P-Spiro phosphonium salts catalyzed asymmetric fluorination of 3-substituted benzofuran-2(3H)-ones

Article abstract of DOI:10.1016/j.jfluchem.2013.03.007

Abstract Asymmetric electrophilic fluorination of 3-substituted benzofuran-2(3H)-ones was realized under liquid-liquid phase-transfer catalysis with 2 mol% of chiral phosphonium salts to afford the fluorinated products with up to 96% yield and 56% ee.

Full text of DOI:10.1016/j.jfluchem.2013.03.007

Journal of Fluorine Chemistry 150 (2013) 60–66
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
P-Spiro phosphonium salts catalyzed asymmetric fluorination of
3-substituted benzofuran-2(3H)-ones
a,
Chuan-Le Zhu a,b, Xiao-Yun Fu a, Ai-Jia Wei a, Dominique Cahard b, , Jun-An Ma
*
*
a Department of Chemistry, Tianjin University, Tianjin 300072, China
b UMR 6014 CNRS, laboratoire COBRA de l’IRCOF, Universite´ et INSA de Rouen, Mont Saint Aignan, France
A R T I C L E I N F O
A B S T R A C T
Article history:
Asymmetric electrophilic fluorination of 3-substituted benzofuran-2(3H)-ones was realized under
liquid–liquid phase-transfer catalysis with 2 mol% of chiral phosphonium salts to afford the fluorinated
products with up to 96% yield and 56% ee.
Received 27 February 2013
Received in revised form 11 March 2013
Accepted 12 March 2013
Available online 18 March 2013
ß 2013 Elsevier B.V. All rights reserved.
Keywords:
Phosphonium salts
Phase-transfer catalysis
Fluorination
Enantioselectivity
Benzofuran-2(3H)-ones
1. Introduction
investigating benzofuran-2(3H)-ones that feature a chiral quater-
nary center at the C3 position of the heterocyclic ring as privileged
The unique physical and chemical advantages resulting from
the presence of fluorine atom(s) on chiral organic compounds used
in pharmaceutical [1–3], agrochemical [4–6], and materials
industries [7,8] have led to a rapidly increasing need for synthetic
methodologies providing efficient and practical access to chiral
organofluorine molecules. In this context, considerable works on
catalytic enantioselective electrophilic fluorination have been
reported over the last decade. Both chiral metal complex-catalyzed
reactions and organocatalysis have been intensively explored in
catalytic enantioselective fluorinations [9–14]. A tool of choice in
asymmetric synthesis is the phase-transfer catalysis [15–19] that
exploits many chiral ammonium salts and in a lesser extent chiral
phosphonium salts [20–28] as powerful catalysts in many
asymmetric reactions. Chiral ammonium salts have demonstrated
structural motifs encountered in many natural products [31–35]
and potential medicines [36,37]. Enantioselective syntheses of
these important chiral benzofuran-2(3H)-ones have been de-
scribed through C-C bond formation at C3 [38–44]. However,
enantioselective creation of a carbon–heteroatom bond at the C3
position is less explored. In 2011, we reported a phosphonium salt
catalyzed asymmetric electrophilic amination of benzofuran-
2(3H)-ones by (E)-dibenzyl diazene-1, 2-dicarboxylate leading to
the corresponding amino derivatives in up to 99% ee [27].
Development of new asymmetric reactions for the synthesis of
chiral fluorinated compounds has been of our interest and research
objective [45–50]. As part of our ongoing studies, herein we
present our results on the enantioselective electrophilic fluorina-
tion of 3-substituted benzofuran-2(3H)-ones with the aid of
phosphonium salts as chiral catalysts.
high efficiency in asymmetric fluorination of b-keto esters [29,30];
however, to the best of our knowledge, a chiral phosphonium salt
has never been reported in a catalyzed enantioselective electro-
philic fluorination. Application of phase-transfer catalysis in the
field of organofluorine chemistry still requires further research
investigation, in particular for a comparison of ammonium versus
phosphonium salts in a given reaction and a comparison of a
catalyst family in different reactions. In our laboratory, we are
2. Results and discussion
Our investigations started with the reaction conditions that
were successful for the electrophilic amination of benzofuran-
2(3H)-one [27]: 2 mol% of (S)-3c at room temperature in toluene
for 48 h without base and in the presence of N-fluorobis(benze-
nesulfonimide) (NFSI) instead of the amination reagent. Unfortu-
nately, we recovered the starting material quantitatively without
any formation of the desired fluorinated product (Table 1, entry 1).
Base-free conditions don’t seem appropriate in the fluorination
* Corresponding authors. Tel.: +86 22 2740 2903; fax: +86 22 2740 3475.
E-mail address: majun_an68@tju.edu.cn (J.-A. Ma).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.03.007

C.-L. Zhu et al. / Journal of Fluorine Chemistry 150 (2013) 60–66
61
Table 1
Screening of the reaction conditions.a
.
Entry
3 (mol%)
Base
–
Solvent ([conc.] (M))
Toluene (0.1)
Time (h)
Yield (%)b
Ee (%)c
1
2
3c (2)
3c (2)
3c (2)
3c (2)
3c (2)
3c (2)
3c (2)
3c (2)
3c (2)
3a (2)
3b (2)
3d (2)
3e (2)
3f (2)
3e (2)
3e (2)
3e (2)
3e (2)
3e (2)
3e (2)
3e (2)
3e (2)
3e (2)
3f (2)
3e (2)
3e (5)
3e (2)
3e (2)
3e (0.2)
48
144
144
144
72
12
144
72
72
72
72
72
72
72
72
96
72
12
12
24
12
12
12
12
12
12
48
12
48
0
54
23
0
0
40
47
0
K2HPO4 (3 equiv)
Toluene (0.1)
Toluene (0.1)
Toluene (0.1)
Toluene (0.1)
Toluene (0.1)
Toluene (0.2)
Toluene (0.33)
Toluene (1)
3
K2CO3 (3 equiv)
4
KOH (3 equiv)
5
Et3N (1.1 equiv)
17
78
76
76
52
76
74
78
78
78
32
42
88
93
0
3
6
DMAP (1.1 equiv)
12
40
39
34
15
20
33
50
45
20
32
46
50
0
7
K2HPO4 (3 equiv)
8
K2HPO4 (3 equiv)
9
K2HPO4 (3 equiv)
10
11
12
13
14
15d
16
17
18
19
20
21
22
23
24
25
26
27e
28f
29
K2HPO4 (3 equiv)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Benzene (0.33)
Xylene (0.33)
THF (0.33)
K2HPO4 (3 equiv)
K2HPO4 (3 equiv)
K2HPO4 (3 equiv)
K2HPO4 (3 equiv)
K2HPO4 (3 equiv)
10% aq. K2HPO4 (0.1 mL)
30% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K3PO4 (0.1 mL)
50% aq. K2HPO4 (0.05 mL)
50% aq. K2HPO4 (0.2 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
50% aq. K2HPO4 (0.1 mL)
92
93
90
89
88
79
93
60
87
91
49
50
43
47
11
5
CH2Cl2 (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
Toluene (0.33)
50
50
6
47
a
The reactions were carried out with 3-benzylbenzofuran-2(3H)-one 1a (0.1mmol) and N-fluorobis(benzenesulfonimide) (0.15mmol) in the presence of 2mol% of catalyst 3.
b
c
d
e
f
Isolated yield.
Determined by HPLC analysis using a chiral stationary phase.
˚
4 A MS (50 mg) was used as additive.
The reaction was run at 0 8C.
1.5 equiv of Selectfluor was used as fluorinating agent.
process; indeed, when 3 equivalents of anhydrous K2HPO4 was
employed as base, we obtained product 2a in 54% yield and 40% ee
although after a long reaction time (Table 1, entry 2). The use of
other bases, e.g. K2CO3, KOH, Et3N, and DMAP, resulted in either a
decreased yield or a complete loss of enantioselectivity (Table 1,
entries 3–6). It is worth noting that the low yield of the desired
fluorinated product obtained in the presence of K2CO3 was partly
due to the formation of 28% of 3-benzylidenebenzofuran-2(3H)-
one (E/Z = 2/1), resulting of HF elimination on 2a (Table 1, entry 3).
Further optimization indicated that the initial concentration of the
substrate was important to accelerate the reaction with
[1a]0 = 0.33 as optimal value (Table 1, entries 7–9). Subsequent
screening with a series of phosphonium salts (Table 1, entries 10–
14) revealed that increasing the steric hindrance of the 3,30-
positions of 1,10-binaphthyl moieties led to the improvement of the
enantioselectivity of the product 2a. Accordingly, the bulky
catalyst (S)-3e delivered the fluorinated product 2a in 78% yield
with 50% enantioselectivity. So far, fluorinations were run under
solid–liquid phase-transfer catalysis by means of a solid base;
however, traces of water may help the reaction by dissolving the
˚
base. By adding 4 A molecular sieves as an additive, significant
reductions both in yield and enantioselectivity were observed
(Table 1, entry 15), thus we turned our attention to liquid–liquid
phase-transfer catalysis through the use of aqueous bases (Table 1,
entries 16–29). The concentration and the amount of the base were
then evaluated. To our delight, the use of 50% aqueous K2HPO4 gave
93% yield as well as 50% ee after 12 h at room temperature (Table 1,
entry 18). No desired product was obtained with 50% aqueous
K3PO4 as base (Table 1, entry 19). With the phosphonium salt (S)-
3e, the solvent effect was investigated (Table 1, entries 22–25). A
polar solvent (THF) or a chlorinated one (CH2Cl2) led to the
decrease of the enantioselectivity whereas toluene was found to be
the best solvent in an aromatic series. Increasing the amount of the
catalyst did not lead to an improved enantiomeric excess;
however, it should be noted that as low as 0.2 mol% of (S)-3e
still allowed the asymmetric fluorination (Table 1, entry 26 vs

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C.-L. Zhu et al. / Journal of Fluorine Chemistry 150 (2013) 60–66
Table 2
Asymmetric fluorination of a library of substituted benzofuran-2(3H)-ones.a
.
a
Unless specified, the reaction was carried out with 1.5 equiv. of N-fluorobis(benzensulfonimide) in the presence of 2 mol% of 3e and 50% aq. K2HPO4 (0.1 mL) in toluene
(0.3 M) at 25 8C. Yields are for isolated products after column chromatography. Enantiopurity of the fluorinated products was determined by HPLC analysis using chiral
columns with hexane–isopropanol as eluent.
entry 29). A fluorination run at 0 8C required longer reaction
time and gave an important decline of yield but without any
increase of the enantioselectivity (Table 1, entry 27). Replacement
of N-fluorobis(benzenesulfonimide) by Selectfluor gave the
product 2a in high yield but almost as racemic product (Table 1,
entry 28).
In order to provide a comparison between ammonium and
phosphonium salts, we conducted the fluorination with Maruoka’s
catalyst, (S)-4,4-dibutyl-2,6-bis(3,4,5-trifluorophenyl)-4,5-dihy-
dro-3H-dinaphtho[7,6,1,2-cde]azepinium bromide), and various
cinchona alkaloid derived quaternary ammonium salts. Very
poor enantioselectivities were observed (up to 8% ee) with
these quaternary ammonium salt catalysts. These results
indicated the superiority of phosphonium salts 3 in this fluorination
reaction.
Under the optimal conditions, the generality of the current
catalytic asymmetric electrophilic fluorination was evaluated by
employing a variety of benzofuran-2(3H)-ones. The results are
summarized in Table 2. Substrates with electron-donating and
electron-neutral groups on the benzyl group gave the desired
products in high yields and moderate enantioselectivites (2a–e).
Halogen substitution on the para-, meta-, ortho- or disubstitution
of the benzyl group had no impact on the activity and
enantioselectivity (2f–k). In addition, the desired adduct was
obtained in good yield and moderate ee value for 5-methyl-
substituted benzofuranone (2l). When we applied this methodol-
ogy to 3-aryl-substituted benzofuran-2(3H)-ones, excellent yields
were observed while the enantioselectivity decreased substantial-
ly due to the higher reactivity of the substrates (2m–t). Substrates
with electron-withdrawing groups on the benzofuranone ring gave

C.-L. Zhu et al. / Journal of Fluorine Chemistry 150 (2013) 60–66
63
higher enantioselectivities than those with electron-donating
4.2.1. 3-Benzyl-3-fluorobenzofuran-2(3H)-one (2a)
groups (2m–q). Poor enantioselectivites were obtained for 3-
arylbenzofuranones (2r–t). The scope of the reaction was further
extended to the fluorination of 3-methylbenzofuran-2(3H)-one, 3-
isopropylbenzofuran-2(3H)-one, and 3-butylbenzofuran-2(3H)-
one with N-fluorobis(benzenesulfonimide). These substrates were
found to be unsuitable for this asymmetric transformation and no
desired product was observed.
22.8 mg, light yellow solid, mp 60ꢀ62 8C, 94% yield, ½a D25
ꢁ
ꢀ5.8
(c 1.0, CH2Cl2); 50% ee, determined by HPLC analysis [Daicel
chiralcel AD-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV
detector, tmajor = 8.3 min, tminor = 7.8 min]; 1H NMR (400 MHz,
CDCl3)
d 7.41 (t, J = 8.0 Hz, 1H), 7.23–7.29 (m, 3H), 7.17 (t,
J = 7.6 Hz, 1H), 7.08–7.10 (m, 3H), 7.03 (d, J = 8.0 Hz, 1H), 3.66 (dd,
J = 10.8, 10.8 Hz, 1H), 3.34 (dd, J = 22.0, 22.0 Hz, 1H); 13C NMR
From a mechanistic viewpoint, the current electrophilic
fluorination is clearly distinct from our previously reported
electrophilic amination of 3-substituted benzofuran-2(3H)-ones
[27]. Indeed, the fluorination required a base to proceed whereas
the amination was conducted under base-free conditions. In the
amination case, the favorable enol formation combined with the
electrophilic activation of the nitrogen donor reagent explained
the high enantioselection, whereas the fluorination in the
presence of a base proceeds through a phosphonium enolate
probably without any cooperative activation of the fluorinating
agent.
(100 MHz, CDCl3) d 171.6 (d, J = 22.5 Hz), 153.7 (d, J = 6.5 Hz), 132.2
(d, JF–C = 2.9 Hz), 131.5 (d, JF–C = 6.5 Hz), 130.6, 128.5, 127.8, 125.9,
124.6 (d, J = 2.4 Hz), 123.5 (d, J = 19.9 Hz), 111.4, 92.0 (d, JF–
C = 193.2 Hz), 41.7 (d, JF–C = 28.1 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢀ147.35 (dd, J = 8.4, 8.4 Hz); IR (KBr)
n 3031, 2963, 2934, 1816,
1620, 1603, 1465, 1334, 1296, 1225, 1130, 1070, 1034, 880,
756 cmꢀ1; HRMS (ESI) found: m/z 265.0632 [M+Na]+, Calcd for
C15H11FO2 + Na 265.0641.
4.2.2. 3-Fluoro-3-(4-methylbenzyl)benzofuran-2(3H)-one (2b)
23.3 mg, light yellow solid, mp 49–50 8C, 91% yield, ½a D25
ꢀ12.6
ꢁ
(c 1.0, CH2Cl2); 48% ee, determined by HPLC analysis [Daicel
chiralcel IC-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV
detector, tmajor = 8.1 min, tminor = 8.4 min]; 1H NMR (400 MHz,
3. Conclusions
We have developed a mild and practical catalytic enantiose-
lective fluorination reaction using chiral phosphonium salt
catalysts and N-fluorobis(benzenesulfonimide). These P-spiro
phosphonium salts have showed high efficiency under phase
transfer catalysis conditions in the fluorination reaction. A series
of the fluorinated benzofuran-2(3H)-ones were obtained with up
to 96% yield and 56% ee. Further improvement of enantioselec-
tivity of this transformation and additional mechanistic studies
are ongoing in our laboratory and will be reported in due
course.
CDCl3)
(m, 5H), 3.62 (dd, J = 10.8, 10.4 Hz, 1H), 3.32 (dd, J = 21.6, 21.6 Hz,
1H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3)
171.7 (d, J = 22.8 Hz),
153.7 (d, J = 6.6 Hz), 137.4, 132.2 (d, JF–C = 2.8 Hz), 130.4, 129.2,
128.3 (d, JF–C = 6.8 Hz), 125.9, 124.6 (d, J = 2.1 Hz), 123.7 (d,
J = 19.9 Hz), 111.4, 92.1 (d, JF–C = 193.0 Hz), 41.3 (d, JF–C = 27.9 Hz),
d 7.39–7.43 (d, J = 7.8 Hz, 1H), 7.12–7.20 (m, 2H), 6.95–7.06
d
20.1; 19F NMR (376 MHz, CDCl3)
d
ꢀ147.16 (dd, J = 8.4, 8.4 Hz, 1F);
IR (KBr)
n 3052, 2967, 2924, 1820, 1724, 1622, 1602, 1464, 1333,
1294, 1221, 1132, 1077, 1032, 880, 772 cmꢀ1; HRMS (ESI) found:
m/z 279.0790 [M+Na]+, Calcd for C16H13FO2 + Na 279.0797.
4. Experimental
4.2.3. 3-Fluoro-3-(4-methoxybenzyl)benzofuran-2(3H)-one (2c)
25.8 mg, light yellow oil, 95% yield, ½a D25
ꢀ14.0 (c 1.0, CH2Cl2);
ꢁ
4.1. General information
49% ee, determined by HPLC analysis [Daicel chiralcel IB-H, n-
hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tma-
All purchased reagents were used without further purification.
Analytical thin layer chromatography was performed on 0.20 mm
Qingdao Haiyang silica gel plates. Silica gel (200–300 mesh) (from
Qingdao Haiyang Chem. Company, Ltd.) was used for flash
chromatography. 1H, 13C and 19F NMR were recorded on Bruker
AV 400 MHz spectrometer at 400 MHz (1H), 100 MHz (13C),
376 MHz (19F) or Varian 600 MHz spectrometer at 600 MHz
(1H), 150 MHz (13C), 565 MHz (19F). Chemical shifts were reported
in parts per million (ppm) from the solvent resonance as the
jor = 8.7 min, tminor = 9.7 min]; 1H NMR (400 MHz, CDCl3)
d 7.39–
7.43 (d, J = 7.8 Hz, 1H), 6.98–7.19 (m, 5H), 6.76–6.78 (m, 2H), 3.78
(s, 3H), 3.60 (dd, J = 10.4, 10.4 Hz, 1H), 3.29 (dd, J = 21.6, 21.6 Hz,
1H); 13C NMR (100 MHz, CDCl3)
d 171.7 (d, J = 22.8 Hz), 159.2,
153.7 (d, J = 6.6 Hz), 132.2 (d, JF–C = 2.8 Hz), 131.6, 125.8, 124.6 (d,
JF–C = 2.5 Hz), 123.7 (d, J = 19.8 Hz), 123.3 (d, J = 5.8 Hz), 113.9,
111.4, 92.2 (d, JF–C = 192.8 Hz), 55.2, 40.9 (d, JF–C = 28.1 Hz); 19F
NMR (376 MHz, CDCl3)
d
ꢀ147.47 (dd, J = 8.1, 8.1 Hz); IR (KBr)
n
3051, 2960, 2931, 1820, 1615, 1516, 1464, 1333, 1300, 1257, 1218,
1181, 1078, 1032, 881, 775 cmꢀ1; HRMS (ESI) found: m/z 295.0737
[M+Na]+, Calcd for C16H13FO3 + Na 295.0746.
internal standard (CDCl3:
dH = 7.26 ppm, dC = 77.16 ppm). High
resolution mass spectrometry (HRMS) spectra were obtained on a
micrOTOF-QII Instrument. Optical rotations were determined
using an Autopol IV automatic polarimeter. IR spectra were
recorded on an AVATAR 360 FT-IR spectrometer. HPLC analysis
were carried out on a Hewlett Packard Model HP 1200 instrument.
Melting points were measured on a WRS-1A digital melting point
apparatus and are uncorrected.
4.2.4. 3-Fluoro-3-(naphthalen-1-ylmethyl)benzofuran-2(3H)-one
(2d)
27.2 mg, light yellow solid, mp 107–108 8C, 93% yield, ½a D25
ꢁ
ꢀ19.7 (c 1.0, CH2Cl2); 45% ee, determined by HPLC analysis
[Daicel chiralcel AD-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min,
254 nm UV detector, tmajor = 11.7 min, tminor = 9.7 min]; 1H
4.2. General procedure for catalyzed fluorination
NMR (400 MHz, CDCl3) d 7.95–7.97 (d, J = 7.6 Hz, 1H), 7.83–
7.88 (m, 2H), 7.28–7.50 (m, 5H), 7.06–7.09 (d, J = 8.4 Hz, 1H),
6.93–6.97 (t, J = 7.6 Hz, 1H), 6.73–6.75 (d, J = 7.6 Hz, 1H), 4.18 (dd,
J = 12.0, 12.0 Hz, 1H), 3.73 (dd, J = 27.6, 27.6 Hz, 1H); 13C NMR
A mixture of substituted benzofuran-2(3H)-one (0.1 mmol), N-
fluorobis(benzenesulfonimide) (47.2 mg, 0.15 mmol), 50% aque-
ous K2HPO4 (0.1 mL) and (S, S)-3e (2.7 mg, 2 mol%) in toluene
(0.3 mL) was stirred vigorously at 25 8C for 12 h. The resulting
mixture was purified by column chromatography on silica gel
(ethyl acetate/petroleum ether = 1/50 as eluent) to afford the
desired 2. The product was identified by NMR spectroscopy. The
enantiomeric excess of the product was determined by HPLC using
a chiral column.
(100 MHz, CDCl3)
d 172.0 (d, J = 22.6 Hz), 153.6 (d, J = 6.7 Hz),
133.9, 132.6, 132.1 (d, JF–C = 2.8 Hz), 129.7, 128.7 (d, JF–C = 6.3 Hz),
128.2 (d, JF–C = 3.0 Hz), 126.4, 126.1, 125.8, 125.0, 124.3 (d,
J = 2.4 Hz), 124.1 (d, J = 2.3 Hz), 123.6 (d, J = 20.5 Hz), 111.3, 91.9
(d, JF–C = 194.2 Hz), 37.9 (d, JF–C = 28.2 Hz); 19F NMR (376 MHz,
CDCl3)
d
ꢀ148.70 (dd, J = 9.3, 9.6 Hz); IR (KBr)
n 3051, 2958, 2926,
1819, 1623, 1600, 1510, 1461, 1397, 1293, 1226, 1133, 1075,

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C.-L. Zhu et al. / Journal of Fluorine Chemistry 150 (2013) 60–66
1030, 876, 776 cmꢀ1; HRMS (ESI) found: m/z 315.0795 [M+Na]+,
Calcd for C19H13FO2 + Na 315.0797.
111.5, 91.9 (d, JF–C = 192.8 Hz), 40.9 (d, JF–C = 28.2 Hz); 19F NMR
(376 MHz, CDCl3)
ꢀ114.26 to ꢀ114.34 (m, 1F), ꢀ147.81 (dd,
J = 8.1, 8.4 Hz); IR (KBr) 3046, 2964, 2933, 1825, 1621, 1603,
1510, 1466, 1440, 1290, 1261, 1126, 1132, 1072, 879, 762 cmꢀ1
HRMS (ESI) found: m/z 283.0543 [M+Na]+, Calcd for
15H10F2O2 + Na 283.0547.
d
n
4.2.5. 3-Fluoro-3-(naphthalen-2-ylmethyl)benzofuran-2(3H)-one
;
(2e)
27.2 mg, light yellow solid, mp 74–75 8C, 93% yield, ½a D25
ꢁ
ꢀ14.3
C
(c 1.0, CH2Cl2); 46% ee, determined by HPLC analysis [Daicel
chiralcel AD-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV
detector, tmajor = 11.2 min, tminor = 11.8 min]; 1H NMR (400 MHz,
4.2.9. 3-(3-Bromobenzyl)-3-fluorobenzofuran-2(3H)-one (2i)
29.9 mg, light yellow solid, mp 42–43 8C, 93% yield, ½a D25
ꢀ10.1
ꢁ
CDCl3)
7.41 (t, J = 8.0 Hz, 1H), 7.09–7.21 (m, 3H), 7.01 (d, J = 8.0 Hz, 1H),
3.84 (dd, J = 10.0, 10.0 Hz, 1H), 3.51 (dd, J = 18.0, 18.0 Hz, 1H); 13
NMR (100 MHz, CDCl3) 171.6 (d, J = 22.5 Hz), 153.7 (d, J = 6.5 Hz),
d
7.72–7.83 (m, 3H), 7.59 (s, 1H), 7.48–7.50 (m, 2H), 7.37–
(c 1.0, CH2Cl2); 44% ee, determined by HPLC analysis [Daicel
chiralcel AD-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV
detector, tmajor = 9.9 min, tminor = 9.2 min]; 1H NMR (400 MHz,
C
d
CDCl3)
3.62 (dd, J = 11.2, 11.2 Hz, 1H), 3.27 (dd, J = 22.8, 22.8 Hz, 1H); 13
NMR (100 MHz, CDCl3) 171.2 (d, J = 22.5 Hz), 153.7 (d, J = 6.5 Hz),
d 7.42–7.46 (m, 2H), 7.13–7.25 (m, 3H), 7.04–7.09 (m, 3H),
133.2, 132.7, 132.3 (d, JF–C = 3.0 Hz), 129.8, 129.0 (d, JF–C = 6.3 Hz),
128.1 (d, JF–C = 5.2 Hz), 127.8, 127.6, 126.2 (d, J = 5.7 Hz), 125.9,
124.6 (d, J = 2.3 Hz), 123.6 (d, J = 20.0 Hz), 111.5, 92.1 (d, JF–
C
d
133.8 (d, JF–C = 5.7 Hz), 133.6, 132.5 (d, JF–C = 3.0 Hz), 131.0, 130.0,
129.2, 125.8, 124.7 (d, JF–C = 2.3 Hz), 123.2 (d, J = 20.1 Hz), 122.4,
111.6, 91.5 (d, JF–C = 193.9 Hz), 41.3 (d, JF–C = 28.3 Hz); 19F NMR
C = 193.1 Hz), 41.9 (d, JF–C = 28.1 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢀ146.85 (dd, J = 8.1, 8.4 Hz); IR (KBr)
n 3056, 2959, 2927, 1816,
1623, 1601, 1508, 1464, 1438, 1295, 1220, 1128, 1077, 1028, 877,
(376 MHz, CDCl3)
d
ꢀ147.87 (dd, J = 87, 8.7 Hz); IR (KBr)
n 3067,
774 cmꢀ1; HRMS (ESI) found: m/z 315.0790 [M+Na]+, Calcd for
2963, 2927, 1818, 1725, 1621, 1599, 1463, 1332, 1294, 1261, 1227,
1078, 1023, 879, 803 cmꢀ1; HRMS (ESI) found: m/z 342.9736
[M+Na]+, Calcd for C15H10BrFO2 + Na 342.9746.
C
19H13FO2 + Na 315.0797.
4.2.6. 3-(4-Bromobenzyl)-3-fluorobenzofuran-2(3H)-one (2f)
30.5 mg, light yellow solid, mp 39–40 8C, 95% yield, ½a D25
ꢁ
ꢀ7.3 (c
4.2.10. 3-(2-Bromobenzyl)-3-fluorobenzofuran-2(3H)-one (2j)
1.0, CH2Cl2); 46% ee, determined by HPLC analysis [Daicel chiralcel
29.5 mg, light yellow oil, 92% yield, ½a D25
ꢀ9.5 (c 1.0, CH2Cl2);
ꢁ
IC-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector,
tmajor = 8.2 min, tminor = 8.7 min]; 1H NMR (400 MHz, CDCl3)
47% ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-
hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tma-
d
7.38–7.45 (m, 3H), 7.19 (t, J = 7.6 Hz, 1H), 7.05–7.11 (m, 2H), 6.96–
6.98 (m, 2H), 3.60 (dd, J = 10.8, 10.8 Hz, 1H), 3.29 (dd, J = 21.6,
jor = 7.5 min, tminor = 7.0 min]; 1H NMR (400 MHz, CDCl3)
d 7.53–
7.55 (d, J = 8.0 Hz, 1H), 7.41–7.49 (m, 2H), 7.32–7.36 (t, J = 7.2 Hz,
1H), 7.18–7.22 (m, 1H), 7.08–7.12 (m, 2H), 6.86–6.88 (d, J = 7.2 Hz,
1H), 3.77–3.84 (m, 1H), 3.61 (dd, J = 27.6, 27.6 Hz, 1H); 13C NMR
21.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 171.3 (d, J = 22.7 Hz),
153.7 (d, J = 6.5 Hz), 132.4 (d, JF–C = 2.9 Hz), 132.2, 131.5, 130.5 (d,
JF–C = 6.5 Hz), 125.7, 124.7 (d, J = 2.5 Hz), 123.2 (d, J = 19.9 Hz),
122.1, 111.6, 91.0 (d, JF–C = 192.5 Hz), 41.2 (d, JF–C = 28.4 Hz); 19F
(100 MHz, CDCl3)
d 171.4 (d, J = 22.6 Hz), 153.5 (d, J = 7.0 Hz),
133.0, 132.3 (d, JF–C = 1.7 Hz), 132.2 (d, JF–C = 2.8 Hz), 132.1 (d, JF–
C = 2.0 Hz), 129.5, 127.6, 126.1, 124.6 (d, JF–C = 2.5 Hz), 123.2 (d,
J = 20.1 Hz), 111.3, 91.6 (d, JF–C = 194.0 Hz), 40.8 (d, JF–C = 27.8 Hz);
NMR (376 MHz, CDCl3)
d
ꢀ147.57 (dd, J = 8.4, 8.4 Hz); IR (KBr)
n
3029, 2925, 2854, 1821, 1622, 1600, 1488, 1461, 1331, 1289, 1227,
1142, 1070, 1018, 875, 756 cmꢀ1; HRMS (ESI) found: m/z 342.9738
[M+Na]+, Calcd for C15H10BrFO2 + Na 342.9746.
19F NMR (376 MHz, CDCl3)
d
ꢀ149.47 (dd, J = 12.6, 12.6 Hz); IR
(KBr)
n 3028, 2926, 1823, 1725, 1623, 1601, 1466, 1333, 1288,
1227, 1141, 1070, 1031, 875, 755 cmꢀ1; HRMS (ESI) found: m/z
4.2.7. 3-(4-Chlorobenzyl)-3-fluorobenzofuran-2(3H)-one (2g)
342.9742 [M+Na]+, Calcd for C15H10BrFO2 + Na 342.9746.
24.9 mg, light yellow solid, mp 67–68 8C, 90% yield, ½a D25
ꢀ21.1
ꢁ
(c 1.0, CH2Cl2); 47% ee, determined by HPLC analysis [Daicel
chiralcel AD-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV
detector, tmajor = 7.8 min, tminor = 8.3 min]; 1H NMR (400 MHz,
4.2.11. 3-(4-Bromo-2-fluorobenzyl)-3-fluorobenzofuran-2(3H)-one
(2k)
31.9 mg, light yellow solid, mp 71–72 8C, 94% yield, ½a D25
ꢀ27.1
ꢁ
CDCl3)
(m, 4H), 3.62 (dd, J = 10.8, 10.8 Hz, 1H, 3.31 (dd, J = 21.6, 21.6 Hz,
1H); 13C NMR (100 MHz, CDCl3)
171.3 (d, J = 22.7 Hz), 153.7 (d,
d
7.41–7.45 (t, J = 8.0 Hz, 1H), 7.17–7.24 (m, 3H), 7.02–7.11
(c 1.0, CH2Cl2); 50% ee, determined by HPLC analysis [Daicel
chiralcel IC-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV
detector, tmajor = 7.7 min, tminor = 8.1 min]; 1H NMR (400 MHz,
d
J = 6.6 Hz), 133.9, 132.4 (d, JF–C = 2.9 Hz), 131.9, 130.0 (d, JF–
C = 6.4 Hz), 128.7, 125.7, 124.7 (d, JF–C = 2.4 Hz), 123.3 (d,
J = 20.0 Hz), 111.6, 91.8 (d, JF–C = 193.7 Hz), 41.1 (d, JF–
CDCl3)
J = 8.0 Hz, 1H), 3.61–3.68 (m, 1H), 3.41 (dd, J = 20.0, 20.4 Hz, 1H);
13C NMR (100 MHz, CDCl3)
171.2 (d, J = 22.3 Hz), 160.9 (d,
J = 250.7 Hz), 153.6 (d, J = 8.5 Hz), 133.4 (d, JF–C = 3.8 Hz), 132.3 (d,
JF–C = 2.9 Hz), 127.7 (d, JF–C = 3.7 Hz), 125.6, 124.9, 123.1 (d, JF–
C = 19.8 Hz), 122.3 (d, J = 9.5 Hz), 119.2 (d, J = 25.5 Hz), 118.3 (dd,
J = 5.7, 5.7 Hz), 111.5, 91.1 (d, JF–C = 193.7 Hz), 34.9 (d, JF–
d 7.42–7.45 (m, 1H), 7.14–7.28 (m, 5H), 7.07–7.09 (d,
d
C = 28.5 Hz); 19F NMR (376 MHz, CDCl3)
8.4 Hz); IR (KBr)
d
ꢀ147.62 (dd, J = 7.8,
n
3111, 2961, 2928, 1824, 1621, 1601, 1492, 1466,
1409, 1295, 1228, 1107, 1074, 1018, 879, 754 cmꢀ1; HRMS (ESI)
found: m/z 299.0253 [M+Na]+, Calcd for C15H10ClFO2 + Na
299.0251.
C = 29.9 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢀ112.72 to ꢀ112.77
3057, 2962, 2937,
(m, 1F), ꢀ147.39 to ꢀ147.48 (m, 1F); IR (KBr)
n
4.2.8. 3-Fluoro-3-(4-fluorobenzyl)benzofuran-2(3H)-one (2h)
1830, 1607, 1577, 1485, 1463, 1400, 1289, 1226, 1147, 1091, 1027,
25.0 mg, light yellow oil, 96% yield, ½a D25
ꢁ
ꢀ17.3 (c 1.0, CH2Cl2);
871, 755 cmꢀ1; HRMS (ESI) found: m/z 360.9643 [M+Na]+, Calcd for
56% ee, determined by HPLC analysis [Daicel chiralcel IC-H, n-
hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tma-
C15H9BrF2O2 + Na 360.9652.
jor = 7.9 min, tminor = 8.4 min]; 1H NMR (400 MHz, CDCl3)
d
7.41–
4.2.12. 3-Benzyl-3-fluoro-5-methylbenzofuran-2(3H)-one (2l)
7.46 (t, J = 8.0 Hz, 1H), 7.17–7.20 (t, J = 7.6 Hz, 1H), 7.04–7.11 (m,
4H), 6.92–6.96 (m, 1H), 3.62 (dd, J = 10.8, 10.4 Hz, 1H), 3.32 (dd,
24.6 mg, light yellow solid, mp 82–83 8C, 96% yield, ½a D25
ꢀ11.3
ꢁ
(c 1.0, CH2Cl2); 46% ee, determined by HPLC analysis [Daicel
chiralcel IC-H, n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV
detector, tmajor = 8.4 min, tminor = 8.9 min]; 1H NMR (400 MHz,
J = 21.2, 21.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 171.4 (d,
J = 22.6 Hz), 162.4 (d, J = 245.2 Hz), 153.7 (d, J = 6.7 Hz), 132.4 (d,
J = 2.8 Hz), 132.2 (d, J = 8.0 Hz), 127.2 (q, J = 3.3 Hz), 125.7, 124.7 (d,
JF–C = 2.2 Hz), 123.4 (d, JF–C = 20.3 Hz), 115.4 (d, JF–C = 21.3 Hz),
CDCl3)
d 7.19–7.28 (m, 4H), 7.08–7.09 (m, 2H), 6.90–6.92 (m, 2H),
3.63 (dd, J = 10.8, 10.4 Hz, 1H), 3.33 (dd, J = 21.2, 21.2 Hz, 1H), 2.33

C.-L. Zhu et al. / Journal of Fluorine Chemistry 150 (2013) 60–66
65
(s, 3H); 13C NMR (100 MHz, CDCl3)
J = 6.6 Hz), 134.4 (d, JF–C = 2.4 Hz), 132.6 (d, JF–C = 3.0 Hz), 131.6 (d,
JF–C = 5.6 Hz), 130.6, 128.4, 127.7, 126.1, 123.3 (d, J = 19.7 Hz),
111.0, 92.3 (d, JF–C = 193.1 Hz), 41.8 (d, JF–C = 28.1 Hz), 21.0; 19F
d
171.9 (d, J = 22.7 Hz), 151.6 (d,
4.2.17. 5-Bromo-3-fluoro-3-phenylbenzofuran-2(3H)-one (2q)
29.8 mg, colorless oil, 97% yield, ½a D25
ꢁ
ꢀ37.6 (c 1.0, CH2Cl2); 32%
ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-hexane/
i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tmajor = 12.2 min,
NMR (376 MHz, CDCl3)
d
ꢀ147.04 (dd, J = 8.4, 8.4 Hz); IR (KBr)
n
tminor = 11.3 min]; 1H NMR (600 MHz, CDCl3)
d
7.55–7.56 (m, 1H),
7.44 (s, 1H), 7.29–7.35 (m, 5H), 7.03–7.04 (m, 1H); 13C NMR
(150 MHz, CDCl3) 170.0 (d, J = 27.0 Hz), 153.2 (d, J = 6.3 Hz),
2948, 2927, 1815, 1620, 1485, 1455, 1433, 1296, 1211, 1136, 1089,
1032, 869, 743 cmꢀ1; HRMS (ESI) found: m/z 279.0792 [M+Na]+,
Calcd for C16H13FO2 + Na 279.0797.
d
135.8, 134.1 (d, J = 27.0 Hz), 130.3, 129.6, 129.0, 126.8 (d, JF–
C = 19.4 Hz), 125.8 (d, JF–C = 5.6 Hz), 117.9, 113.5, 91.7 (d, JF–
4.2.13. 3-Fluoro-3-phenylbenzofuran-2(3H)-one (2m)
C = 192.2 Hz); 19F NMR (565 MHz, CDCl3)
3061, 2963, 2926, 1826, 1722, 1617, 1454, 1408, 1262, 1227, 1140,
1088, 1025, 945, 812, 698 cmꢀ1; HRMS (EI) found: m/z 305.9693
[M]+, Calcd for C14H8BrFO2 305.9692.
d
ꢀ145.05 (s); IR (KBr)
n
21.0 mg, colorless oil, 92% yield, ½a D25
ꢁ
ꢀ21.1 (c 1.0, CH2Cl2); 19%
ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-hexane/
i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tmajor = 12.1 min,
tminor = 9.5 min]; 1H NMR (600 MHz, CDCl3)
d
7.51–7.53 (t,
J = 7.8 Hz, 1H), 7.40–7.41 (m, 6H), 7.21–7.29 (m, 2H); 13C NMR
(150 MHz, CDCl3) 170.8 (d, J = 26.6 Hz), 154.4 (d, J = 6.5 Hz), 134.7
(d, J = 27.3 Hz), 132.8, 130.0, 128.9, 126.6, 126.1 (d, JF–C = 5.6 Hz),
125.4, 124.8 (d, JF–C = 18.6 Hz), 111.7, 92.0 (d, JF–C = 190.2 Hz); 19
NMR (565 MHz, CDCl3) 3065, 3034, 1822,
4.2.18. 3-Fluoro-3-(4-fluorophenyl)benzofuran-2(3H)-one (2r)
d
23.4 mg, colorless oil, 95% yield, ½a D25
ꢀ16.1 (c 1.0, CH2Cl2); 14%
ꢁ
ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-hexane/
i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tmajor = 11.6 min,
F
d
ꢀ144.24 (s); IR (KBr)
n
tminor = 9.4 min]; 1H NMR (600 MHz, CDCl3)
d
7.53–7.55 (m, 1H),
7.41–7.43 (m, 3H), 7.31 (q, J = 7.2 Hz, 1H), 7.23 (t, J = 7.2 Hz, 1H),
7.09–7.11 (m, 2H); 13C NMR (150 MHz, CDCl3)
170.6 (d,
1621, 1603, 1464, 1324, 1290, 1224, 1134, 1076, 1023, 948, 871,
759 cmꢀ1; HRMS (ESI) found: m/z 251.0475 [M+Na]+, Calcd for
d
C
14H9FO2 + Na 251.0484.
J = 28.2 Hz), 163.7 (d, J = 249.0 Hz), 154.4 (d, J = 6.8 Hz), 133.0,
130.5 (d, J = 27.3 Hz), 128.5 (q, J = 4.6 Hz), 126.6, 125.4, 124.4 (d,
J = 19.2 Hz), 116.0 (d, JF–C = 21.9 Hz), 111.8, 91.4 (d, JF–
4.2.14. 3-Fluoro-5-methoxy-3-phenylbenzofuran-2(3H)-one (2n)
24.5 mg, colorless oil, 95% yield, ½a D25
ꢁ
ꢀ38.8 (c 1.0, CH2Cl2);
C = 190.4 Hz); 19F NMR (565 MHz, CDCl3)
d
ꢀ110.62 (s), ꢀ141.61
25% ee, determined by HPLC analysis [Daicel chiralcel AD-H,
n-hexane/i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tma-
jor = 15.6 min, tminor = 14.1 min]; 1H NMR (600 MHz, CDCl3)
7.41–7.42 (m, 5H), 7.15 (d, J = 9.0 Hz, 1H), 7.04–7.06 (m, 1H), 6.92
(s, 1H), 3.79 (s, 3H); 13C NMR (150 MHz, CDCl3)
171.2 (d,
to ꢀ141.63 (m, 1F); IR (KBr)
n 3080, 1825, 1621, 1604, 1510, 1464,
1290, 1229, 1134, 1079, 1020, 954, 872, 759 cmꢀ1; HRMS (ESI)
found: m/z 259.0781 [M+Na+NH4–CO]+, Calcd for C14H8F2O2 + -
Na + NH4–CO 259.0785.
d
d
J = 26.3 Hz), 157.3, 148.1 (d, J = 6.9 Hz), 134.8 (d, J = 27.6 Hz),
129.9, 128.8, 126.0 (d, J = 5.9 Hz), 125.4 (d, J = 18.8 Hz), 118.7 (d,
JF–C = 2.9 Hz), 112.4, 111.3, 92.1 (d, JF–C = 190.7 Hz), 56.0; 19F
4.2.19. 3-(4-Chlorophenyl)-3-fluorobenzofuran-2(3H)-one (2s)
24.4 mg, colorless oil, 93% yield, ½a D25
ꢀ23.3 (c 1.0, CH2Cl2); 14%
ꢁ
ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-hexane/
i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tmajor = 11.5 min,
NMR (565 MHz, CDCl3)
d
ꢀ145.30 (s); IR (KBr)
n 3070, 3015,
2973, 2941, 1820, 1726, 1617, 1488, 1312, 1290, 1219, 1135,
1094, 1022, 952, 869, 767 cmꢀ1; HRMS (ESI) found: m/z 281.0583
[M+Na]+, Calcd for C15H11FO2 + Na 281.0590.
tminor = 9.7 min]; 1H NMR (600 MHz, CDCl3)
d
7.44–7.47 (m, 1H),
7.29–7.32 (m, 3H), 7.25–7.26 (m, 2H), 7.21 (t, J = 7.2 Hz, 1H), 7.14
(d, J = 7.8 Hz, 1H); 13C NMR (150 MHz, CDCl3)
170.4 (d,
d
J = 27.2 Hz), 154.4 (d, J = 6.6 Hz), 136.3 (d, J = 2.0 Hz), 133.3,
133.1, 129.1, 127.7 (d, J = 5.4 Hz), 126.5, 125.5, 124.3 (d, JF–
C = 19.2 Hz), 111.9, 91.5 (d, JF–C = 192.0 Hz); 19F NMR (565 MHz,
4.2.15. 3-Fluoro-5-methyl-3-phenylbenzofuran-2(3H)-one (2o)
23.5 mg, colorless oil, 97% yield, ½a D25
ꢀ40.3 (c 1.0, CH2Cl2); 24%
ꢁ
ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-hexane/
i-PrOH = 95/5, 0.8 mL/min, 254 nm UV detector, tmajor = 6.8 min,
CDCl3)
d
ꢀ143.31 (s); IR (KBr)
n 3067, 2924, 1822, 1621, 1600,
1491, 1465, 1323, 1290, 1225, 1135, 1076, 1016, 937, 873,
759 cmꢀ1; HRMS (ESI) found: m/z 285.0092 [M+Na]+, Calcd for
C14H8ClFO2 + Na 285.0095.
tminor = 6.2 min]; 1H NMR (600 MHz, CDCl3)
d
7.31–7.35 (m, 5H),
7.24 (d, J = 7.8 Hz, 1H), 7.13 (s, 1H), 7.03 (d, J = 8.4 Hz, 1H), 2.30 (s,
1H); 13C NMR (150 MHz, CDCl3)
171.2 (d, J = 26.6 Hz), 152.3 (d,
d
J = 6.6 Hz), 135.2 (d, J = 2.1 Hz), 134.9 (d, J = 27.6 Hz), 133.3 (d,
J = 3.2 Hz), 129.9, 128.8, 126.8, 126.0 (d, JF–C = 5.6 Hz), 124.7 (d, JF–
C = 18.9 Hz), 111.3, 92.2 (d, JF–C = 189.8 Hz), 21.1; 19F NMR
4.2.20. 3-(4-Bromophenyl)-3-fluorobenzofuran-2(3H)-one (2t)
27.6 mg, colorless oil, 90% yield, ½a D25
ꢀ25.7 (c 1.0, CH2Cl2); 9%
ꢁ
ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-hexane/
i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tmajor = 10.7 min,
(565 MHz, CDCl3)
2866, 1821, 1620, 1487, 1450, 1285, 1225, 1137, 1074, 1003, 947,
816, 760 cmꢀ1; HRMS (ESI) found: m/z 265.0635 [M+Na]+, Calcd for
d
ꢀ144.65 (s); IR (KBr)
n 3064, 3030, 2924,
tminor = 9.4 min]; 1H NMR (600 MHz, CDCl3)
d
7.53–7.56 (m, 3H),
7.40 (d, J = 7.8 Hz, 1H), 7.23–7.32 (m, 4H); 13C NMR (150 MHz,
CDCl3) 170.3 (d, J = 26.6 Hz), 154.4 (d, J = 6.6 Hz), 133.7 (d,
C15H11FO2 + Na 265.0641.
d
J = 28.2 Hz), 133.1 (d, J = 3.2 Hz), 132.1, 127.8 (d, J = 5.4 Hz), 126.6,
125.5, 124.6 (d, JF–C = 2.1 Hz), 124.2 (d, JF–C = 18.8 Hz), 111.9, 91.5
4.2.16. 5-Chloro-3-fluoro-3-phenylbenzofuran-2(3H)-one (2p)
25.2 mg, colorless oil, 96% yield, ½a D25
ꢁ
ꢀ47.2 (c 1.0, CH2Cl2); 29%
(d, JF–C = 190.4 Hz); 19F NMR (565 MHz, CDCl3)
d
ꢀ143.80 (s); IR
ee, determined by HPLC analysis [Daicel chiralcel AD-H, n-hexane/
i-PrOH = 98/2, 0.8 mL/min, 254 nm UV detector, tmajor = 10.1 min,
(KBr) n 3061, 2955, 2924, 2853, 1821, 1621, 1599, 1488, 1461,
1323, 1289, 1225, 1135, 1075, 1011, 873, 756 cmꢀ1; HRMS (ESI)
found: m/z 328.9596 [M+Na]+, Calcd for C14H8BrFO2 + Na
328.9589.
tminor = 9.2 min]; 1H NMR (600 MHz, CDCl3)
d
7.40–7.41 (m, 1H),
7.33–7.35 (m, 3H), 7.29–7.30 (m, 3H), 7.09 (d, J = 8.4 Hz, 1H); 13C
NMR (150 MHz, CDCl3) 170.1 (d, J = 26.0 Hz), 152.7 (d, J = 6.6 Hz),
d
Acknowledgements
134.1 (d, J = 27.4 Hz), 132.9, 130.7 (d, J = 3.2 Hz), 130.3, 129.0,
126.7, 126.4 (d, JF–C = 19.1 Hz), 125.9 (d, JF–C = 7.2 Hz), 113.1, 91.8
(d, JF–C = 192.2 Hz); 19F NMR (565 MHz, CDCl3)
d
ꢀ145.13 (s); IR
We gratefully appreciate the National Natural Science Founda-
tion of China (Nos. 21172170 and 21225208) for financial support.
Chuan-Le Zhu is grateful to the French ministry of foreign affairs for
an Eiffel excellence doctorate scholarship (9/2011–6/2012).
(KBr)
n 3067, 3037, 1828, 1727, 1618, 1468, 1423, 1290, 1228,
1140, 1085, 1033, 947, 821, 709 cmꢀ1; HRMS (ESI) found: m/z
285.0092 [M+Na]+, Calcd for C14H8ClFO2 + Na 285.0095.

66
C.-L. Zhu et al. / Journal of Fluorine Chemistry 150 (2013) 60–66
[27] C.-L. Zhu, F.-G. Zhang, W. Meng, J. Nie, D. Cahard, J.-A. Ma, Angew. Chem. Int. Ed. 50
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