Noncatalytic pyridyl-directed alkylation and arylation carbon-fluorine bond of polyfluoroarenes with grignard reagents

Article abstract of DOI:10.1021/jo400424d

Cross-coupling reaction of polyfluoroarenes with Grignard reagents via pyridine-directed cleavage of C-F bond in the absence of metal catalysts was developed. A possible mechanism was suggested.

Full text of DOI:10.1021/jo400424d

Note
pubs.acs.org/joc
Noncatalytic Pyridyl-Directed Alkylation and Arylation Carbon−
Fluorine Bond of Polyfluoroarenes with Grignard Reagents
Yang Xiong,† Jingjing Wu,†,‡ Senhan Xiao,† Juan Xiao,† and Song Cao*,†,‡
†Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai
200237, China
‡Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai
200032, China
S
* Supporting Information
ABSTRACT: Cross-coupling reaction of polyfluoroarenes with
Grignard reagents via pyridine-directed cleavage of C−F bond in
the absence of metal catalysts was developed. A possible mechanism
was suggested.
he cleavage of unactivated of carbon−fluorine bonds is a
bearing electron-donating groups (OH, CH2OH, NH2) with
Grignard reagents in the presence of Pd-based catalysts.7h As far
as we know, until now, there has been no report available on
the reaction of fluoroarenes with Grignard reagents via
pyridine-directed C−F bond cleavage with or without metal
catalysts. In continuation of our research on the functionaliza-
tion of C−F bond,11 in this paper we report a new method for
the alkylation and arylation of polyfluoroarenes with Grignard
reagents via pyridine-directed regioselective cleavage of
carbon−fluorine bond in the absence of transition metal
(Scheme 1).
T
great challenge in organic synthesis.1 Until now, many
efforts have been made in the development of novel methods
for the cleavage of carbon−fluorine bonds. Catalytic conversion
of the C−F bond to the C−C bond has received increasing
attention in recent years.2 These transformations include
Kumada,3 Negishi,4 Suzuki,5 and Sonogashira6 reactions. One
of the facile methods for activation of the C−F bond is to
introduce a directing group (such as hydroxyl, hydroxymethyl,
amino, imino, pyridinyl, pyrazolyl, and oxazolinyl) at the
position ortho to the C−F bond of fluoroarenes, followed by
coupling of this activated C−F bond with a functionalized
starting material such as RMgX, RB(OH)2, or R2Zn in the
presence of metal catalyst.7
Scheme 1. Alkylation and Arylation of Polyfluoroarenes with
Grignard Reagents via Pyridine-Directed Cleavage of C−F
Bond
The metal-catalyzed cross-coupling reactions of alkyl, vinyl,
or aryl halides or aryl triflates with Grignard reagents are
powerful synthetic methods for the construction of C−C
bonds.8 The most common electrophiles used in these kinds of
coupling reactions are aryl (alkyl) chlorides, bromides, iodides,
and tosylates. However, the use of aryl fluorides as coupling
partner remains limited due to the exceptional stability of the
C−F bonds. Although a few excellent examples of metal-
catalyzed cross-coupling reactions involving C−F bond
cleavage have been reported, expensive metal complex catalysts
or very complicated ligands are required in most of these
reaction systems.9 Until now, there were very few examples of
coupling reactions of Grignard reagents with aryl fluorides
using a directing group strategy. In 1978, Meyers reported the
first directing group-promoted coupling reactions between
Grignard reagent and fluorobenzene bearing an oxazoline
moiety as activating group in the ortho-position to the C−F
bond.10 In 1999, Cahiez et al. described the cross-coupling
reaction of Grignard reagents with an aryl fluoride bearing
imino group in the ortho-position in the presence of MnCl2 (10
mol %). They also indicated that in the absence of MnCl2 the
yield of coupling product decreased obviously (40%, GC, 24
h).7g In 2008, Manabe et al. developed the first examples of
ortho-selective cross-coupling of fluorobenzene derivatives
Encouraged by the recent exciting progress in the field of
pyridine-directed C−H bond activation12 and also inspired by
the Meyers reaction involving the displacement of an oxazoline-
activated aromatic fluorine atom,13 we envisaged that the metal-
catalyzed coupling reaction of Grignard reagents with aryl
fluorides could take place using pyridine as activating group in
aromatic substitution. We began our investigation by using the
cross-coupling reaction of n-butylmagnesium chloride 2a with
2-(2-fluorophenyl)pyridine 1a as the model reaction in the
presence of various metal catalysts or in the absence of metal
catalyst (Table 1). Screening of the suitable conditions for the
Received: February 28, 2013
© XXXX American Chemical Society
A
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The Journal of Organic Chemistry
Note
ophenyl pyridines as substrates to examine the scope of this
reaction under the optimized reaction conditions.
Table 1. Reaction of 2-(2-Fluorophenyl)pyridine 1a with n-
Butylmagnesium Chloride 2a in the Presence or Absence of
a
The yields of the reaction of 2-polyfluorophenyl pyridines
(1a−f) with Grignard reagents are summarized in Table 2.
Most 2-polyfluorophenylpyridines could undergo the coupling
reaction efficiently in the absence of metal catalyst. Both
aliphatic Grignard reagents and aromatic Grignard reagent
could react smoothly and provided the coupling products in
high isolated yields (Table 2, entries 1−10); however, the
reaction of PhMgBr needed a longer reaction time (24 h,
entries 4 and 6). In most cases, 2-polyfluorophenylpyridines
gave alkylated or phenylated 2-phenylpyridines as the main
products, and no dialkylated or diphenylated products were
observed. In the case of 2-(2-chlorophenyl)pyridine 1g, the
monoalkylated product 3b was isolated in slightly lower yield
than was obtained with 1a (Table 2, entries 11 and 1,
respectively). When 4-(2-fluorophenyl)pyridine 1h, 2-(4-
fluorophenyl)pyridine 1i, and 2-(3-fluorophenyl)pyridine 1j
were used as substrates, no alkylated products 3k, 3l, and 3m
were detected, and the starting materials were recovered
completely (entries 12−14).
Metal Catalyst
b
entry
cat. (10 mol %)
temp (°C)
time (h)
yield (%)
1
NiCl2
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
20
12
24
24
24
24
24
24
24
24
12
24
24
24
24
24
24
24
2
51
21
44
13
21
16
0
2
AlCl3
3
ZnCl2
CeCl3
RhCl2
BiCl3
4
5
6
7
ZrCl4
8
PdCl2
FeCl3
8
9
5
10
11
12
13
14
15
16
18
19
20
21
22
NiBr2
20
3
CuCl2
CuCl
5
The results revealed that the distance between the nitrogen
atom and the fluorine atom in fluorophenylpyridine derivatives
played an important role in the formation of alkylated product.
Finally, the reaction of 2-phenylpyridine 1k with ethyl-
magnesium chloride 2b was performed under the same reaction
conditions. As expected, the C−H bond ortho to the pyridyl
nitrogen could not be activated without metal catalyst and no
reaction has occurred. It is suggested that the C−F bond in the
benzene ring are activated by the pyridine directing group in
preference to C−H bond in the absence of metal catalyst.
LaCl3
4
NbCl5
CoCl2
Co(acac)3
NiCl2(dppp)
MnCl2
none
3
18
16
19
94
76
87
93
12
12
none
40
none
reflux
12
a
b
Based on these experimental results and literatures,13,16
a
THF was used as solvent. BuMgCl (2.5 equiv). Yields were based on
GC analysis.
plausible mechanism for the noncatalyzed reaction of 2-(2-
fluorophenyl)pyridine derivatives with Grignard reagent was
suggested in Scheme 2. In the first step, the magnesium ion in
Grignard reagent (RMgX) coordinated to the lone-pair
electrons at the nitrogen atom of pyridine to form a magnesium
complex (I). The C−F bond was slightly activated by both
pyridine-directing group and magnesium ion. Subsequently, the
addition of alkyl or aryl to benzene ring led to the formation of
C−C bond via a six-membered ring transition state (II).
Finally, cleavage of C−F bond of analogue of Meisenheimer
complex (III) afforded the cross-coupling product.
In summary, we have developed ortho-selective cross-
coupling of polyfluoroarenes with Grignard reagents via
pyridinyl-directed C−F bond cleavage in the absence of metal
catalyst. We also suggested a possible pyridyl mediated C−F
bond cleavage mechanism. Although pyridinyl is not strongly
electron-withdrawing group in the SNAr reaction, it can serve as
coordinating ligand and activating moiety in the ortho-position
to the C−F bond. The suitable distance between the pyridyl
nitrogen and the fluorine atom in 2-fluorophenylpyridine
derivatives ensure the transformation of C−F bond to C−C
bond to proceed smoothly.
reaction revealed that the manganese chloride (MnCl2) was the
best catalyst among the tested metal catalysts and provided the
corresponding alkylation product 3a in 94% yield within 2 h
(entry 19). Much to our delight, the reaction also proceeded
well in the absence of metal catalyst. Further optimization of
reaction conditions indicated that when the reaction was
performed at reflux of THF with prolonged reaction time (12
h), the desired product 3a was obtained in high yield (entry
22). In addition, a decrease in the amount of BuMgCl to less
than 2.5 equiv led to lower conversion of the C−F bonds to
C−C bonds.
Today, the transition-metal-free protocols appear particularly
attractive and have found tremendous importance in the
pharmaceutical industry due to the strict demand for the
absence of any transition-metal impurity in final product.14
From a green chemistry point of view, we carried out this
coupling reaction without any additional metal catalyst in the
following studies.
The partially fluorinated aromatic compounds have always
been used as intermediates for the synthesis of pharmaceuticals
and agrochemicals.2,15 Although these functionalized polyfluor-
oarenes could be prepared by cross coupling of the
corresponding fluorinated aryl chloride, bromide, or iodide,
the mixed aryl halides which used as starting materials are very
expensive and not readily available. Therefore, the selective
activation and functionalization of C−F bonds in the
commercially available polyfluoroarenes or perfluoroarenes
have become a subject of great interest for fluorine chemistry.
Thus, we used a range of structurally diverse 2-polyfluor-
EXPERIMENTAL SECTION
■
General Comments. All reagents were of analytical grade and
obtained from commercial suppliers and used without further
purification. THF was dried by standard methods prior to use and
1
degassed. H NMR and 13C NMR spectra were recorded on a 400
1
spectrometer (400 MHz for H and 100 MHz for 13C) using TMS as
internal standard, The 19F NMR spectra were obtained using a 400
spectrometer (376 MHz). CDCl3 was used as the NMR solvent in all
B
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Note
a
Table 2. Noncatalyzed Ortho-Alkylation or Phenylation of 2-(2-Fluorophenyl)pyridine Derivatives with Grignard Reagents
a
b
Reaction condition: RMgX (2.5 equiv), THF, reflux, 6−24 h. Isolated yields.
Scheme 2. Possible Mechanism for the Noncatalyzed Reaction of 2-(2-Fluorophenyl)pyridine Derivatives with RMgX
Scheme 3. Synthesis of 2-(2-Fluorophenyl)pyridine Derivatives via Suzuki−Miyaura Coupling Reaction
C
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Note
cases. The GC and GC−MS were calibrated by authentic standards.
High-resolution mass spectra (HRMS) were acquired in the electron-
impact mode (EI) using a TOF mass analyzer.
Preparation of 2-(2-Fluorophenyl)pyridine derivatives (1a−
f). 2-(2-Fluorophenyl)pyridine derivatives 1a−f were prepared by
Pd(PPh3)4-catalyzed Suzuki−Miyaura coupling of the corresponding
polyfluoroarylboronic acid and the 2-bromopyridine (1g−k was
prepared by the same procedure) (Scheme 3).
13.8; 19F NMR δ −114.4 (dd, J1 = 15.8 Hz, J2 = 9.0 Hz, 1F); HRMS
(EI) calcd for C15H16FN [M]+ 229.1267, found 229.1268.
2-(5-Fluorobiphenyl-2-yl)pyridine (3f, CAS: 1024586-00-2):19 yield
80% (198.2 mg), white solid; mp 92.5−93.8 °C; 1H NMR δ 8.64 (d, J
= 4.4 Hz, 1H), 7.73−7.69 (m, 1H), 7.41−7.37 (m, 1H), 7.27−7.26 (m,
3H), 7.18−7.10 (m, 5H), 6.86 (d, J = 8.0 Hz, 1H); 13C NMR δ 162.6
1
3
(d, JCF = 246.3 Hz), 158.3, 149.4, 142.7 (d, JCF = 7.9 Hz), 140.3,
135.7 (d, 4JCF = 3.0 Hz), 135.3, 132.4 (d, 3JCF = 8.4 Hz), 129.5, 128.2,
2
2
127.2, 125.3, 121.4, 117.0 (d, JCF = 21.7 Hz), 114.4 (d, JCF = 20.9
Hz); 19F NMR δ −113.8 (dd, J1 = 14.7 Hz, J2 = 7.9 Hz, 1F).
2-(2-Ethyl-3-(trifluoromethyl)phenyl)pyridine (3g): yield 89%
(222.6 mg), light yellow liquid; 1H NMR δ 8.72 (d, J = 4.4 Hz,
1H), 7.82−7.78 (m, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 7.2 Hz,
1H), 7.40−7.29 (m, 3H), 2.94 (q, J = 7.6 Hz, 2H), 0.93 (t, J = 7.6 Hz,
3H); 13C NMR δ 157.9, 151.9, 150.0, 136.6, 135.1, 129.0, 127.5 (q,
3JCF = 10.1 Hz), 124.8, 124.3, 123.1, 122.7 (q, 1JCF = 273.7 Hz), 119.0
To a stirred solution of 2-bromopyridine (0.79 g, 5 mmol), Na2CO3
(1.06 g, 10 mmol), and Pd(PPh3)4 (0.29 g, 0.25 mmol) in 6 mL of
dioxane/H2O (5:1) was added fluorophenylboronic acid (6 mmol) in
6 mL of dioxane/H2O (5:1) was added dropwise via syringe, and the
mixture was heated to 120 °C and then stirred for 12−24 h
(monitored by TLC) in a Schlenk tube. The reaction mixture was
allowed to cool to room temperature, filtered, and extracted with H2O
(20 mL) and CH2Cl2 (3 × 10 mL). The organic layer was separated
and dried over MgSO4, filtered, and evaporated under vacuum. The
crude product was purified by column chromatography on silica gel
using a petroleum ether/ethyl acetate (10:1) mixture as eluent to
afford the pure target compounds (light orange oil or white solid, 83−
91%).
2
(q, JCF = 22.0 Hz), 26.1, 15.6; 19F NMR δ −59.1 (s, 3F); HRMS
(ESI) calcd for C14H13F3N [M + H]+ 252.1000, found 252.1001.
2-(2-Butyl-5-(trifluoromethyl)phenyl)pyridine (3h): yield 82%
(227.7 mg), light yellow liquid; 1H NMR δ 8.72 (d, J = 4.0 Hz,
1H), 7.80−7.76 (m, 1H), 7.63 (s, 1H), 7.59 (d, J = 8.0 Hz, 1H) 7.42
(dd, J = 11.2 Hz, J = 8.0 Hz, 2H), 7.30 (dd, J = 7.2 Hz, J = 4.8 Hz,
1H), 2.77 (t, J = 8.0 Hz, 2H), 1.49−1.45 (m, 2H), 1.24 (q, J = 7.6 Hz,
2H), 0.81 (t, J = 7.2 Hz, 3H); 13C NMR δ 158.2, 148.7, 144.8, 140.6,
135.8, 129.8, 127.3 (q, 2JCF = 32.4 Hz), 126.0 (q, 3JCF = 3.8 Hz), 124.0
(q, 3JCF = 3.6 Hz), 123.9 (q, 1JCF = 272.7 Hz), 123.4, 121.6, 32.6, 32.0,
21.7, 12.6; 19F NMR δ −62.3 (s, 3F); HRMS (EI) calcd for
C16H16F3N [M]+ 279.1235, found 279.1236.
General Procedure for Compounds 3a−n. To a stirred solution
of aryl fluorides (1a−f, h−j), 1g, and 1k (2 mmol) in 5 mL of THF at
room temperature was added a THF solution of RMgX (5 mmol, 2.5
mL, 2.00 M) dropwise via syringe, and the mixture was heated to 70
°C and then stirred for 6−24 h (monitored by TLC) in a Schlenk
tube. The reaction mixture was quenched by the addition of saturated
aqueous solution of NH4Cl (5 mL) and extracted with H2O (20 mL)
and ethyl acetate (3 × 10 mL). The organic layer was separated and
dried over MgSO4, filtered, and evaporated under vacuum. The crude
product was purified by column chromatography on silica gel using a
petroleum ether/ethyl acetate (20:1) mixture as eluent to afford the
pure target compounds.
2-(2-Butyl-3,4-difluorophenyl)pyridine (3i): yield 87% (215.9 mg),
light yellow liquid; 1H NMR δ 8.71 (d, J = 3.2 Hz, 1H), 7.81−7.77 (m,
1H), 7.38−7.36 (m, 1H), 7.32−7.30 (m, 1H), 7.14−7.05 (m, 2H),
2.78−2.61 (m, 2H), 1.46−1.44 (m, 2H), 1.26−1.23 (m, 2H), 0.80 (t, J
1
2
= 7.2 Hz, 3H); 13C NMR δ 158.4, 150.4 (dd, JCF = 268.4 Hz, JCF
=
1
2
2-(2-Butylphenyl)pyridine (3a, CAS: 914253-98-8):17 yield 89%
15.5 Hz), 149.2, 149.2 (dd, JCF = 243.4 Hz, JCF = 11.6 Hz), 137.4,
3
1
136.4, 126.8 (d, JCF = 8.3 Hz), 125.4−125.2 (m), 124.1, 122.1, 114.1
(188.2 mg), light yellow liquid; H NMR (400 MHz, CDCl3) δ 8.71
(d, JCF = 16.9 Hz), 32.2, 25.6, 22.5, 13.6; 19F NMR δ −138.3 to
2
(d, J = 2.8 Hz, 1H), 7.76−7.72 (m, 1H), 7.41−7.25 (m, 6H), 2.75 (t, J
= 7.8 Hz, 2H), 1.52−1.44 (m, 2H), 1.28−1.22 (m, 2H), 0.82 (t, J = 7.3
Hz, 3H).
−138.4 (m, 1F), −142.1 to −142.2 (m, 1F); HRMS (EI) calcd for
C15H15F2N [M]+ 247.1173, found 247.1174.
2-(3,4-Difluoro-2-methylphenyl)pyridine (3j): yield 85% (174.7
2-(2-Ethylphenyl)pyridine (3b, CAS: 914253-97-7):17 yield 90%
1
mg), white solid; mp 61.9−63.4 °C; H NMR δ 8.71 (d, J = 4.0 Hz,
1
(171.1 mg), light yellow liquid; H NMR δ 8.68 (d, J = 4.0 Hz, 1H),
1H), 7.80−7.76 (m, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.32−7.29 (m,
1H), 7.19−7.15 (m, 1H), 7.12−7.05 (m, 1H), 2.32 (d, J = 4.0 Hz,
7.87−7.83 (m, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.36−7.33 (m, 4H),
7.30−7.26 (m, 1H), 2.76 (q, J = 7.5 Hz, 2H), 1.09 (t, J = 7.5 Hz, 3H).
2-(2-Butyl-3-fluorophenyl)pyridine (3c): yield 88% (202.4 mg),
light yellow liquid; 1H NMR δ 8.71 (d, J = 4.0 Hz, 1H), 7.79−7.75 (m,
1H), 7.39 (d, J = 7.6 Hz, 1H), 7.30−7.27 (m, 1H), 7.24−7.21 (m,
1H), 7.15 (d, J = 6.8 Hz, 1H), 7.11−7.06 (m, 1H), 2.75−2.71 (m,
2H), 1.50−1.43 (m, 2H), 1.26−1.21 (m, 2H), 0.80 (t, J = 7.6 Hz, 3H);
13C NMR δ 161.6 (d, 1JCF = 242.8 Hz), 159.1 (d, 4JCF = 2.7 Hz), 149.2,
1
2
3H); 13C NMR δ 158.0, 150.5 (dd, JCF = 247.3 Hz, JCF = 13.7 Hz),
149.4, 149.2 (dd, 1JCF = 243.4 Hz, 2JCF = 12.4 Hz), 137.6, 136.4, 125.9
2
3
4
(d, JCF = 13.6 Hz), 125.0 (dd, JCF = 6.6 Hz, JCF = 4.1 Hz), 124.2,
122.2, 114.6 (d, JCF = 17.0 Hz), 12.1 (d, JCF = 3.3 Hz); 19F NMR δ
−138.4 to −138.4 (m, 1F), −140.4 (d, J = 15.0 Hz, 1F); HRMS (EI)
calcd for C12H9F2N [M]+ 205.0703, found 205.0699.
2
3
3
2
142.6 (d, JCF = 4.7 Hz), 136.2, 128.4 (d, JCF = 16.5 Hz), 126.8 (d,
ASSOCIATED CONTENT
3JCF = 9.0 Hz), 125.3 (d, 4JCF = 3.1 Hz), 124.1, 122.0, 115.1 (d, 2JCF
=
■
23.3 Hz), 32.4, 29.7, 22.6, 13.7; 19F NMR δ −117.5 (s, 1F); HRMS
(EI) calcd for C15H16FN [M]+ 229.1267, found 229.1264.
S
* Supporting Information
1H NMR spectra for compounds 3a−b and H, 19F and 13C
1
2-(6-Fluorobiphenyl-2-yl)pyridine (3d, CAS: 1174895-61-4):18
NMR spectra for compounds 3c−j. This material is available
1
yield 83% (206.2 mg), white solid; mp 91.8−92.9 °C; H NMR δ
free of charge via the Internet at http://pubs.acs.org.
8.62 (d, J = 4.0 Hz, 1H), 7.56−7.54 (m, 1H), 7.49−7.43 (m, 1H),
7.40−7.36 (m, 1H), 7.29−7.16 (m, 6H), 7.12−7.09 (m, 1H), 6.86 (d, J
AUTHOR INFORMATION
Corresponding Author
*Tel: +86-21-64253452. Fax: +86-21-64252603. E-mail: scao@
ecust.edu.cn.
■
= 7.6 Hz, 1H); 13C NMR δ 159.8 (d, 1JCF = 243.5 Hz), 157.9 (d, 4JCF
=
3.1 Hz), 149.3, 142.1 (d, 3JCF = 2.7 Hz), 135.2, 134.1, 130.7, 128.9 (d,
3JCF = 8.9 Hz), 128.2 (d, 2JCF = 16.3 Hz), 127.9, 127.3, 126.0 (d, 4JCF
=
3.1 Hz), 125.2, 121.6, 115.6 (d, 2JCF = 23.3 Hz); 19F NMR δ −115.6 (s,
1F).
Notes
2-(2-Butyl-4-fluorophenyl)pyridine (3e): yield 87% (200.2 mg),
light yellow liquid; 1H NMR δ 8.68 (d, J = 4.0 Hz, 1H), 7.74−7.70 (m,
1H), 7.38−7.30 (m, 2H), 7.25−7.22 (m, 1H), 7.02 (dd, J = 10.4 Hz, J
= 2.8 Hz, 1H), 6.97−6.92 (m, 1H), 2.71 (t, J = 7.6 Hz, 2H), 1.49−1.42
(m, 2H), 1.23 (q, J = 7.6 Hz, 2H), 0.80 (t, J = 7.2 Hz, 3H); 13C NMR
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the National Natural
Science Foundation of China (Grant Nos. 21072057 and
21272070), the Key Project in the National Science &
Technology Pillar Program of China in the twelfth five-year
1
3
δ 162.7 (d, JCF = 245.0 Hz), 159.4, 149.2, 143.4 (d, JCF = 7.5 Hz),
136.4 (d, 4JCF = 3.0 Hz), 136.2, 131.4 (d, 3JCF = 8.4 Hz), 124.2, 121.7,
2
2
116.1 (d, JCF = 20.9 Hz), 112.6 (d, JCF = 21.0 Hz), 33.1, 32.6, 22.4,
D
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The Journal of Organic Chemistry
Note
plan period (2011BAE06B01-15), and the 973 Program
(2010CB126101).
REFERENCES
■
(1) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119.
(2) (a) Sun, A. D.; Love, J. A. Dalton Trans. 2010, 39, 10362. (b) Yu,
D.; Lu, L.; Shen, Q. Org. Lett. 2013, 15, 940.
(3) (a) Mo, Z.; Zhang, Q.; Deng, L. Organometallics 2012, 31, 6518.
(b) Saeki, T.; Takashima, Y.; Tamao, K. Synlett 2005, 1771.
(c) Ackermann, L.; Wechsler, C.; Kapdi, A. R.; Althammer, A. Synlett
2010, 294.
(4) Keyes, L.; Sun, A. D.; Love, J. A. Eur. J. Org. Chem. 2011, 3985.
(5) (a) Tobisu, M.; Xu, T.; Shimasaki, T.; Chatani, N. J. Am. Chem.
Soc. 2011, 133, 19505. (b) Schaub, T.; Backes, M.; Radius, U. J. Am.
Chem. Soc. 2006, 128, 15964.
(6) Cargill, M. R.; Sandford, G.; Kilickiran, P.; Nelles, G. Tetrahedron
2013, 69, 512.
(7) (a) Yu, D.; Shen, Q.; Lu, L. J. Org. Chem. 2012, 77, 1798.
(b) Doxsee, K. M.; Feigel, M.; Stewart, K. D.; Canary, J. W.; Knobler,
C. B.; Cram, D. J. J. Am. Chem. Soc. 1987, 109, 3098. (c) Cram, D. J.;
Katz, H. E.; Dicker, I. B. J. Am. Chem. Soc. 1984, 106, 4987. (d) Wang,
J.-R.; Manabe, K. Org. Lett. 2009, 11, 741. (e) Korn, T. J.; Schade, M.
A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725. (f) Ishikawa, S.;
Manabe, K. Synthesis 2008, 3180. (g) Cahiez, G.; Lepifre, F.;
Ramiandrasoa, P. Synthesis 1999, 2138. (h) Manabe, K.; Ishikawa, S.
Synthesis 2008, 2645. (i) Aissaoui, R.; Nourry, A.; Coquel, A.; Dao, T.
T. H.; Derdour, A.; Helesbeux, J.-J.; Duval, O.; Castanet, A.-S.;
Mortier, J. J. Org. Chem. 2012, 77, 718. (j) Wang, T.; Alfonso, B. J.;
Love, J. A. Org. Lett. 2007, 9, 5629.
(8) Heravi, M. M.; Hajiabbasi, P. Monatsh. Chem. 2012, 1575.
(9) (a) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc.
2009, 131, 9590. (b) Guan, B.-T.; Xiang, S.-K.; Wu, T.; Sun, Z.-P.;
Wang, B.-Q.; Zhao, K.-Q.; Shi, Z.-J. Chem. Commun. 2008, 1437.
(c) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc.
2003, 125, 5646. (d) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am.
Chem. Soc. 2005, 127, 17978. (e) Nova, A.; Reinhold, M.; Perutz, R.
N.; Macgregor, S. A.; McGrady, J. E. Organometallics 2010, 29, 1824.
(10) Meyers, A. I.; Williams, B. E. Tetrahedron Lett. 1978, 223.
(11) (a) Zhang, J.; Wu, J.-J.; Xiong, Y.; Cao, S. Chem. Commun. 2012,
48, 8553. (b) Wu, J.-J.; Cao, S. ChemCatChem. 2011, 3, 1582.
(c) Zhao, W.-W.; Wu, J.-J.; Cao, S. Adv. Synth. Catal. 2012, 354, 574.
(12) (a) Li, B.; Wu, Z.-H.; Gu, Y.-F.; Sun, C.-L.; Wang, B.-Q.; Shi, Z.-
J. Angew. Chem., Int. Ed. 2011, 50, 1109. (b) Chen, K.; Li, H.; Li, Y.;
Zhang, X.-S.; Lei, Z.-Q.; Shi, Z.-J. Chem. Sci 2012, 3, 1645. (c) Chen,
Q.; Ilies, L.; Yoshikai, N.; Nakamura, E. Org. Lett. 2011, 13, 3232.
(d) Li, Y.; Zhang, X.-S.; Zhu, Q.-L.; Shi, Z.-J. Org. Lett. 2012, 14, 4498.
(e) Wang, X.; Truesdale, L.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132,
3648.
(13) (a) Mortier, J. Curr. Org. Chem. 2011, 15, 2413. (b) Gant, T. G.;
Meyers, A. I. Tetrahedron 1994, 50, 2297. (c) Reuman, M.; Meyers, A.
I. Tetrahedron 1985, 41, 837.
(14) (a) Mohanan, K.; Coquerel, Y.; Rodriguez, J. Org. Lett. 2012, 14,
4686. (b) Truong, T.; Daugulis, O. Org. Lett. 2011, 13, 4172.
(c) Terao, J.; Nakamurab, M.; Kambe, N. Chem. Commun. 2009, 6011.
(15) Sun, A. D.; Love, J. A. Org. Lett. 2011, 13, 2750.
(16) (a) Matsubara, K.; Ishibashi, T.; Koga, Y. Org. Lett. 2009, 11,
1765. (b) Zhang, F.; Zhang, S.; Duan, X. Org. Lett. 2012, 14, 5618.
(c) Meyers, A. I.; Mihelich, E. D. J. Am. Chem. Soc. 1975, 97, 7383.
(d) Meyers, A. I.; Gabel, R. J. Org. Chem. 1977, 42, 2653. (e) Wang, J.-
R.; Manabe, K. Org. Lett. 2009, 11, 741.
(17) Chen, X.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128,
12634.
(18) Yu, W.-Y.; Sit, W. N.; Zhou, Z.; Chan, A. S.-C. Org. Lett. 2009,
11, 3174.
(19) Norinder, J.; Matsumoto, A.; Yoshikai, N.; Nakamura, E. J. Am.
Chem. Soc. 2008, 130, 5858.
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