Palladium-catalyzed C-H alkylation of 2-phenylpyridines with alkyl iodides

Article abstract of DOI:10.1039/c7ob01232b

Palladium-catalyzed C-H alkylation reaction of 2-phenylpyridines with alkyl iodides has been successfully developed. The palladacycles obtained from 2-phenylpyridines should act as the key intermediates in the alkylation reaction.

Full text of DOI:10.1039/c7ob01232b

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Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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DOI: 10.1039/C7OB01232B
Organic &Biomolecular Chemistry
ARTICLE
Palladium-Catalyzed CH Alkylation of 2-Phenylpyridines with
Alkyl Iodides
Xiaoling Wang, Xiaoming Ji, Changdong Shao, Yu Zhang, and Yanghui Zhang*
Palladium-catalyzed CH alkylation reaction of 2-phenylpyridines with alkyl iodides has been successfully
developed. The palladacycles obtained from 2-phenylpyridines should act as the key intermediate in the
alkylation reaction.
Introduction
Transition metal-catalyzed cross-coupling with unactivated
alkyl (pseudo)halides remains to be one of the greatest
challenges.1 However, alkyl (pseudo)halides exhibit high
reactivity in some reactions. For instance, in Catellani reaction,
the key palladacycles formed from aryl iodides and
norbornene can react with alkyl halides efficiently (Figure 1,
a).2
Recently,
our
group
found
that
dibenzometallacyclopentadienes exhibited novel reactivity
that was distinct from that of other common arylmetal
complexes. The palladacycle could selectively react with alkyl
halides (Figure 1, b).3 Inspired by these reactions, we
envisioned that palladacycles might be desirable models for
the development of Pd-catalyzed alkylation with alkyl halides.
One of the major methods for the formation of
palladacylces is the palladation of C-H bonds.4 In the past few
decades, C-H functionalization has experienced a noticeable
progress. The majority of transition metal-catalyzed C-H
functionalization reactions rely on the use of directing groups.5
The directing groups usually contain heteroatoms such as N
and O, so they can coordinate with transition metals and assist
the metalation of C-H bonds. Therefore, the directed C-H
metalation often forms metallacycles comprising one chelating
heteroatom6. In Catellani reaction and the reactions reported
by our group, both palladacycles consist of two metal-carbon
bonds. Since metallacycles comprising one chelating
heteroatom are ubiquitous, we were curious the reactivity
about of the palladacycles of this type towards alkyl halides.
Actually, it has been reported that a few palladacycles
School of Chemical Science and Engineering, and Shanghai Key Lab of Chemical
Assessment and Sustainability, Tongji University, 1239 Siping Road, Shanghai,
200092, P. R. China. E-mail: zhangyanghui@tongji.edu.cn
Figure 1 Alkylation of palladacycles with alkyl halides.
Electronic Supplementary Information (ESI) available: [Copies of 1H and 13C NMR
spectral data]. See DOI: for all compounds (PDF)
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comprising chelating heteroatoms could react with alkyl halides. A (entry 12). Finally, the yield decreased at a higVhieewr AortircleloOwnliener
DOI: 10.1039/C7OB01232B
typical example is carboxylate-directed C-H alkylation reported by temperature (entries 13 and 14), and no desired alkylated products
the Yu group (Figure 1, c).7 Such a reaction could also be enabled by were observed when n-butyl bromide or chloride was used as the
using a highly acidic amide directing group.8 Noticeably, pyrroles alkylating reagent (entries 15 and 16).
could act as the directing group in the Pd-catalyzed alkylation of
The substrate scope was next examined. We first investigated
C(sp2)−H bonds (Figure 1, d).9 In all these reactions, an anion, O- or the performance of a range of 2-phenylpyridne derivatives under
N-, bonded with the palladium and formed a C, O-/N-palladacycle. In the optimized reaction conditions. As shown in Figure 2,
addition, it should be mentioned that bidentate directing groups unsubstituted 2-phenylpyridine 1b underwent the alkylation
proved to be very effective in Pd-catalyzed C-H alkylation reactions reaction, forming mono- and dialkylated products
with alkyl halides.10 In these reactions, tridentate-palladacycles
were formed. In summary, in all the above-mentioned reactions, Table 1 Condition Survey for Pd-Catalyzed C-H n-butylation of
the palladacycles were formed through the chelation of two anions. 2-(4-methoxyphenyl)pyridine with n-butyl iodide
The reports on the alkylation of palladacycles comprising
a
carbanion and a neutral chelating heteroatom are very rare. One of
the few examples is the alkylation of acetanilides with alkyl iodides
(Figure 1, e).11 In this reaction, a six-membered C, O-palladacycle
was formed and it reacted with alkyl iodides. However, a variety of
neutral donors can act as the directing group and form
palladacycles comprising one neutral chelating heteroatom. In this
context, nitrogen is one of the most important donor atoms.
Therefore, we set out to study the alkylation of C, N-palladcycles,
comprising a neutral chelating nitrogen atom, with alkyl halide.
Pyridine is one of the most common directing groups in palladium-
catalyzed C-H functionalization reaction.12 The nitrogen atom of
pyridine coordinates to palladium and form C, N-palladacycle, so
pyridine-chelated palladacycles are the desirable models for
studying the alkylation of C, N-palladacycles with alkyl halides. It
should be mentioned that C-H alkylation reactions with alkyl
halides catalyzed by other transition metals such as ruthenium,
nickel, copper, and cobalt have been reported.13 Herein, we report
the alkylation of palladacycle derived from 2-phenylpyridines with
alkyl idodides (Figure 1, f).
entry ligand (equiv)
solvent
yield (%)a
3aa
6
3aa-di
trace
trace
trace
trace
4
1a
90
92
90
91
64
68
60
1
2
3
4
5
6
7
/
/
/
/
/
/
/
THF
toluene
3
DMSO
7
1,4-dioxane
CH3CN
6
28
25
32
t-BuOH
t-AmylOH
4
5
t-AmylOH:CH3CN
8
/
38
6
53
52
49
35
20
64
72
9:1
Ac-Gly-OH
(0.2)
t-AmylOH:CH3CN
Results and discussion
9
40
5
9:1
Boc-Gly-OH
(0.2)
t-AmylOH:CH3CN
We commenced our study by investigating the reaction of 2-(4-
methoxyphenyl)pyridine 1a with n-butyl iodide 2a under palladium
catalysis in the presence of Ag2CO3. As shown in Table 1, whereas
the reaction formed a small amount of the alkylated product in a
range of common organic solvents (entries 1-4), 3aa was obtained
in 28% yield when the reaction was carried out in CH3CN (entry 5).
t-BuOH was also effective solvent and 25% product was formed
(entry 6). The yield increased slightly to 32% when t-AmylOH was
used (entry 7). It should be noted that a trace or small amount of
dialkylated product 3aa-di was observed in all the above-mentioned
reactions. The yield was further improved to 38% when the reaction
was carried out in a mixture of t-AmylOH and CH3CN.(entry 8).
Amino acids proved to be powerful ligands in some Pd-catalyzed C-
H functionalization reactions.14 Therefore, we investigated the
impact of amino acids on this alkylation reaction. Extensive
screening of a range of amino acids revealed that they had little
effect on the reaction. For example, the yields of the reaction in the
presence of Ac-Gly-OH or Boc-Gly-OH remained almost unchanged
(entries 9 and 10). Interestingly, when we added 20 mol %
(BnO)2PO2H instead of amino acids, the reaction produced 52% 3aa
as well as 11% dialkylated product 3aa-di (entry 11). The yield was
further improved to 64% when 80 mol % (BnO)2PO2H was used
10
11
12
13c
14d
15e
16f
39
7
9:1
(BnO)2PO2H
(0.2)
t-AmylOH:CH3CN
52
11
9:1
(BnO)2PO2H
(0.8)
t-AmylOH:CH3CN
64(62)b
11(10)b
9:1
(BnO)2PO2H
(0.8)
t-AmylOH:CH3CN
26
20
/
6
4
9:1
(BnO)2PO2H
(0.8)
t-AmylOH:CH3CN
9:1
(BnO)2PO2H
(0.8)
t-AmylOH:CH3CN
/
100
9:1
(BnO)2PO2H
(0.8)
t-AmylOH:CH3CN
/
/
100
9:1
a The yields were determined by H NMR analysis of the crude
1
b
reaction mixture using CHCl2CHCl2 as the internal standard.
c
o
Isolated yield. 80 C. d 50 oC. e n-butyl bromide instead of n-
f
butyl iodide. n-butyl chloride instead of n-butyl iodide.
(
3ba and 3ba-di) in 53% and 11% yield respectively. The
substrates bearing a methyl, t-butyl, or phenyl group at the
para positions of the benzene rings exhibited similar
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reactivities to 1a, and the corresponding alkylated products disubstituted one (3ka and 3ka-iso).The reactViieownAsrticolefOntlhinee
DOI: 10.1039/C7OB01232B
were obtained in moderate yields (3ca, 3da, and 3ea). It is substrate with two methoxy groups at the para and meta
noted that the chloro group was well-tolerated under the positions formed one mono-substituted product
(3la).
reaction conditions (3fa). The substrates bearing electron- Interestingly, the substrates containing two substituents,
withdrawing groups such as acetyl and trifluoromethyl group methoxy or methyl groups, at the meta positions were also
were also reactive. However, the reactions were low-yielding suitable, and mono- and dialkylated products were obtained
(3ga and 3ha).
(3ma and 3na). 2-Phenylpyridines bearing an ortho-substituent
Next, we examined the performance of substrate such as methyl and fluoro could also be alkylated, albeit in low
containing meta arene substituents. In the presence of a meta- yields (3oa and 3pa). Likewise, the reaction of 2-(naphthalen-
methyl group, the reaction took place selectively at the less- 1-yl)pyridine was also low-yielding (3qa).
hindered position and produced a single monoalkylated
Finally, the reactions using other nitrogen-containing
product (3ia). However, a dialkylated product was also isolated. heterarene as the directing groups were also examined.
On the contrary, for the substrate with a meta-methxoy group Pyrazole was an effective directing group, and only the
on the benzene ring, two monoalkylated products were monoalkylated product was formed. Unfortunately, the yield
formed, but the product with n-butyl group at the less- was poor (3ra). 2-Phenylpyrimidine was alkylated under the
crowded site was still the major one (3ja and 3ja-iso). The standard conditions, affording mono- and dialkylated products
reactivities of disubstituted substrates were also examined. 2- in 19% and 11% yield respectively (3sa).
(Naphthalen-2-yl)pyridine was reactive, and the reaction
yielded two monoalkylated products as well as the
Next, the compatibility of various alkyl iodides was
examined using 1b as the reactants. As shown in Figure 3, n-
heptyl iodide could alkylate 1b and the corresponding
alkylated products were formed in slightly higher yields than
those in the reactions of n-butyl iodide
(3bb). The
functionalities, benzyl, cyano, and methoxy, at the terminals of
the alkyl chains were well tolerated, but a higher loading of
palladium catalyst had to be used (3bc, 3bd, and 3be). It is
noted that only monoalkylated products were isolated in the
reaction of 1-iodo-4-methoxybutane and 5-iodopentanenitrile.
More bulky isopropyl iodide was reactive, but the yields were
low (3bf). Finally, the phthalimide group was also tolerated.
The monoalkylated product was formed in 80% yield, and only
a trace amount of di-alkylated product was observed (3bg).
Figure 3 Substrate scope with respect to alkyl iodide. Isolated
yield. a Pd(OAc)2 20%; b Pd(OAc)2 15%.
Finally, to investigate if the alkylation reaction proceeded
through the palladacycle derived from 2-phenylpyridine as the
intermediate, we prepared the complex from 2-phenylpyridine
Figure 2 Substrate scope with respect to 2-phenylpyridine.
Isolated yield
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and Pd(OAc)2 (Scheme 1, 4b). Subsequently, the complex was palladacycle to exhibit great reactivity towards alkyVliehwaAlirdticeles.OnTlhinee
DOI: 10.1039/C7OB01232B
subjected to the standard alkylation reaction conditions. The reaction may shed light on other Pd-catalyzed alkylation reaction
corresponding mono- and dialkylated products were formed in with alkyl halides, and provide inspiration to develop new reactions
76% overall yield in the absence of (BnO)2PO2H. In the of this type.
presence of (BnO)2PO2H, the compex was alkylated almost
quantitatively. These experimental results provide evidences
to support palladacycles as the key intermediates in the
Experimental Section
alkylation reaction. Furthermore, (BnO)2PO2H promoted the
alkylation of the palladacycle. The mechanism of the
promotion remains to be investigated. (BnO)2PO2H might act
as a ligand.16
General information
All the solvents were purified by distillation prior to use. Unless
otherwise noted, the other commercial chemicals were used
without further purification. 1H NMR and 13C NMR spectra were
recorded on Bruker ARX400. High resolution mass spectra were
measured on Bruker Micro TOF II ESI-TOF mass spectrometer. 1H
NMR spectra were recorded in CDCl3, and referenced to residual
CHCl3 at 7.26 ppm. 13C NMR spectra are referenced to the central
peak of CDCl3 at 77.0 ppm. Multiplicities are reported using the
following abbreviations: s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, br = broad resonance.
General procedure for the C-H alkylation. A 35 mL Schlenk
tube equipped with a stir bar was charged with Pd(OAc)2 (4.5 mg,
10 mol %) followed by 2-arylpyridines (0.2 mmol, 1equiv), alkyl
iodides (0.8 mmol, 4 equiv), Ag2CO3 (165.5 mg, 0.6 mmol, 3 equiv),
(BnO)2PO2H (44.5 mg, 1.6 mmol, 0.8 equiv), and t-AmylOH:CH3CN
(9:1, 1 mL). The tube was placed into an oil bath under desired
temperature. After the reaction was completed, it was allowed to
cool down to room temperature. The reaction mixture was diluted
with ethyl acetate and washed with aqueous Na2S solution (4 mL, 1
time) and brine (4 mL, 2 times), then filtered through a small pad of
Celite. The filtrate was concentrated in vacuo. The residue was
purified by chromatography on silica gel using petroleum ether and
ethyl acetate as the eluent to afford products.
Scheme 1 n-Butylation of the Palladacycle Derived from 2-
Phenylpyridine with n-BuI
Based on the experimental results and the previous reports,3, 11,
a tentative mechanism was proposed as shown in Scheme 2.
15
Therefore, the catalytic cycle was initiated by the pyridine-directed
C-H cleavage by PdII catalyst, forming the palladacycle. The resulted
palladacycle reacts with alkyl iodide, via either an oxidative addition
or substitution pathway, to generate the alkylated product and
release PdII. Ag(I) should function as iodide scavenger.17 The
monoalkylated 2-phenylpyridine undergoes the same catalytic cycle
to yield the dialkylated product.
2-(2-butyl-4-methoxyphenyl)pyridine (3aa). White solid (29.8
1
mg, 62%). H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 4.2 Hz, 1H), 7.76
(ddd, J = 7.7, 7.7, 1.5 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.34 (d, J = 8.3
Hz, 1H), 7.29 – 7.22 (m, 1H), 6.93 – 6.81 (m, 2H), 3.88 (s, 3H), 2.75 (t,
J = 8.0 Hz, 2H), 1.54 – 1.42 (m, 2H), 1.33 – 1.21 (m, 2H), 0.83 (t, J =
7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.12, 159.56, 149.08,
142.43, 136.02, 133.25, 131.08, 124.17, 121.27, 115.27, 110.98,
55.25, 33.41, 32.89, 22.51, 13.83. HRMS (ESI-TOF) m/z: calcd for
C16H19NNaO+: 264.1359 (M + Na)+, found: 264.1364.
2-(2,6-dibutyl-4-methoxyphenyl)pyridine (3aa-di). White solid
1
(5.9 mg, 10%). H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 4.2 Hz, 1H),
7.77 (ddd, J = 7.6, 7.6, 1.7 Hz, 1H), 7.32 – 7.26 (m, 1H), 6.71 (s, 2H),
3.87 (s, 3H), 2.32 (t, J = 7.9 Hz, 4H), 1.50 – 1.36 (m, 4H), 1.25 – 1.13
(m, 4H), 0.77 (t, J = 7.3 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 159.68,
149.27, 140.71, 139.87, 135.75, 127.93, 126.52, 125.05, 121.61,
33.32, 33.20, 22.56, 13.79. HRMS (ESI-TOF) m/z: calcd for
C20H27NNaO+: 320.1985 (M + Na)+, found: 320.1983.
2-(2-butylphenyl)pyridine (3ba). Colorless liquid (22.4 mg ,
53%). 1H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 3.5 Hz, 1H), 7.79 (ddd,
J = 7.7, 7.7, 1.6 Hz, 1H), 7.43 (d, J = 7.8 Hz, 1H), 7.40 – 7.33 (m, 3H),
7.33 – 7.26 (m, 2H), 1.48 (t, J = 7.9 Hz, 2H), 1.55 – 1.39 (m, 2H), 1.30
– 1.21 (m, 2H), 0.83 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
160.35, 149.12, 140.75, 140.37, 136.09, 129.74, 129.72, 128.28,
125.73, 124.16, 121.63, 33.49, 32.61, 22.51, 13.83. HRMS (ESI-TOF)
m/z: calcd for C15H17NNa+: 234.1253 (M + Na)+, found: 234.1242.
Scheme 2 Proposed Mechanism for the Pd-Catalyzed C-H
Alkylation of 2-Phenylpyridine with Alkyl Iodide
Conclusions
In conclusion, we have successfully developed the Pd-catalyzed
C-H alkylation reaction of 2-phenylpyridines with alkyl iodides. The
reaction should proceed through C, N-palladacycle obtained from 2-
phenylpyridine as the key intermediate, which represents another
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2-(2,6-dibutylphenyl)pyridine (3ba-di). Colorless liquid (5.9 mg, 1.28 – 1.17 (m, 4H), 0.80 (t, J = 7.3 Hz, 6H). 13C NMR (101 MHz,
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11%). 1H NMR (400 MHz, CDCl3) δ 8.75 (d, J = 4.0 Hz, 1H), 7.78 (ddd, CDCl3) δ 159.52, 149.39, 141.52, 141.25, 140.77, 139.00, 135.80,
J = 7.7, 7.7, 1.8 Hz, 1H), 7.34 – 7.26 (m, 2H), 7.16 (d, J = 7.6 Hz, 2H), 128.69, 127.25, 127.15, 125.52, 125.13, 121.69, 33.39, 22.62, 13.82.
2.34 (t, J = 8.8 Hz, 4H), 1.53 – 1.37 (m, 4H), 1.24 – 1.14 (m, 4H), 0.78 HRMS (ESI-TOF) m/z: calcd for C25H29NNa+: 366.2192 (M + Na)+,
(t, J = 7.3 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 159.68, 149.27, found: 366.2196.
DOI: 10.1039/C7OB01232B
140.71, 139.87, 135.75, 127.93, 126.52, 125.05, 121.61, 33.32,
33.20, 22.56, 13.79. HRMS (ESI-TOF) m/z: calcd for C19H25NNa+: mg, 40%). H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.7 Hz, 1H), 7.78
290.1879 (M + Na)+, found: 290.1881.
(ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 2.0
2-(2-butyl-4-chlorophenyl)pyridine (3fa). Colorless liquid (19.6
1
2-(2-butyl-4-methylphenyl)pyridine (3ca). Colorless liquid Hz, 1H), 7.32 – 7.24 (m, 3H), 2.72 (t, J = 7.9 Hz, 2H), 1.53 – 1.41 (m,
1
(24.8 mg, 55%). H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.8 Hz, 1H), 2H), 1.29 – 1.20 (m, 2H), 0.82 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz,
7.76 (ddd, J = 7.7, 7.7, 1.8 Hz, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.30 – CDCl3) δ 159.21, 149.29, 142.83, 138.81, 136.28, 134.04, 131.13,
7.23 (m, 2H), 7.16 (s, 1H), 7.12 (d, J = 7.7 Hz, 1H), 2.73 (t, J = 7.9 Hz, 129.61, 125.89, 124.11, 121.93, 33.21, 32.53, 22.45, 13.81. HRMS
2H), 2.42 (s, 3H), 1.56 – 1.42 (m, 2H), 1.33 – 1.24 (m, 2H), 0.83 (t, J = (ESI-TOF) m/z: calcd for C15H16ClNNa+: 268.0863 (M + Na)+, found:
7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.40, 149.09, 140.61, 268.0867.
137.94, 137.56, 136.03, 130.47, 129.74, 126.50, 124.18, 121.42,
33.61, 32.60, 22.58, 21.29, 13.86. HRMS (ESI-TOF) m/z: calcd for liquid (5.4 mg, 9%). H NMR (400 MHz, CDCl3) δ 8.75 (d, J = 4.4 Hz,
C16H19NNa+: 248.1410 (M + Na)+, found: 248.1404.
1H), 7.79 (ddd, J = 7.7, 7.7, 1.6 Hz, 1H), 7.35 – 7.31 (m, 1H), 7.26 (d,
2-(2,6-dibutyl-4-chlorophenyl)pyridine (3fa-di). Colorless
1
2-(2,6-dibutyl-4-methylphenyl)pyridine (3ca-di). Colorless J = 7.7 Hz, 1H), 7.15 (s, 2H), 2.30 (t, J = 8.9 Hz, 4H), 1.49 – 1.33 (m,
liquid (7.9 mg, 14%). 1H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 6.8 Hz, 4H), 1.24 – 1.11 (m, 4H), 0.78 (t, J = 7.3 Hz, 6H). 13C NMR (101 MHz,
1H), 7.76 (ddd, J = 7.7, 7.7, 1.8 Hz, 1H), 7.32 – 7.24 (m, 2H), 6.98 (s, CDCl3) δ 158.64, 149.49, 142.81, 138.39, 135.94, 133.45, 126.40,
2H), 2.39 (s, 3H), 2.31 (t, J = 8.0 Hz, 4H), 1.51 – 1.33 (m, 4H), 1.27 – 125.07, 121.91, 33.05, 33.00, 22.47, 13.75. HRMS (ESI-TOF) m/z:
1.14 (m, 4H), 0.78 (t, J = 7.3 Hz, 6H).13C NMR (101 MHz, CDCl3) δ calcd for C19H24ClNNa+: 324.1489 (M + Na)+, found: 324.1492.
159.85, 149.25, 140.62, 137.34, 137.16, 135.66, 127.29, 125.26,
1-(3-butyl-4-(pyridin-2-yl)phenyl)ethan-1-one (3ga). White
1
121.46, 33.41, 33.17, 22.62, 21.33, 13.80. HRMS (ESI-TOF) m/z: solid (20.2mg, 40%). H NMR (400 MHz, CDCl3) δ 8.75 (d, J = 4.1 Hz,
calcd for C20H27NNa+: 304.2036 (M + Na)+, found: 304.2034.
2-(4-(tert-butyl)-2-butylphenyl)pyridine (3da). Colorless liquid
(32.6 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.2 Hz, 1H),
7.77 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.35 (s,
1H), 7.95 (d, J = 1.4 Hz, 1H), 7.88 (dd, J = 7.9, 1.7 Hz, 1H), 7.82 (ddd,
J = 7.7, 7.7, 1.8 Hz, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.43 (d, J = 7.8 Hz,
1H), 7.34 (ddd, J = 7.5, 4.9, 1.0 Hz, 1H), 2.79 (t, J = 8.2 Hz, 2H), 2.68
(s, 3H), 1.56 – 1.43 (m, 2H), 1.32 – 1.19 (m, 2H), 0.83 (t, J = 7.3 Hz,
1H), 7.34 (s, 2H), 7.27 (dd, J = 7.0, 5.4 Hz, 1H), 2.76 (t, J = 7.9 Hz, 2H), 3H). 13C NMR (101 MHz, CDCl3) δ 198.21, 159.21, 149.34, 144.83,
1.54 – 1.44 (m, 2H), 1.40 (s, 9H), 1.31 – 1.24 (m, 2H), 0.84 (t, J = 7.3
141.44, 136.81, 136.32, 130.12, 129.67, 125.86, 124.03, 122.22,
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.41, 151.14, 149.12, 140.24, 33.36, 32.65, 26.79, 22.49, 13.78. HRMS (ESI-TOF) m/z: calcd for
137.51, 136.02, 129.50, 126.81, 124.07, 122.79, 121.42, 34.60,
33.76, 33.03, 31.41, 22.64, 13.90. HRMS (ESI-TOF) m/z: calcd for
C19H25NNa+: 290.1879 (M + Na)+, found: 290.1887.
C17H19NNaO+: 276.1359 (M + Na)+, found: 276.1359.
2-(2-butyl-4-(trifluoromethyl)phenyl)pyridine (3ha). White
solid (17.8 mg, 32%). 1H NMR (400 MHz, CDCl3) δ 8.75 (d, J = 4.3 Hz,
2-(4-(tert-butyl)-2,6-dibutylphenyl)pyridine (3da-di). Colorless 1H), 7.82 (ddd, J = 7.7, 7.7, 1.8 Hz, 1H), 7.60 (s, 1H), 7.56 (d, J = 8.1
liquid (6.4 mg, 12%). 1H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 4.8 Hz, Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.38 – 7.32
1H), 7.77 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.34 – 7.31 (m, 1H), 7.30 – (m, 1H), 2.78 (t, J = 7.9 Hz, 2H), 1.55 – 1.45 (m, 2H), 1.32 – 1.23 (m,
7.25 (m, 1H), 7.16 (s, 2H), 2.34 (t, J = 7.9 Hz, 4H), 1.38 (s, 9H), 1.36 – 2H), 0.83 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 158.97,
1.28 (m, 4H), 1.23 – 1.15 (m, 4H), 0.78 (t, J = 7.3 Hz, 6H). 13C NMR 149.37, 143.67, 141.80, 136.35, 130.36 (q, J = 32.0 Hz), 130.17,
(101 MHz, CDCl3) δ 159.91, 150.51, 149.19, 140.16, 137.02, 135.65, 126.47 (q, J = 3.7 Hz), 124.26 (q, J = 272.3 Hz), 124.01, 122.55 (q, J =
125.12, 123.64, 121.45, 34.51, 33.59, 33.56, 31.44, 22.63, 13.83. 3.8 Hz), 122.25, 33.20, 32.61, 22.45, 13.73. HRMS (ESI-TOF) m/z:
HRMS (ESI-TOF) m/z: calcd for C23H33NNa+: 346.2505 (M + Na)+, calcd for C16H16F3NNa+: 302.1127 (M + Na)+, found: 320.1153.
found: 346.2519.
2-(2-butyl-5-methylphenyl)pyridine (3ia). Colorless liquid
2-(3-butyl-[1,1'-biphenyl]-4-yl)pyridine (3ea). White solid (27.9 mg, 62%). 1H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 4.5 Hz, 1H),
1
(29.9 mg, 52%). H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 4.7 Hz, 1H), 7.77 (ddd, J = 7.7, 7.7, 1.4 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H), 7.32 –
7.81 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.70 (d, J = 7.8 Hz, 2H), 7.59 (s, 7.26 (m, 1H), 7.26 – 7.16 (m, 3H), 2.70 (t, J = 8.29 Hz, 2H), 2.40 (s,
1H), 7.56 (d, J = 8.0 Hz, 1H), 7.50 (dd, J = 15.6, 7.7 Hz, 4H), 7.41 (t, J 3H), 1.53 – 1.38 (m, 2H), 1.32 – 1.19 (m, 2H), 0.82 (t, J = 7.3 Hz, 3H).
= 7.3 Hz, 1H), 7.34 – 7.28 (m, 1H), 2.84 (t, J = 7.8 Hz, 2H), 1.60 – 1.50 13C NMR (101 MHz, CDCl3) δ 160.39, 149.20, 140.20, 137.59, 136.00,
(m, 2H), 1.36 – 1.25 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H). 13C NMR (101 135.18, 130.42, 129.68, 128.95, 124.14, 121.56, 33.65, 32.19, 22.52,
MHz, CDCl3) δ 160.05, 149.23, 141.24, 141.13, 141.07, 139.34, 20.98, 13.88. HRMS (ESI-TOF) m/z: calcd for C16H19NNa+: 248.1410
136.16, 130.32, 128.78, 128.64, 127.35, 127.23, 124.58, 124.16, (M + Na)+, found: 248.1404.
121.68, 33.60, 32.84, 22.59, 13.88. HRMS (ESI-TOF) m/z: calcd for
2-(2,6-dibutyl-3-methylphenyl)pyridine (3ia-di). Colorless
C21H21NNa+: 310.1566 (M + Na)+, found: 310.1560.
liquid (3.1 mg, 7%). 1H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 3.6 Hz,
2-(3,5-dibutyl-[1,1'-biphenyl]-4-yl)pyridine (3ea-di). White 1H), 7.78 (ddd, J = 7.7, 7.7, 1.6 Hz, 1H), 7.34 – 7.26 (m, 2H), 7.17 (d,
solid (11.6 mg, 17%). 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J = 4.7 Hz, J = 7.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 2.37 (s, 3H), 2.34 – 2.19 (m,
1H), 7.88 – 7.76 (m, 1H), 7.68 (d, J = 7.5 Hz, 2H), 7.50 (t, J = 7.6 Hz, 4H), 1.50 – 1.33 (m, 4H), 1.24 – 1.08 (m, 4H), 0.82 – 0.69 (m, 6H).
2H), 7.43 – 7.31 (m, 5H), 2.42 (t, J = 7.7 Hz, 4H), 1.54 – 1.42 (m, 4H), 13C NMR (101 MHz, CDCl3) δ 160.27, 149.19, 140.21, 139.06, 138.38,
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Organic &Biomolecular Chemistry
135.63, 133.49, 130.04, 126.31, 125.04, 121.53, 33.37, 33.10, 31.98, 124.61, 121.70, 33.48, 28.79, 23.03, 13.82. HRMS (ESI-TOF) m/z:
View Article Online
30.23, 23.07, 22.59, 19.51, 13.83, 13.61. HRMS (ESI-TOF) m/z: calcd calcd for C19H19NNa+: 284.1410 (M + Na)+, foDuOndI::1208.140.3194/2C07O. B01232B
for C16H19NNa+:304.2046 (M + Na)+, found: 304.2046.
2-(2-butyl-3,4-dimethoxyphenyl)pyridine (3la). White solid
2-(2-butyl-5-methoxyphenyl)pyridine (3ja). White solid (28.5 (33.6 mg, 62%). 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 4.6 Hz, 1H),
1
mg, 60%) H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 4.1 Hz, 1H), 7.78 7.77 (t, J = 7.7 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.30 – 7.24 (m, 1H),
(ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.32 – 7.21 (m, 7.10 (d, J = 8.4 Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 3.94 (s, 3H), 3.90 (s,
2H), 6.93 (dd, J = 5.4, 2.7 Hz, 2H), 3.85 (s, 3H), 2.66 (t, J = 7.9 Hz, 2H), 3H), 2.77 (t, J = 8.1 Hz, 2H), 1.38 (dd, J = 15.3, 8.0 Hz, 2H), 1.27 –
1.50 – 1.37 (m, 2H), 1.30 – 1.15 (m, 2H), 0.81 (t, J = 7.3 Hz, 3H). 13C 1.16 (m, 2H), 0.78 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
NMR (101 MHz, CDCl3) δ 160.16, 157.47, 149.19, 141.23, 136.09, 160.18, 152.74, 149.00, 147.36, 136.09, 135.48, 125.48, 124.21,
132.87, 130.78, 124.09, 121.73, 114.71, 114.36, 55.38, 33.72, 31.78, 121.43, 109.55, 100.22, 60.76, 55.72, 32.89, 26.39, 22.81, 13.75.
+
22.44, 13.86. HRMS (ESI-TOF) m/z: calcd for C16H19NNaO+:264.1359 HRMS (ESI-TOF) m/z: calcd for C17H21NNaO2 :294.1465 (M + Na)+,
(M + Na)+, found: 264.1364.
found: 294.1466.
2-(2,6-dibutyl-3,4-dimethoxyphenyl)pyridine (3la-di). White
2-(2,6-dibutyl-3-methoxyphenyl)pyridine (3ja-di). White solid
(2.3 mg, 8%). 1H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 4.6 Hz, 1H), solid (4.3 mg, 8%). H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 3.8 Hz,
7.78 (ddd, J = 7.7, 7.7, 1.6 Hz, 1H), 7.31 (s, 1H), 7.28 (s, 1H), 7.11 (d, 1H), 7.77 (t, J = 7.5 Hz, 1H), 7.31 – 7.24 (m, 2H), 6.72 (s, 1H), 3.93 (s,
J = 8.4 Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H), 3.87 (s, 3H), 2.37 – 2.19 (m, 3H), 3.87 (s, 3H), 2.43 – 2.32 (m, 2H), 2.31 – 2.23 (m, 2H), 1.51 –
4H), 1.49 – 1.28 (m, 4H), 1.23 – 1.09 (m, 4H), 0.81 – 0.62 (m, 6H). 1.33 (m, 4H), 1.24 – 1.10 (m, 4H), 0.78 (t, J = 7.3 Hz, 3H), 0.72 (t, J =
13C NMR (101 MHz, CDCl3) δ 159.65, 155.67, 149.19, 141.08, 135.64, 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 159.41, 152.11, 149.16,
132.77, 129.67, 126.90, 124.95, 121.60, 110.26, 55.64, 33.50, 32.62, 145.05, 136.61, 135.75, 135.09, 133.23, 125.53, 121.59, 110.61,
1
32.07, 27.16, 22.94, 22.53, 13.83, 13.75. HRMS (ESI-TOF) m/z: calcd 60.74, 55.70, 33.52, 33.33, 32.82, 27.32, 22.92, 22.60, 13.85, 13.58.
+
for C20H27NNaO+:320.1985 (M + Na)+, found: 320.1996.
HRMS (ESI-TOF) m/z: calcd for C21H29NNaO2 : 350.2091 (M + Na)+,
2-(2-butyl-3-methoxyphenyl)pyridine (3ja-iso). White solid found: 350.2094.
(2.9 mg, 6%). 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.3 Hz, 1H),
2-(2-butyl-3,5-dimethoxyphenyl)pyridine (3ma). White solid
7.78 (ddd, J = 7.7, 7.7, 1.6 Hz, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.27 (dd, J (22.8 mg, 42%). 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.1 Hz, 1H),
= 9.2, 6.8 Hz, 2H), 6.97 (dd, J = 10.2, 8.2 Hz, 2H), 3.89 (d, J = 14.3 Hz, 7.77 (t, J = 7.7 Hz, 1H), 7.38 (t, J = 14.0 Hz, 1H), 7.29 (d, J = 9.9 Hz,
3H), 2.75 – 2.59 (m, 2H), 1.51 – 1.40 (m, 2H), 1.27 – 1.16 (m, 2H), 1H), 6.53 (d, J = 10.3 Hz, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 2.56 (t, J = 7.9
0.80 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.34, 157.89, Hz 2H), 1.50 – 1.35 (m, 2H), 1.26 – 1.13 (m, 2H), 0.79 (t, J = 7.3 Hz,
149.07, 141.85, 135.94, 129.82, 126.28, 124.21, 122.00, 121.64, 3H). 13C NMR (101 MHz, CDCl3) δ 160.40, 158.90, 158.17, 149.12,
110.33, 55.68, 32.16, 26.29, 22.84, 13.82. HRMS (ESI-TOF) m/z: 142.05, 135.89, 124.15, 122.42, 121.72, 105.36, 98.87, 55.65, 55.42,
calcd for C16H19NNaO+:264.1359 (M + Na)+, found: 264.1365.
32.42, 25.81, 22.68, 13.81. HRMS (ESI-TOF) m/z: calcd for
+
2-(3-butylnaphthalen-2-yl)pyridine (3ka). White solid (21.4 mg, C17H21NNaO2 :294.1465 (M + Na)+, found: 294.1469.
1
41%). H NMR (400 MHz, CDCl3) δ 8.78 (d, J = 4.5 Hz, 1H), 7.93 –
2-(2,6-dibutyl-3,5-dimethoxyphenyl)pyridine (3ma-di). White
1
7.76 (m, 5H), 7.59 – 7.45 (m, 3H), 7.34 (dd, J = 6.9, 5.4 Hz, 1H), 2.94 solid (9.1 mg, 14%). H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.4 Hz,
(t, J = 7.9 Hz, 2H), 1.56 – 1.42 (m, 2H), 1.35 – 1.22 (m, 2H), 0.84 (t, J 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.6 Hz, 2H), 6.56 (s, 1H), 3.89
= 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.32, 149.12, 139.30, (s, 6H), 2.34 – 2.12 (m, 4H), 1.46 – 1.32 (m, 2H), 1.31 – 1.22 (m, 2H),
138.79, 136.30, 133.40, 131.79, 129.10, 127.95, 127.87, 127.16, 1.19 – 1.08 (m, 4H), 0.73 (t, J = 7.3 Hz, 6H). 13C NMR (101 MHz,
126.26, 125.47, 124.34, 121.80, 33.19, 33.04, 22.53, 13.90. HRMS CDCl3) δ 159.69, 156.26, 149.04, 141.90, 135.47, 124.89, 121.85,
(ESI-TOF) m/z: calcd for C19H19NNa+: 284.1410 (M + Na)+, found: 121.54, 95.72, 55.85, 32.39, 26.64, 22.86, 13.72. HRMS (ESI-TOF)
+
284.1420.
2-(1,3-dibutylnaphthalen-2-yl)pyridine (3ka-di). White solid
m/z: calcd for C21H29NNaO2 :350.2091 (M + Na)+, found: 350.2098.
2-(2-butyl-3,5-dimethylphenyl)pyridine (3na). Colorless liquid
1
1
(6.3 mg, 10%). H NMR (400 MHz, CDCl3) δ 8.80 (d, J = 3.6 Hz, 1H), (33.6 mg, 70%). H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.7 Hz, 1H),
8.06 (dd, J = 13.9, 8.1 Hz, 1H), 7.92 – 7.77 (m, 2H), 7.65 (s, 1H), 7.59 7.77 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.40 (d, J = 7.8 Hz, 1H), 7.28 (ddd,
– 7.48 (m, 2H), 7.35 (d, J = 7.7 Hz, 2H), 2.76 (t, J = 7.9 Hz, 2H), 2.50 – J = 7.4, 5.4, 2.5 Hz, 1H), 7.08 (s, 1H), 7.01 (s, 1H), 2.65 (t, J = 7.9 Hz,
2.40 (m, 2H), 1.72 – 1.60 (m, 1H), 1.59 – 1.41 (m, 3H), 1.36 – 1.18 2H), 2.43 (s, 3H), 2.36 (s, 3H), 1.47 – 1.33 (m, 2H), 1.28 – 1.16 (m,
(m, 4H). 0.81 (t, J = 7.3 Hz, 6H).13C NMR (101 MHz, CDCl3) δ 160.19, 2H), 0.80 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 161.24,
149.35, 138.55, 138.45, 136.85, 135.82, 133.75, 130.43, 128.19, 148.90, 140.91, 136.58, 136.12, 135.96, 134.73, 131.29, 128.24,
125.57, 125.24, 125.17, 124.43, 121.78, 121.35, 33.71, 33.18, 32.89, 124.21, 121.48, 32.40, 28.90, 22.89, 20.85, 19.78, 13.72. HRMS (ESI-
29.65, 23.18, 22.61, 13.86, 13.73. HRMS (ESI-TOF) m/z: calcd for TOF) m/z: calcd for C17H21NNa+: 262.1566 (M + Na)+, found:
C23H27NNa+: 340.2036 (M + Na)+, found: 340.2047.
262.1564.
2-(2,6-dibutyl-3,5-dimethylphenyl)pyridine (3na-di). Colorless
2-(1-butylnaphthalen-2-yl)pyridine (3ka-iso). White solid (9.9
1
mg, 19%). H NMR (400 MHz, CDCl3) δ 8.79 (d, J = 4.3 Hz, 1H), 8.19 liquid (6.4 mg, 11%). 1H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 4.2 Hz,
(d, J = 8.4 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.84 (dd, J = 13.3, 5.1 Hz, 1H), 7.76 (ddd, J = 7.7, 7.7, 1.8 Hz, 1H), 7.33 – 7.28 (m, 2H), 7.04 (s,
2H), 7.61 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.4 Hz, 1H), 2.33 (s, 6H), 2.27 – 2.16 (m, 4H), 1.47 – 1.34 (m, 2H), 1.34 –
2H), 7.35 (dd, J = 7.0, 5.4 Hz, 1H), 3.12 (t, J = 8.13 Hz, 2H), 1.79 – 1.21 (m, 2H), 1.19 – 1.08 (m, 4H), 0.73 (t, J = 7.3 Hz, 6H). 13C NMR
1.63 (m, 2H), 1.42 – 1.29 (m, 2H), 0.92 – 0.77 (t, J = 7.3 Hz, 3H). 13C (101 MHz, CDCl3) δ 160.85, 149.05, 140.60, 136.76, 135.46, 133.28,
NMR (101 MHz, CDCl3) δ 160.99, 149.28, 137.61, 136.80, 136.06, 132.25, 125.04, 121.43, 32.10, 30.15, 23.04, 19.29, 13.58. HRMS
133.68, 132.15, 128.73, 127.54, 126.23, 126.13, 125.70, 124.80,
6 | J. Name., 2012, 00, 1-3
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(ESI-TOF) m/z: calcd for C21H29NNa+: 318.2192 (M + Na)+, found: (101 MHz, CDCl3) δ 160.36, 149.12, 140.82, 140.34, 136.10, 129.75,
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318.2205.
129.73, 128.30, 125.74, 124.15, 121.63, 32.D96O,I:3110..71023,93/1C.73O0B,02192.3422B,
2-(2-butyl-6-methylphenyl)pyridine (3oa). Colorless liquid (9.5 28.98, 22.66, 14.12. HRMS (ESI-TOF) m/z: calcd for C18H23NNa+:
mg, 21%). 1H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 4.4 Hz, 1H), 7.86 – 276.1723 (M + Na)+, found: 276.1729.
7.76 (m, 1H), 7.35 – 7.26 (m, 3H), 7.21 – 7.11 (m, 2H), 2.37 (t, J = 7.9
2-(2,6-diheptylphenyl)pyridine (3bb-di). Colorless liquid (8.4
Hz, 2H), 2.06 (s, 3H), 1.43 (d, J = 7.4 Hz, 2H), 1.25 – 1.12 (m, 2H), mg, 12%). 1H NMR (400 MHz, CDCl3) δ 8.75 (dd, J = 5.9, 1.6 Hz, 1H),
0.78 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 159.85, 149.50, 7.78 (ddd, J = 7.7, 7.7, 1.8 Hz, 1H), 7.30 (d, J = 6.5 Hz, 3H), 7.15 (d, J
140.65, 140.20, 136.05, 135.86, 127.91, 127.46, 126.64, 124.72, = 7.6 Hz, 2H), 2.41 – 2.27 (m, 4H), 1.53 – 1.35 (m, 4H), 1.28 – 1.22
121.64, 33.33, 33.11, 22.52, 20.34, 13.79. HRMS (ESI-TOF) m/z: (m, 4H), 1.16 (s, 12H), 0.87 (t, J = 7.1 Hz, 6H). 13C NMR (101 MHz,
calcd for C16H19NNa+: 248.1410 (M + Na)+, found: 248.1413.
CDCl3) δ 159.69, 149.28, 140.78, 139.83, 135.73, 127.94, 126.51,
2-(2-butyl-4,6-difluorophenyl)pyridine (3pa). Colorless liquid 125.03, 121.60, 33.57, 31.67, 31.12, 29.50, 28.92, 22.64, 14.10.
1
(9.9 mg, 20%). H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 4.2 Hz, 1H), HRMS (ESI-TOF) m/z: calcd for C25H37NNa+: 374.2818 (M + Na)+,
7.82 (td, J = 7.7, 1.8 Hz, 1H), 7.43 – 7.31 (m, 2H), 6.88 (d, J = 9.5 Hz, found: 374.2818
1H), 6.78 (td, J = 9.3, 2.4 Hz, 1H), 2.63 – 2.50 (m, 2H), 1.43 (dt, J =
2-(2-(3-phenylpropyl)phenyl)pyridine (3bc). White solid (33.8
1
15.3, 7.5 Hz, 2H), 1.22 (dq, J = 14.5, 7.3 Hz, 2H), 0.80 (t, J = 7.3 Hz, mg, 62%) . H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.2 Hz, 1H), 7.75
3H). 13C NMR (101 MHz, CDCl3) δ 153.54, 149.60, 145.61（t, JCF
=
(t, J = 7.7 Hz, 1H), 7.40 (t, J = 17.2 Hz, 5H), 7.32 – 7.25 (m, 3H), 7.25
– 7.17 (m, 1H), 7.13 (d, J = 7.4 Hz, 2H), 2.84 (t, J = 7.6 Hz, 2H), 2.59 (t,
J = 7.5 Hz, 2H), 1.92 – 1.80 (m, 2H). 13C NMR (101 MHz, CDCl3) δ
5.36 Hz）, 136.19, 125.81, 122.45, 111.96 (d, JCF = 3.32 Hz), 111.78
（d, JCF = 3.36 Hz）, 101.54, 101.28, 101.02, 32.70, 32.56, 22.30,
13.71. HRMS (ESI-TOF) m/z: calcd for C15H15F2NNa+: 270.1065 (M + 160.26, 149.23, 142.31, 140.48, 140.35, 136.19, 129.91, 128.45,
Na)+, found: 270.1057.
128.28, 126.02, 125.68, 124.10, 121.69, 35.77, 32.87, 32.72. HRMS
2-(2-butylnaphthalen-1-yl)pyridine (3qa). Colorless liquid (ESI-TOF) m/z: calcd for C20H19NNa+: 296.1410 (M + Na)+, found:
1
(12.5 mg, 24%). H NMR (400 MHz, CDCl3) δ 8.86 (d, J = 4.1 Hz, 1H), 296.1409.
7.88 (t, J = 7.5 Hz, 3H), 7.51 – 7.47 (m, 1H), 7.46 – 7.34 (m, 4H), 7.28
2-(2,6-bis(3-phenylpropyl)phenyl)pyridine (3bc-di). White
(s, 1H), 2.57 (t, J = 7.9 Hz, 2H), 1.56 (dtd, J = 20.7, 13.4, 7.2 Hz, 2H), solid (14.86 mg, 19%). 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 4.3 Hz,
1.25 (dt, J = 14.5, 7.3 Hz, 2H), 0.83 (t, J = 7.3 Hz, 3H). 13C NMR (101 1H), 7.75 – 7.64 (m, 1H), 7.34 – 7.21 (m, 7H), 7.18 (dd, J = 7.3, 5.4 Hz,
MHz, CDCl3) δ 158.94, 149.73, 138.35, 136.48, 136.04, 132.57, 4H), 7.07 (d, J = 7.2 Hz, 4H), 2.50 (t, J = 7.6 Hz, 4H), 2.40 (t, J = 8.0 Hz,
132.02, 128.24, 127.83, 127.75, 126.05, 125.85, 125.64, 124.91, 4H), 1.88 – 1.67 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 159.33,
121.99, 33.57, 33.31, 22.61, 13.85. HRMS (ESI-TOF) m/z: calcd for 149.35, 142.20, 140.30, 140.04, 135.75, 128.33, 128.17, 128.06,
C15H11NNa+: 288.0784 (M + Na)+, found: 288.0781.
126.75, 125.55, 124.85, 121.67, 35.75, 33.22, 32.55. HRMS (ESI-TOF)
1-(2-butylphenyl)-1H-pyrazole (3ra). Colorless liquid (7.2 mg, m/z: calcd for C29H29NNa+: 414.2192 (M + Na)+, found: 414.2192.
18%). 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 1.2 Hz, 1H), 7.62 (d, J =
5-(2-(pyridin-2-yl)phenyl)pentanenitrile (3bd). Colorless liquid
1
2.2 Hz, 1H), 7.44 – 7.36 (m, 2H), 7.35 – 7.29 (m, 2H), 6.48 (t, J = 1.8 (24.0 mg, 51%). H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.7 Hz, 1H),
Hz, 1H), 2.67 – 2.53 (m, 2H), 1.51 – 1.39 (m, 2H), 1.34 – 1.22 (m, 3H), 7.80 (t, J = 7.0 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.37 (d, J = 4.9 Hz,
0.86 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 140.16, 139.70, 2H), 7.31 (dd, J = 11.8, 5.9 Hz, 3H), 2.80 (t, J = 7.5 Hz, 2H), 2.23 (t, J =
139.01, 130.76, 130.30, 128.63, 126.70, 126.44, 106.09, 32.79, 6.9 Hz, 2H), 1.73 – 1.62 (m, 2H), 1.62 – 1.52 (m, 2H). 13C NMR (101
30.99, 22.50, 13.81. HRMS (ESI-TOF) m/z: calcd for C13H16N2Na+: MHz, CDCl3) δ 160.12, 149.12, 140.36, 139.36, 136.47, 129.95,
223.1206 (M + Na)+, found: 223.1205.
129.79, 128.50, 126.25, 124.12, 121.87, 119.70, 31.94, 30.08, 24.98,
2-(2-butylphenyl)pyrimidine (3sa). Colorless liquid (8.1 mg, 16.83. HRMS (ESI-TOF) m/z: calcd for C16H16N2Na+: 259.1206 (M +
19%). 1H NMR (400 MHz, CDCl3) δ 8.88 (t, J = 7.6 Hz, 1H), 7.75 (d, J = Na)+, found: 259.1202.
7.3 Hz, 1H), 7.46 – 7.38 (m, 1H), 7.38 – 7.32 (m, 1H), 7.27 (t, J = 4.8
2-(2-(4-methoxybutyl)phenyl)pyridine (3be). White solid (24.0
1
Hz, 1H), 3.05 – 2.87 (m, 1H), 1.58 – 1.43 (m, 1H), 1.35 – 1.21 (m, 2H), mg, 50%). H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.6 Hz, 1H), 7.78
0.86 (t, J = 7.3 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 168.08, 156.90, (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.39 – 7.33 (m,
141.97, 138.04, 130.50, 130.39, 129.38, 125.88, 118.59, 33.73, 3H), 7.32 – 7.25 (m, 2H), 3.32 – 3.26 (m, 5H), 2.77 (t, J = 7.2 Hz, 2H),
33.08, 22.60, 13.89. HRMS (ESI-TOF) m/z: calcd for C14H16N2Na+: 1.63 – 1.45 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 160.27, 149.11,
235.1206 (M + Na)+, found: 235.1209.
140.33, 140.32, 136.19, 129.79, 129.73, 128.34, 125.88, 124.16,
2-(2,6-dibutylphenyl)pyrimidine (3sa-di). Colorless liquid (5.9 121.67, 72.54, 58.49, 32.64, 29.35, 27.76. HRMS (ESI-TOF) m/z:
mg, 11%). 1H NMR (400 MHz, CDCl3) δ 8.91 (d, J = 4.9 Hz, 1H), 7.37 – calcd for C16H19NNaO+: 264.1359 (M + Na)+, found: 264.1361.
7.29 (m, 1H), 7.16 (d, J = 7.6 Hz, 1H), 2.49 – 2.27 (m, 2H), 1.53 – 1.37
2-(2-isobutylphenyl)pyridine (3bf). Colorless liquid (11.4 mg,
(m, 2H), 1.26 – 1.11 (m, 2H), 0.78 (t, J = 7.3 Hz, 2H). 13C NMR (101 27%). 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 4.3 Hz, 1H), 7.78 (ddd,
MHz, CDCl3) δ 168.64, 156.79, 140.28, 138.54, 128.43, 126.72, J = 7.7, 7.7, 1.6 Hz, 1H), 7.48 – 7.22 (m, 6H), 2.68 (d, J = 7.2 Hz, 2H),
118.83, 33.15, 33.07, 22.54, 13.79. HRMS (ESI-TOF) m/z: calcd for 1.70 – 1.58 (m, 1H), 0.76 (d, J = 6.6 Hz, 6H). 13C NMR (101 MHz,
C18H24N2Na+: 291.1832 (M + Na)+, found: 291.1832.
CDCl3) δ 160.58, 149.08, 140.74, 139.58, 136.09, 130.56, 129.79,
2-(2-heptylphenyl)pyridine (3bb). Colorless liquid (30.4 mg, 128.03, 125.84, 124.29, 121.57, 42.05, 29.81, 22.43. HRMS (ESI-TOF)
60%). 1H NMR (400 MHz, CDCl3) δ 8.73 (dd, J = 4.8, 0.7 Hz, 1H), 7.78 m/z: calcd for C15H17NNa+: 234.1253 (M + Na)+, found: 234.1250.
(ddd, J = 7.7, 7.7, 1.6 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.40 – 7.34 (m,
2-(2,6-diisobutylphenyl)pyridine (3bf-di). Colorless liquid (5.9
3H), 7.30 (ddd, J = 7.5, 6.7, 4.9 Hz, 2H), 2.74 (t, J = 7.9 Hz, 2H), 1.56 – mg, 11%). 1H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 4.7 Hz, 1H), 7.77
1.43 (m, 2H), 1.29 – 1.16 (m, 8H), 0.88 (t, J = 7.0 Hz, 3H). 13C NMR (t, J = 8.1 Hz, 1H), 7.27 (d, J = 7.7 Hz, 3H), 7.13 (d, J = 7.6 Hz, 2H),
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Organic & Biomolecular Chemistry
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Organic &Biomolecular Chemistry
2.35 – 2.17 (m, 4H), 1.68 – 1.58 (m, 2H), 0.83 – 0.68 (m, 12H). 13C
NMR (101 MHz, CDCl3) δ 159.75, 149.14, 140.58, 139.52, 135.59,
127.54, 127.33, 125.50, 121.51, 42.78, 29.41, 22.68, 22.43. HRMS
(ESI-TOF) m/z: calcd for C19H25NNa+: 290.1879 (M + Na)+, found:
290.1880.
5
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Sanford, Chem. Rev., 2010, 110, 1147−1169.
Although this type of cyclometalated products, comprising
one chelating heteroatom, are not metallacycles in the strict
sense of the word, the conventions are not rigidly followed,
and they are still often treated as metallacycles. See
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2-(4-(2-(pyridin-2-yl)phenyl)butyl)isoindoline-1,3-dione (3bg).
1
White solid (56.9 mg, 80%). H NMR (400 MHz, CDCl3) δ 8.67 (d, J =
7
8
9
4.5 Hz, 1H), 7.92 – 7.78 (m, 2H), 7.71 (dd, J = 7.8, 6.1 Hz, 3H), 7.42 –
7.28 (m, 5H), 7.25 – 7.19 (m, 1H), 3.61 (t, J = 6.9 Hz, 2H), 2.80 (t, J =
7.3 Hz, 2H), 1.67 – 1.57 (m, 2H), 1.57 – 1.47 (m, 2H). 13C NMR (101
MHz, CDCl3) δ 168.35, 160.17, 149.09, 140.29, 139.96, 136.22,
133.86, 132.13, 129.81, 128.38, 125.99, 124.04, 123.14, 121.69,
37.78, 32.53, 28.36, 28.35. HRMS (ESI-TOF) m/z: calcd for
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