, 1H), 5.07 (d, J＝54.6 Hz, 1H),
4.81 (dd, J＝28.6, 2.8 Hz, 1H), 4.32－4.24 (m, 2H),
4.11 (ddd, J＝10.8, 8.3, 6.0 Hz, 1H), 4.07－4.00 (m,
1H), 2.48－2.25 (m, 2H), 2.25－1.97 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ: 138.9 (dd, J＝10.6, 1.3 Hz),
135.5 (dd, J＝4.6, 1.1 Hz), 127.2, 125.1, 99.4 (dd, J＝
180.7, 1.4 Hz), 93.9 (dd, J＝185.3, 2.0 Hz), 85.6 (dd,
J＝25.0, 2.4 Hz), 84.0 (dd, J＝19.3, 4.2 Hz), 67.4, 66.6,
33.7 (d, J＝22.1 Hz), 32.00 (d, J＝21.0 Hz); 19F NMR
(376 MHz, CDCl3) δ: −172.9－−173.3 (m), −186.9－
−187.3 (m). HRMS: m/z (EI) calculated C14H16F2O2
[M]＋: 254.1118, measured: 254.1124.
[4] (a) Welch, J. T. Tetrahedron 1987, 43, 3123; (b) Inagaki, T.; Naka-
mura, Y.; Sawaguchi, M.; Yoneda, N.; Ayuba, S.; Hara, S. Tetrahe-
dron Lett. 2003, 44, 4117.
[5] For some recent reviews on transition metal-catalyzed fluorination,
see: (a) Brown, J. M.; Gouverneur, V. Angew. Chem., Int. Ed. 2009,
48, 8610; (b) Grushin, V. V. Acc. Chem. Res. 2010, 43, 160; (c) Fu-
ruya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470; (d) Hop-
kinson, M. N.; Gee, A. D.; Gouverneur, V. Isr. J. Chem. 2010, 50,
675; (e) Liu, G. Org. Biomol. Chem. 2012, 10, 6243; (f) Lv, C.;
Shen, Q.; Liu, D. Chin. J. Org. Chem. 2012, 32, 1380 (in Chinese);
(g) Qing, F. Chin. J. Org. Chem. 2012, 32, 815 (in Chinese).
[6] Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006,
128, 7134.
[7] Tang, P.; Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2010, 132, 12150.
[8] (a) Akana, J. A.; Bhattacharyya, K. X.; Muller, P.; Sadighi, J. P. J.
Am. Chem. Soc. 2007, 129, 7736; (b) Schuler, M.; Silva, F.; Bobbio,
C.; Tessier, A.; Gouverneur, V. Angew. Chem., Int. Ed. 2008, 47,
7927; (c) de Haro, T.; Nevado, C. Chem. Commun. 2011, 47, 248; (d)
de Haro, T.; Nevado, C. Adv. Synth. Catal. 2010, 352, 2767; (e)
Qian, J.; Liu, Y.; Zhu, J.; Jiang, B.; Xu, Z. Org. Lett.2011, 13, 4220.
[9] (a) Wu, T.; Yin, G.; Liu, G. J. Am. Chem. Soc. 2009, 131, 16354; (b)
Qiu, S.; Xu, T.; Zhou, J.; Guo, Y.; Liu, G. J. Am. Chem. Soc. 2010,
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Ed. 2011, 50, 8176; (d) Peng, H.; Liu, G. Org. Lett. 2011, 13, 772; (e)
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2012, 70, 2404 (in Chinese).
F
Ph
O
7a
1H NMR (400 MHz, CDCl3) δ: 7.45－7.40 (m, 2H),
7.39－7.32 (m, 2H), 7.31－7.24 (m, 1H), 4.40 (d, J＝
48.0 Hz, 2H), 4.07 (dd, J＝14.2, 7.3 Hz, 1H), 3.94 (dd,
J＝14.4, 7.3 Hz, 1H), 2.50－2.36 (m, 1H), 2.22－2.10
(m, 1H), 2.10－1.95 (m, 1H), 1.93－1.78 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 142.6 (d, J＝4.7 Hz), 128.2,
127.3, 125.6, 87.5 (d, J＝181.4 Hz), 85.6 (d, J＝17.9
Hz), 68.6, 33.9 (d, J＝3.0 Hz), 26.0; 19F NMR (376
MHz, CDCl3) δ: −220.8 (t, J＝48.0 Hz).
[10] The observation of poor diastereoselectivity from the reaction of
E-1a possibly resulted from the facile oxidation of cis-2a.
[11] The free F anion is possibly generated from the reaction of NFSI
with Pd catalyst, for details, see reference 9d.
Acknowledgement
[12] For details, see reference 9f.
We are grateful for the financial support from the
(Lu, Y.)
914
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Chin. J. Chem. 2013, 31, 908—914