Selective palladium-catalyzed C-F activation/carbon-carbon bond formation of polyfluoroaryl oxazolines

Article abstract of DOI:10.1021/jo2023262

A selective palladium-catalyzed Suzuki-Miyaura coupling reaction of polyfluorophenyl oxazolines through ortho C-F activation is described. It was found that reactions with DPPF as the ligand occurred much faster than those with other ligands. A variety of arylboronic acids including challenging functionalized arylboronic acids such as enolizable ketones, aldehyde, cyano, ester, and trifluoromethyl groups were tolerated with the reaction conditions.

Full text of DOI:10.1021/jo2023262

Article
pubs.acs.org/joc
Selective Palladium-Catalyzed C−F Activation/Carbon−Carbon Bond
Formation of Polyfluoroaryl Oxazolines
Daohong Yu, Qilong Shen,* and Long Lu*
Key Laboratory of Organofluorine Chfigemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Road, Shanghai 200032, People’s Republic of China
S
* Supporting Information
ABSTRACT: A selective palladium-catalyzed Suzuki−Miyaura
coupling reaction of polyfluorophenyl oxazolines through ortho
C−F activation is described. It was found that reactions with
DPPF as the ligand occurred much faster than those with other
ligands. A variety of arylboronic acids including challenging
functionalized arylboronic acids such as enolizable ketones,
aldehyde, cyano, ester, and trifluoromethyl groups were tolerated with the reaction conditions.
INTRODUCTION
RESULTS AND DISCUSSION
Preparation of 2-(Polyfluorophenyl)oxazolines. 2-
(Polyfluorophenyl)oxazolines 1a−g were readily prepared
from commercially available polyfluorobenzoic acids in two
steps according to a literature procedure,13 as illustrated in
Scheme 1. Condensation of polyfluorobenzoic acids with 2-
■
■
The carbon−fluorine bond is known as the strongest single
bond to carbon,1 and activation of the carbon−fluorine bond is
of great current interests2 because such a process offers great
potential in the preparation of bioactive fluorocarbons.3 Even
though many stoichiometric transition-metal-mediated C−F
activation reactions have been reported in the past two decades,
highly selective catalytic activation of C−F bond and further
transformation to form new carbon−carbon bonds remains
poorly developed and still a challenge in synthetic organic
chemistry.2,4 Interestingly, most of the C−F bond activation/
functionalization known to date involves the conversion of
monofluoroarenes into nonfluorinated derivatives;5 similar
reactions of polyfluorinated arene electrophiles remain elusive.6
Only recently, substantial progress has been achieved in the
activation of the C−F bond in polyfluorinated arenes by groups
of Braun,7 Radius,8 Sandford,9 and Love.10 Certainly, these
pioneering studies revealed the feasibility of such a process.
However, to gain deep understanding of the fundamentals of
the process, development of new transition-metal-catalyzed C−
F bond activation/functionalization of polyfluorinated arene
electrophiles is still a great demand.
Inspired by the recent progress in the field of the transition-
metal-catalyzed highly selective C−H activation of arenes with
a directing group,11 we envisioned that polyfluorinated arenes
with a directing group such as oxazoline12 might facilitate the
selective activation of the ortho C−F bond of polyfluoroaryl
oxazolines and subsequent trans-metalation of the resulting
metal-fluoride bond, followed by reductive-elimination, would
afford the functionalized products. In addition, oxazolines can
be easily transformed into other functional groups such as acids
and amines, and thus this strategy would provide a valuable
synthetic method for the preparation of functionalized
fluoroaromatics. Herein, we reported a palladium-catalyzed
Suzuki−Miyaura coupling reaction of polyfluoroaryl oxazolines
via C−F activation.
Scheme 1. Preparation of 2-(Polyfluorophenyl)oxazolines 1
aminoethanol in the presence of N-hydroxybenzotriazole
(HOBt) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide
(EDCI), followed by cyclization of the resulting amide
intermediates, afforded the desired 2-(polyfluorophenyl)-
oxazolines 1a−g in good to excellent yields.
Optimization of Conditions for Pd-Catalyzed Cou-
pling of 2-(Pentafluorophenyl)oxazoline 1a and 4-
Methoxyphenylboronic Acid. The reaction of 2-
(pentafluorophenyl)oxazoline 1a and 4-methoxyphenylboronic
acid 2 in the presence of 10 mol % Pd(MeCN)2Cl2 and
different phosphine ligands using 2.0 equiv of Cs2CO3 as the
base in diethoxyethane (DEE) was chosen as model reaction to
optimize the reaction conditions. Reactions using DPPF,
Davephos, cyclohexyl JohnPhos, XPhos, SPhos, or RuPhos
occurred to full conversion after 10 h at 130 °C. It was found
Received: November 17, 2011
Published: January 10, 2012
© 2012 American Chemical Society
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Table 1. Optimization of Conditions for the Coupling of 1a with 4-Methoxyphenyl Boronic Acid
a
yield
entry
catalyst
ligand
DPPF
base
solvent
time (h)
conv (%)
A
B
c
1
2
3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
DEE
3
3
<10
<10
96
tr
0
0
0
4
0
0
0
0
0
0
0
0
0
0
0
0
0
9
8
2
0
0
0
0
7
tr
5
0
0
0
3
0
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(dba)2
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DEE
DMF
NMP
DMSO
toluene
DCE
dioxane
tr
96
96
49
77
35
0
DPPF
3
b
4
DPPF
3
100
55
5
BINAP
DPPP
3
6
3
78
7
Xantphos
DPPE
3
64
8
3
28
9
Cy3P-HBF4
tBu3P-HBF4
Ad2PBu
P(o-tol)3
L1
3
71
66
47
87
44
<5
96
61
50
20
81
92
98
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
11
8
47
87
7
44
10
7
<5
96
L2
L3
14
8
61
tbutylXPhos
JohnPhos
MePhos
SPhos
50
14
10
10
10
3
20
90
100
100
20
DavePhos
Ruphos
Xphos
DPPF
3
44
16
69
74
53
tr
3
70
Pd(OAc)2
DPPF
3
78
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
DPPF
3
60
DPPF
Na2CO3
K3PO4
3
tr
DPPF
3
100
<20
<10
<10
100
<10
91
tr
DPPF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
3
DPPF
3
tr
DPPF
3
tr
DPPF
3
88
<10
90
DPPF
3
DPPF
3
95
5
a
b
c
Yields were determined by 19F NMR analysis of the crude product using 1,4-difluorobenzene as an internal standard. 0.5 equiv of Cs2CO3 DEE =
diethoxyethane.
that reactions using DPPF as the ligand were much faster than
those using Davephos, cyclohexyl JohnPhos, XPhos, SPhos, or
RuPhos as the ligand (Table 1, entries 3, 4, 14, 19−22). The
reaction proceeded to full conversion after 3 h at 130 °C to
afford the desired product in 96% yield as determined by 19F
NMR spectroscopy when DPPF was used (Table 1, entry 3).
The same reactions required 10 h to proceed to full conversion
when SPhos, DavePhos or ligand L2 was use as the ligand
(Table 1, entries 19 and 20). Less than 50% conversion was
observed after 3 h at 130 °C when RuPhos or XPhos was used
(Table 1, entries 21 and 22). Reactions in the presence of other
t
monodentate ligands such as Cy3P, Bu3P, Ad2PBu, P(o-tol)3,
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tBuXPhos, JohnPhos, and MePhos did not proceed to full
conversion (3−14 h) (Table 1, entries 9−13, 15−18).
Bidentate ligands such as BINAP, DPPP, Xantphos, and
DPPE were further studied but found to give less than 80%
conversion after 3 h at 130 °C (Table 1, entries 5−8).
Table 2. Palladium-Catalyzed Suzuki−Miyaura Coupling of
a
1a with Aryl Boronic Acids via C−F Bond Activation
Since DPPF is much cheaper than SPhos, DavePhos, or
ligand L2, DPPF was chosen for further optimization. Various
palladium precursors were studied to understand the effect of
the precursor on the reaction. Palladium catalyst was essential
to the reaction efficiency as no conversion was observed in the
absence of palladium catalyst (Table 1, entry 1). Likewise, in
the absence of DPPF, the reaction occurred to less than 10%
conversion (Table 1, entry 2). Using other palladium
precursors such as Pd(OAc)2 or Pd(dba)2 led to lower yields
(Table 1, entries 23 and 24). Next, the effect of the solvents
and bases was further evaluated. No product was observed
when the reactions was conducted in polar, aprotic solvents
such as DMF, DMSO, or NMP (Table 1, entries 28−30).
Reactions in less polar solvents such as toluene or dioxane
occurred to full conversion to afford the desired product in
slightly lower yield (Table 2, entries 31 and 33). Reaction in
dichloroethane (DCE) occurred to less than 10% conversion
(Table 1, entry 32). The reaction was sensitive to the base.
Using base such as K2CO3 led to much lower yields, and no
detectable product was observed when the reaction was
conducted with Na2CO3 as the base (Table 1, entries 25 and
26). Reactions with K3PO4 as the base gave comparable yield
under the same conditions (Table 1, entry 27). It was found
that 0.5 equiv of Cs2CO3 was enough for the reaction to occur
to full converison and to give the desired products in
comparable yield (Table 1, entry 4).
Scope of Pd-Catalyzed Suzuki−Miyaura Coupling of 1
with Aryl Boronic Acids via C−F Bond Activation. With
optimized conditions now in hand, we investigated the scope of
the palladium-catalyzed C−F bond activation/carbon−carbon
bond formation reaction of polyfluoroaryl oxazolines, and the
results are summarized in Table 2. A variety of arylboronic
acids are compatible with the reaction conditions, providing the
desired products in good-to-excellent yields. Reactions of both
arylboronic acids with electron-donating groups (Table 2,
entries 1, 2, 5−7) and electron-withdrawing groups (Table 2,
entries 3, 8−, 9, 11−17) gave the corresponding products in
good to excellent yields. Stereically hindered aryl boronic acid,
however, occurred in much lower 32% yield (Table 2, entry 3).
Challenging functionalized arylboronic acids were compatible
with the reaction conditions. Reactions of arylboronic acids
with functional groups such as enolizable ketones, aldehyde,
cyano, ester, and trifluoromethyl groups occurred in good
yields (Table 2, entries 11−16). Of particular significance, C−F
activation occurs exclusively in the presence of a weaker C−Cl
bond, an indication that the directing group favors the cleavage
of the strong C−F bond (Table 2, entry 11). Notably, the
presence of Cl in the products is very useful for further
synthetic manipulations. It is interesting to note that
alkenylboronic acids also converted into corresponding
carbon−carbon bond-forming product, albeit in low yield
(Table 2, entry 19).
a
Reaction conditions: 2-(pentafluorophenyl)oxazoline 1a (0.5 mmol),
arylboronic acid (0.6 mmol), Pd(CH3CN)2Cl2 (10 mol %), DPPF (10
mol %) and Cs2CO3 (0.25 mmol) in diethoxyethane (5.0 mL) at 130
°C for 3 h; Isolated yields. Pd(CH3CN)2Cl2 (1.0 mol %) and DPPF
(1.0 mol %) in toluene was used.
b
c
carbon−carbon bond formation than pentafluorophenyl oxazo-
line 1. The reactions were much slower to give the desired
products in moderate to good yields. In some cases, reactions
did not occur to full conversion even after long reaction time
(48 h). It was proposed that the strength of the metal−carbon
bond increases with the increasing of the electronegativity of
the aryl group. As a result, the activation energy for C−F
activation decreased as the number of fluorine increased. The
similar phenomena was observed by Crespo and Martinez,14
Love,10c,15 and Sandford.9 No C−F bond activation was
observed for the reaction of monofluorophenyl oxazoline as
substrate (Table 3, entry 14). Likewise, reactions of 2,3,6-
trifluorophenyl oxazoline occurred preferentially at the 2-
position due to the electron-withdrawing effect of the adjacent
fluorine atom. When the substrate containing both ortho C−H
bond and C−F bond, only the product resulting from the C−F
activation was observed (Table 3, entries 7−10).
To further expand the scope of our methodology for the
functionalization of polyfluoroaromatics, tetrafluorophenyl
oxazoline and three other trifluorophenyl oxazolines were
studied under the same reaction conditions. The tetrafluo-
phenyl and trifluorophenyl oxazoline derivatives are signifi-
cantly less reactive toward Pd-catalyzed C−F bond activation/
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dried over sodium sulfate, filtered, and concentrated under vacuum.
The residue was purified by column chromatography (SiO2, 300−400
mesh, petroleum/ethyl acetate = 6:1) to give the corresponding
product.
Table 3. Palladium-Catalyzed Suzuki−Miyaura Coupling of
2-Polyfluorophenyl Oxazoline with Aryl Boronic Acids via
a
C−F Bond Activation
2-(3,4,5,6-Tetrafluoro-4′-methoxybiphenyl-2-yl)-4,5-dihy-
drooxazole (3a). 1H NMR (CDCl3, 300 MHz) δ 7.28 (d, J = 8.2 Hz,
2 H), 6.96 (d, J = 8.2 Hz, 2 H), 4.17 (t, J = 9.5 Hz, 2 H), 3.89 (t, J =
9.5 Hz, 2 H), 3.85 (s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 159.0,
157.1, 145.0 (dd, J = 251.6, 10.2 Hz), 144.7 (dd, J = 235.4, 10.9 Hz),
140.9 (ddd, J = 256.8, 8.1, 5.1 Hz), 138.2 (ddd, J = 234.8, 12.4, 3.7
Hz), 129.7, 125.0 (d, J = 14.7 Hz), 121.9, 112.8, 66.9, 54.2; 19F NMR
(CDCl3, 282 MHz) δ −138.48 (ddd, J = 23.0, 12.5, 4.9 Hz, 1 F),
−140.64 (dd, J = 24.0, 13.2 Hz, 1 F), −152.29 (dd, J = 22.4, 4.0 Hz, 1
F), −156.30 (dd, J = 21.3, 21.3 Hz, 1 F) ppm. IR (thin film): νmax
1667, 1610, 1505, 1483, 1407, 1253, 956, 836, 800, 773 cm−1. MS
(ESI) m/z (%): 326 (M+ + 1), 325 (M+). Anal. Calcd for
C16H11F4NO2: C 59.08; H 3.41. Found: C 59.13; H 3.59. Mp: 85 °C.
2-(3,4,5,6-Tetrafluoro-3′-methoxybiphenyl-2-yl)-4,5-dihy-
drooxazole (3b). 1H NMR (CDCl3, 300 MHz) δ 7.34 (t, J = 8.0 Hz,
1 H), 6.99−6.90 (m, 3 H), 4.16 (t, J = 9.6 Hz, 2 H), 3.90 (t, J = 9.6 Hz,
2 H), 3.82 (s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 159.4, 157.9,
148.9 (dddd, J = 252.83, 10.6, 3.8, 2.3 Hz), 144.7 (dddd, J = 247.5,
10.7, 3.8, 2.3 Hz), 141.9 (dddd, J = 255.9, 17.4, 12.1, 4.5 Hz), 139.8
(dddd, J = 256.3, 16.7, 12.9, 3.8 Hz), 132.0 129.3, 126.1 (dt, J = 15.2,
2.3 Hz), 121.7, 114.8, 114.7, 114.1 (dt, J = 12.9, 3.0 Hz), 67.9, 55.3;
19F NMR (CDCl3, 282 MHz) δ −138.23 (ddd, J = 23.0, 13.1, 5.4 Hz,
1 F), −140.16 (ddd, J = 24.2, 13.4, 3.3 Hz, 1 F), −151.93 (ddd, J =
22.6, 22.6, 3.3 Hz, 1 F), −155.55 (ddd, J = 22.4, 22.4, 3.3 Hz, 1 F)
ppm. IR (thin film): νmax 2963, 1674, 1609, 1580, 1517, 1477, 1433,
1246, 1204, 957, 805, 778, 696 cm−1. MS (ESI) m/z (%): 326.0 (M+ +
1), 325.0 (M+). Anal. Calcd for C16H11F4NO2: C 59.08; H 3.41; N
4.31. Found: C 59.24; H 3.43; N 4.30. Mp: 61 °C.
2-(3,4,5,6-Tetrafluoro-2′-methoxybiphenyl-2-yl)-4,5-dihy-
drooxazole (3c). 1H NMR (CDCl3, 300 MHz) δ 7.39 (t, J = 7.8 Hz,
1 H), 7.17 (d, J = 7.5 Hz, 1 H), 6.99 (t, J = 8.9 Hz, 2 H), 4.1 (dq, J =
42.7, 9.0 Hz, 2 H), 3.84 (t, J = 9.6 Hz, 2 H), 3.79 (s, 3 H); 13C NMR
(CDCl3, 100 MHz) δ 158.2, 156.9, 145.8 (dddd, J = 256.2, 16.9, 3.5,
2.5 Hz), 145.0 (dddd, J = 244.7, 9.9, 3.5, 2.0 Hz), 141.6 (ddd, J =
259.3, 16.0, 4.0 Hz), 139.8 (dtt, J = 252.3, 16.4, 3.0 Hz), 130.7, 130.5,
123.2 (m), 120.3, 114.5 (m), 110.4 (m), 110.89, 67.7, 55.7, 55.2; 19F
NMR (CDCl3, 282 MHz) δ −137.23 (ddd, J = 22.1, 11.6, 3.1 Hz, 1 F),
−138.42 (ddd, J = 21.6, 12.0, 4.0 Hz, 1 F), −152.73 (ddd, J = 21.7,
21.7, 4.2 Hz, 1 F), −156.03 (ddd, J = 21.2, 21.2, 3.1 Hz, 1 F) ppm. IR
(thin film): νmax 2977.1, 2905.5, 1667.1, 1614.5, 1517.6, 1466.6,
1402.9, 1251.4, 1026.9, 975.8, 952.6, 866.9, 776.6, 637.8 cm−1. MS
(ESI) m/z (%): 326.6 (M+ + 1), 325.3 (M+). HRMS (ESI) calcd for
C16H12F4NO2: 326.0804, found 326.0799. Mp: 119−120 °C.
a
Reaction conditions: 2-(polyphenyl)oxazoline 1a (0.5 mmol),
arylboronic acid (0.6 mmol), Pd(CH3CN)2Cl2 (10 mol %), DPPF
(10 mol %) and Cs2CO3 (0.25 mmol) in diethoxyethane (5.0 mL) at
130 °C for 29−48 h. Isolated yields. No reaction.
b
c
2-(4′-tert-Butyl-3,4,5,6-tetrafluorobiphenyl-2-yl)-4,5-dihy-
drooxazole (3d). 1H NMR (CDCl3, 300 MHz) δ 7.44 (d, J = 8.4 Hz,
2 H), 7.27 (d, J = 8.4 Hz, 2 H), 4.13 (t, J = 9.4 Hz, 2 H), 3.88 (t, J =
9.4 Hz, 2 H), 1.35 (s, 9 H); 13C NMR (CDCl3, 100 MHz) δ 158.1,
151.9, 145.9 (dm, J = 255.2 Hz), 144.7 (dm, J = 245.0 Hz), 140.7 (dm,
J = 255.2 Hz), 139.7 (dm, J = 251.6 Hz), 129.0, 127.9, 126.3 (m),
125.3, 114.1 (m), 67.9, 55.3, 34.7, 31.2; 19F NMR (CDCl3, 282 MHz)
δ −138.41 (ddd, J = 22.7, 12.9, 4.5 Hz, 1 F), −140.48 (dd, J = 24.1,
13.0 Hz, 1 F), −152.13 (ddd, J = 22.7, 22.7, 4.5 Hz, 1 F), −156.06
(ddd, J = 22.4 Hz, 22.4, 2.8 Hz, 1 F) ppm. IR (thin film): νmax 2966,
1673, 1504, 1474, 1406, 1034, 956, 868, 842, 796 cm−1. MS (ESI) m/z
(%): 352.4 (M+ + 1), 351.3(M+). Anal. Calcd for C19H17F4NO: C
64.95; H 4.88. Found: C 65.22; H 5.09. Mp: 124 °C.
2-(3,4,5,6-Tetrafluoro-4′-methylbiphenyl-2-yl)-4,5-dihy-
drooxazole (3e). 1H NMR (CDCl3, 300 MHz) δ 7.24 (s, 4 H), 4.16
(t, J = 9.6 Hz, 2 H), 3.89 (t, J = 9.6 Hz, 2 H), 2.40 (s, 3 H); 13C NMR
(CDCl3, 100 MHz) δ 158.1, 146.0 (dm, J = 246.0 Hz), 144.8 (dm, J =
242.1 Hz), 141.8 (dm, J = 255.2 Hz), 139.7 (dm, J = 253.2 Hz) 138.8,
129.2, 129.1, 127.9, 126.2 (m), 114.1 (m), 67.9, 55.3, 21.3; 19F NMR
(CDCl3, 282 MHz) δ −138.15 (ddd, J = 22.2, 12.3, 4.4 Hz, 1 F),
−140.25 (dd, J = 23.4, 12.6 Hz, 1 F), −151.89 (ddd, J = 22.7, 22.7, 4.4
Hz, 1 F), −155.78 (ddd, J = 22.5, 22.5, 3.3 Hz, 1 F) ppm. IR (thin
film): νmax 2882, 1660, 1509, 1480, 1401, 1203, 1031, 955, 865, 801,
CONCLUSIONS
■
In summary, we have developed an efficiently palladium-
catalyzed Suzuki−Miyaura coupling reaction of polyfluoro-
phenyl oxazoline through ortho C−F activation. The reaction
was compatible with a variety of functional groups. Efforts to
expand the substrate scope with mild reaction conditions, as
well as detailed mechanistic studies, are underway.
EXPERIMENTAL SECTION
■
General Procedure for Catalytic C−F Activation/Functional-
ization. Pd(MeCN)2Cl2 (13 mg, 0.050 mmol), DPPF (28 mg, 0.050
mmol), Cs2CO3 (81 mg, 0.25 mmol), polyfluoroaryl oxazoline (0.5
mmol), and aryl boronic acid (0.6 mmol) were added to a Schlenk
tube capped with a rubber septum under argon atmosphere. DEE (5.0
mL) was added, and the reaction system was quickly degassed through
three freeze−pump−thaw cycles and refilled with Ar. The mixture was
then stirred at 130 °C and monitored by 19F NMR spectroscopy until
the disappearance of starting material (typically 3 h). The solution was
cooled to room temperature, and 30 mL of ethyl acetate was added.
The mixture was filtered through a short plug filled with Celite. The
filtrate was washed with water. The combined organic layers were
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776 cm−1. MS (ESI) m/z (%): 310.3 (M+ + 1), 309.3 (M+). Anal.
Calcd. for C16H11F4NO: C 62.14; H 3.59. Found: C 62.37; H.3.84.
Mp: 87 °C.
2-(3,4,5,6-Tetrafluoro-4′-(trifluoromethyl)biphenyl-2-yl)-4,5-
dihydrooxazole (3f). 1H NMR (CDCl3, 300 MHz) δ 7.70 (d, J = 7.8
Hz, 2 H), 7.47 (d, J = 7.8 Hz, 2 H), 4.15 (t, J = 9.6 Hz, 2 H), 3.88 (t, J
= 9.6 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ 157.6, 146.2 (dm, J =
248.3 Hz), 144.7 (dm, J = 257.4 Hz), 141.9 (dm, J = 251.2 Hz), 140.5
(dm, J = 152.1 Hz), 134.6, 131.5 (q, J = 32.7 Hz), 129.7, 129.6 (m),
126.6 (q, J = 271.0 Hz), 125.3 (q, J = 3.8 Hz), 114.1 (m), 68.0, 55.2;
19F NMR (CDCl3, 282 MHz) δ - 62.6 (s, 3 F), −137.2 (ddd, J = 21.7,
12.4, 5.4 Hz, 1 F), −139.9 (ddd, J = 21.5, 12.4, 3.1 Hz, 1 F), −151.1
(ddd, J = 21.6, 21.6, 5.4 Hz, 1 F), −153.9 (ddd, J = 22.2, 22.2, 3.1 Hz,
1 F) ppm. IR (thin film): νmax 2885.9, 1667.8, 1506.9, 1487.2, 1409.6,
1325.3, 1032.9, 853.0, 798.0 cm−1; MS (ESI) m/z (%): 364.3 (M+ +
1), 363.2 (M+). Anal. Calcd for C16H8F7NO: C 52.91; H 2.22; N 3.86.
Found: C 53.21; H 2.22; N 3.78. Mp: 85 °C.
C17H11F4NO3: C 57.80; H 3.14; N 3.96. Found: C 57.89; H 3.24; N
3.86. Mp: 106 °C.
1-(2′-(4,5-Dihydrooxazol-2-yl)-3′,4′,5′,6′-tetrafluorobiphen-
1
yl-4-yl)ethanone (3k). H NMR (CDCl3, 300 MHz) δ 8.02 (d, J =
7.8 Hz, 2 H), 7.45 (d, J = 7.8 Hz, 2 H), 4.16 (t, J = 9.6 Hz, 2 H), 3. 88
(t, J = 9.6 Hz, 2 H), 2.66 (s, 3 H); 13C NMR (CDCl3, 100 MHz) δ
197.4, 157.7, 146.3 (dm, J = 252.0 Hz), 144.6 (dm, J = 267.2 Hz),
141.9 (dm, J = 252.0 Hz), 140.3 (dm, J = 249.0 Hz), 137.2, 135.7,
129.8, 128.2, 125.2 (m), 114.0 (m), 68.0, 55.3, 26.6; 19F NMR
(CDCl3, 282 MHz) δ −137.90 (ddd, J = 21.7, 12.2, 4.0 Hz, 1 F),
−140.55 (ddd, J = 23.7, 11.8, 4.0 Hz, 1 F), −151.82 (ddd, J = 20.9,
20.9, 5.9 Hz, 1 F), −154.74 (ddd, J = 20.9, 20.9, 4.0 Hz, 1 F) ppm. IR
(thin film): νmax 2884.1, 1689.6, 1664.1, 1503.5, 1486.9, 1286.1,
1204.4, 1033.0, 956.4, 850.4, 797.3, 729.0, 595.7 cm−1. MS (ESI) m/z
(%): 338.1 (M+ + 1), 337.2 (M+). Anal. Calcd for C17H11F4NO2: C
60.54; H 3.29; N 4.15. Found: C 60.38; H 3.17; N 4.25. Mp: 121 °C.
2′-(4,5-Dihydrooxazol-2-yl)-3′,4′,5′,6′-tetrafluorobiphenyl-
4-carbaldehyde (3l). 1H NMR (CDCl3, 300 MHz) δ 10.08 (s, 1 H),
7.96 (d, J = 8.1 Hz, 2 H), 7.52 (d, J = 8.1 Hz, 2 H), 4.16 (t, J = 9.6 Hz,
2 H), 3.88 (t, J = 9.6 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ 191.6,
157.9, 146.6 (ddd, J = 254.6, 10.7, 2.5 Hz), 144.7 (dd, J = 247.6, 9.5
Hz), 142.0 (dtt, J = 258.3, 12.4, 2.9 Hz), 140.3 (dtt, J = 252.1, 13.2, 3.3
Hz), 137.0, 136.3, 130.2, 129.5, 124.9 (m), 113.8 (m), 68.1, 55.0; 19F
NMR (CDCl3, 282 MHz) δ −138.15 (ddd, J = 21.2, 11.8, 5.1 Hz, 1 F),
−139.39 (ddd, J = 21.2, 11.8 Hz, 1 F), −151.88 (ddd, J = 21.1, 21.1,
5.4 Hz, 1 F), −155.46 (ddd, J = 21.7, 21.7, 3.1 Hz, 1 F) ppm. IR (thin
film): νmax 2978.2, 1707.5, 1670.6, 1608.4, 1507.8, 1484.1, 1408.0,
1207.2, 1032.3, 822.7, 796.1, 512.2 cm−1. MS (ESI) m/z (%): 324.1
(M+ + 1), 323.2 (M+). Anal. Calcd for C16H9F4NO2: C 59.45; H 2.81;
N 4.33. Found: C 59.39; H 2.58; N 4.26. Mp: 101 °C.
2-(3,4,4′,5,6-Pentafluorobiphenyl-2-yl)-4,5-dihydrooxazole
(3m). 1H NMR (CDCl3, 300 MHz) δ 7.34 (dd, J = 7.8, 5.4 Hz, 2 H),
7.14 (dd, J = 7.8, 5.4, 2 H), 4.18 (t, J = 9.6 Hz, 2 H), 3.90 (t, J = 9.6
Hz, 2 H). 13C NMR (CDCl3, 100 MHz) δ 163.0 (d, J = 248.3 Hz),
157.8, 145.9 (dm, J = 253.6 Hz), 144.8 (dm, J = 243.8 Hz), 142.0 (dm,
J = 250.6 Hz), 139.9 (dm, J = 253.6 Hz), 131.3 (d, J = 8.4 Hz), 125.2
(m), 115.6, 115.4, 114.2 (m), 67.9, 55.2; 19F NMR (CDCl3, 282 MHz)
δ −111.89 (tt, J = 6.3 Hz, 9.0 Hz, 1 F), −137.77 (ddd, J = 23.0, 13.0,
5.4 Hz, 1 F), −140.12 (ddd, J = 19.5, 12.4, 3.1 Hz, 1 F), −151.59 (ddd,
J = 22.5, 22.5, 4.8 Hz, 1 F), −155.00 (ddd, J = 22.4, 22.4, 3.3 Hz, 1 F)
ppm. IR (thin film): νmax 2936, 1675, 1607, 1506, 1476, 1405, 1225,
1029, 956, 848, 810, 758 cm−1; MS (ESI) m/z (%): 314.3 (M+ + 1),
313.2 (M+). Anal. Calcd for C15H8F5NO: C 57.52; H 2.57; N 4.47.
Found: C 57.86; H 2.45; N 4.46. Mp: 54 °C.
2-(2,3,4,5-Tetrafluoro-6-(thiophen-3-yl)phenyl)-4,5-dihy-
drooxazole (3n). 1H NMR (CDCl3, 300 MHz) δ 7.45 (s, 1 H), 7.40
(d, J = 4.8 Hz, 1 H), 7.16 (d, J = 4.8 Hz, 1 H), 4.25 (t, J = 9.6 Hz, 2
H), 3.97 (t, J = 9.6 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ 157.1,
145.1 (dm, J = 250.5 Hz), 143.9 (dm, J = 246.0 Hz), 141.3 (dm, J =
258.1 Hz), 138.5 (dm, J = 253.8 Hz), 137.4 (m), 129.0, 127.2 (d, J =
6.9 Hz), 124.8 (d, J = 6.9 Hz), 124.6, 120.3 (m), 113.0 (m), 67.0, 54.3;
19F NMR (CDCl3, 282 MHz) δ −138.17 (ddd, J = 21.6, 12.4, 5.5 Hz,
1 F), −139.4 (dd, J = 21.6, 12.4 Hz, 1 F), −151.92 (ddd, J = 21.2, 21.2,
4.2 Hz, 1 F), −155.50 (ddd, J = 20.8, 20.8, 3.1 Hz, 1 F) ppm. IR (thin
film): νmax 3110.2, 1671.7, 1507.2, 1480.0, 1384.4, 1196.6, 1097.1
1035.6, 956.2, 804.4, 742.2 cm−1. MS (ESI) m/z (%): 302.3 (M+ + 1),
301.2 (M+). Anal. Calcd for C13H7F4NOS: C 51.83; H 2.34; N 4.65.
Found: C 51.86; H 2.20; N 4.78. Mp: 72 °C.
(E)-2-(2,3,4,5-Tetrafluoro-6-(prop-1-enyl)phenyl)-4,5-dihy-
drooxazole (3o). 1H NMR (CDCl3, 300 MHz) δ 6.40 (dd, J = 15.9,
6.6 Hz, 1 H), 6.26 (d, J = 15.5 Hz, 1 H), 4.46 (t, J = 9.6 Hz, 2 H), 4.13
(t, J = 9.6 Hz, 2 H), 1.92 (d, J = 6.3 Hz, 3 H); 13C NMR (CDCl3, 100
MHz) δ 158.2, 145.1 (dm, J = 252.0 Hz), 143.9 (dm, J = 246.8 Hz),
141.3 (dm, J = 252.2 Hz), 138.8 (dm, J = 248.8 Hz), 135.8 (m), 122.6
(m), 120.0 (m), 112.6 (m), 68.0, 55.4, 19.7; 19F NMR (CDCl3, 282
MHz) δ −138.65 (ddd, J = 21.3, 11.9, 3.1 Hz, 1 F), 141.05 (dd, J =
20.6, 12.1 Hz, 1 F), −152.86 (ddd, J = 20.6, 20.6, 3.1 Hz, 1 F),
−157.52 (dd, J = 20.6, 20.6 Hz, 1 F) ppm. IR (thin film): νmax 2964.5,
2918.0, 1673.9, 1510.6, 1485.6, 1398.6, 1196.1, 1072.3, 953.7, 914.9,
804.3 cm−1. MS (EI) m/z (%): 258 (M+-1), 259(M+) 244 (100).
2′-(4,5-Dihydrooxazol-2-yl)-3′,4′,5′,6′-tetrafluorobiphenyl-
1
4-carbonitrile (3g). H NMR (CDCl3, 300 MHz) δ 7.76 (d, J = 8.1
Hz, 2 H), 7.48 (d, J = 8.1 Hz, 2 H), 4.19 (t, J = 9.6 Hz, 2 H), 3.90 (t, J
= 9.6 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ 157.4, 146.2 (dddd, J
= 239.8, 11.6, 5.3, 3.3 Hz), 144.7 (dddd, J = 246.7, 10.7, 4.9, 2.0 Hz),
141.9 (ddd, J = 258.3, 13.2, 4.2 Hz), 140.5 (dtt, J = 255.0, 12.3, 3.3
Hz), 135.7, 132.1, 130.3, 124.2 (m), 118.2, 114.0 (m), 112.9, 68.0,
55.3; 19F NMR (CDCl3, 282 MHz) δ −136.53 (ddd, J = 21.7, 12.4, 5.4
Hz, 1 F), −139.64 (ddd, J = 21.5, 12.1, 3.1 Hz, 1 F), −150.60 (ddd, J =
21.6, 21.6, 5.4 Hz, 1 F), −153.08 (ddd, J = 21.0, 21.0, 4.2 Hz, 1 F)
ppm. IR (thin film): νmax 2913.3, 2229.7, 1663.7, 1506.0, 1482.0,
1406.7, 1204.8, 1032.8, 864.0, 848.3, 799.7, 557.8 cm−1; MS (ESI) m/z
(%): 321.3 (M+ + 1), 320.2 (M+). Anal. Calcd for C16H8F4N2O: C
60.01; H 2.52; N 8.75. Found: C 60.08; H 2.25; N 8.75. Mp: 86 °C.
2-(2,3,4,5-Tetrafluoro-6-(naphthalen-1-yl)phenyl)-4,5-dihy-
drooxazole (3h). 1H NMR (CDCl3, 300 MHz) δ 7.92 (t, J = 7.2 Hz,
2 H), 7.50 (m, 4 H), 7.38 (d, J = 6.9 Hz, 1 H), 3.88−3.74 (m, 2 H),
3.67−3.60 (m, 2 H). 13C NMR (CDCl3, 100 MHz) δ 157.8, 146.1
(dm, J = 250.2 Hz), 144.1 (dm, J = 239.6 Hz), 141.6 (dm, J = 252.3
Hz), 140.7 (dm, J = 260.0 Hz), 133.3, 131.5, 129.4, 128.5 (m), 128.3,
127.8, 126.7, 126.1, 124.9, 115.2 (m), 67.6, 54.9; 19F NMR (CDCl3,
282 MHz) δ −136.62 (ddd, J = 24.0, 13.2, 3.3 Hz, 1 F), −137.40 (ddd,
J = 21.9, 13.2, 5.4 Hz, 1 F), −151.67 (ddd, J = 24.0, 21.9, 5.4 Hz, 1 F),
−154.73 (ddd, J = 22.1, 22.1, 4.2 Hz, 1 F) ppm. IR (thin film): νmax
2962, 1652, 1506, 1486, 1475, 1413, 1197, 953, 881, 805, 774, 640
cm−1; MS (ESI) m/z (%): 346.4 (M+ + 1), 345.3 (M+). Anal. Calcd
for C19H11F4NO: C 66.09; H 3.21; N 4.06. Found: C 66.64; H 3.23; N
4.08. Mp: 64 °C.
2-(4′-Chloro-3,4,5,6-tetrafluorobiphenyl-2-yl)-4,5-dihy-
drooxazole (3i). 1H NMR (CDCl3, 300 MHz) δ 7.42 (d, J = 8.4 Hz,
2 H), 7.29 (d, J = 8.4 Hz, 2 H), 4.18 (t, J = 9.6 Hz, 2 H), 3.90 (t, J =
9.6 Hz, 2 H); 13C NMR (CDCl3, 300 MHz) δ 157.7, 146.1 (dm, J =
255.8 Hz), 144.8 (dm, J = 246.0 Hz), 141.9 (dm, J = 241.4 Hz), 140.1
(dm, J = 252.8 Hz), 135.1, 130.8, 129.2, 128.7, 125.0 (m), 114.1 (m),
67.9, 55.3; 19F NMR (CDCl3, 300 MHz) δ −137.57 (ddd, J = 23.0,
13.1, 5.4 Hz, 1 F), −140.02 (ddd, J = 23.5, 13.6, 3.3 Hz, 1 F), −151.48
(ddd, J = 22.5, 22.5, 5.4 Hz, 1 F), −154.70 (ddd, J = 21.9, 21.9, 3.3 Hz,
1 F) ppm. IR (thin film): νmax 2946, 1667, 1513, 1496, 1485, 1409,
1204, 1091, 1033, 958, 840, 797 cm−1; MS (ESI) m/z (%): 329.9 (M+
+ 1), 329.7 (M+). HRMS (ESI) calcd for C15H9ClF4NO: 330.0309,
found 330.0303. Mp: 65−66 °C.
Methyl 2′-(4,5-Dihydrooxazol-2-yl)-3′,4′,5′,6′-tetrafluorobi-
1
phenyl-4-carboxylate (3j). H NMR (CDCl3, 300 MHz) δ 8.10
(d, J = 7.8 Hz, 2 H), 7.42 (d, J = 7.8 Hz, 2 H), 4.14 (t, J = 9.6 Hz, 2
H), 3.95 (s), 3.86 (t, J = 9.6 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ
165.5, 156.6, 143.2 (dm, J = 252.2 Hz), 143.7 (dm, J = 244.5 Hz),
140.9 (dm, J = 244.5 Hz), 139.3 (dm, J = 254.4 Hz), 134.5, 129.5,
128.5, 124.2 (m), 113.1 (m), 66.9, 54.2, 51.3; 19F NMR (CDCl3, 282
MHz) δ −137.27 (ddd, J = 21.7, 12.4, 5.1 Hz, 1 F), −139.76(dd, J =
21.7, 12.4 Hz, 1 F), −151.17 (ddd, J = 21.2, 21.2, 5.1 Hz, 1 F),
−154.12 (dd, J = 20.6, 20.6 Hz, 1 F) ppm. IR (thin film): νmax 2956.8,
1720.0, 1665.9, 1503.5, 1411.0, 1290.8, 1033.0, 956.3, 794.5 cm−1. MS
(ESI) m/z (%): 354.0 (M+ + 1), 353.0 (M+). Anal. Calcd for
1802
dx.doi.org/10.1021/jo2023262 | J. Org. Chem. 2012, 77, 1798−1804

The Journal of Organic Chemistry
Article
HRMS (EI) calcd for C12H9F4NO: 259.0620, found 259.0622. Mp: 58
Methyl 2′-(4,5-Dihydrooxazol-2-yl)-3′,4′,6′-trifluorobiphen-
1
yl-4-carboxylate (4f). H NMR (CDCl3, 300 MHz) δ 8.09 (d, J =
°C.
8.4 Hz, 2 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.14 (ddd, J = 17.0, 7.8, 2.1 Hz,
1 H), 4.15 (t, J = 9.6 Hz, 2 H), 3.94 (s, 3 H), 3.88 (t, J = 9.6 Hz, 2 H);
13C NMR (CDCl3, 100 MHz) δ 166.6, 158.2, 154.5 (ddd, J = 246.2,
2-(3,4,6-Trifluoro-4′-methoxybiphenyl-2-yl)-4,5-dihydrooxa-
1
zole (4a). H NMR (CDCl3, 300 MHz) δ 7.30 (d, J = 8.4 Hz, 2 H),
7.10 (dd, J = 16.4, 9.0 Hz, 1 H), 6.95(d, J = 8.4 Hz, 2 H), 4.19 (t, J =
9.6 Hz, 2 H), 3.91 (t, J = 9.6 Hz, 2 H), 3.85 (s, 3 H); 13C NMR
(CDCl3, 100 MHz) δ 159.6, 158.7, 154.7 (ddd, J = 243.9, 10.3, 3.3
Hz), 149.0 (dt, J = 250.1, 12.8 Hz), 145.5 (ddd, J = 248.4, 14.1, 3.3
Hz), 130.7, 125.8 (dd, J = 18.6, 4.1 Hz), 124.0, 120.2 (dd, J = 12.3, 3.3
Hz), 113.6, 107.1 (dd, J = 87.3, 60.6 Hz), 67.8, 55.1, 55.1; 19F NMR
(CDCl3, 282 MHz) δ −116.21 (ddd, J = 14.0, 14.0, 3.1, 1 F), −133.87
(ddd, J = 22.0, 9.3, 4.2 Hz, 1 F),-141.83 (ddd, J = 21.9, 14.4, 7.5 Hz, 1
F) ppm. IR (thin film): νmax 2962.4, 1671.3, 1610.3, 1485.5, 1370.1,
1249.5, 1179.5, 1037.3, 986.6, 875.2, 833.9, 550.6 cm−1. MS (EI) m/z
(%): 306 (M+ − 1), 307.1 (M+) 306 (100). HRMS (EI) calcd for
C16H12F3NO2: 307.0820, found 307.0821. Mp: 100−101 °C.
9.4, 2.5 Hz), 149.9 (ddd, J = 252.3, 15.1, 13.0 Hz), 145.7 (ddd, J =
250.2, 14.1, 4.2 Hz), 136.6, 130.1, 129.6 (m), 129.4, 124.9 (dd, J =
18.5, 4.8 Hz), 120.1 (m), 107.4 (dd, J = 28.8, 20.5 Hz), 67.9, 55.2,
52.2; 19F NMR (CDCl3, 282 MHz) δ −115.58 (ddd, J = 14.1, 9.0, 5.1
Hz, 1 F), −132.79 (ddd, J = 21.7, 10.3, 4.2 Hz, 1 F), −140.86 (ddd, J =
21.6, 15.0, 6.6 Hz, 1 F) ppm. IR (thin film): νmax 2954.9, 1724.7,
1670.0, 1628.3, 1487.8, 1278.6, 1110.2, 1030.1, 978.8, 777.3, 718.0
cm−1. MS (EI) m/z (%): 334 (M+ − 1), 335 (M+) 304 (100). HRMS
(EI) Calcd for C17H12F3NO3: 335.0769, found 335.0770. Mp: 67 - 68
°C.
2-(5,6-Difluoro-4′-methoxybiphenyl-2-yl)-4,5-dihydrooxa-
zole (4g). 1H NMR (CDCl3, 300 MHz) δ 7.55 (m, 1 H), 7.29 (d, J =
6.3 Hz, 2 H), 7.18 (m, 1 H), 6.97 (d, J = 6.3 Hz, 2 H), 4.11 (t, J = 7.1
Hz, 2 H), 3.91 (t, J = 7.1 Hz, 2 H), 3.86 (s, 3 H); 13C NMR (CDCl3,
100 MHz) δ 164.5, 159.5, 152.1 (dd, J = 253.3, 14.4 Hz), 147.9 (dd, J
= 246.5, 12.5 Hz), 131.7 (d, J = 14.0 Hz), 130.5 (d, J = 2.0 Hz), 125.9
(m), 125.4 (m), 125.1 (d, J = 2.5 Hz), 115.6 (d, J = 17.5 Hz), 113.5,
67.9, 55.2, 54.9; 19F NMR (CDCl3, 282 MHz) δ −133.16 (ddd, J =
22.2, 9.1, 5.1 Hz, 1 F), −139.63 (dd, J = 21.7, 7.1 Hz, 1 F) ppm. IR
(thin film): νmax 2961.0, 1651.9, 1 611.9, 1519.1, 1494.7, 1438.8,
1250.0, 1101.7, 1032.4, 830.1, 668.6 cm−1. MS (EI) m/z (%): 288 (M+
−1), 289.1 (M+). HRMS (EI) calcd for C16H13F2NO2: 289.0914,
found 289.0918. Mp: 65−66 °C.
2-(4′-tert-Butyl-3,4,6-trifluorobiphenyl-2-yl)-4,5-dihydrooxa-
1
zole (4b). H NMR (CDCl3, 300 MHz) δ 7.43 (d, J = 8.4 Hz, 2 H),
7.28 (d, J = 8.4 Hz, 2H), 7.11 (dd, J = 16.1, 6.6, Hz, 1 H), 4.14 (t, J =
9.6 Hz, 2 H), 3.89 (t, J = 9.6 Hz, 2 H), 1.35 (s, 9 H); 13C NMR
(CDCl3, 100 MHz) δ 158.6 (m), 154.7 (ddd, J = 244.3, 9.8, 3.1 Hz),
155.3, 149.3 (ddd, J = 250.7, 14.6, 12.5 Hz), 145.4 (ddd, J = 249.1,
13.9, 4.2 Hz), 129.1 (dd, J = 1.6, 0.7 Hz), 128.9, 126.0 (dd, J = 18.8,
5.1 Hz), 125.1, 120.3 (dd, J = 4.7, 2.8 Hz), 107.1 (dd, J = 29.2, 20.4
Hz), 67.8, 55.3, 34.6, 31.3; 19F NMR (CDCl3, 282 MHz) δ −116.16
(ddd, J = 9.3, 9.3, 5.1 Hz, 1 F), −133.74 (ddd, J = 21.6, 10.3, 5.1 Hz, 1
F), −141.81 (ddd, J = 21.9, 14.4, 7.5 Hz, 1 F) ppm. IR (thin film): νmax
2962.2, 1668.6, 1626.6, 1485.0, 1371.2, 1139.5, 987.9, 877.4, 731.0,
619.0 cm−1. MS (ESI) m/z (%): 334.4 (M+ + 1), 333.1 (M+). Anal.
Calcd for C19H18F3NO: C 68.48; H 5.44; N 4.20. Found: C 68.64; H
5.71; N 4.49. Mp: 105 - 106 °C.
2-(4′,5,6-Trifluorobiphenyl-2-yl)-4,5-dihydrooxazole (4h). 1H
NMR (CDCl3, 300 MHz) δ 7.58 (m, 1 H), 7.31 (t, J = 4.2 Hz, 2H),
7.20 (dd, J = 12.8, 6.4 Hz, 1 H), 7.11(t, J = 6.4 Hz, 2 H), 4.09 (t, J =
7.2 Hz, 2 H), 3.86 (t, J = 7.2 Hz, 2 H); 13C NMR (CDCl3, 100 MHz)
δ 163.9, 162.6 (d, J = 246.7 Hz), 152.0 (dd, J = 254.0, 14.0 Hz), 147.8
(dd, J = 246.5, 12.1 Hz), 131.1 (dd, J = 7.9, 1.5 Hz), 130.9, 128.9 (dd, J
= 3.5, 2.5 Hz), 126.2 (dd, J = 7.5, 4.5 Hz), 125.3 (m), 116.1 (d, J =
17.5 Hz), 115.1 (d, J = 21.6 Hz), 67.8, 54.9; 19F NMR (CDCl3, 282
MHz) δ −113.28 (dd, J = 8.2, 6.2 Hz, 1 F), −132.72 (ddd, J = 21.6,
9.2, 5.1 Hz, 1 F), −139.10 (dd, J = 21.6, 7.2 Hz, 1 F) ppm. IR (thin
film): νmax 2938.1, 1904.1, 1646.9, 1518.4, 1491.7, 1448.8, 1361.2,
960.5, 826.6, 806.2, 667.1, 532.7 cm−1. MS (EI) m/z (%): 276 (M+ −
1), 277.1 (M+) 276 (100). HRMS (EI) calcd for C15H10F3NO:
277.0714, found 277.0719. Mp: 70−71 °C.
2-(3,4,6-Trifluoro-4′-methylbiphenyl-2-yl)-4,5-dihydrooxa-
1
zole (4c). H NMR (CDCl3, 300 MHz) δ 7.20−7.38 (m, 4 H), 7.10
(m, 1 H), 4.16 (t, J = 9.6 Hz, 2 H), 3.89 (t, J = 9.6 Hz, 2 H), 2.39 (s, 3
H); 13C NMR (CDCl3, 100 MHz) δ 158.6, 154.7 (ddd, J = 244.3, 10.0,
3.5 Hz), 149.2 (ddd, J = 250.2, 19.0, 17.5 Hz), 145.6 (ddd, J = 249.1,
13.4, 4.0 Hz), 138.2, 129.3 (m), 128.9, 126.1 (dd, J = 19.0, 4.5 Hz),
120.2 (ddd, J = 13.5, 4.5, 2.0 Hz), 107.1 (dd, J = 30.0, 20.5 Hz), 67.9,
55.2, 21.3; 19F NMR (CDCl3, 282 MHz) δ −116.11 (ddd, J = 12.4,
9.3, 3.1 Hz, 1 F), −133.65 (ddd, J = 21.8, 9.3, 4.2 Hz, 1 F), −141.76
(ddd, J = 21.3, 14.5, 6.8 Hz, 1 F) ppm. IR (thin film): νmax 2963.2,
1671.4, 1629.4, 1485.8, 1370.6, 1138.6, 987.6, 875.5, 816.3 cm−1. MS
(EI) m/z (%): 290 (M+ − 1), 291.1 (M+), 290 (100). HRMS (EI)
calcd for C16H12F3NO: 291.0871, found 291.0873.
2-(2-(Benzo[b]thiophen-2-yl)-3,4-difluorophenyl)-4,5-dihy-
drooxazole (4i). 1H NMR (CDCl3, 300 MHz) δ 8.03 (m, 2 H), 7.56
(m, 1 H), 7.39 (m, 3 H), 7.25(m, 2 H), 4.18 (t, J = 9.6 Hz, 2 H), 3.93
(t, J = 9.6 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ 163.4, 151.7 (dd,
J = 252.9, 12.4 Hz), 147.9 (dd, J = 249.6, 15.2 Hz), 140.5, 139.1, 132.6
(m), 130.5, 128.4, 125.6 (dd, J = 7.0, 4.1 Hz), 125.2 (d, J = 2.5 Hz),
124.2, 124.0, 123.6, 121.9, 116.6 (dd, J = 17.7, 1.2 Hz), 67.8, 54.7; 19F
NMR (CDCl3, 282 MHz) δ −132.14 (ddd, J = 21.9, 9.3, 5.1 Hz, 1 F),
−135.75 (dd, J = 21.7, 7.4 Hz, 1 F) ppm. IR (thin film): νmax 2962.4,
2924.5, 1652.1, 1495.7, 1261.4, 1096.2, 1021.8, 800.2 cm−1. MS (EI)
m/z (%): 314 (M+ − 1), 315 (M+), 43 (100). HRMS (EI) calcd for
C17H11F2NOS: 315.0529, found 315.0526. Mp: 80−81 °C
2′-(4,5-Dihydrooxazol-2-yl)-3′,4′,6′-trifluorobiphenyl-4-car-
bonitrile (4d). 1H NMR (CDCl3, 400 MHz) δ 7.72 (d, J = 8.4 Hz, 2
H), 7.47(d, J = 8.4 Hz, 2 H), 7.17 (td, J = 9.0, 6.4 Hz, 1 H), 4.19 (t, J =
9.6 Hz, 2 H), 3.90 (t, J = 9.6 Hz, 2 H); 13C NMR (CDCl3, 100 MHz)
δ 158.0, 154.4 (dm, J = 241.7 Hz), 150.2 (dm, J = 258.8 Hz), 145.9
(dm, J = 251.8 Hz), 136.8, 131.9, 124.0 (m), 120.1 (m), 118.4, 112.4,
107.6 (dd, J = 29.1, 20.5 Hz), 68.0, 55.3; 19F NMR (CDCl3, 282 MHz)
δ −115.50 (ddd, J = 14.7, 9.3, 3.9 Hz, 1 F), −130.64 (ddd, J = 21.8,
9.3, 3.9 Hz, 1 F), −140.11 (ddd, J = 21.6, 15.0, 6.6 Hz, 1 F) ppm. IR
(thin film): νmax 2223.5, 1673.3, 1630.5, 1483.1, 1373.4, 1170.1,
1139.6, 986.0, 842.2, 556.9 cm−1. MS (EI) m/z (%): 301 (M+ − 1),
302 (M+) 301 (100). HRMS (EI) calcd for C16H9F3N2O: 302.0667,
found 302.0670. Mp: 116−117 °C.
2′-(4,5-Dihydrooxazol-2-yl)-3′,4′,6′-trifluorobiphenyl-4-car-
baldehyde (4e). 1H NMR (CDCl3, 300 MHz) δ 10.09 (s, 1 H), 7.95
(d, J = 8.1 Hz, 2 H), 7.54 (d, J = 8.1 Hz, 2 H), 7.18 (m, 1 H), 4.18 (t, J
= 9.6 Hz, 2 H), 3.90 (t, J = 9.6 Hz, 2 H); 13C NMR (CDCl3, 100
MHz) δ 191.8, 169.8, 158.5, 154.5 (dm, J = 251.9 Hz), 150.0 (dm, J =
243.0 Hz), 145.9 (dm, J = 246.3 Hz), 136.0, 130.3 (m), 129.9, 129.7,
129.5, 124.9 (m), 112.0 (m), 107.6 (dd, J = 27.7, 19.9 Hz), 68.1, 55.0;
19F NMR (CDCl3, 282 MHz) δ −115.58 (m, 1 F), −131.32 (ddd, J =
2-(3,6-Difluoro-2-(phenanthren-9-yl)phenyl)-4,5-dihydroox-
1
azole (4j). H NMR (CDCl3, 300 MHz) δ 8.73 (t, J = 7.8 Hz, 2 H),
7.88 (d, J = 7.5 Hz, 1 H), 7.70−7.51 (m, 6 H), 7.26 (m, 2 H), 3.82
(dd, J = 17.0, 9.0 Hz, 1 H), 3.73−3.56 (m, 3 H); 13C NMR (CDCl3,
100 MHz) δ 159.3, 156.8 (dd, J = 249.4, 2.5 Hz), 156.2 (dd, J = 243.3,
2.3 Hz), 131.1, 130.7, 130.5, 130.1, 129.3 (dd, J = 20.9, 2.3 Hz), 129.4
(d, J = 1.9 Hz), 128.9, 128.6, 127.2, 126.8, 126.8, 126.7, 126.2 (d, J =
1.0 Hz), 122.8, 122.6, 119.9 (dd, J = 17.2, 3.7 Hz), 118.3 (dd, J = 25.4,
9.3 Hz), 116.6 (dd, J = 24.4, 8.6 Hz), 67.5, 54.9; 19F NMR (CDCl3,
282 MHz) δ −116.08 (m, 1 F), −116.93 (m, 1 F) ppm. IR (thin film):
νmax 2921.0, 1663.7, 1470.0, 1348.5, 1255.6, 1107.9, 979.5, 958.5,
919.9, 822.6, 750.6, 725.9 cm−1 MS (EI) m/z (%): 359 (M+), 359
(100). HRMS (EI) calcd for C23H15F2NO: 359.1122, found 359.1125.
Mp: 119−120 °C.
20.0, 9.3, 4.2 Hz, 1 F), −140.57 (m, 1 F) ppm. IR (thin film): νmax
2918.1, 1698.4, 1488.2, 1369.6, 1208.8, 1167.9, 832.4, 694.1 cm−1. MS
(EI) m/z (%): 304 (M+ − 1), 305 (M+), 304(100). HRMS (EI) calcd
for C16H10F3NO2: 305.0664, found 305.0668. Mp: 84−85 °C.
2-(3,6-Difluoro-4′-methoxybiphenyl-2-yl)-4,5-dihydrooxa-
1
zole (4k). H NMR (CDCl3, 300 MHz) δ 7.32 (d, J = 7.8 Hz, 2 H),
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dx.doi.org/10.1021/jo2023262 | J. Org. Chem. 2012, 77, 1798−1804

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Article
7.18 (td, J = 6.6, 4.8 Hz, 1 H), 7.07 (td, J = 8.8, 3.9 Hz, 1 H), 6.94 (d, J
= 7.8 Hz, 2 H), 4.20 (t, J = 6.0 Hz, 2 H), 3.89 (t, J = 6.0 Hz, 2 H),
3.85(s, 3 H); 13C NMR (CDCl3, 100 MHz) δ 159.5, 156.6 (dd, J =
247.9, 2.7 Hz), 155.6 (dd, J = 242.4, 2.7 Hz), 130.6, 130.6, 130.4 (d, J
= 2.8 Hz), 124.9 (d, J = 1.8 Hz), 118.8 (dd, J = 17.4, 3.7 Hz), 118.3
(dd, J = 26.0, 9.3 Hz), 115.4 (dd, J = 24.3, 8.5 Hz), 113.6, 67.7, 55.2,
55.2; 19F NMR (CDCl3, 282 MHz) δ −118.15 (ddd, J = 16.9, 8.7, 4.2
Hz, 1 F), −120.57 (ddd, J = 16.9, 8.7, 4.2 Hz, 1 F) ppm. IR (thin film):
νmax 2924.2, 1677.1, 1606.3, 1522.7, 1474.9, 1261.7, 1186.6, 1074.3,
959.3, 838.3, 825.1, 692.8 cm−1. MS (EI) m/z (%): 288 (M+ − 1),
289.1 (M+). HRMS (EI) calcd for C16H13F2NO2: 289.0914, found
289.0912. Mp: 76 °C.
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Queguiner, G. J. Org. Chem. 2002, 67, 8991. (c) Terao, J.; Ikumi, A.;
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Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2003, 125, 5646.
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2-(3,5-Difluoro-4′-methoxybiphenyl-2-yl)-4,5-dihydrooxa-
1
zole (4l). H NMR (CDCl3, 300 MHz) δ 7.36 (d, J = 8.4 Hz, 2 H),
Hatano, M. Chem. Commun. 2004, 2082. (h) Bohm, V. P. W;
̈
6.95 (d, J = 8.4 Hz, 3 H), 6.83 (t, J = 8.4 Hz, 1 H), 4.23 (t, J = 9.6 Hz,
2 H), 3.94 (t, J = 9.6 Hz, 2 H), 3.85 (s, 3 H); 13C NMR (CDCl3, 100
MHz) δ 163.3 (dd, J = 252.1, 13.3 Hz), 161.4 (dd, J = 253.1, 13.0 Hz),
160.1, 159.7, 145.2 (dd, J = 9.8, 4.2 Hz), 131.1 (m), 129.3, 113.8,
113.0 (dd, J = 15.3, 3.7 Hz), 112.6 (dd, J = 21.8, 3.3 Hz), 102.5 (dd, J
= 26.0 Hz), 67.6, 55.2, 55.2; 19F NMR (CDCl3, 282 MHz) δ −106.63
(dd, J = 17.5, 9.3 Hz, 1 F), −108.77 (t, J = 9.3 Hz, 1 F) ppm. IR (thin
film): νmax 2934.4, 1667.1, 1610.9, 1518.3, 1434.6, 1208.6, 1108.3,
1055.2, 936.9, 834.5, 610.7, 588.6 cm−1. MS (EI) m/z (%): 288 (M+ −
1), 289 (M+) 288 (100). HRMS (EI) calcd for C16H13F2NO2:
289.0914, found 289.0917.
Gstottmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem.,
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Int. Ed. 2001, 40, 3387. (i) Steffen, A.; Sladek, M. I.; Braun, T.;
Neumann, B.; Stammler, H.-G. Organometallics 2005, 24, 4057.
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2005, 1771. (l) Ackermann, L. Synlett 2010, 294.
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(b) Braun, T.; Perutz, R. N. Chem. Commun. 2002, 2749. (c) Braun,
T.; Wehmeier, F. Eur. J. Inorg. Chem. 2011, 25, 613.
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2254. (b) Braun, T.; Izundu, J.; Steffen, A.; Neumann, B.; Stammler,
H.-G. Dalton Trans. 2006, 35, 5118.
2′-(4,5-Dihydrooxazol-2-yl)-3′,5′-difluorobiphenyl-4-carbal-
dehyde (4m). 1H NMR (CDCl3, 300 MHz) δ 10.07 (s, 1 H), 7.93 (d,
J = 8.1 Hz, 2 H), 7.57 (d, J = 8.1 Hz, 2 H), 6.96 (t, J = 8.7 Hz, 2 H),
4.20 (t, J = 9.6 Hz, 2 H), 3.91(t, J = 9.6 Hz, 2 H); 13C NMR
(CDCl3,100 MHz) δ 191.7, 163.4 (dd, J = 253.2, 13.0 Hz), 161.5 (dd,
J = 255.0, 13.0 Hz), 157.2, 144.7 (m), 144.1 (dd, J = 9.5, 4.0 Hz),
135.9, 129.7, 128.9, 113.3 (dd, J = 15.8, 4.2 Hz), 112.9 (dd, J = 22.6,
3.5 Hz), 104.0 (dd, J = 25.5 Hz), 67.7, 55.2; 19F NMR (CDCl3, 282
MHz) δ −105.27 (dd, J = 17.5, 9.3 Hz, 1 F), −107.26 (t, J = 9.3 Hz, 1
F) ppm. IR (thin film): νmax 2925.9, 1704.9, 1663.7, 1607.1, 1344.8,
1250.6, 1214.2, 1111.6, 1057.3, 1003.1, 936.9, 832.8, 756.9, 612.2
cm−1. MS (EI) m/z (%): 286 (M+ - 1), 287 (M+) 286(100). HRMS
(EI) calcd for C16H11F2NO2: 287.0758, found 287.0760. Mp: 89−90
°C.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of NMR spectra for compounds 3c, 3i, 3o, 4a, and 4c−
m. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: shenql@mail.sioc.ac.cn; lulong@mail.sioc.ac.cn.
(14) (a) Crespo, M.; Martinez, M.; Sales, J. Organometallics 1993, 12,
4297. (b) Crespo, M.; Martinez, M.; de Pablo, E. Dalton Trans. 1997,
1231.
ACKNOWLEDGMENTS
■
(15) Love, J. A. Synthesis 2007, 2237.
The authors gratefully acknowledge financial support from the
Special Fund for Agro-scientific Research in the Public Interest
(201103007), the National Key Technologies R&D Program
(2011BAE06B05), Shanghai Scientific Research Program
(10XD1405200), National Basic Research Program of China
(2010CB126103, 2012CB821600), the Key Program of
National Natural Science Foundation of China (21032006)
and SIOC startup fund for financial support.
REFERENCES
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