Palladium-catalyzed Hiyama cross-coupling of aryltrifluorosilanes with aryl and heteroaryl chlorides

Article abstract of DOI:10.1021/jo201840n

An efficient, palladium-catalyzed Hiyama cross-coupling reaction of aryltrifluorosilanes with aryl chlorides has been developed. A wide variety of functionalized biaryl derivatives were isolated in good to excellent yields. The scope of this reaction has also been extended to heteroaryl chlorides, affording the corresponding heterobiaryl compounds in high yields.

Full text of DOI:10.1021/jo201840n

Note
pubs.acs.org/joc
Palladium-Catalyzed Hiyama Cross-Coupling of Aryltrifluorosilanes
with Aryl and Heteroaryl Chlorides
Gary A. Molander* and Laura Iannazzo
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323,
United States
S
* Supporting Information
ABSTRACT: An efficient, palladium-catalyzed Hiyama cross-coupling
reaction of aryltrifluorosilanes with aryl chlorides has been developed. A
wide variety of functionalized biaryl derivatives were isolated in good to
excellent yields. The scope of this reaction has also been extended to
heteroaryl chlorides, affording the corresponding heterobiaryl com-
pounds in high yields.
etal-mediated cross-coupling reactions are among the
knowledge, there are no examples of aryltrifluorosilane cross-
couplings with aryl chlorides. Therefore, we were intrigued to
see if they could be suitable partners for this transformation.
Herein, we describe an efficient palladium-catalyzed Hiyama
cross-coupling of aryltrifluorosilanes with both aryl and
heteroaryl chlorides for the synthesis of biaryls and
heterobiaryls. The catalytic system was first optimized on a
model reaction between phenyltrifluorosilane 1a and 4-
chloroanisole in the presence of 2.5 mol % of Pd(OAc)2 as
catalyst. After a ligand screen with various ligands (Figure 1)
M
most powerful methods of creating carbon−carbon
bonds in organic chemistry. In the past 40 years, organo-
magnesium (Kumada−Corriu), organoboron (Suzuki−
Miyaura), organotin (Stille), organozinc (Negishi), and
organosilane (Hiyama) derivatives have been developed as
nucleophilic partners for cross-coupling reactions.1−5 Each of
these classes has its own limitations, often because of the
instability or toxicity of the reagent. In this context,
organosilicon derivatives, known to be easy to handle, stable
(toward air and moisture), and less toxic compared to other
organometallic reagents such as organostannanes, appeared as
interesting partners for the development of cross-coupling
reactions.5
Previously, silane derivatives have been seen as poor cross-
coupling partners because of the weak polarization of the
carbon−silicon bond. This limitation has been overcome
through the generation of a pentacoordinate silicon inter-
mediate in situ,6 using a fluoride activator7 such as tetra-n-
butylammonium fluoride (TBAF) or an inorganic base.8−12
Subsequently, efficient partners for Hiyama cross-coupling such
as organo(trialkoxy)silanes,13−19 organosilanolates,20−23
organobis(catechol)silicates,24 organosilatranes,25 and organo-
halosilanes26−32 have been developed.
Among these types of organosilanes, organotrifluorosilanes
are interesting because of their stability to heat, air, and
moisture, easy handling, and facile accessibility from
commercially available trichlorosilanes.33 Surprisingly, although
they have been used in a wide range of metal-mediated
reactions as efficient partners,34−39 only a few examples of
Hiyama cross-coupling reactions of trifluorosilanes have been
reported. The first report came from Hiyama and co-workers,
who achieved the cross-coupling reaction of alkyltrifluorosilanes
with a variety of aryl iodides and bromides using a catalytic
amount of Pd(PPh3)4, but a large excess of TBAF.29,30 More
recently, Fu has developed a nickel-catalyzed Hiyama cross-
coupling of aryltrifluorosilanes with secondary alkyl halides
(iodides, bromides, and chlorides).31,32 To the best of our
Figure 1. Ligands utilized in optimization studies.
was performed in t-BuOH as solvent (Table 1, entries 1−3),
XPhos emerged as the most efficient, yielding 2a in 71% yield.
Other solvents were tested (Table 1, entries 4 and 5), but all
of them led to a decrease in reaction yield. When TBAF was
replaced with various inorganic bases (Table 1, entries 6−8), no
reaction occurred. Finally, the ratio of aryltrifluorosilane 1a and
TBAF was studied, and 2a was isolated in 78% yield by
employing 1.5 equiv of 1a and 2.5 equiv of TBAF at 60 °C.
We then chose to investigate the electrophile compatibility in
this palladium-catalyzed Hiyama cross-coupling reaction under
the conditions previously optimized. The iodide, bromide, and
triflate provided the desired product in 95, 88, and 86% yields,
respectively (Table 2, entries 1, 2, and 4). The aryl chloride
afforded a slightly lower yield (78%) (Table 2, entry 3). On the
Received: September 6, 2011
Published: October 6, 2011
© 2011 American Chemical Society
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The Journal of Organic Chemistry
Note
Table 1. Optimization
Table 3. Scope of Aryl Chlorides
1a
additive
(equiv)
% isolated
yield
entry
equiv
ligand
SPhos
solvent
1
2
1
TBAF (2)
TBAF (2)
TBAF (2)
TBAF (2)
TBAF (2)
CsF (3)
t-BuOH
t-BuOH
t-BuOH
THF
53
38
71
51
47
0
1
CatacXiumA
XPhos
3
1
4
1
XPhos
5
1
XPhos
toluene
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
6
1
XPhos
7
1
XPhos
NaOH (3)
KF (3)
0
8
1
XPhos
0
9
1
XPhos
TBAF (2)
TBAF (2.5)
73
78
10
1.5
XPhos
Table 2. Electrophile Compatibility
entry
X
% isolated yield
1
2
3
4
5
6
I
95
88
78
86
16
24
Br
Cl
OTf
OTs
OMs
other hand, the tosylate and mesylate were not effective
coupling partners under these conditions, affording the cross-
coupled product in low yields. Given the low price and wide
range of commercially available aryl chlorides, we used them as
the electrophiles of choice.
We were pleased to find that a wide variety of substituted aryl
chlorides provided the expected biaryl derivatives in good to
excellent yields (Table 3). Even the hindered 1-chloro-4-
methoxy-2,6-dimethylbenzene could be used with phenyl-
trifluorosilane 1a to give the coupling product 2d with an
excellent yield of 97% by simply increasing the temperature to
100 °C (Table 3, entry 4). We were delighted to observe the
compatibility of this reaction with both electron-rich (Table 3,
entries 1−5) and electron-poor (Table 3, entries 6−12) aryl
chlorides. Notably, a large functional group array including
ether, amine, nitrile, nitro, ester, aldehyde, and ketone
functional groups was tolerated. Substituted 3-methoxy- and
4-methylbenzenetrifluorosilanes 1b and 1c were also suitable
partners in this process, affording the corresponding products
2m and 2n in 80 and 81% yields, respectively (Table 3, entries
13 and 14). Interestingly, scaling the reaction up to 6.4 mmol of
4-chloroacetophenone allowed a reduction in the catalyst
loading to 2 mol % of palladium and 4 mol % of ligand, yielding
the biaryl 2l in 96% yield.
a
b
100 °C. Reaction performed on a 6.4 mmol scale using 2 mol % of
Pd(OAc)2, 4 mol % of XPhos, 1.5 equiv of 1a, and 2.5 equiv of TBAF.
chlorides also reacted, affording coupled products 3g and 3h in
90 and 74% yields, respectively (Table 4, entries 7 and 8). As
before, sensitive functional groups such as aldehydes were
tolerated under the reaction conditions. In addition, 6-
chloroisoquinoline gave the desired heterobiaryl derivatives 3i
and 3j in good yields, although it required a higher temperature
To expand the scope of this transformation even further,
heteroaryl chlorides were next examined. 3-Arylpyridines 3a−e
were obtained in yields ranging from 74 to 94% (Table 4,
entries 1−5). 4-Chloroquinaldine was coupled with phenyl-
trifluorosilane 1a, providing the corresponding heterobiaryl 3f
in moderate yield (Table 4, entry 6). Thienyl and furanyl
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The Journal of Organic Chemistry
Note
degassed with argon each time prior to use. Standard benchtop
techniques were employed for handling air-sensitive reagents. Melting
points (°C) are uncorrected. NMR spectra were recorded on a 500
MHz spectrometer. Data are presented as follows: chemical shift
(ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet,
br = broad), coupling constant J (Hz), and integration. Analytical thin-
layer chromatography (TLC) was performed on TLC silica or alumina
gel plates (0.25 mm) precoated with a fluorescent indicator. Standard
flash chromatography procedures were followed using 32−63 μm silica
gel. Visualization was effected with ultraviolet light.
Table 4. Scope of Heteroaryl Chlorides
General Procedure for Preparation of Organotrifluorosi-
lanes. The organotrichlorosilane (1 equiv) and Na2SiF6 (2 equiv)
were heated to 200 °C for 1 h.33 After being cooled to rt, the crude
mixture was purified by distillation, affording the desired organo-
trifluorosilane.
Phenyltrifluorosilane (1a).31 Following the general procedure
for preparation of organotrifluorosilane, 1a was obtained as a colorless
1
oil (2.95 g, 59%). H NMR (500 MHz, CDCl3): δ = 7.52 (t, J = 7.5
Hz, 2 H), 7.64−7.67 (m, 1 H), 7.76−7.78 (m, 2 H). 13C NMR (125
MHz, CDCl3): δ = 120.3, 128.8, 133.5, 134.7. 19F NMR (471 MHz,
CDCl3): δ = −141.1. IR (neat): νmax
= 1537, 1589, 3078 cm−1.
̃
̃
Trifluoro(3-methoxyphenyl)silane (1b).40 Following the gen-
eral procedure for preparation of organotrifluorosilane, 1b was
obtained as a colorless oil (1.29 g, 45%). 1H NMR (500 MHz,
CDCl3): δ = 3.84 (s, 3 H), 7.15−7.17 (m, 1 H), 7.22−7.23 (m, 1 H),
7.30−7.32 (m, 1 H), 7.41−7.45 (m, 1 H). 13C NMR (125 MHz,
CDCl3): δ = 55.4, 119.4, 119.6, 121.4, 126.8, 130.3, 159.6. 19F NMR
̃
(471 MHz, CDCl3): δ = −141.0. IR (neat): νmax = 1267, 1507, 1567,
̃
3089 cm−1.
Trifluoro(p-tolyl)silane (1c).31 Following the general procedure
for preparation of organotrifluorosilane, 1c was obtained as a colorless
1
oil (2.06 g, 42%). H NMR (500 MHz, CDCl3): δ = 2.43 (s, 3 H),
7.33 (d, J = 8.0 Hz, 2 H), 7.65 (d, J = 8.0 Hz, 2 H). 13C NMR (125
MHz, CDCl3): δ = 21.9, 116.8, 117.0, 129.6, 133.3, 134.7, 144.2. 19F
̃
NMR (471 MHz, CDCl3): δ = −140.9. IR (neat): νmax = 1540, 1609,
̃
3056 cm−1.
General Procedure for Hiyama Cross-Coupling with Aryltri-
fluorosilanes. Pd(OAc)2 (0.17 mmol, 3.9 mg) and XPhos (0.35
mmol, 17 mg) were added under argon to a solution of
aryltrifluorosilane 1a−c (1.05 mmol) in t-BuOH (1 mL) in a Biotage
microwave vial. TBAF was added and the vial sealed with a cap lined
with a disposable Teflon septum. After being stirred for 5 min at rt, a
solution of aryl chloride (0.7 mmol) in t-BuOH (1 mL) was added and
the reaction mixture heated conventionally to 60 °C overnight. After
being cooled to rt, the crude mixture was filtered through a pad of
silica, concentrated in vacuo, and purified by flash column
chromatography using a gradient mixture of hexanes and EtOAc as
eluent.
4-Methoxybiphenyl (2a).41 Following the general procedure for
Hiyama cross-coupling with aryltrifluorosilanes, 2a was obtained as a
white solid directly from the chromatographic solvent. Mp: 84−86 °C
(100 mg, 78%). 1H NMR (500 MHz, CDCl3): δ = 3.86 (s, 3 H), 6.69
(d, J = 8.5 Hz, 2 H), 7.32 (t, J = 7.2 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 2 H),
7.54−7.58 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 55.4, 114.3,
a
100 °C.
to cross-couple (Table 3, entries 9 and 10). Moreover,
substituted trifluorosilanes 1b and 1c performed as efficient
partners in Hiyama cross-coupling with heteroaryls, leading to
the expected products 3b and 3e with good yields (Table 4,
entries 2 and 5).
In summary, we have demonstrated that aryltrifluorosilanes
can be cross-coupled with a wide variety of substituted aryl and
heteroaryl chlorides. The corresponding cross-coupled prod-
ucts were obtained in good to excellent yields.
̃
126.7, 126.8, 128.2, 128.8, 133.9, 140.9, 159.2. IR (neat): νmax = 1290,
̃
1579, 3098 cm−1. HRMS: calcd for C13H13O [M + H]+ 185.0966,
found 185.0970.
3,5-Dimethoxybiphenyl (2b).42 Following the general proce-
dure for Hiyama cross-coupling with aryltrifluorosilanes, 2b was
obtained as a yellow oil (135 mg, 90%). 1H NMR (500 MHz, CDCl3):
δ = 3.85 (s, 6 H), 6.48 (t, J = 2.0 Hz, 1 H), 6.75 (d, J = 2.0 Hz, 2 H),
7.34−7.36 (m, 1 H), 7.42−7.45 (m, 2 H), 7.58−7.59 (m, 2 H). 13C
NMR (125 MHz, CDCl3): δ = 55.5, 99.4, 105.6, 127.3, 127.6, 128.8,
141.3, 143.6, 161.1. IR (neat): νmax .
= 1167, 1534, 1589, 3045 cm−1
̃
̃
EXPERIMENTAL SECTION
HRMS: calcd for C14H15O2 [M + H]+ 215.1072, found 215.1077.
■
2-Methoxybiphenyl (2c).41 Following the general procedure for
Hiyama cross-coupling with aryltrifluorosilane, 2c was obtained as a
colorless oil (90 mg, 70%). 1H NMR (500 MHz, CDCl3): δ = 3.82 (s,
3 H), 6.99−7.01 (m, 1 H), 7.04 (t, J = 7.5 Hz, 1 H), 7.32−7.35 (m, 3
H), 7.42 (t, J = 7.5 Hz, 2 H), 7.55 (d, J = 7.5 Hz, 2 H). 13C NMR (125
General Considerations. All reactions were carried out under an
argon atmosphere. Pd(OAc)2, XPhos, and TBAF were used as
received. Phenyltrichlorosilane and trichloro(4-methylphenyl)silane
were purchased and used as received. Trichloro(3-methoxyphenyl)-
silane was prepared as described in the literature.40 Solvents were
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The Journal of Organic Chemistry
Note
MHz, CDCl3): δ = 55.6, 111.3, 120.9, 127.7, 128.1, 128.7, 129.6,
CDCl3): δ = 7.40−7.43 (m, 1 H), 7.46−7.49 (m, 2 H), 7.62−7.64 (m,
2 H), 7.73−7.74 (m, 2 H), 7.93−7.95 (m, 2 H), 10.05 (s, 1 H). 13C
NMR (125 MHz, CDCl3): δ = 127.3, 127.6, 128.5, 129.0, 130.2, 135.2,
̃
130.8, 131.0, 138.6, 156.5. IR (neat): νmax = 1178, 1508, 1567, 3029
̃
cm−1. HRMS: calcd for C13H12O [M]+ 184.0888, found 184.0889.
2-Phenyl-5-methoxy-1,3-dimethylbenzene (2d). Following
the general procedure for Hiyama cross-coupling with aryltrifluor-
139.7, 147.1, 191.8. IR (neat): νmax .
= 1527, 1604, 1689, 3087 cm−1
̃
̃
HRMS: calcd for C13H10O [M]+ 182.0732, found 182.0732.
osilane, 2d was obtained as a colorless oil (143 mg, 97%). H NMR
4-Acetylbiphenyl (2l).41 Following the general procedure for
Hiyama cross-coupling with aryltrifluorosilanes, 2l was obtained as a
white solid directly from the chromatographic solvent. Mp: 118−120
1
(500 MHz, CDCl3): δ = 2.12 (s, 6 H), 3.90 (s, 3 H), 6.78 (s, 2 H),
7.23 (d, J = 7.5 Hz, 2 H), 7.40 (t, J = 7.5 Hz, 1 H), 7.49 (t, J = 7.5 Hz,
2 H). 13C NMR (125 MHz, CDCl3): δ = 21.2, 55.1, 112.6, 126.5,
1
°C (118 mg, 86%). H NMR (500 MHz, CDCl3): δ = 2.62 (s, 3 H),
̃
128.4, 129.7, 134.6, 137.4, 140.9, 158.3. IR (neat): νmax
̃
= 1234, 1567,
7.38−7.41 (m, 1 H), 7.46 (t, J = 7.5 Hz, 2 H), 7.62 (d, J = 7.5 Hz, 2
H), 7.67 (d, J = 8.0 Hz, 2 H), 8.02 (d, J = 8.0 Hz, 2 H). 13C NMR
(125 MHz, CDCl3): δ = 26.6, 127.1, 127.2, 128.2, 128.8, 128.9, 135.8,
1590, 3028 cm−1. HRMS: calcd for C15H16O [M]+ 212.1201, found
212.1210.
4-Phenyl-1H-benzopyrrole (2e). Following the general proce-
dure for Hiyama cross-coupling with aryltrifluorosilanes, 2e was
obtained as a white solid directly from the chromatographic solvent.
139.7, 145.6, 197.6. IR (neat): v = 1549, 1579, 1721, 3023 cm−1
.
̃
max
HRMS: calcd for C14H13O [M + H]+ 197.0966, found 197.0968.
3-(3-Methoxybenzene)methylbenzoate (2m). Following the
1
Mp: 185−186 °C (139 mg, 90%). H NMR (500 MHz, CDCl3): δ =
general procedure for Hiyama cross-coupling with aryltrifluorosilanes,
1
6.39 (t, J = 2.0 Hz, 2 H), 7.15 (t, J = 2.0 Hz, 2 H), 7.38 (t, J = 7.5 Hz, 1
H), 7.46−7.49 (m, 4 H), 7.62 (d, J = 8.0 Hz, 2 H), 7.66 (d, J = 8.0 Hz,
2 H). 13C NMR (125 MHz, CDCl3): δ = 110.6, 119.3, 120.7, 126.9,
2m was obtained as a yellow oil (136 mg, 80%). H NMR (500 MHz,
CDCl3): δ = 3.86 (s, 3 H), 3.94 (s, 3 H), 6.91−6.93 (m, 1 H), 7.16 (s,
1 H), 7.21 (d, J = 8.0 Hz, 1 H), 7.37 (t, J = 7.7 Hz, 1 H), 7.49 (t, J =
7.7 Hz, 1 H), 7.77 (d, J = 7.5 Hz, 1 H), 8.03 (d, J = 7.5 Hz, 1 H), 8.29
(s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 52.1, 55.3, 112.9, 113.1,
127.4, 128.2, 128.9, 138.5, 139.9, 140.2. IR (neat): v = 1123, 1597,
̃
max
1690, 3043, cm−1. HRMS: calcd for C16H14N [M + H]+ 220.1126,
found 220.1126.
119.6, 128.2, 128.5, 128.8, 129.9, 130.6, 131.5, 141.3, 141.6, 160.0,
1-Phenylnaphthalene (2f).43 Following the general procedure
for Hiyama cross-coupling with aryltrifluorosilanes, 2f was obtained as
̃
167.0. IR (neat): νmax
̃
= 1178, 1230, 1567, 1609, 1715, 3067 cm−1
.
HRMS: calcd for C15H15O3 [M + H]+ 243.1021, found 243.1015.
4-Methyl-4-acetylbiphenyl (2n).47 Following the general pro-
cedure for Hiyama cross-coupling with aryltrifluorosilanes, 2n was
obtained as a white solid directly from the chromatographic solvent.
1
a colorless oil (107 mg, 75%). H NMR (500 MHz, CDCl3): δ =
7.44−7.47 (m, 3 H), 7.50−7.57 (m, 6 H), 7.89 (d, J = 8.5 Hz, 1 H),
7.94 (d, J = 9.0 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 125.4,
125.8, 126.1 (2C), 127.0, 127.3, 127.7, 128.3, 130.1, 131.7, 133.9,
1
Mp: 116−118 °C (120 mg, 81%). H NMR (500 MHz, CDCl3): δ =
140.3, 140.8. IR (neat): v = 1578, 1590, 3067, 3090 cm−1. HRMS:
̃
2.41 (s, 3 H), 2.62 (s, 3 H), 7.28 (d, J = 7.5 Hz, 2 H), 7.53 (d, J = 7.5
max
calcd for C16H13 [M + H]+ 205.1017, found 205.1012.
Hz, 2 H), 7.66 (d, J = 7.5 Hz, 2 H), 8.01 (d, J = 7.5 Hz, 2 H). 13C
4-(Trifluoromethyl)biphenyl (2g).44 Following the general
procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2g
was obtained as a white solid directly from the chromatographic
solvent. Mp: 65−67 °C (138 mg, 89%). 1H NMR (500 MHz, CDCl3):
δ = 7.43−7.46 (m, 1 H), 7.51 (t, J = 7.5 Hz, 2 H), 7.63 (d, J = 7.5 Hz,
2 H), 7.70−7.74 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 123.4
(q, J = 272.1 Hz), 125.8 (q, J = 3.7 Hz), 127.4, 127.5, 128.3, 128.8,
129.1 (q, J = 32.2 Hz), 139.9, 144.9. 19F NMR (471 MHz, CDCl3): δ
NMR (125 MHz, CDCl3): δ = 21.1, 26.5, 126.8, 127.0, 128.8, 129.6,
̃
135.5, 136.8, 138.1, 145.6, 197.6. IR (neat): νmax
̃
= 1534, 1605, 1708,
3026 cm−1. HRMS: calcd for C15H15O [M + H]+ 211.1123, found
211.1126.
3-Phenylpyridine (3a).41 Following the general procedure for
Hiyama cross-coupling with aryltrifluorosilanes, 3a was obtained as a
1
colorless oil (80 mg, 74%). H NMR (500 MHz, CDCl3): δ = 7.33−
7.38 (m, 1 H), 7.39−7.41 (m, 1 H), 7.45−7.48 (m, 2 H), 7.56−7.58
(m, 2 H), 7.85 (d, J = 8.0 Hz, 1 H), 8.59 (d, J = 5.0 Hz, 1 H), 8.85 (s,
= −62.3. IR (neat): νmax
= 1545, 1607, 3067 cm−1. HRMS: calcd for
̃
̃
C13H9F3 [M]+ 222.0656, found 222.0648.
1 H). 13C NMR (125 MHz, CDCl3): δ = 123.6, 127.2, 128.1, 129.1,
4-Phenylbenzonitrile (2h).41 Following the general procedure
for Hiyama cross-coupling with aryltrifluorosilanes, 2h was obtained as
a white solid directly from the chromatographic solvent. Mp: 85−87
°C (91 mg, 73%). 1H NMR (500 MHz, CDCl3): δ = 7.41−7.44 (m, 1
H), 7.47−7.50 (m, 2 H), 7.58−7.59 (m, 2 H), 7.66−7.72 (m, 4 H).
13C NMR (125 MHz, CDCl3): δ = 110.8, 118.9, 127.2, 127.7, 128.7,
̃
̃
̃
134.4, 136.6, 137.9, 148.4, 148.5. IR (neat): νmax
= 1534, 1569, 3089
cm−1. HRMS: calcd for C11H10N [M + H]+ 156.0813, found 156.0811.
3-(3-Methoxyphenyl)pyridine (3b).48 Following the general
procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3b
1
was obtained as a yellow oil (98 mg, 76%). H NMR (500 MHz,
CDCl3): δ = 3.82 (s, 3 H), 6.91 (d, J = 7.5 Hz, 1 H), 7.07 (s, 1 H),
7.12 (d, J = 7.0 Hz, 1 H), 7.29−7.31 (m, 1 H), 7.35 (t, J = 8.0 Hz, 1
H), 7.81 (d, J = 7.5 Hz, 1 H), 8.56 (s, 1 H), 8.82 (s, 1 H). 13C NMR
(125 MHz, CDCl3): δ = 55.2, 112.9, 113.3, 119.5, 123.4, 130.1, 134.3,
129.1, 132.6, 139.1, 145.6. IR (neat): νmax = 1567, 1601, 2307, 3110
̃
cm−1. HRMS: calcd for C13H9N [M]+ 179.0735, found 179.0743.
4-Nitrobiphenyl (2i).45 Following the general procedure for
Hiyama cross-coupling with aryltrifluorosilanes, 2i was obtained as a
yellow solid directly from the chromatographic solvent. Mp: 100−102
̃
136.4, 139.2, 148.3, 148.5, 160.1. IR (neat): νmax = 1178, 1549, 1590,
̃
3034 cm−1. HRMS: calcd for C12H12NO [M + H]+ 186.0919, found
186.0911.
1
°C (127 mg, 91%). H NMR (500 MHz, CDCl3): δ = 7.43−7.46 (m,
6-Methoxy-3-phenylpyridine (3c).41 Following the general
procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3c was
obtained as a yellow oil (100 mg, 78%). 1H NMR (500 MHz, CDCl3):
δ = 3.99 (s, 3 H), 6.82 (d, J = 8.5 Hz, 1 H), 7.34−7.37 (m, 1 H), 7.45
(t, J = 8.2 Hz, 2 H), 7.52−7.54 (m, 2 H), 7.79 (dd, J = 8.5, 2.5 Hz, 1
H), 8.40−8.41 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 53.5,
110.8, 126.7, 127.3, 129.0, 130.1, 137.5, 137.9, 145.0, 163.6. IR (neat):
1 H), 7.49−7.52 (m, 2 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.72−7.74 (m, 2
H), 8.28−8.30 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 124.2,
̃
̃
127.4, 127.8, 129.0, 129.2, 138.8, 147.1, 147.7. IR (neat): νmax
= 1343,
1508, 1643, 3078 cm−1. HRMS: calcd for C12H9NO2 [M]+ 199.0633,
found 199.0639.
3-Phenylmethylbenzoate (2j).46 Following the general proce-
dure for Hiyama cross-coupling with aryltrifluorosilanes, 2j was
obtained as a colorless oil (146 mg, 98%). 1H NMR (500 MHz,
CDCl3): δ = 3.94 (s, 3 H), 7.36−7.39 (m, 1 H), 7.44−7.53 (m, 3 H),
7.61−7.63 (m, 2 H), 7.78−7.79 (m, 1 H), 8.02 (d, J = 7.5 Hz, 1 H),
8.28 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 52.3, 127.3, 127.8,
128.4 (2C), 128.9, 129.0, 130.8, 131.6, 140.2, 141.6, 167.2. IR (neat):
νmax
= 1290, 1508, 1567, 3045 cm−1. HRMS: calcd for C12H12NO [M
̃
̃
+ H]+ 186.0919, found 186.0914.
6-Fluoro-3-phenylpyridine (3d). Following the general proce-
dure for Hiyama cross-coupling with aryltrifluorosilanes, 3d was
obtained as a yellow oil (101 mg, 84%). 1H NMR (500 MHz, CDCl3):
δ = 7.00 (dd, J = 8.5, 2.5 Hz, 1 H), 7.39−7.42 (m, 1 H), 7.47 (t, J = 7.5
Hz, 2 H), 7.52−7.53 (m, 2 H), 7.96 (dt, J = 8.0, 2.5 Hz, 1 H), 8.41 (s,
1 H). 13C NMR (125 MHz, CDCl3): δ = 109.3, 109.6, 127.1, 128.2,
129.2, 134.9, 136.7, 139.7, 145.8, 162.2, 164.1. 19F NMR (471 MHz,
νmax
= 1234, 1576, 1705, 3090 cm−1. HRMS: calcd for C14H13O2 [M +
̃
̃
H]+ 213.0916, found 213.0911.
Biphenyl-4-carboxaldehyde (2k).43 Following the general
procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2k
was obtained as a yellow solid directly from the chromatographic
solvent. Mp: 182−184 °C (108 mg, 85%). 1H NMR (500 MHz,
= 1567, 3089 cm−1. HRMS: calcd
̃
CDCl3): δ = −71.06. IR (neat): νmax
̃
for C11H8FN [M]+ 173.0641, found 173.0640.
9185
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The Journal of Organic Chemistry
Note
3-(4-Methylbenzene)-6-fluoropyridine (3e). Following the
general procedure for Hiyama cross-coupling with aryltrifluorosilanes,
3e was obtained as a white solid directly from the chromatographic
solvent. Mp: 55−57 °C (122 mg, 94%). 1H NMR (500 MHz, CDCl3):
δ = 2.41 (s, 3 H), 6.97−6.99 (m, 1 H), 7.28 (d, J = 7.5 Hz, 2 H), 7.43
(d, J = 6.5 Hz, 2 H), 7.92−7.96 (m, 1 H), 8.40 (s, 1 H). 13C NMR
(125 MHz, CDCl3): δ = 21.2, 109.3, 109.6, 127.0, 129.9, 133.9, 134.9,
138.2, 139.6, 145.7, 162.1, 164.0. 19F NMR (471 MHz, CDCl3): δ =
ACKNOWLEDGMENTS
■
This research was supported by NIGMS (GM R01 035249).
We acknowledge Johnson Matthey for its donation of
Pd(OAc)2. Dr. Rakesh Kohli (University of Pennsylvania) is
acknowledged for obtaining HRMS data.
REFERENCES
−71.0. IR (neat): νmax
= 1569, 1607, 3032 cm−1. HRMS: calcd for
̃
■
̃
C12H11NF [M + H]+ 188.0876, found 188.0879.
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δ = 2.76 (s, 3 H), 7.20 (s, 1 H), 7.40 (t, J = 7.5 Hz, 1 H), 7.46−7.50
(m, 5 H), 7.66 (t, J = 7.5 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 8.10 (d, J
= 8.0 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 25.3, 122.2, 125.1,
125.6, 125.7, 128.3, 128.5, 129.0, 129.3, 129.5, 138.1, 148.4, 148.5,
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̃
̃
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δ = 7.36−7.41 (m, 4 H), 7.62−7.64 (m, 2 H), 7.70 (d, J = 4.0 Hz, 1
H), 9.86 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 124.1, 126.3,
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̃
̀
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1
was obtained as a yellow oil (89 mg, 74%). H NMR (500 MHz,
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7.42 (m, 3 H), 7.78 (m, 2 H), 9.60 (s, 1 H). 13C NMR (125 MHz,
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7.53 (m, 5 H), 7.67 (d, J = 4.5 Hz, 2 H), 7.73 (d, J = 5.5 Hz, 1 H), 7.99
(t, J = 4.5 Hz, 1 H), 8.49 (d, J = 6.0 Hz, 1 H), 9.31 (s, 1 H). 13C NMR
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̃
134.2, 139.1, 139.3, 143.5, 153.0. IR (neat): νmax = 1589, 1609, 3034
̃
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectral data for compounds 1a−c,
2a−n and 3a−j. This material is available free of charge via the
Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gmolandr@sas.upenn.edu.
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