Palladium(II)-Catalyzed Oxidative Homo- and Cross-Coupling of Aryl ortho -sp2 C-H Bonds of Anilides at Room Temperature

Article abstract of DOI:10.1021/acs.joc.8b00120

The preparation of secondary 2,2'-bisanilides has been successfully achieved through an oxidative coupling of aryl ortho-sp² C-H bonds of anilides in the presence of catalytic Pd(OAc)₂ and K₂S₂O₈ as an oxidant in MsOH/CF₃CO₂H (TFA) at room temperature (25 °C). The aromatic rings of anilides substituted by various electron-donating or electron-withdrawing groups are tolerant in these coupling reactions.

Full text of DOI:10.1021/acs.joc.8b00120

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Palladium(II)-Catalyzed Oxidative Homo- and Cross-Coupling
of Aryl ortho-sp2C-H Bonds of Anilides at Room Temperature
Chong Mei, and Wenjun Lu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00120 • Publication Date (Web): 03 Apr 2018
Downloaded from http://pubs.acs.org on April 3, 2018
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Palladium(II)-Catalyzed Oxidative Homo- and Cross-Coupling of Aryl ortho-sp C-H Bonds
of Anilides at Room Temperature
Chong Mei and Wenjun Lu*
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Department of Chemistry, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240,
China
Eꢀmail: luwj@sjtu.edu.cn
R
1
O
R
2
NH
cat. Pd(OAc)
2
R
2
H
N
R4
H
N
R2
R
1
R
3
K
2
S
2
O
8
NH2
+
NH
2
O
O
MsOH/CF
3
CO
2
H
R
4
H
H
5 oC, 2~48 h
2
HN
O
R
4
R
3
R
R
1
, R
, R
3
= tBu, iPr, nPr, Et, Me, Ph, etc.
2 3
= MeO, Me, Et, F, Cl, Br, I, CO Et, CF , etc.
2
4
Homo-coupling: 38 examples, isolated yield up to 93%
Cross-coupling: 20 examples, isolated yield up to 73%, selectivity up to 98%
ABSTRACT: Preparation of secondary 2,2'ꢀbisanilides has been successfully achieved through an
2
oxidative coupling of aryl orthoꢀsp CꢀH bonds of anilides in the presence of catalytic Pd(OAc) and
2
o
K S O as an oxidant in MsOH/CF CO H (TFA) at room temperature (25 C). The aromatic rings of
2
2
8
3
2
anilides substituted by various electronꢀdonating or electronꢀwithdrawing groups are tolerant in
these coupling reactions.
2
,2'ꢀDiaminobiaryls are very important structural units in functional molecules, such as
1
2
organocatalysts and ligands for transitionꢀmetal catalysts. Among them, secondary 2,2'ꢀbisanilides
with their conformational isomers and stereodynamics are also greatly studied by medicinal and
3
synthetic chemists. Nevertheless, a traditional synthesis of symmetric 2,2'ꢀdiaminobiaryls is from
4
2
ꢀiodonitrobenzene through the Ullmann reaction followed by a reduction of nitro groups.
Unsymmetric 2,2'ꢀdiaminobiaryls can be prepared by the Suzuki−Miyaura reaction using two
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different prefunctionalized arenes. Obviously, these are multipleꢀstep processes accompanying
with many wastes generated.
2
Currently direct oxidative homocoupling of aryl sp CꢀH bonds of aryl amines or anilides to afford
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,2'ꢀdiaminobiaryl products is limited to electronꢀrich substrates such as naphthylamine or
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dimethoxyanilide. On the other hand, the examples of oxidative crossꢀcoupling are reported rarely,
7
and the yields of dimerization products are poor. Most recently, Waladvogel and coꢀworkers
disclosed a direct anodic crossꢀcoupling of anilides to give unsymmetric 2,2'ꢀbisanilides in 40ꢀ74%
o
8
yields at 50 C. However, it is still necessary that anilide substrates are more electronꢀrich arenes.
Herein, we present Pd(II)ꢀcatalyzed oxidative homoꢀ and crossꢀcouplings of various anilides with
2
electronꢀdonating groups (EDGs) or electronꢀwithdrawing groups (EWGs) via dual aryl sp CꢀH
activation to afford symmetric and unsymmetric 2,2'ꢀbisanilides respectively in moderate to
o
excellent yields at room temperature (25 C) (Scheme 1).
2
In fact, to establish a selectively oxidative coupling of simple aryl sp CꢀH bonds to form new aryl
2
2
9
sp Cꢀsp C bonds is always a challenge to researchers. In the past decade, some progress has been
2
made in the preparation of 2,2'ꢀbiaryls via aryl orthoꢀsp CꢀH bond activation in transitionꢀmetal
(TM) catalysis. For example, Sanford and coꢀworkers reported the first synthesis of symmetric
2
,2'ꢀbiaryls through Pd(II)ꢀcatalyzed oxidative homoꢀcoupling of 2ꢀphenylpyridine derivatives
o
10,11
using Oxone as an oxidant at 25 C in 2006.
Since then, other directingꢀgroupꢀcontaining arenes
1
2a
12b
12c
12d
including phenylacetamides, aryloxazolines, benzoic acids, amioquinoline benzamides,
12e
benzophenones,
etc. have been found to proceed transitionꢀmetalꢀcatalyzed dimerization
2
smoothly via aryl orthoꢀsp CꢀH bond activation. In these oxidative coupling reactions, either
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electronꢀrich or electronꢀdeficient arenes can be employed as substrates generally. However,
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although amides are the more effective directing groups in many functionalizations of aryl sp CꢀH
1
3
bonds, oxidative coupling of anilides to prepare their 2,2'ꢀbiaryls has not been achieved in
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homogeneous palladium catalysis until now.
Scheme 1. Oxidative Couplings of Anilides
Homo-Coupling Reaction
It is found that Pd(OAc) (catalyst)/K S O (oxidant)/acid CF CO H (TFA) system is very
2
2
2
8
3
2
15
16
effective to the oxidative coupings of various simple arenes and βꢀacyloxylation of primary
3
sp CꢀH bond directed by simple amide group. Based on these reports, the Pd(II) catalytic system
was chosen initially in the oxidative homoꢀcoupling of anilides. An anilide substituted by a weak
electronꢀwithdrawing group (EWG), Nꢀ(pꢀchlorophenyl)pivalamide 1a was employed as a test
substrate, and the results are listed in Table 1.
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o
In TFA at room temperature (25 C), the target homoꢀcoupling product, 2,2'ꢀbisanilide 2aa was
detected just in 37% yield with a 73% conversion of 1a. (Table 1, Entry 1) Many byproducts
including phenol and 1,4ꢀbenzoquinone derivative were formed by oxidations of 1a at the same time.
When acetic acid (AcOH) and 2,2,2ꢀtrifluoroethanol (TFE) was used instead of TFA respectively,
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o
o
2
aa was not found at 25 C. After the temperature was up to 80 C, acyloxylation or alkyloxylation
obviously happened, but 2aa was still not produced in these weak acidic solvents. (Entries 2 and 3)
In a neutral solvent 1,2ꢀdichloroethane (DCE), no effective reactions were observed. (Entry 4)
o
However, in a more acidic solvent methanesulfonic acid (MsOH) at 25 C, 2aa was formed in 42%
yield, a little better than in TFA, but the substrate 1a was decomposed much more. (Entry 5) Then,
we tried to adjust the acidity and to control the amount of acidic solvent for accelerating the reaction
rate of homoꢀcoupling of 1a in this catalytic system. Gratefully, after many studies, it was found that
the yield of homoꢀcoupling product 2aa could be improved to 75% when MsOH/TFA (1:1, 10 equiv)
o
was used as a mixed solvent at 25 C (Entry 6). Certainly, dimerization products could not be
prepared in the absence of either Pd(OAc) or K S O . (Entries 7 and 8) In contrast, although the
2
2
2
8
homoꢀcoupling of 1a could occur, other oxidants including Na S O , (NH ) S O , and Oxone were
2
2
8
4 2
2
8
not as effective as K S O under the similar conditions. (Entries 9−11) Thus, an effective catalytic
2
2
8
system, Pd(OAc) /K S O /MsOH/TFA was established for the oxidative coupling of anilides at
2
2
2
8
room temperature.
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Table 1. Pd(II)-Catalyzed Homo-Coupling of N-(p-chlorophenyl)pivalamide (1a) to Give Its
a
2
,2'-Bisanilide (2aa)
1
1
1
1
1
1
1
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2
2
2
2
2
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6
0
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0
entry
oxidant
K S O
solvent
conv.
%)
73
yield of
2aa(%)
(
1
2
TFA
AcOH
37
ꢀ
2
2
8
8
K S O
<1,
2
2
b
b
3
5
ꢀ
b
3
4
K S O
TFE
DCE
MsOH
39
7
84
trace
ꢀ
42
2
2
8
8
8
b
K S O
2
2
5
K S O
2
2
6
7
8
9
K S O
MsOH/TFA >99
MsOH/TFA <1
MsOH/TFA 25
MsOH/TFA 46,d
46
75(69)
ꢀ
ꢀ
2
2
8
c
K S O
8
2
2
ꢀ
Na S O
32,
2
2
8
d
32
10
11
(NH ) S O
8
Oxone
MsOH/TFA >99
MsOH/TFA 89
68
47
4
2
2
a
Conditions: substrate (0.4 mmol, 1 equiv), Pd(OAc) (8 mol %), oxidant (1 equiv), solvent (0.2 mL),
2
1
MsOH/TFA= 1:1, 18 h. Yield based on substrate and determined by H NMR, CH Br as an internal
2
2
b
o
c
d
standard. Isolated yield in parentheses. 80 C. Without Pd(OAc) . 36 h.
2
In the investigation of the reaction scope, many Nꢀphenylpivalamides with various substituted
groups were tested. As shown in Table 2, for the anilides containing EDGs such as ꢀMe and ꢀEt
group, the isolated yields of all 2,2'ꢀbisanilides were from 62% to 93% in the presence of only 4 mol %
o
Pd(OAc) with a ratio of MsOH/TFA 1:3 at 25 C. Under the identical conditions, the simple
2
Nꢀphenylpivalamide
1b
could
give
its
2,2'ꢀbisanilide
2bb
(
N,N'ꢀ([1,1'ꢀbiphenyl]ꢀ2,2'ꢀdiyl)bis(2,2ꢀdimethylpropanamide)) in 56%. When there were alkyl
substituted groups at metaꢀposition of Nꢀphenylpivalamides, the excellent yields (over 90%) of
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dimerization products were obtained in short time. In contrast, for those anilides with EWGs, more
loading of catalyst (8 mol % Pd(OAc) ) with more acidic solvent (MsOH/TFA1:1) was necessary in
2
the homoꢀcoupling reactions. All halogen atoms including F, Cl, Br, and I as substituted groups on
Nꢀphenylpivalamides were available in these dimerization reactions and the yields were from 43%
to 83%. However, the anilides with very electronꢀdeficient groups such as ꢀCO Et , ꢀCF and ꢀNO
2
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give their corresponding 2,2'ꢀbisanilide in poor yields because the homoꢀcouplings were very slow
compared with either the decompositions at room temperature or the oxidations at higher
temperature in acidic solvents. Moreover, those anilides with steric hindered groups such as
Nꢀ(3,5ꢀdimethylphenyl)pivalamide 1v could not be dimerized under the conditions.
a
Table 2 Scope of Homo-Coupling of N-Phenylpivalamide
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Table 3 Homo-Coupling of Anilides with Different N-acyl groups
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Meanwhile, amides (–NHCOR) as the directing groups of anilides were also investigated, and the
results are listed in Table 3. Among these R groups (R = tBu, iPr, nPr, Et, Me and Ph), tBu group was
the first choice to give the highest yields in almost all cases, and iPr group was the second one. But
the performances of others were fluctuant with various substituted aromatic rings. When the
directing group was methylsulfonyl or trifluoroacetyl, the substrates would decompose more
quickly and no homoꢀcoupling products were obtained no matter how electronꢀrich the anilides
might be. Thus, it seems that more electronꢀdonating R groups are beneficial to the oxidative
dimerization reactions.
Cross-Coupling Reaction
It is more significant and difficult to establish any oxidative crossꢀcoupling of two different inert
CꢀH bonds. In the crossꢀcoupling of anilides, not only side reactions such as decomposition and
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oxidation but also homoꢀcoupling would be avoided if it is possible. However, as shown in Table 4,
the maximum selectivity of crossꢀcoupling product was ~50% when Nꢀ(mꢀtolyl)isobutyramide 1d1
and Nꢀ(mꢀethylphenyl)pivalamide 1g (1:1) were employed as substrate partners with similar
structure and chemical characters, which is consistent with the statistical distribution. A simple way
to enhance the selectivity is to choose two substrates with different reactivity in the crossꢀcoupling
reaction. Electronical and steric effects are still considered first. For example,
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Nꢀ(3,5ꢀdimethylphenyl)isobutyramide 1v with EDG and steric hindrance for orthoꢀposition was
1
used as one substrate since it underwent its homoꢀcoupling reaction hardly.
Nꢀ(pꢀchlorophenyl)pivalamide 1a with EWG was selected as the partner in their crossꢀcoupling
reaction. As expected, the selectivity was 90% with a product yield of 67% when the ratio of them
was 1:3. The ratio of MsOH/TFA was 1:1 to keep CꢀH activation of 1a happening very well. For
normal anilides without steric hindrance, the selectivity could be over 50% if one active anilide with
EDG and another inactive one with EWG were employed, and the ratio of substrates, the amount
and ratio of acidic solvent, loading of catalyst, etc. were tuned carefully in their crossꢀcouplings. In
the crossꢀcoupling of Nꢀ(mꢀtolyl)isobutyramide 1d with Nꢀ(pꢀchlorophenyl)pivalamide 1a, the
1
ratio of 1d /1a was down to 1:14 for blocking the homoꢀcoupling of active anilide 1d , and 100
1
1
equiv of MsOH/TFA (1:1) was added for reducing the homoꢀcoupling of inactive 1a by decreasing
the concentration of 1a. Meanwhile, more loading of Pd(OAc) (16 mol %) could accelerate the rate
2
of crossꢀcoupling of 1d with 1a. In this catalytic system at room temperature, the corresponding
1
unsymmetric 2,2'ꢀbisanilide was obtained as a major product in 68% yield with a crossꢀcoupling
selectivity of 67%.
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a
Table 4 Pd(II)-Catalyzed Cross-Coupling of Anilides
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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According to the above principles and methods on crossꢀcoupling reactions, many anilide
partners were studied further, as shown in Table 5. Anilides with different amide directing groups
and substituted by EDG such as ꢀMe or ꢀOMe group were chosen as active anilides (ArꢀH). Other
anilides with EWG including ꢀF, ꢀCl, ꢀBr, ꢀI, ꢀCF and ꢀCO Et group were inactive ones (Ar'ꢀH).
3
2
After tuning the ratio of substrates (ArꢀH/Ar'ꢀH), the amount of MsOH/TFA, reaction time and so on,
unsymmetric 2,2'ꢀbisanilides from two kinds of anilides were prepared in moderate isolated yields
(
49ꢀ73%) and all selectivites were over 50%. Of course, when an active anilide with steric hindered
1v was employed, the selectivites were very good, up to 98% and the ratios of substrates could be
1
:1. Interestingly, those inactive anilides containing very electronꢀdeficient groups such as ꢀCO Et
2
and ꢀCF could undergo the crossꢀcouplings very well at room temperature even though they were
3
not available in their homoꢀcouplings. Meanwhile, 1v could also react with 1d (9:1) substituted by
1
methyl group smoothly to afford an unsymmetric 2,2'ꢀbisanilide 2vd in 80% yield with a selectivity
1
of 95%, which is a crossꢀcoupling of two anilides with EDG groups.
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Table 5 Scope of Cross-Coupling of Anilides
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Furthermore, unsymmetric or symmetric 2,2'ꢀbisanilides (2) were readily converted to their
corresponding 2,2'ꢀdiaminobiaryls (3) as shown in experimental section and SI, which are very
useful compounds in synthesis.
In summary, oxidative homoꢀ and crossꢀcouplings of anilides to afford symmetric and
unsymmetric 2,2'ꢀbisanilides respectively have been established at room temperature. A catalytic
Pd(OAc) /K S O /MsOH/TFA system is very effective in these dimerization processes. Anilides not
2
2
2
8
only containing EDGs but also EWGs are available in the couplings. By tuning the ratio of reaction
partners and the amount of MsOH/TFA, the crossꢀcoupling products could be obtained as major
ones.
EXPERIMENTAL SECTION
General. All reagents and solvent were obtained from commercial sources and used without
further purification. Progress of reaction was monitored by thinꢀlayer chromatography (TLC) using
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silica gel F254 plates and UV detection at 254 and 365 nm. Purification of the coupling products
was performed by flash column chromatography using silica gel (200ꢀ300 mesh). Melting points
were measured with XT4A Microscopic Meltingꢀpoint Detector, produced by Beijing Keyi
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Electroꢀoptic Instrument Plant. H and C NMR spectra were recorded on a Bruker AVANCE III
HD 400 (400 MHz) spectrometer and referenced (calibrated) to residual solvent peaks: proton
(CDCl : 7.26 ppm, DMSOꢀd : 2.50 ppm) and carbon (CDCl : 77.160 ppm, DMSOꢀd : 39.520
3
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3
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ppm). Signal positions were recorded in δ ppm with the abbreviations s, d, t, q, sept., br., app. and m
19
denoting singlet, doublet, triplet, quartet, septet, broad, apparent and multiplet respectively.
F
NMR spectra were recorded on the same spectrometer listed above at 376 MHz and were referenced
in the same way. All NMR chemical shifts are quoted in ppm. All coupling constants, J, are quoted
in Hz. HRMS were measured with ACQUITYTM UPLC & QꢀTOF MS Premier.
General Procedure for the Preparation of Substrates. To a stirring solution of aniline (20
mmol), Et N (2.5298 g, 25 mmol) in CH Cl (50 mL), was added dropwise acyl chloride (20 mmol)
3
2
2
o
at 0 C (ice/water bath) for 10 minutes. Then, the reaction mixture was stirred at room temperature
overnight. Water (20 mL) was added to the crude mixture after the mixture was evaporated. After
that, the reaction mixture was extracted with ethyl acetate (30 mL×3), washed with brine (20
mL×2), and dried over anhydrous Na SO . Then, the extract was concentrated and recrystallization
2
4
from hexane/ethyl acetate mixture to afford the amide.
o
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N-(p-chlorophenyl)pivalamide (1a). white needle (3.60 g, 85% yield); m.p. 149–150 C (lit.
o
1
1
48ꢀ149 C); H NMR (400 MHz, CDCl ) δ 7.52 – 7.44 (m, 2H), 7.35 (s, 1H, br), 7.29 – 7.22 (m,
3
2H), 1.30 (s, 9H).
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N-phenylpivalamide (1b). white needles (2.66 g, 75% yield); m.p. 134–135 C (lit. 132–133
o
1
C); H NMR (400 MHz, CDCl ) δ 7.53 (d, J = 8.0 Hz, 2H), 7.36 (s, 1H, br), 7.31 (t, J = 8.0 Hz,
3
2
H), 7.09 (t, J = 7.4 Hz, 1H), 1.31 (s, 9H).
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13a
N-(o-tolyl)pivalamide (1c). white powder (3.25 g, 85% yield); m.p. 110–112 C (lit. 110–112
o
1
C); H NMR (400 MHz, CDCl ) δ 7.80 (d, J = 8.0 Hz, 1H), 7.30 (s, 1H, br), 7.24 – 7.12 (m, 2H),
3
7.06 (td, J = 7.6, 1.2 Hz, 1H), 2.23 (s, 3H), 1.33 (s, 9H).
o
13a
o
N-(m-tolyl)pivalamide (1d). white needles (3.18 g, 83% yield); m.p. 127–128 C (lit. 125 C);
1
H NMR (400 MHz, CDCl ) δ 7.43 (s, 1H), 7.30 – 7.25 (m, 2H), 7.19 (t, J = 8.0 Hz, 1H), 6.92 (d,
3
J = 7.2 Hz, 1H), 2.33 (s, 3H), 1.31 (s, 9H).
o
19
o
N-(p-tolyl)pivalamide (1e). white needles (2.49 g, 65% yield); m.p. 119–120 C (lit. 118 C);
1
H NMR (400 MHz, CDCl ) δ 7.40 (d, J = 8.4 Hz, 2H), 7.34 (s, 1H, br), 7.11 (d, J = 8.4 Hz, 2H),
3
2
.30 (s, 3H), 1.30 (s, 9H).
o
1
N-(2-ethylphenyl)pivalamide (1f). white solid (3.61 g, 88% yield); m.p. 103–105 C; H NMR
(
400 MHz, CDCl ) δ 7.88 (dd, J = 8.0, 1.2 Hz, 1H), 7.29 (s, 1H, br), 7.21 (m, 2H), 7.14 – 7.07 (m,
3
1
H), 2.60 (q, J = 7.6 Hz, 2H), 1.34 (s, 9H), 1.25 (t, J = 7.6 Hz, 3H).
o
20
N-(3-ethylphenyl)pivalamide (1g). white solid (3.04 g, 74% yield); m.p. 113–115 C (lit.
o
1
1
21–122 C); H NMR (400 MHz, CDCl ) δ 7.45 (t, J = 1.6 Hz, 1H), 7.30 (m, 2H), 7.23 (t, J = 7.8
3
Hz, 1H), 6.98 – 6.92 (m, 1H), 2.63 (q, J = 7.6 Hz, 2H), 1.32 (s, 9H), 1.23 (t, J = 7.6 Hz, 3H).
o
20
N-(4-ethylphenyl)pivalamide (1h). white solid (2.46 g, 60% yield); m.p. 106–108 C. (lit.
o
1
1
17–118 C); H NMR (400 MHz, CDCl ) δ 7.43 (d, J = 8.4 Hz, 2H), 7.36 (s, 1H, br), 7.13 (d, J =
3
8.8 Hz, 2H), 2.60 (q, J = 7.6 Hz, 2H), 1.30 (s, 9H), 1.21 (t, J = 7.6 Hz, 3H).
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N-(2,4-dimethylphenyl)pivalamide (1i). white solid (2.87 g, 70% yield); m.p. 112–114 C
21
o
1
(
lit. 111.5 C); H NMR (400 MHz, CDCl ) δ 7.65 (d, J = 7.6 Hz, 1H), 7.16 (s, 1H, br), 7.00 (m,
3
2
H), 2.29 (s, 3H), 2.21 (s, 3H), 1.33 (s, 9H).
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N-(3,4-dimethylphenyl)pivalamide (1j). white solid (2.71 g, 66% yield); m.p. 132–133 C
22
o
1
(
lit. 130 C); H NMR (400 MHz, CDCl ) δ 7.36 – 7.35 (m, 2H), 7.22 (dd, J = 8.4, 2.0 Hz, 1H),
3
7.04 (d, J = 8.0 Hz, 1H), 2.22 (s, 3H), 2.20 (s, 3H), 1.30 (s, 9H).
N-(4-bromo-3-methylphenyl)pivalamide (1k). white solid (3.78 g, 70% yield); m.p. 139–140
o
1
C; H NMR (400 MHz, CDCl ) δ 7.49 (d, J = 2.8 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.28 (s, 1H,
3
br), 7.20 (dd, J = 8.4, 2.8 Hz, 1H), 2.36 (s, 3H), 1.30 (s, 9H).
o
23
N-(3-fluorophenyl)pivalamide (1l). white solid (2.93 g, 75% yield); m.p. 110–112 C (lit.
o
1
112.5–113 C); H NMR (400 MHz, CDCl ) δ 7.56 (s, 1H, br), 7.51 (dt, J = 11.2, 2.4 Hz, 1H), 7.20
3
(
td, J = 8.0, 6.4 Hz, 1H), 7.13 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 6.76 (tdd, J = 8.2, 2.4, 1.0 Hz, 1H),
1
.29 (s, 9H).
o
24
N-(3-chlorophenyl)pivalamide (1m). white solid (2.96 g, 70% yield); m.p. 135–136 C (lit.
o
1
1
24–126 C); H NMR (400 MHz, CDCl ) δ 7.68 (t, J = 2.0 Hz, 1H), 7.41 – 7.29 (m, 2H), 7.23 (t,
3
J = 8.0 Hz, 1H), 7.13 – 7.01 (m, 1H), 1.31 (s, 9H).
o
25
N-(3-bromophenyl)pivalamide (1n). white solid (3.59 g, 70% yield); m.p. 144–145 C (lit.
o
1
1
37–138 C); H NMR (400 MHz, CDCl ) δ 7.80 (t, J = 2.0 Hz, 1H), 7.44 (s, 1H, br), 7.40 (ddd, J
3
=
8.0, 2.0, 1.2 Hz, 1H), 7.20 (ddd, J = 8.0, 2.0, 1.2 Hz, 1H), 7.14 (t, J = 8.0 Hz, 1H), 1.29 (s, 9H).
o
1
N-(3-iodophenyl)pivalamide (1o). pale solid (3.94 g, 65% yield); m.p. 146–147 C; H NMR
(400 MHz, CDCl ) δ 7.95 (t, J = 1.6 Hz, 1H), 7.47 (dd, J = 8.0, 1.6 Hz, 1H), 7.40 (m, 2H), 7.00 (t,
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J = 8.0 Hz, 1H), 1.29 (s, 9H).
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26
N-(4-fluorophenyl)pivalamide (1p). white solid (2.93 g, 75% yield); m.p. 123–124 C (lit.
o
1
1
2
21–123 C); H NMR (400 MHz, CDCl ) δ 7.56 – 7.41 (m, 2H), 7.30 (s, 1H, br), 7.06 – 6.95 (m,
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H), 1.31 (s, 9H).
o
27
N-(4-bromophenyl)pivalamide (1q). white needles (3.84 g, 75% yield); m.p. 152–153 C (lit.
o
1
150.3–151.8 C); H NMR (400 MHz, CDCl ) δ 7.43 (s, 4H), 7.30 (s, 1H, br), 1.31 (s, 9H).
3
o
28
N-(4-iodophenyl)pivalamide (1r). white solid (3.82 g, 63% yield); m.p. 147–149 C (lit. 150
o
1
C); H NMR (400 MHz, CDCl ) δ 7.68 – 7.55 (m, 2H), 7.42 – 7.27 (m, 3H), 1.30 (s, 9H).
3
o
25
ethyl 3-pivalamidobenzoate (1s). pale solid (3.99 g, 80% yield); m.p. 62–63 C (lit. 59–60
o
1
C); H NMR (400 MHz, CDCl ) δ 8.02 – 7.91 (m, 2H), 7.78 (dt, J = 7.6, 1.4 Hz, 1H), 7.48 – 7.35
3
(m, 2H), 4.38 (q, J = 7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H), 1.33 (s, 9H).
o
21
o
ethyl 4-pivalamidobenzoate (1t). white solid (3.79 g, 76% yield); m.p. 86–89 C (lit. 93 C);
1
H NMR (400 MHz, CDCl ) δ 8.05 – 7.93 (m, 2H), 7.67 – 7.58 (m, 2H), 7.48 (s, 1H, br), 4.35 (q, J
3
=
7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H), 1.33 (s, 9H).
N-(3-(trifluoromethyl)phenyl)pivalamide(1u). white solid (3.63 g, 74% yield); m.p. 107–108
o
29
o
1
C (lit. 107–109 C); H NMR (400 MHz, CDCl ) δ 7.85 (s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.45 (s,
3
1
H, br), 7.42 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H), 1.33 (s, 9H).
o
N-(3,5-dimethylphenyl)pivalamide (1v). white solid (2.42 g, 59% yield); m.p. 126ꢀ127 C
2
9
o
1
(
(
lit. 126–127 C); H NMR (400 MHz, CDCl ) δ 7.28 (s, 1H, br), 7.18 (s, 2H), 6.74 (s, 1H), 2.29
3
s, 6H), 1.30 (s, 9H).
o
30
N-(3-methoxyphenyl)pivalamide (1w). white solid (3.03 g, 73% yield); m.p. 123–125 C (lit.
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125–126 C); H NMR (400 MHz, CDCl ) δ 7.39 (t, J = 2.4 Hz, 1H), 7.32 (s, 1H, br), 7.20 (t, J =
3
8
1
.0 Hz, 1H), 6.93 (ddd, J = 8.0, 2.0, 0.8 Hz, 1H), 6.66 (ddd, J = 8.0, 2.4, 0.8 Hz, 1H), 3.81 (s, 3H),
.31 (s, 9H).
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2
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N-(3-nitrophenyl)pivalamide (1x). yellow solid (2.09 g, 47% yield); m.p. 108–109 C (lit.
o
1
1
08–109 C); H NMR (400 MHz, CDCl ) δ 8.39 (t, J = 2.2 Hz, 1H), 7.99 – 7.91 (m, 2H), 7.56 (s,
3
1H, br), 7.48 (td, J = 8.2, 1.6 Hz, 1H), 1.34 (s, 9H).
o
N-(4-chlorophenyl)isobutyramide (1a ). white solid (2.29 g, 58% yield); m.p. 149–150 C
1
32
o
1
(
lit. 149–150 C); H NMR (400 MHz, CDCl ) δ 7.47 (d, J = 8.8 Hz, 2H), 7.36 – 7.20 (m, 3H),
3
2
.49 (sept, J = 6.8 Hz, 1H), 1.23 (d, J = 6.8 Hz, 6H).
o
N-(4-chlorophenyl)propionamide (1a ). white solid (3.16 g, 86% yield); m.p. 137–139 C
2
33
o
1
(lit. 137–139 C); H NMR (400 MHz, CDCl ) δ 7.46 (m, 3H), 7.25 (dd, J = 8.8, 1.2 Hz, 2H),
3
2
.38 (q, J = 7.6 Hz, 2H), 1.23 (td, J = 7.6, 1.2 Hz, 3H).
o
34
N-(4-chlorophenyl)acetamide (1a ). white solid (2.75 g, 81% yield); m.p. 183–184 C (lit.
3
o
1
1
1
80–181 C); H NMR (400 MHz, CDCl ) δ 7.45 (d, J = 8.8 Hz, 2H), 7.33 – 7.26 (m, 2H), 7.24 (s,
3
H, br), 2.17 (s, 3H).
o
35
N-phenylisobutyramide (1b ). white solid (1.93 g, 59% yield); m.p. 104–105 C (lit. 104–105
1
o
1
C); H NMR (400 MHz, CDCl ) δ 7.53 (d, J = 7.6 Hz, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.21 (s, 1H,
3
br), 7.10 (t, J = 7.6 Hz, 1H), 2.51 (sept, J = 6.8 Hz, 1H), 1.26 (d, J = 6.8 Hz, 6H).
o
36
o
N-(m-tolyl)isobutyramide (1d ). white solid (2.76 g, 78% yield); m.p. 81–82 C (lit. 83 C);
1
1
H NMR (400 MHz, CDCl ) δ 7.42 (s, 1H), 7.37 – 7.27 (m, 2H), 7.18 (t, J = 7.6 Hz, 1H), 6.91 (d,
3
J = 7.6 Hz, 1H), 2.50 (sept, J = 6.8 Hz, 1H), 2.32 (s, 3H), 1.24 (d, J = 6.8 Hz, 6H).
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N-(m-tolyl)butyramide (1d ). white solid (3.44 g, 97% yield); m.p. 39–41 C; H NMR (400
2
MHz, CDCl ) δ 8.61 (s, 1H, br), 7.43 (s, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H),
3
6
.90 (d, J = 7.6 Hz, 1H), 2.34 (t, J = 7.4 Hz, 2H), 2.27 (s, 3H), 1.80 – 1.69 (m, 2H), 0.97 (t, J = 7.4
0
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6
7
8
9
0
Hz, 3H).
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N-(m-tolyl)propionamide (1d ). white solid (2.29 g, 70% yield); m.p. 77–78 C (lit. 79–81
3
o
1
C); H NMR (400 MHz, CDCl ) δ 7.39 (s, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.24 – 7.15 (m, 2H),
3
6
.91 (d, J = 7.6 Hz, 1H), 2.38 (q, J = 7.6 Hz, 2H), 2.33 (s, 3H), 1.24 (t, J = 7.6 Hz, 3H).
o
38
o
N-(m-tolyl)acetamide (1d ). cream solid (2.75 g, 92% yield); m.p. 64–66 C (lit. 64–66 C);
4
1
H NMR (400 MHz, CDCl ) δ 8.13 (s, 1H, br), 7.36 (s, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.16 (t, J =
3
7
.6 Hz, 1H), 6.90 (d, J = 7.6 Hz, 1H), 2.29 (s, 3H), 2.14 (s, 3H).
o
39
N-(m-tolyl)benzamide (1d ). gray solid (3.59 g, 85% yield); m.p. 123–124 C (lit. 124–125
5
o
1
C); H NMR (400 MHz, CDCl ) δ 7.90 – 7.81 (m, 3H), 7.57 – 7.51 (m, 2H), 7.50 – 7.44 (m, 2H),
3
7
.42 (d, J = 8.0 Hz, 1H), 7.25 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 7.6 Hz, 1H), 2.36 (s, 3H).
o
36
N-(p-tolyl)isobutyramide (1e ). white solid (2.34 g, 66% yield); m.p. 107–108 C (lit. 108–
1
o
1
1
09 C); H NMR (400 MHz, CDCl ) δ 7.84 (s, 1H, br), 7.42 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0
3
Hz, 2H), 2.51 (sept, J = 6.8 Hz, 1H), 2.29 (s, 3H), 1.21 (d, J = 6.8 Hz, 6H).
o
1
N-(2-ethylphenyl)isobutyramide (1f ). white solid (2.30 g, 60% yield); m.p. 104–106 C; H
1
NMR (400 MHz, CDCl ) δ 7.84 (d, J = 8.0 Hz, 1H), 7.25 – 7.17 (m, 2H), 7.12 (t, J = 7.2 Hz, 1H),
3
7
.04 (s, 1H, br), 2.67 – 2.51 (m, 3H), 1.29 (d, J = 7.2 Hz, 6H), 1.24 (t, J = 7.4 Hz, 3H).
o
N-(3,4-dimethylphenyl)isobutyramide (1j ). white solid (2.68 g, 70% yield); m.p.137–138 C
1
40
o
1
(lit. 137 C); H NMR (400 MHz, CDCl ) δ 7.35 (d, J = 1.6 Hz, 1H), 7.25 (s, 1H, br), 7.22 (dd, J
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= 8.0, 2.0 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 2.49 (sept, J = 6.8 Hz, 1H), 2.22 (s, 3H), 2.21 (s, 3H),
1
.23 (d, J = 6.8 Hz, 6H).
o
41
N-(3,4-dimethylphenyl)butyramide (1j ). white solid (3.06 g, 80% yield); m.p. 74–75 C (lit.
2
1
1
1
1
1
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1
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8
9
0
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o
1
7
1.5–72.5 C); H NMR (400 MHz, CDCl ) δ 7.48 (s, 1H, br), 7.32 (s, 1H), 7.23 (dd, J = 8.0, 1.6
3
Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 2.30 (t, J = 7.6 Hz, 2H), 2.21 (s, 3H), 2.20 (s, 3H), 1.80 – 1.68
(m, 2H), 0.98 (t, J = 7.6 Hz, 3H).
o
N-(3,4-dimethylphenyl)propionamide (1j ). white solid (2.84 g, 80% yield); m.p. 103–104 C
3
41
o
1
(
lit. 105.5–106.5 C); H NMR (400 MHz, CDCl ) δ 7.66 (s, 1H, br), 7.32 (d, J = 2.0 Hz, 1H),
3
7
.23 (dd, J = 8.0, 2.4 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 2.35 (q, J = 7.6 Hz, 2H), 2.20 (s, 6H), 1.21
(
t, J = 7.6 Hz, 3H).
o
41
N-(3,4-dimethylphenyl)acetamide (1j ). white solid (2.81 g, 86% yield); m.p. 96–98 C (lit.
4
o
1
9
6
7–98 C); H NMR (400 MHz, CDCl ) δ 8.41 (s, 1H, br), 7.26 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H),
3
.99 (d, J = 8.0 Hz, 1H), 2.16 (s, 3H), 2.15 (s, 3H), 2.09 (s, 3H).
o
N-(3,5-dimethylphenyl)isobutyramide (1v ). white solid (2.14 g, 56% yield); m.p. 149–151 C
1
40
o
1
(
lit. 143 C); H NMR (400 MHz, CDCl ) δ 7.32 (s, 1H, br), 7.18 (s, 2H), 6.73 (s, 1H), 2.49 (sept,
3
J = 6.8 Hz, 1H), 2.27 (s, 6H), 1.23 (d, J = 6.8 Hz, 6H).
o
N-(3-methoxyphenyl)isobutyramide (1w ). white solid (3.59 g, 93% yield); m.p. 60–61 C
1
36
o
1
(
lit. 60–61 C); H NMR (400 MHz, CDCl ) δ 7.54 (s, 1H, br), 7.37 (t, J = 2.0 Hz, 1H), 7.18 (t, J
3
=
8.0 Hz, 1H), 6.97 (dd, J = 8.0, 1.2 Hz, 1H), 6.64 (dd, J = 8.0, 2.0 Hz, 1H), 3.77 (s, 3H), 2.51
(
sept, J = 6.8 Hz, 1H), 1.23 (d, J = 6.8 Hz, 6H).
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General Procedure 1A for the Homo-Coupling Reaction. Amide (0.4 mmol), Pd(OAc) (3.6
2
mg, 0.016 mmol, 4 mol %), Potassium persulfate (108.1 mg, 0.4 mmol, 1 equiv),
2
0
,2,2ꢀtrifluoroacetic acid (342.1 mg, 3.0 mmol, 0.15 mL), methanesulfonic acid (96.1 mg, 1.0 mmol,
0
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0
o
.05 mL) were added in 35 mL seal tube. The reaction mixture was stired at 25 C for 3 h. After that,
saturated NaHCO (10.0 mL) was added to it. The solution was extracted with CH Cl (10 mL×3)
3
2
2
and washed with brine (10 mL), and dried over anhydrous Mg SO . Then, the extract was
2
4
concentrated and the residue was purified by flash column chromatography on silica gel to give
product.
General Procedure 1B for the Homo-Coupling Reaction. Amide (0.4 mmol), Pd(OAc) (7.2
2
mg, 0.032 mmol, 8 mol %), Potassium persulfate (108.1 mg, 0.4 mmol, 1 equiv),
2,2,2ꢀtrifluoroacetic acid (228.0 mg, 2.0 mmol, 0.10 mL), methanesulfonic acid (192.2 mg, 2.0
o
mmol, 0.10 mL) were added in 35 mL seal tube. The reaction mixture was stired at 25 C for 18 h.
After that, saturated NaHCO (10.0 mL) was added to it. The solution was extracted with CH Cl
2
3
2
(
10 mL×3) and washed with brine (10 mL), and dried over Mg SO . Then, the extract was
2 4
concentrated and the residue was purified by flash column chromatography on silica gel to give
product.
General Procedure 1C for the Homo-Coupling Reaction. Amide (1.6 mmol, 4 equiv),
Pd(OAc)2 (7.2 mg, 0.032 mmol, 8 mol %), Potassium persulfate (108.1 mg, 0.4 mmol),
2
0
,2,2ꢀtrifluoroacetic acid (342.1 mg, 3.0 mmol, 0.15 mL), methanesulfonic acid (96.1 mg, 1.0 mmol,
o
.05 mL) were added in 35 mL seal tube. The reaction mixture was stired at 40 C for 48 h. After
that, saturated NaHCO (10.0 mL) was added to it. The solution was extracted with CH Cl (20
3
2
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mL×3) and washed with brine (10 mL), and dried over Mg SO . Then, the extract was concentrated
2
4
and the residue was purified by flash column chromatography on silica gel to give product.
N,N'-(5,5'-dichloro-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2aa). The
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0
reaction was performed according to the general procedure 1B using amide 1a. Purification by
flash column chromatography eluting with petroleum ether/dichloromethane (1/1, v/v) gave 2aa
o
1
(58.0 mg. yield: 69%) as white solid; m.p. 142–144 C; H NMR (400 MHz, CDCl ) δ 8.07 (d, J =
3
8
.8 Hz, 2H), 7.40 (dd, J = 8.8, 2.4 Hz, 2H), 7.20 (s, 2H, br), 7.19 (d, J = 2.4 Hz, 2H), 1.02 (s, 18H);
13
C NMR (100 MHz, CDCl ) δ 177.2, 134.5, 130.3, 130.1, 129.8, 129.7, 124.6, 39.7, 27.2; HRMS
3
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+Na] calcd for C H Cl N NaO 443.1264; found
22 26
2
2
2
4
43.1262.
N,N'-([1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2bb). The reaction was
performed according to the general procedure 1A using amide 1b. Purification by flash column
chromatography eluting with petroleum ether/dichloromethane (1/1, v/v) gave 2bb (39.2 mg, 56%
o
1
yield) as white solid; m.p. 120–122 C; H NMR (400 MHz, CDCl ) δ 8.29 (d, J = 8.4 Hz, 2H), 7.49
3
13
–
7.40 (m, 2H), 7.26 – 7.21 (m, 4H), 7.18 (s, 2H, br), 0.99 (s, 18H); C NMR (100 MHz, CDCl ) δ
3
176.9, 136.1, 129.9, 129.7, 128.3, 124.8, 122.1, 39.7, 27.3. HRMS (ESIꢀQ/TOF MS) with
+
Acetonitrile (m/z): [M+H] calcd for C H N O 353.2224; found 353.2234.
22
29
2
2
N,N'-(3,3'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2cc). The
reaction was performed according to the general procedure 1A in 9h using amide 1c. Purification
by flash column chromatography eluting with petroleum ether/ethyl acetate (4/1, v/v) gave 2cc
o
1
(52.3 mg, 69% yield) as white solid; m.p. 245–246 C; H NMR (400 MHz, CDCl ) δ 7.40 (s, 2H,
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br), 7.20 (dd, J = 7.2, 1.2 Hz, 2H), 7.15 (t, J = 7.6 Hz, 2H), 6.93 (dd, J = 7.2, 0.8 Hz, 2H), 2.21 (s, 6H),
1
3
0
.95 (s, 18H); C NMR (100 MHz, CDCl ) δ 178.3, 138.4, 137.0, 134.3, 129.9 (two overlapped
3
+
peaks), 126.9, 38.9, 27.3, 18.2; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for
0
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C H N O 381.2537; found 381.2546.
24 33
2
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N,N'-(4,4'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2dd). The
reaction was performed according to the general procedure 1A using amide 1d. Purification by
flash column chromatography eluting with petroleum ether/ethyl acetate (10/1, v/v) gave 2dd (70.8
o
1
mg, 93% yield) as yellow solid; m.p. 158–160 C; H NMR (400 MHz, CDCl ) δ 8.18 (s, 2H), 7.19
3
13
(
s, 2H, br), 7.06 (d, J = 7.6 Hz, 2H), 7.00 (dd, J = 7.6, 1.2 Hz, 2H), 2.39 (s, 6H), 0.99 (s, 18H);
C
NMR (100 MHz, CDCl ) δ 176.8, 139.7 136.0, 129.8, 125.3, 124.8, 122.0, 39.7, 27.2, 21.7; HRMS
3
+
(ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O 381.2537; found 381.2544.
24
33
2
2
N,N'-(5,5'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2ee). The
reaction was performed according to the general procedure 1A using amide 1e. Purification by
flash column chromatography eluting with petroleum ether/dichloromethane (1/1, v/v) gave 2ee
o
1
(
47.0 mg, 62% yield) as yellow solid; m.p. 140–142 C; H NMR (400 MHz, CDCl ) δ 8.12 (d, J =
3
8.4 Hz, 2H), 7.23 (dd, J = 8.4, 1.6 Hz, 2H), 7.15 (s, 2H, br), 7.02 (d, J = 1.6 Hz, 2H), 2.35 (s, 6H),
1
3
1
2
3
.00 (s, 18H); C NMR (100 MHz, CDCl ) δ 176.7, 134.3, 133.4, 130.3, 129.9, 128.7, 122.2, 39.6,
3
+
7.2, 20.9; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O
24
33
2
2
81.2537; found 381.2541.
N,N'-(3,3'-diethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2ff).
The
reaction was performed according to the general procedure 1A in 9h using amide 1f. Purification
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by flash column chromatography eluting with petroleum ether/ethyl acetate (5/1, v/v) gave 2ff (55.0
o
1
mg, 67% yield) as white solid; m.p. 193–196 C; H NMR (400 MHz, CDCl ) δ 7.41 (s, 2H, br),
3
7
.26 – 7.16 (m, 4H), 6.98 (dd, J = 6.4, 2.4 Hz, 2H), 2.67 – 2.49 (m, 4H), 1.17 (t, J = 7.6 Hz, 6H), 0.95
1
1
1
1
1
1
1
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1
1
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2
2
2
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3
4
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4
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0
1
2
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4
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6
7
8
9
0
1
2
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8
9
0
1
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7
8
9
0
1
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5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
(
s, 18H); C NMR (100 MHz, CDCl ) δ 178.6, 142.8, 139.0, 133.9, 128.2, 127.3, 127.1, 38.8, 27.3,
3
+
2
5.0, 14.7; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O
26
37
2
2
409.2850; found 409.2868.
N,N'-(4,4'-diethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2gg).
The
reaction was performed according to the general procedure 1A using amide 1g. Purification by
flash column chromatography eluting with petroleum ether/dichloromethane (1:1, v/v) gave 2gg
o
1
(
73.5 mg, 90% yield) as white solid; m.p. 134–135 C; H NMR (400 MHz, CDCl ) δ 8.22 (s, 2H),
3
7.18 (s, 2H, br), 7.12 (d, J = 7.6 Hz, 2H), 7.04 (dd, J = 7.6, 1.2 Hz, 2H), 2.70 (q, J = 7.6 Hz, 4H), 1.26
1
3
(
t, J = 7.6 Hz, 6H), 0.99 (s, 18H); C NMR (100 MHz, CDCl ) δ 176.8, 146.2, 136.2, 129.9, 125.1,
3
+
1
24.1, 121.0, 39.8, 29.1, 27.3, 15.8; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd
for C H N O 409.2850; found 409.2858.
26 37
2
2
N,N'-(5,5'-diethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2hh).
The
reaction was performed according to the general procedure 1A (solvent is only 10 equiv TFA) in
4
8h using amide 1h. Purification by flash column chromatography eluting with petroleum
o
1
ether/ethyl acetate (5/1, v/v) gave 2hh (30.2 mg, 37% yield) as yellow solid; m.p. 81–84 C; H
NMR (400 MHz, CDCl ) δ 8.13 (d, J = 8.4 Hz, 2H), 7.26 (dd, J = 8.4, 2.0 Hz, 2H), 7.18 (s, 2H, br),
3
13
7
.05 (d, J = 2.0 Hz, 2H), 2.64 (q, J = 7.6 Hz, 4H), 1.23 (t, J = 7.6 Hz, 6H), 0.99 (s, 18H); C NMR
(100 MHz, CDCl ) δ 176.9, 140.9, 133.7, 129.0, 128.9, 128.9, 122.4, 39.6, 28.4, 27.3, 15.9; HRMS
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5
5
6
+
(ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O 409.2850; found 409.2853.
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2
N,N'-(3,3',5,5'-tetramethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2ii).
The reaction was performed according to the general procedure 1A in 4h using amide 1i.
0
1
2
3
4
5
6
7
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9
0
1
2
3
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9
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0
Purification by flash column chromatography eluting with petroleum ether/ethyl acetate (5/1, v/v)
o
1
gave 2ii (59.2 mg, 72% yield) as white solid; m.p. 255–258 C; H NMR (400 MHz, CDCl ) δ 7.23
3
13
(s, 2H, br), 7.01 (s, 2H), 6.79 (s, 2H), 2.27 (s, 6H), 2.17 (s, 6H), 0.96 (s, 18H); C NMR (100 MHz,
CDCl ) δ 178.4, 138.2, 136.6, 136.5, 131.6, 130.4, 127.4, 38.9, 27.3, 21.0, 18.1; HRMS
3
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O 409.2850; found 409.2851.
26
37
2
2
N,N'-(4,4',5,5'-tetramethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2jj).
The reaction was performed according to the general procedure 1A using amide 1j. Purification by
flash column chromatography eluting with petroleum ether/ethyl acetate (6/1, v/v) gave 2jj (71.9
o
1
mg, 88% yield) as white solid; m.p. 168–171 C; H NMR (400 MHz, CDCl ) δ 8.08 (s, 2H), 7.18 (s,
3
13
2
1
H, br), 6.94 (s, 2H), 2.29 (s, 6H), 2.23 (s, 6H), 1.00 (s, 18H); C NMR (100 MHz, CDCl ) δ 176.8,
3
37.9, 133.7, 132.9, 131.0, 125.4, 122.8, 39.7, 27.3, 20.0, 19.3; HRMS (ESIꢀQ/TOF MS) with
+
Acetonitrile (m/z): [M+Na] calcd for C H N NaO 431.2669; found 431.2679.
26
36
2
2
N,N'-(5,5'-dibromo-4,4'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
2kk). The reaction was performed according to the general procedure 1A using amide 1k.
(
Purification by flash column chromatography eluting with petroleum ether/dichloromethane (1/1,
o
1
v/v) gave 2kk (77.5 mg, 72% yield) as white solid; m.p. 204–205 C; H NMR (400 MHz, CDCl ) δ
3
13
8
.15 (s, 2H), 7.35 (s, 2H), 7.16 (s, 2H, br), 2.43 (s, 6H), 1.03 (s, 18H); C NMR (100 MHz, CDCl3)
δ 177.0, 139.7, 135.1, 133.3, 126.6, 124.6, 120.0, 39.8, 27.3, 23.2; HRMS (ESIꢀQ/TOF MS) with
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Acetonitrile (m/z): [M+Na] calcd for C H Br N NaO 559.0566; found 559.0560.
24
30
2
2
2
N,N'-(4,4'-difluoro-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2ll).
The
reaction was performed according to the general procedure 1B in 3h using amide 1l. Purification
by flash column chromatography eluting with petroleum ether/dichloromethane (2/1, v/v) 2ll (48.9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
mg, 63% yield) as white solid; m.p. 117–119 C; H NMR (400 MHz, CDCl ) δ8.28 – 8.13 (m, 2H),
3
13
7.24 – 7.09 (m, 4H), 6.99 – 6.89 (m, 2H), 1.01 (s, 18H); C NMR (100 MHz, CDCl ) δ 176.9, 163.4
3
(
d, JCꢀF = 247 Hz), 137.9 (d, JCꢀF = 12 Hz), 131.4 (d, JCꢀF = 9 Hz), 122.1 (d, JCꢀF = 3 Hz), 111.5 (d, JCꢀF
19
=
22 Hz), 109.1 (d, JCꢀF = 28 Hz), 39.9, 27.2; F NMR (376 MHz, CDCl ) δ ꢀ109.2; HRMS
3
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+Na] calcd for C H F N NaO 411.1855; found
22 26
2
2
2
4
11.1856.
N,N'-(4,4'-dichloro-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2mm). The
reaction was performed according to the general procedure 1B in 3h using amide 1m. Purification
by flash column chromatography eluting with petroleum ether/dichloromethane (1/1, v/v) gave
o
1
2
mm (70.0 mg, 83% yield) as white solid; m.p. 195–197 C; H NMR (400 MHz, CDCl ) δ 8.39 (d,
3
J = 2.0 Hz, 2H), 7.22 (dd, J = 8.0, 2.0 Hz, 2H), 7.15 (s, 2H, br), 7.11 (d, J = 8.0 Hz, 2H), 1.03 (s,
1
3
18H); C NMR (100 MHz, CDCl ) δ 177.0, 137.1, 135.9, 130.9, 125.5, 125.0, 122.3, 39.9, 27.3;
3
+
HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+Na] calcd for C H Cl N NaO 443.1264;
22
26
2
2
2
found 443.1270.
N,N'-(4,4'-dibromo-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2nn). The
reaction was performed according to the general procedure 1B in 3h using amide 1n. Purification
by flash column chromatography eluting with petroleum ether/dichloromethane (1:1, v/v) gave 2nn
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1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
1
(79.6 mg, 78% yield) as white solid; m.p. 214–216 C; H NMR (400 MHz, CDCl ) δ 8.51 (d, J =
3
2
.0 Hz, 2H), 7.37 (dd, J = 8.0, 2.0 Hz, 2H), 7.15 (s, 2H, br), 7.04 (d, J = 8.0 Hz, 2H), 1.03 (s, 18H);
13
C NMR (100 MHz, CDCl ) δ 177.0, 137.1, 131.1, 128.0, 126.4, 125.4, 123.7, 39.8, 27.2; HRMS
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H Br N O 509.0434 found
22 27
2
2
2
5
09.0449.
N,N'-(4,4'-diiodo-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2oo).
The
reaction was performed according to the general procedure 1B in 3h using amide 1o. Purification
by flash column chromatography eluting with petroleum ether/dichloromethane (2/1, v/v) gave 2oo
o
1
(
77.3 mg, 64% yield) as white solid; m.p. 208–211 C; H NMR (400 MHz, CDCl ) δ 8.66 (d, J =
3
2
.0 Hz, 2H), 7.57 (dd, J = 8.0, 1.6 Hz, 2H), 7.13 (s, 2H, br), 6.89 (d, J = 8.0 Hz, 2H), 1.02 (s, 18H);
13
C NMR (100 MHz, CDCl ) δ 177.0, 136.9, 134.0, 131.2, 131.2, 127.3, 95.2, 39.8, 27.3; HRMS
3
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+Na] calcd for C H I N NaO 626.9976; found
22
26 2
2
2
6
26.9984.
N,N'-(5,5'-difluoro-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2pp). The
reaction was performed according to the general procedure 1A (1.5 equiv K S O ) in 48h using
2
2
8
amide 1p. Purification by flash column chromatography eluting with petroleum
o
ether/dichloromethane (1/1, v/v) gave 2pp (33.4 mg, 43% yield) as white solid; m.p. 166–167 C;
1
H NMR (400 MHz, CDCl ) δ 8.01 – 7.85 (m, 2H), 7.24 (s, 2H, br), 7.17 – 7.08 (m, 2H), 6.91 (dd, J
3
1
3
=
8.4, 3.2 Hz, 2H), 1.01 (s, 18H); C NMR (100 MHz, CDCl ) δ 177.6, 159.8 (d, J = 247 Hz),
3 CꢀF
1
32.1 (d, JCꢀF = 8 Hz), 131.9 (d, JCꢀF = 3 Hz), 126.2 (d, JCꢀF = 8 Hz), 116.5 (d, JCꢀF = 21 Hz), 116.3 (d,
1
9
JCꢀF = 20 Hz), 39.5, 27.2; F NMR (376 MHz, CDCl ) δ ꢀ116.2; HRMS (ESIꢀQ/TOF MS) with
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Acetonitrile (m/z): [M+Na] calcd for C H F N NaO 411.1855; found 411.1859.
22
26
2
2
2
N,N'-(5,5'-dibromo-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2qq). The
reaction was performed according to the general procedure 1B using amide 1q. Purification by
flash column chromatography eluting with petroleum ether/dichloromethane (2/1, v/v) gave 2qq
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
(
69.8 mg, 68% yield) as white solid; m.p. 205–207 C; H NMR (400 MHz, CDCl ) δ 8.05 (d, J =
3
8.8 Hz, 2H), 7.56 (dd, J = 8.8, 2.4 Hz, 2H), 7.35 (d, J = 2.4 Hz, 2H), 7.18 (s, 2H, br), 1.03 (s, 18H);
13
C NMR (100 MHz, CDCl3) δ 177.1, 135.0, 132.9, 132.6, 130.0, 124.7, 117.8, 39.8, 27.3; HRMS
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H Br N O 509.0434; found
22
27
2
2
2
5
09.0441.
N,N'-(5,5'-diiodo-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide) (2rr). The reaction
was performed according to the general procedure 1B using amide 1r. Purification by flash column
chromatography eluting with petroleum ether/dichloromethane (2/1, v/v) gave 2rr (54.0 mg, 45%
o
1
yield) as white solid; m.p. 113–115 C; H NMR (400 MHz, CDCl ) δ 7.94 (d, J = 8.8 Hz, 2H), 7.73
3
13
(
dd, J = 8.8, 2.0 Hz, 2H), 7.53 (d, J = 2.0 Hz, 2H), 7.17 (s, 2H, br), 1.03 (s, 18H); C NMR (100
MHz, CDCl ) δ 177.1, 138.8, 138.4, 135.7, 129.9, 124.7, 88.3, 39.8, 27.3; HRMS (ESIꢀQ/TOF MS)
3
+
with Acetonitrile (m/z): [M+Na] calcd for C H I N NaO 626.9976; found 626.9980.
22
26 2
2
2
Diethyl 2,2'-dipivalamido-[1,1'-biphenyl]-4,4'-dicarboxylate (2ss). The reaction was
performed according to the general procedure 1C using amide 1s. Purification by flash column
chromatography eluting with petroleum ether/ethyl acetate (10/1, v/v) gave 2ss (20.9 mg, 21% yield)
o
1
as white solid; m.p. 151–154 C; H NMR (400 MHz, CDCl ) δ 8.72 (s, 2H), 7.94 (d, J = 8.0 Hz,
3
2H), 7.29 (s, 2H, br), 7.25 – 7.28 (m, 2H), 4.41 (q, J = 7.2 Hz, 4H), 1.42 (t, J = 7.2 Hz, 6H), 1.02 (s,
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1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
18H); C NMR (100 MHz, CDCl ) δ 177.3, 166.0, 136.0, 134.2, 132.1, 129.8, 126.4, 124.7, 61.6,
3
+
3
4
9.7, 27.3, 14.5. HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O
28
37
2
6
97.2646; found 497.2663.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Diethyl 6,6'-dipivalamido-[1,1'-biphenyl]-3,3'-dicarboxylate (2tt). The reaction was
performed according to the general procedure 1C using amide 1t. Purification by flash column
chromatography eluting with petroleum ether/ethyl acetate (9/1, v/v) gave 2tt (49.7 mg, 50% yield)
o
1
white solid; m.p. 206–207 C; H NMR (400 MHz, CDCl ) δ 8.48 (d, J = 8.8 Hz, 2H), 8.15 (dd, J =
3
8
7
1
.8, 2.0 Hz, 2H), 7.94 (d, J = 2.0 Hz, 2H), 7.27 (s, 2H, br), 4.37 (qd, J = 7.2, 1.0 Hz, 4H), 1.38 (t, J =
1
3
.2 Hz, 6H), 1.00 (s, 18H); C NMR (100 MHz, CDCl ) δ 176.9, 165.7, 140.0, 131.8, 131.6, 126.5,
3
+
26.2, 121.0, 61.4, 40.0, 27.2, 14.4; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd
for C H N O 497.2646; found 497.2661.
2
8
37
2
6
N,N'-(4,4'-bis(trifluoromethyl)-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
2uu). The reaction was performed according to the general procedure 1C using amide 1u.
(
Purification by flash column chromatography eluting with petroleum ether/dichloromethane (1/1,
o
1
v/v) gave 2uu (26.4 mg, 27% yield) as white solid; m.p. 148–150 C; H NMR (400 MHz, CDCl )
3
δ 8.54 (d, 2H, J = 0.8 Hz), 7.53 (dd, J = 7.6, 0.8 Hz, 2H), 7.33 (d, J = 7.6 Hz, 2H), 7.24 (s, 2H, br),
1
3
1
1
.03 (s, 18H); C NMR (100 MHz, CDCl ) δ 177.3, 136.6, 132.48 (q, J = 33 Hz), 131.7, 130.4,
3 CꢀF
19
23.67 (q, JCꢀF = 273 Hz), 121.78 (q, JCꢀF = 4 Hz), 120.20 (q, JCꢀF = 4 Hz), 39.8, 27.2; F NMR (376
+
MHz, CDCl ) δ ꢀ62.9. HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for
3
C H F N O 489.1971; found 489.1978.
24
27
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2
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N,N'-(4,4'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2ww).
Nꢀ(3ꢀmethoxyphenyl)pivalamide (82.9 mg, 0.4 mmol), Pd(OAc) (7.2 mg, 0.032 mmol, 8 mol %),
2
Potassium persulfate (162.2 mg, 0.6 mmol, 1.5 equiv), methanol (256.3 mg, 8.0 mmol, 0.30 mL),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
methanesulfonic acid (76.8 mg, 0.8 mmol, 0.05 mL) were added in 35 mL seal tube. The reaction
o
mixture was stired at 25 C for 3 h. After that, saturated NaHCO (10.0 mL) was added to it. The
3
solution was extracted with CH Cl (10 mL×3) and washed with brine (10 mL), and dried over
2
2
Mg SO . Then, the extract was concentrated and the residue was purified by flash column
2
4
chromatography on silica gel with a gradient eluent of petroleum ether/ethyl acetate (6/1, v/v) to
o
1
give 2ww (49.5 mg, 60% yield) as a white solid. m.p. 78–81 C; H NMR (400 MHz, CDCl ) δ 8.14
3
(
d, J = 2.8 Hz, 2H), 7.25 (s, 2H, br), 7.09 (d, J = 8.4 Hz, 2H), 6.76 (dd, J = 8.4, 2.8 Hz, 2H), 3.87 (s,
1
3
6H), 1.02 (s, 18H); C NMR (100 MHz, CDCl ) δ 176.8, 160.6, 137.7, 131.1, 118.5, 111.3, 105.4,
3
+
5
4
5.6, 40.0, 27.4; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O
2
4
33
2
4
13.2435; found 413.2450.
N,N'-(4,4'-dinitro-[1,1'-biphenyl]-2,2'-diyl)bis(2,2-dimethylpropanamide)
(2xx).
The
reaction was performed according to the general procedure 1C using amide 1x. Purification by
flash column chromatography eluting with petroleum ether/ethyl acetate (4/1, v/v) gave 2xx (1.0
o
1
mg, 1% yield) as brown solid; m.p. 226–227 C; H NMR (400 MHz, CDCl ) δ 8.95 (d, J = 2.4 Hz,
3
1
3
2
H), 8.14 (dd, J = 8.4, 2.4 Hz, 2H), 7.39 (s, 2H, br), 7.36 (d, J = 8.4 Hz, 2H), 1.06 (s, 18H). C NMR
(
100 MHz, CDCl ) δ 177.5, 149.0, 137.0, 135.4, 130.6, 120.1, 119.4, 39.8, 27.2. HRMS
3
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O 443.1925; found
22
27
4
6
443.1923.
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1
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
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4
4
4
4
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5
5
5
5
5
5
6
N,N'-(4,4'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2-methylpropanamide)
(2d d ).
The
1
1
reaction was performed according to the general procedure 1A using amide 1d . Purification by
1
flash column chromatography eluting with petroleum ether:ethyl acetate (4/1, v/v) gave 2d d (55.8
1
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
mg, 79% yield) as white solid; m.p. 85–88 C; H NMR (400 MHz, CDCl ) δ 8.07 (s, 2H), 7.05 (d, J
3
=
8.0 Hz, 2H), 7.01 (dd, J = 7.6, 0.4 Hz, 2H), 6.97 (s, 2H, br), 2.40 (s, 6H), 2.25 (sept, J = 6.8 Hz,
13
2H), 1.02 (d, J = 6.8 Hz, 6H), 1.00 (d, J = 6.8 Hz, 6H); C NMR (100 MHz, CDCl ) δ 175.6, 139.6,
3
1
35.7, 130.2, 125.7, 125.5, 123.0, 36.5, 21.6, 19.5, 19.3; HRMS (ESIꢀQ/TOF MS) with Acetonitrile
+
(
m/z): [M+Na] calcd for C H N NaO 375.2043; found 375.2059.
2
2
28
2
2
N,N'-(4,4'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)dibutyramide (2d d ). The reaction was
2
2
performed according to the general procedure 1A using amide 1d . Purification by flash column
2
chromatography eluting with petroleum ether/ethyl acetate (4/1, v/v) gave 2d d (47.8 mg, 68%
2
2
o
1
yield) as yellow solid; m.p. 38–42 C; H NMR (400 MHz, CDCl ) δ 8.03 (s, 2H), 7.05 (d, J = 8.4
3
Hz, 2H), 7.01 (dd, J = 8.0, 1.2 Hz, 2H), 6.92 (s, 2H, br), 2.41 (s, 6H), 2.13 – 2.07 (m, 4H), 1.61 –
13
1
1
.47 (m, 4H), 0.86 (t, J = 7.4 Hz, 6H); C NMR (100 MHz, CDCl ) δ 171.9, 139.5, 135.6, 130.4,
3
25.8, 125.7, 123.3, 39.4, 21.6, 18.9, 13.7; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z):
+
[M+Na] calcd for C H N NaO 375.2043; found 375.2054.
2
2
28
2
2
N,N'-(4,4'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)dipropionamide (2d d ). The reaction was
3
3
performed according to the general procedure 1A using amide 1d . Purification by flash column
3
chromatography eluting with petroleum ether:ethyl acetate (4/1, v/v) gave 2d d (41.3 mg, 64%
3
3
o
1
yield) as yellow solid; m.p. 124–126 C; H NMR (400 MHz, CDCl ) δ 8.00 (s, 2H), 7.05 (d, J = 7.6
3
Hz, 2H), 7.01 (dd, J = 7.6, 1.2 Hz, 2H), 6.93 (s, 2H, br), 2.39 (s, 6H), 2.14 (q, J = 7.6 Hz, 4H), 1.02
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1
3
(t, J = 7.6 Hz, 6H); C NMR (100 MHz, CDCl ) δ 172.6, 139.5, 135.5, 130.4, 125.8, 125.5, 123.3,
3
+
3
3
0.5, 21.6, 9.5; HRMS (ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+Na] calcd for C H N NaO
20
24
2
2
47.1730; found 347.1736.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N,N'-(4,4'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)diacetamide(2d d ).
The
reaction
was
4
4
performed according to the general procedure 1A using amide 1d . Purification by flash column
4
chromatography eluting with petroleum ether/ethyl acetate (1/1, v/v) gave 2d d (36.3 mg, 61%
4
4
o
1
yield) as white solid; m.p. 187–189 C; H NMR (400 MHz, CDCl ) δ 7.89 (s, 2H), 7.05 (d, J = 7.6
3
13
Hz, 2H), 7.02 (dd, J = 7.6, 0.8 Hz, 2H), 6.97 (s, 2H, br), 2.39 (s, 6H), 1.94 (s, 6H); C NMR (100
MHz, CDCl ) δ 169.2, 139.4, 135.4, 130.5, 126.1 (two overlapped peaks), 123.8, 24.3, 21.6. HRMS
3
+
(
ESIꢀQ/TOF MS) with Acetonitrile (m/z): [M+H] calcd for C H N O 297.1598; found
18
21
2
2
297.1599.
N,N'-(4,4'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)dibenzamide (2d d ). The reaction was
5
5
performed according to the general procedure 1A using amide 1d . Purification by flash column
5
chromatography eluting with petroleum ether/ethyl acetate (4/1, v/v) gave 2d d (53.0 mg, 63%
5
5
o
1
yield) as yellow solid; m.p. 160–162 C; H NMR (400 MHz, CDCl ) δ 8.35 (s, 2H), 7.87 (s, 2H, br),
3
7.58 – 7.51 (m, 4H), 7.49 – 7.43 (m, 2H), 7.39 – 7.33 (m, 4H), 7.19 (d, J = 7.6 Hz, 2H), 7.09 (ddd, J
13
=
7.6, 1.6, 0.8 Hz, 2H), 2.46 (s, 6H); C NMR (100 MHz, CDCl ) δ 165.6, 139.9, 135.9, 134.5,
3
1
32.0, 130.3, 128.9, 126.9, 125.9, 125.4, 122.7, 21.8; HRMS (ESIꢀQ/TOF MS) with Acetonitrile
+
(
m/z): [M+Na] calcd for C H N NaO 443.1730; found 443.1733.
28 24
2
2
N,N'-(4,4',5,5'-tetramethyl-[1,1'-biphenyl]-2,2'-diyl)bis(2-methylpropanamide) (2j j ). The
1
1
reaction was performed according to the general procedure 1A using amide 1j . Purification by
1
ACS Paragon Plus Environment