Palladium-Catalyzed Late-Stage ortho-C-H Bond Aroylation of Anilines Using 4-Methoxy-2-pyridinyl as a Removable Directing Group

Article abstract of DOI:10.1021/acs.organomet.9b00119

A synthetic methodology for the late-stage ortho-C-H bond aroylation of anilines with aryl aldehydes led to a variety of ortho-aroylated anilines by the use of palladium(II) acetate, tert-butyl hydroperoxide, and 1,4-dioxane as the catalyst, oxidant, and solvent, respectively, is presented. An N-phenylpyridin-2-amine palladacycle was isolated and characterized by X-ray crystallography. Controlled experiments, radical trapping experiments, and the experiments of the kinetic isotope effect were undertaken to support the proposed reaction mechanism. Syntheses of 2-aminobenzophenone and 9(10H)-acridanone based on the developed methodology were successfully demonstrated.

Full text of DOI:10.1021/acs.organomet.9b00119

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Palladium-Catalyzed Late-Stage ortho-C−H Bond Aroylation of
Anilines Using 4‑Methoxy-2-pyridinyl as a Removable Directing
Group
Jean-Ho Chu,*,† Meng-Fan Chiang,‡ Chin-Wei Li,‡ Zhe-Hong Su,† Shao-Chi Lo,‡
and Ming-Jung Wu*,‡
†Department of Applied Science, National Taitung University, Taitung 95092, Taiwan
‡Department of Chemistry, National Sun Yat-sen University, Kaohsiung 804, Taiwan
S
* Supporting Information
ABSTRACT: A synthetic methodology for the late-stage
ortho-C−H bond aroylation of anilines with aryl aldehydes led
to a variety of ortho-aroylated anilines by the use of
palladium(II) acetate, tert-butyl hydroperoxide, and 1,4-
dioxane as the catalyst, oxidant, and solvent, respectively, is
presented. An N-phenylpyridin-2-amine palladacycle was
isolated and characterized by X-ray crystallography. Con-
trolled experiments, radical trapping experiments, and the
experiments of the kinetic isotope effect were undertaken to
support the proposed reaction mechanism. Syntheses of 2-
aminobenzophenone and 9(10H)-acridanone based on the
developed methodology were successfully demonstrated.
a radical initiator, respectively, in terms of the synthetic
practicability. Moreover, various directing groups, such as the
pyridinyl, acetyl, carbamate, isoxazole, and so on were involved
in these reported reactions.
INTRODUCTION
■
In the past decade, transition-metal-catalyzed C−H bond
functionalization has seen an increased interest in organic
synthesis.1 In comparison with conventional methods, the
synthetic strategy can efficiently reduce reaction steps and the
formation of byproducts, and the preactivation of starting
substrates is not required. Therefore, the way of C−H bond
functionalization enables molecular synthesis to become more
efficient and simpler. To date, a number of research works have
been conducted in the literature.2
On the other hand, the so-called directing group often plays
an important role in the transition-metal-catalyzed C−H bond
functionalization.3 It is not only able to promote the reactivity
but also to control the regioselectivity for the type of reaction,
such as the ortho-, meta-, and para-position of a phenyl ring.4
The pyridinyl is believed to be the most common directing
group due to its good affinity with transition metals, especially
for the palladium ion. Therefore, it is often used in our studies
with respect to the palladium-catalyzed selective ortho-C−H
bond functionalization.5
In view of the importance of benzophenones in organic
synthesis6 and biological activity,7 organic chemists are
devoted to developing versatile synthetic methods to target
this molecular skeleton. So far, numerous methodologies for
the synthesis of benzophenones have been conducted in
literature, especially for the ortho cross-dehydrogenative
coupling (CDC) of arenes and aryl aldehydes.5a,8 In these
methods, the palladium ion and tert-butyl hydroperoxide
(TBHP) have been examined to be the best metal catalyst and
In 2015, we successfully demonstrated that the palladium-
catalyzed ortho-C−H bond aroylation of phenols with aryl
aldehydes using the pyridinyl as a directing group. The
reaction was undertaken via the intermolecular CAr−H/
CAldehyde−H bond cross-coupling to afford a variety of 2-
hydroxybenzophenones followed by the removal of the
pyridinyl group.5a Moreover, the synthesis of 1-hydroxy-9H-
fluoren-9-ones9 was achieved by the intramolecular CAr−H/
CAr−H bond cross-coupling reaction of 2-hydroxybenzophe-
nones. Finally, this work encouraged us to continuously study
the palladium-catalyzed ortho-C−H bond aroylation of ani-
lines.
In the presented study, the palladium-catalyzed ortho-C−H
bond aroylation of 4-methoxy-N-arylpyridin-2-amines with aryl
aldehydes in the presence of TBHP was undertaken to afford a
variety of ortho-aroylated 4-methoxy-N-arylpyridin-2-amines in
modest to good yields. Meanwhile, a possible reaction
mechanism was presented based on the investigation of
controlled and radical trapping experiments as well as the
experiments of the kinetic isotope effect. Toward the synthetic
application, 2-aminobenzophenone can be given by removing
the pyridinyl group of ortho-phenylated 4-methoxy-N-phenyl-
Received: February 22, 2019
© XXXX American Chemical Society
A
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Table 1. Reactivity Investigation of the Pyridinyl and N-Protecting Groups in the Palladium-Catalyzed ortho-C−H Bond
Aroylation of 1
a
b
Product ratio was determined as an average of three runs by GC-FID. Product yield was determined as an average of three runs by the isolation.
pyridin-2-amine. In addition, 9(10H)-acridanone10 can be
directly synthesized through the palladium-catalyzed intra-
molecular C−H/N−H bond cross-coupling of 2-amino-
benzophenone or ortho-phenylated 4-methoxy-N-phenylpyr-
idin-2-amine followed by the removal of the pyridinyl group.
desired product 3-H/H was found under the above reaction
conditions (entry 1, Table 1). On the basis of our previous
experience, the directing group bearing an electron-donating
group (e.g., methyl or methoxy) can significantly promote the
reactivity of the palladium-catalyzed site-selective (e.g., ortho)
C−H bond activation.5b Therefore, we turned to employ
compounds 1-Me/H and 1-OMe/H as new starting substrates
by using 4-methyl and 4-methoxy as the directing group,
respectively. However, there was still none of the desired ortho-
aroylated products 3-Me/H and 3-OMe/H obtained from the
reaction of 1-Me/H or 1-OMe/H with 2a, and the starting
substrate (i.e., 1-Me/H or 1-OMe/H) was recovered (entries
2−3, Table 1). These results made us consider the role of the
free amino group of 1 in the reaction. Thus, we tagged a
protecting group, tert-butyloxycarbonyl (Boc) on the secon-
RESULTS AND DISCUSSION
■
Reactivity Investigation of the Directing Group and
N-Protecting Group for the Palladium-Catalyzed ortho-
C−H Bond Aroylation of 1. At the beginning of this study,
we first carried out the reaction of N-phenylpyridin-2-amine
(1-H/H) with benzaldehyde (2a) in the presence of
palladium(II) acetate and TBHP as the catalyst and a radical
initiator, respectively. 1,4-Dioxane was the solvent and the
reaction was held at 120 °C for 24 h. However, none of the
B
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dary amino groups of 1-H/H, 1-Me/H, and 1-OMe/H led to
1-H/Boc, 1-Me/Boc, and 1-OMe/Boc. The subsequent ortho-
C−H bond aroylation of N-Boc protected substrates 1-H/Boc,
1-Me/Boc, and 1-OMe/Boc with 2a was carried out under the
aforementioned reaction conditions. The experimental results
showed that the desired ortho-benzoylated products 3-H/Boc,
3-Me/Boc, and 3a (accompanied dibenzoylated product 4a)
were generated in the trace, 40%, and 87% yield, respectively
(entries 4−6, Table 1). In other words, the electronic property
of the directing group (i.e., pyridinyl) is important for the
reaction, whereas the N-protecting group (e.g., Boc) is also
critical for this case.
On the basis of these above results, we attempted to
understand the influence of the N-protecting group of 1 in the
presented reaction. Therefore, a series of N-protecting groups,
such as methyloxycarbonyl (Moc), tert-butylcarbonyl (Piv),
acetyl (Ac), and benzyl (Bn) were introduced to 1-OMe/H.
Then, various N-protecting substrates 1-OMe/Moc, 1-OMe/
Piv, 1-OMe/Ac, and 1-OMe/Bn was generated and further
examined under the aforementioned reaction conditions.
Experimental results addressed that the yield of ortho-
benzoylated products 3-OMe/Moc, 3-OMe/Piv, 3-OMe/Ac,
and 3-OMe/Bn accompanied dibenzoylated products 4-OMe/
Moc, 4-OMe/Piv, and 4-OMe/Ac was determined to be 88%,
45%, 33%, and 28% yields, respectively (entries 7−10, Table
1). Herein, we chose Boc as the optimal N-protecting group
for the palladium-catalyzed ortho-C−H bond aroylation of 1
with 2. This is because Boc is relatively easy to remove
compared to Moc. By varying the N-protecting group of 1-
OMe/H, the oxygen atom (not the one on the carbonyl
group) of Boc or Moc is critical for the reaction. This might be
due to the electrostatic repulsion between the oxygen atom of
the N-protecting group and the nitrogen atom of the pyridinyl
group. The phenomenon forces the coordination of the
palladium ion and pyridine to orient to the ortho-C−H bond as
well as prevents the interaction between the amine and TBHP.
These two factors might eventually result in the occurrence of
the ortho-C−H bond aroylation of 1-OMe/Boc in good yields.
Moreover, the steric effect of the N-protecting group might
also potentially provide the influence in the reaction (see
entries 8−10, Table 1).
Optimization of the Reaction Conditions. According to
the reactivity investigation of the directing group and N-
protecting group, both of Boc and 4-methoxy-2-pyridinyl
group were eventually chosen as the optimal N-protecting
group and directing group for the palladium-catalyzed ortho-
C−H bond aroylation of anilines 1 with aryl aldehyde 2. Next,
the reaction of 1a with 2a in the presence of palladium(II)
acetate was examined by the variation of the oxidant, solvent,
the amount of reagents, and the reaction temperature (see
Table S1).
First of all, a variety of oxidants (6 equiv) were screened in
the presence of 10 mol % Pd(OAc)2 using 1,4-dioxane as the
reaction solvent in which these reactions were heated at 120
°C for 24 h (entries 1−10 and 18, Table S1). The screening
results showed that the anticipated product 3a was generated
only by the use of TBPB (tert-butyl peroxybenzoate) and
TBHP as the oxidant. The product ratio (yield) of 3a and 4a
was determined to be >99:1 (35%) and 67:33 (87%),
respectively (entries 1 and 18, Table S1). In addition to the
oxidant, we also evaluated the solvent effect in the presence of
10 mol % Pd(OAc)2 and 6 equiv TBHP (entries 11−21, Table
S1). The results of solvent screening showed that 1,4-dioxane
still acted as the best solvent for the reaction. Then, the
reaction temperature was varied from 80 to 140 °C to give 120
°C as the best temperature (entry 18 and 22−24, Table S1).
Finally, the equivalent of TBHP was examined from 0 to 7
(entries 25−29, Table S1) to indicate 6 equiv as the optimal
amount in which a mixture of 3a and 4a was isolated in 87%
total yield with product ratio 67:33 (entry 18, Table S1). On
the basis of the optimized experiments, we finally decided to
use the following reaction conditions for the ortho-C−H bond
aroylation of 1: 10 mol % Pd(OAc)2, 6 equiv TBHP, and 1.5
equiv aryl aldehyde 2 in 1,4-dioxane heated at 120 °C for 24 h.
Substrate Scope. With the optimized reaction conditions
in hand, we subsequently carried out the demonstration of
substrates for the palladium-catalyzed ortho-C−H bond
aroylation of 1a with a variety of aryl aldehyde 2 (Table 2).
Table 2. ortho-C−H Bond Aroylation of 1a with 2
a
b
entry
aldehyde (2)
R = H (2a)
R = 4-OMe (2b)
R = 4-NO2 (2c)
R = 4-CF3 (2d)
R = 4-Ac (2e)
R = 2-F (2f)
R = 3-F (2g)
R = 4-F (2h)
R = 2-Cl (2i)
R = 3-Cl (2j)
R = 4-Cl (2k)
R = 3-Br (2l)
R = 4-Br (2m)
R = 3,5-diMe (2n)
R = 2,4-diMe (2o)
R = 3,5-diOMe (2p)
R = 2,4-diOMe (2q)
R = 3-CHO (2r)
product 3, 4 (ratio)
yield (%)
1
2
3
4
5
6
7
8
3a + 4a (68:32)
3b + 4b (67:33)
not detected
3d
87
89
0
24
44
58
84
86
39
57
62
31
37
88
61
35
29
45
3e
3f + 4f (98:2)
3g + 4g (88:12)
3h + 4h (90:10)
3i
3j + 4j (98:2)
3k + 4k (95:5)
3l
9
10
11
12
13
14
15
16
17
18
3m
3n + 4n (78:22)
3o + 4o (88:12)
3p
3q + 4q (90:10)
3r
a
Product ratio was determined as an average of three runs by GC-
b
FID. Product yield was determined as an average of three runs by the
isolation.
A series of ortho monoaroylated products 3a,b,f−h,j,k,n,o,q
(major) as well as diaroylated products 3a,b,f−h,j,k,n,o,q
(minor) were obtained as following product ratios and yields
3a:4a = 68:32 (87%), 3b:4b = 67:33 (89%), 3f:4f = 98:2
(58%), 3g:4g = 88:12 (84%), 3h:4h = 90:10 (86%), 3j:4j =
98:2 (57%), 3k:4k = 95:5 (64%), 3n:4n = 78:22 (88%), 3o:4o
= 88:12 (61%), and 3q:4q = 90:10 (29%) (entries 1−2, 5−8,
10−11, 14−15, and 17, Table 2). On the other hand, only
monoaroylated products 3d,e,i,l,m,p,r were isolated in 24−
45% yields by the reaction of 1a with 2d,e,i,l,m,p,r (entries 4−
5, 9, 12−13, 16, and 18, Table 2), whereas none of the
anticipated product 3d was generated (entry 3, Table 2).
These experimental results show that aryl aldehyde 2 bearing
an electron-donating group (e.g., OMe) usually exhibits better
reactivity than that of the electron-withdrawing group (e.g.,
C
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NO2) in the presented reaction. This might be due to the
electronic donating effect of the aroyl group could stabilize the
palladium intermediate (see Figure 3). By contrast, the
electronic withdrawing effect may destabilize it. Moreover,
the steric hindrance of aryl aldehydes 2 seems to potentially
offer the influence on the reactivity, which resulted in low
product yields. For instance, ortho-substituted aryl aldehydes
2f, 2i, 2o, and 2q (see entries 6, 9, 15 and 17, Table 2).11 In
addition, when isophthalaldehyde (2r) which contains two
formyl groups at C1 and C3-position of benzene ring was used,
none of the dual C−H/C−H bond coupling product was
given. Only monoaroylated product 3r was isolated in 45%
yield (entry 18, Table 2). Finally, the structure of
dibenzoylated N-Boc protected 4-methoxy-N-phenylpyridin-
2-amine (4a) was secured by X-ray crystallography as shown as
Figure 1a.12
Table 3. ortho-C−H Bond Benzoylation of 1 with 2a
a
b
entry
substrate (1)
product 5, 6 (ratio)
yield (%)
1
2
3
4
5
6
7
8
R = 2-OMe (1b)
R = 3-OMe (1c)
R = 4-OMe (1d)
R = 4-F (1e)
R = 3-F (1f)
R = 2-F (1g)
5b
5c
91
83
93
74
57
94
79
39
5d + 6d (61:39)
5e + 6e (71:29)
5f
5g
5h + 6h (92:8)
5i
R = 4-Cl (1h)
R = 4-Br (1i)
a
Product ratio was determined as an average of three runs by GC-
b
FID. Product yield was determined as an average of three runs by the
isolation.
product yields, the substituent electronic effect in the ortho-C−
H bond aroylation of substrates 1b−i seems not to apparently
influence the reactivity. The structure of ortho monobenzoy-
lated product 5h was eventually secured by X-ray crystallog-
raphy as shown as Figure 1b.12 In addition, ortho dibenzoylated
products 6d, 6e, and 6h were isolated in 39%, 29%, and 8%
product ratios, respectively (entries 3−4, and 7, Table 3).
Mechanistic Investigation. In order to gain an insight of
the reaction, we subsequently carried out a series of
experiments that include the preparation of a palladacycle,
controlled experiments, radical trapping experiments, and the
experiments of kinetic isotope effect to support the proposed
catalytic mechanism.
1. Preparation and Characterization of the Palladacycle I.
The palladacycle I was prepared by the stoichiometric reaction
of 1a with palladium(II) acetate in dichloromethane (see the
Supporting Information). The reaction was heated at 60−70
°C for 1−2 h to afford palladacycle I in 80% yield (Scheme 1).
Scheme 1. Preparation of Palladacycle I
The structure of I was secured by X-ray crystallography as
shown as Figure 2.12 On the basis of the structural analysis of I,
we further confirm that the pyridinyl group of 1a is the
directing group, but not the Boc group. In other words, the
pyridinyl group coordinates with the palladium(II) ion, which
enables the ortho-C−H bond activation of aniline to generate I.
By contrast, the Boc group herein plays only as a protecting
group for the secondary amine of 1a. It does not participate in
the coordination of the palladium(II) ion. The conformation
of I looks like a U-shape geometry, as well as the two ligands
(i.e., 1a) are aligned as a head-to-tail form. Finally, the reaction
of I with 2a in the presence of TBHP (6 equiv) was done;
however, none of the anticipated ortho-benzoylated product 3a
Figure 1. An ORTEP drawing of (a) compound 4a and (b)
compound 5h.12 All hydrogen atoms are omitted for clarity.
In addition to substrate 1a, we also conducted the reaction
of 1b−i with 2a under the optimized reaction conditions to
afford a variety of ortho monobenzoylated N-Boc protected 4-
methoxy-N-arylpyridin-2-amine 5 (a major product) and
dibenzoylated products 6 (a minor product was produced in
some cases) in 39−94% yields. These experimental results are
summarized in Table 3. On the basis of the comparison of
D
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Table 4. Radical Trapping Experiments for the Palladium-
Catalyzed ortho-C−H Bond Benzoylation of 1a with 2a
a
b
entry
radical scavenger (equiv)
product ratio (3a:4a)
yield (%)
1
2
3
4
5
6
7
8
9
10
−
68:32
67:33
93:7
95:5
90:10
95:5
87
65
25
17
70
54
27
52
20
trace
BHT (1)
BHT (2)
BHT (3)
DPE (1)
DPE (2)
DPE (3)
TEMPO (1)
TEMPO (2)
TEMPO (3)
95:5
Figure 2. An ORTEP drawing of palladacycle I.12 All hydrogen atoms
are omitted for clarity.
90:10
90:10
100:0
a
was observed (Scheme 2). This result implies that the
palladacycle I might not be the key intermediate for the
palladium-catalyzed ortho-C−H bond aroylation of 1 with 2.
Product ratio was determined as an average of three runs by GC-
b
FID. Product yield was determined as an average of three runs by the
isolation.
Scheme 2. Controlled Experiment by the Stoichiometric
Reaction of I with 2a
Scheme 3. Investigation of the Kinetic Isotope Effect for
Palladium-Catalyzed ortho-C−H Bond Aroylation of 1
2. Radical Trapping Experiment. To examine whether the
presented reaction occurs via a radical process, the reaction of
1a with 2a in the presence of BHT, DPE, and TEMPO,
respectively, was undertaken (see Table 4) (BHT = butylated
hydroxytoluene, DPE = 1,1-diphenylethylene, and TEMPO =
(2,2,6,6-tetramethylpiperidin-1-yl)oxyl). The experimental re-
sults showed that the total yield of products 3a and 4a
dramatically decreased down to 17%, 27%, and the trace
amount from 87% (in the absence of a radical scavenger) when
3 equiv of BHT, DPE, and TEMPO was added to the reaction,
respectively. This study indicates that a radical species at least
could be involved in the course of the reaction.
3. Investigation of the Kinetic Isotope Effect. To evaluate
the ortho-C−H bond cleavage of 1 in the presented reaction is
whether a rate-determining step, the intra- and intermolecular
kinetic isotope effect (KIE) experiments as well as the KIE
from two parallel reactions were done by the use of 1a-D1, 1a,
and 1a-D5 as starting substrates. Next, we carried out the
reaction of 1a-D1, 1a, and 1a-D5 with 4-methoxybenzaldehyde
(2b) under the optimized reaction conditions. Basically, the
rate-determining steps of the presented reaction. By contrast,
the binding of 1 with the palladium ion is strongly suggested to
be the key rate-determining step in the reaction.14
Proposed Mechanism. On the basis of the above
mechanistic studies, a possible catalytic process for the
palladium-catalyzed ortho-C−H bond aroylation of 1 with 2
is presented as shown as Figure 3. In the beginning, the
binding of substrate 1 and palladium(II) acetate enables the
formation of π-complex II by release of acetate anion. The π-
1
determination of KIE was undertaken on the basis of the H
NMR spectroscopy (see Scheme 3 and Supporting Informa-
tion). The value of (kH/kD)intra, (kH/kD)inter, and (kH/kD)parallel
was determined to be 5.4, 1.0, and 0.9, respectively.13 The
analysis of experimental results indicates that the palladium-
catalyzed ortho-C−H bond cleavage of 1 is not involved in the
E
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oxygen gas in dimethylacetamide (DMAC) heated at 130 °C
for 24 h.15 On the other hand, the synthesis of 8 can be
obviously improved by another synthetic route. That is, the
treatment of 3a by a solution of hydrazine/acetic acid (3/1, v/
v) in methanol heated at 100 °C for 1 h, and then conducted
to the same reaction conditions with the synthesis of 8 from 7,
which underwent the intramolecular C−H/N−H bond
coupling to give N-pyridinyl-9(10H)-acridanone (9) in 88%
yield. Finally, the pyridinyl group of 9 was again removed to
afford 8 in 70% yield by employing the same reaction
conditions with the transformation of 3a to 7.
CONCLUSION
■
We have developed a simple and efficient methodology for the
synthesis of ortho-aroylated N-Boc protected N-arylpyridin-2-
amines using palladium(II) acetate and aryl aldehyde as the
catalyst and coupling reagent, respectively, in the presence of a
key oxidant, tert-butyl hydroperoxide. The ortho-aroylated N-
arylpyridin-2-amines are easily transformed to the alternative of
2-aminobenzophenones and 9(10H)-acridanones. In addition,
we present a possible catalytic mechanism to explain the
reaction through the studies of the palladacycle, controlled
experiments, radical trapping experiments, and kinetic isotope
effects. The methodology provides a facile route to synthesize
ortho-aroylated anilines directed from anilines and aryl
aldehydes. It can serve as a useful tool to target 2-
aminobenzophenone and 9(10H)-acridanone analogue. Fi-
nally, we believe that the developed methodology is able to
play an important role in the synthetic field of pharmaceuticals
and materials.
Figure 3. A proposed catalytic mechanism for the palladium-catalyzed
ortho-C−H bond aroylation of 1 with 2.
complex II is then transformed to the key aroyl palladium(III
or IV) π-complex III by the redox reaction of the π-complex II
and the aroyl radical 2• (generated from aryl aldehydes 2 by
the treatment of TBHP via one electron abstraction). Next, the
π-complex III is fast transformed to intermediate IV via the
palladium(III or IV) insertion at the ortho-C−H bond of
aniline ring accompanied the release of acetic acid. Finally, the
desired product 3 or 5 is generated through the reductive
elimination of the intermediate IV. Meanwhile, the palladium-
(II) acetate is regenerated from the intermediate IV to
continue the catalytic cycle.
Synthetic Applications. The synthetic extension for a
developed methodology is important. To demonstrate the
merit of ortho-aroylated N-Boc protected 4-methoxy-N-
arylpyridin-2-amines 3 and 5 in organic synthesis, we herein
chose compound 3a as a modeling substrate to approach the
syntheses of 2-aminobenzophenone (7), 9(10H)-acridanone
(8), and N-(4-methoxy-2-pyridinyl)-9(10H)-acridanone (9)
(see Scheme 4). First, the pyridinyl and Boc groups of 3a were
EXPERIMENTAL SECTION
■
General Methods. Solvents and reagents were purchased from
commercial suppliers, and used without purification. 1H NMR spectra
were measured on 300, 400, and 500 MHz NMR spectrometers.
Natural abundance 13C NMR spectra were measured by using 300,
400, and 500 MHz NMR spectrometers operating at 75, 100, and 125
MHz, respectively. Chemical shifts are given in parts per million
(ppm) and coupling constant J in hertz (Hz) for both nuclei, with the
solvent (usually CDCl3) peak as an internal standard. The reference
peak for 1H is δ 7.26 of chloroform, and for 13C it is the central peak
at δ 77.0. Low- and high-resolution mass spectrometry was obtained
by the following ionization method and mass analyzer type for most of
the compounds: EI-magnetic sector. Melting points were measured by
using open capillary tubes and uncorrected.
Scheme 4. Synthetic Applications of Compound 3a
General Procedure for the Synthesis of Compounds 3−6. A
well-stirred solution of substrate 1 with aryl aldehydes 2 by the
addition of Pd(OAc)2 (4.5 mg, 0.02 mmol), TBHP (108 mg, 1.2
mmol) in 1,4-dioxane (3 mL) was heated at 120 °C for 24 h. After
cooling down to room temperature, the reaction solution was washed
by water (20 mL). The solution was then extracted by ethyl acetate
(15 mL × 3). Organic layers were combined, dried over MgSO4,
filtered through a pad of Celite, and evaporated in a vacuum. The
residue was purified by silica gel chromatography using n-hexane/
ethyl acetate (30/1 to 10/1) as the eluent to afford products 3-6. The
amounts of 1 and 2 are listed as follows. 1-H/H: 27 mg, 0.20 mmol
for 3-H/H; 1-Me/H: 37 mg, 0.20 mmol for 3-Me/H; 1-OMe/H: 48
mg, 0.20 mmol for 3-OMe/H; 1-H/Boc: 54 mg, 0.20 mmol for 3-H/
Boc; 1-Me/Boc: 57 mg, 0.20 mmol for 3-Me/Boc; 1-OMe/Moc: 52
mg, 0.20 mmol for 3-OMe/Moc and 3-OMe/Moc; 1-OMe/Piv: 57
mg, 0.20 mmol for 3-OMe/Piv and 3-OMe/Piv; 1-OMe/Ac: 49 mg,
0.02 mmol for 3-OMe/Ac and 3-OMe/Ac; 1-OMe/Bn: 58 mg, 0.20
mmol for 3-OMe/Bn and 3-OMe/Bn; 1a: 60 mg, 0.20 mmol for 3-4;
1b: 66 mg, 0.20 mmol for 5b; 1c: 66 mg, 0.20 mmol for 5c; 1d: 66
mg, 0.2 mmol for 5d and 6d; 1e: 64 mg, 0.20 mmol for 5e and 6e: 1f:
64 mg, 0.20 mmol for 5f; 1g: 64 mg, 0.20 mmol for 5g; 1h: 64 mg,
concurrently removed by the treatment of methyl trifluor-
omethanesulfonate (MeOTf) in toluene heated at 100 °C for 6
h and followed by the addition of hydrazine/acetic acid (3/1,
v/v)5c in methanol heated at 130 °C for 6 h to afford 2-
aminobenzophenone (7) in 70% yield. Afterward, compound 7
was directly transformed to 9(10H)-acridanone (8) in 37%
yield under the reaction conditions as shown as follows: 10
mol % CuI/bipyridine (1/1, equiv/equiv) in the presence of
F
DOI: 10.1021/acs.organomet.9b00119
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Article
0.20 mmol for 5h and 6h; 1i: 76 mg, 0.20 mmol for 5i; 2a: 32 mg,
0.30 mmol for 3a and 4a; 2b: 41 mg, 0.30 mmol for 3b and 4b; 2c: 45
mg, 0.30 mmol for 3c; 2d: 52 mg, 0.30 mmol for 3d; 2e: 45 mg, 0.30
mmol for 3e; 2f: 37 mg, 0.30 mmol for 3f and 4f; 2g: 37 mg, 0.30
mmol for 3g and 4g; 2h: 37 mg, 0.30 mmol for 3h and 4h; 2i: 42 mg,
0.30 mmol for 3i; 2j: 42 mg, 0.30 mmol for 3j and 4j; 2k: 42 mg, 0.30
mmol for 3k and 4k; 2l: 56 mg, 0.30 mmol for 3l; 2m: 56 mg, 0.30
mmol for 3m; 2n: 40 mg, 0.30 mmol for 3n and 4n; 2o: 40 mg, 0.30
mmol for 3o and 4o; 2p: 50 mg, 0.30 mmol for 3p; 2q: 50 mg, 0.30
mmol for 3q and 4q; 2r: 40 mg, 0.30 mmol for 3r. All product yields
were determined by the isolation and shown as follows: 3-H/H: 0%
(0 mg, 0 mmol); 3-Me/H: 0% (0 mg, 0 mmol); 3-OMe/H: 0% (0
mg, 0 mmol); 3-H/Boc: trace; 3-Me/Boc: 40% (31 mg, 0.080
mmol); 3-OMe/Moc: 57% (41 mg, 0.11 mmol); 3-OMe/Piv: 35%
(27 mg, 0.070 mmol); 3-OMe/Ac: 33% (23 mg, 0.070 mmol); 3-
OMe/Bn: 28% (22 mg, 0.060 mmol); 3a: 59% (49 mg, 0.12 mmol);
3b: 60% (52 mg, 0.12 mmol); 3c: 0% (0 mg, 0 mmol); 3d: 24% (24
mg, 0.050 mmol); 3e: 44% (40 mg, 0.090 mmol); 3f: 57% (47 mg,
0.11 mmol); 3g: 74% (63 mg, 0.15 mmol); 3h: 77% (65 mg, 0.15
mmol); 3i: 39% (34 mg, 0.080 mmol); 3j: 56% (49 mg, 0.11 mmol);
3k: 61% (54 mg, 0.12 mmol); 3l: 30% (29 mg, 0.060 mmol); 3m:
37% (36 mg, 0.070 mmol); 3n: 69% (60 mg, 0.14 mmol); 3o: 54%
(47 mg, 0.11 mmol); 3p: 35% (33 mg, 0.070 mmol); 3q: 26% (24
mg, 0.050 mmol); 3r: 45% (39 mg, 0.090 mmol); 4-OMe/Moc: 31%
(32 mg, 0.070 mmol); 4-OMe/Piv: 10% (10 mg, 0.020 mmol); 4a:
28% (29 mg, 0.060 mmol); 4b: 29% (33 mg, 0.060 mmol); 4f: 1% (1
mg, 0.002 mmol); 4g: 10% (11 mg, 0.020 mmol); 4h: 9% (10 mg,
0.020 mmol); 4j: 1% (1 mg, 0.002 mmol); 4k: 3% (4 mg, 0.006
mmol); 4n: 19% (22 mg, 0.040 mmol); 4o: 7% (8 mg, 0.01 mmol);
4q: 3% (4 mg, 0.006 mmol); 5b: 91% (79 mg, 0.18 mmol); 5c: 83%
(72 mg, 0.17 mmol); 5d: 57% (50 mg, 0.11 mmol); 5e: 53% (45 mg,
0.11 mmol); 5f: 57% (48 mg, 0.11 mmol); 5g: 94% (79 mg, 0.19
mmol); 5h: 73% (64 mg, 0.15 mmol); 5i: 39% (38 mg, 0.080 mmol);
6d: 36% (39 mg, 0.070 mmol); 6e: 21% (22 mg, 0.040 mmol); 6h:
6% (7 mg, 0.01 mmol).
Synthesis of Compound 7. A well-stirred solution of 3a (81 mg,
0.20 mmol) in toluene (2 mL) by the addition of MeOTf (45 μL, 0.4
mmol) was heated at 100 °C under nitrogen gas for 6 h. After cooling
down to room temperature, the reaction solution was evaporated in a
vacuum. The residue was dissolved in methanol (2 mL) and then the
mixed solution of hydrazine (0.3 mL) and acetic acid (0.9 mL) (1:3,
v/v) was added to the above solution, which was further heated at 130
°C for 6 h. After cooling down to room temperature, water (20 mL)
was added to the solution, which was further extracted by ethyl
acetate (15 mL × 3). Organic layers were combined, dried over
MgSO4, filtered through a pad of Celite, and evaporated in a vacuum.
The residue was purified by silica gel chromatography using n-
hexane/ethyl acetate (30/1 to 10/1) as the eluent to give product 7 in
70% (28 mg, 0.14 mmol).
Synthesis of Compound 8. A well-stirred solution of 7 (500 mg,
2.50 mmol), copper(II) iodide (9.5 mg, 0.050 mmol), 2,2′-bipyridine
(8 mg, 0.05 mmol) in dimethylacetamide (10 mL) was heated at 130
°C for 24 h. After cooling down to room temperature, water (20 mL)
was added to the above solution that was further extracted by ethyl
acetate (15 mL × 3). Organic layers were combined, dried over
MgSO4, filtered through a pad of Celite, and evaporated in a vacuum.
The residue was purified by silica gel chromatography using n-
hexane/ethyl acetate (30/1 to 10/1) as the eluent to give product 8 in
37% (447 mg, 0.98 mmol).
Synthesis of (a) Compound 9 transformed to (b) Com-
pound 8. (a) A well-stirred solution of 3a (500 mg, 2.50 mmol) in
methanol (10 mL) was added by the mixed solution of hydrazine (1.8
mL) and acetic acid (5.4 mL) (1:3, v/v), which was heated at 100 °C
for 3 h. After cooling down to room temperature, 15 mL of water was
added to the above solution, which was extracted by ethyl acetate (15
mL × 2). Organic layers were combined, dried over MgSO4, filtered
through a pad of Celite, and evaporated in vacuum. Next, the residue
was dissolved in dimethylacetamide (5 mL) without purification, and
subsequently, copper(II) iodide (9.5 mg, 0.050 mmol) and 2,2′-
bipyridine (8 mg, 0.05 mmol) were added to the above solution,
which was heated at 130 °C for 24 h. After cooling down to room
temperature, 20 mL of water was added to the above solution that was
further extracted by ethyl acetate (15 mL × 3). Organic layers were
combined, dried over MgSO4, filtered through a pad of Celite, and
evaporated in a vacuum. The residue was purified by silica gel
chromatography using n-hexane/ethyl acetate (30/1 to 10/1) as the
eluent to give product 9 in 88% (447 mg, 0.98 mmol). (b) The
operating procedure for the synthesis of 8 from 9 was the same as that
of 7 to 8, and the yield of 8 is 70% (133 mg, 0.69 mmol).
Characterization Data of Compounds 3−9.16 tert-Butyl
phenyl(pyridin-2-yl)carbamate (1-H/Boc). White solid; mp 64−65
1
°C; Rf = 0.53 (n-hexane/ethyl acetate = 1/1); H NMR (400 MHz,
CDCl3) δ 1.45 (s, 9 H), 7.07 (ddd, J = 5.6, 4.8, 0.8 Hz, 1 H), 7.20−
7.25 (m, 3 H), 7.32−7.37 (m, 2 H), 7.50 (d, J = 8.0 Hz, 1 H), 7.70
(ddd, J = 8.6, 7, 2.0 Hz, 1 H), 8.38 (dd, J = 4.8 Hz, 1 H); 13C NMR
(CDCl3, 100 MHz) δ 28.2 (CH3), 81.6 (Cq), 120.5 (CH), 121.0
(CH), 126.3 (CH), 127.6 (CH × 2), 128.8 (CH × 2), 137.5 (CH),
141.8 (Cq), 148.6 (CH), 153.6 (Cq), 155.4 (Cq); MS (EI, m/z) 270
(M+, 3), 169 (100), 57 (45); HRMS (EI-magnetic sector) m/z [M+]
calcd for C16H18N2O2 270.1368, found 270.1369.
tert-Butyl (4-methylpyridin-2-yl)(phenyl)carbamate (1-Me/Boc).
White solid; mp 64−65 °C; Rf = 0.53 (n-hexane/ethyl acetate = 1/1);
1H NMR (400 MHz, CDCl3) δ 1.44 (s, 9 H), 2.36 (s, 3 H), 6.91 (dd,
J = 5.2, 0.8 Hz, 1 H), 7.19−7.23 (m, 3 H), 7.30−7.36 (m, 3 H), 8.24
(d, J = 5.2 Hz, 1 H); 13C NMR (CDCl3, 100 MHz) δ 21.0 (CH3),
28.2 (CH3 × 3), 81.5 (Cq), 121.6 (CH), 121.9 (CH), 126.1 (CH),
127.5 (CH × 2), 128.7 (CH × 2), 141.9 (Cq), 148.2 (CH), 148.9
(Cq), 153.7 (Cq), 155.4 (Cq); MS (EI, m/z) 284 (M+, 4), 183 (100),
57 (46); HRMS (EI-magnetic sector) m/z [M+] calcd for
C17H20N2O2 284.1525, found 284.1534.
Methyl (4-methoxypyridin-2-yl)(phenyl)carbamate (1-OMe/
Moc). White solid; mp 64−65 °C; Rf = 0.53 (n-hexane/ethyl acetate
1
= 1/1); H NMR (400 MHz, CDCl3) δ 3.76 (s, 3 H), 3.85 (s, 3 H),
6.66 (dd, J = 5.6, 2.4 Hz, 1 H), 7.07 (d, J = 2.0 Hz, 1 H), 7.26 (m, 3
H), 7.35−7.37 (m, 2 H), 8.20 (d, J = 5.6, 1 H); 13C NMR (100 MHz,
CDCl3) δ 53.2 (CH3), 55.3 (CH3), 106.2 (CH), 108.0 (CH), 126.8
(CH), 127.5 (CH × 2), 128.9 (CH × 2), 141.1 (Cq), 149.4 (CH),
155.1 (Cq), 156.4 (Cq), 167.1 (Cq); MS (EI, m/z) 258 (M+, 1), 257
(21), 177 (100), 164 (30), 161 (48); HRMS (EI-magnetic sector) m/
z [M+] calcd for C14H14N2O3 258.1004, found 258.1005.
N-(4-Methoxypyridin-2-yl)-N-phenylpivalamide (1-OMe/Piv).
White solid; mp 66−67 °C; Rf = 0.52 (n-hexane/ethyl acetate = 1/
1); 1H NMR (CDCl3, 400 MHz) δ 1.17 (s, 9 H), 3.80 (s, 3 H), 6.63
(d, J = 2.4 Hz, 1 H), 6.70 (dd, J = 6.0, 2.4 Hz, 1 H), 7.23−7.30 (m, 3
H), 7.33−7.37 (m, 2 H), 8.27 (d, J = 5.6 Hz, 1 H); 13C NMR
(CDCl3, 100 MHz) δ 29.3 (CH3 × 3), 42.1 (Cq), 55.3 (CH3), 107.7
(CH), 108.6 (CH), 127.1 (CH), 128.5 (CH × 2), 129.1 (CH × 2),
143.4 (Cq), 149.6 (CH), 158.6 (Cq), 167.3 (Cq), 181.1 (Cq); MS (EI,
m/z) 284 (M+, 1), 199 (100), 200 (17), 283 (14); HRMS (EI-
magnetic sector) m/z [M+] calcd for C17H20N2O2 284.1525, found
284.1524.
N-(4-Methoxypyridin-2-yl)-N-phenylacetamide (1-OMe/Ac).
White solid; mp 58−59 °C; Rf = 0.43 (n-hexane/ethyl acetate = 1/
2); 1H NMR (400 MHz, CDCl3) δ 2.10 (s, 3 H), 3.84 (s, 3 H), 6.69
(dd, J = 5.6, 2.4 Hz, 1 H), 6.99 (d, J = 1.2 Hz, 1 H), 7.29−7.33 (m, 3
H), 7.38−7.43 (m, 2 H), 8.24 (d, J = 5.6 Hz, 1 H); 13C NMR (100
MHz, CDCl3) δ 24.2 (Cq), 55.4 (CH3), 106.9 (CH), 108.5 (CH ×
2), 127.5 (CH), 128.1 (CH), 129.4 (CH × 2), 142.0 (Cq), 149.6
(CH), 156.7 (Cq), 167.1 (Cq), 170.9 (Cq); MS (EI, m/z) 242 (M+,
1), 199 (100), 200 (47); HRMS (EI-magnetic sector) m/z [M+] calcd
for C14H14N2O2 242.1055, found 242.1056.
N-Benzyl-4-methoxy-N-phenylpyridin-2-amine (1-OMe/Bn).
White solid; mp 81−82 °C; Rf = 0.63 (n-hexane/ethyl acetate = 1/
1); 1H NMR (400 MHz, CDCl3) δ 3.65 (s, 3 H), 5.25 (s, 2 H), 5.99
(d, J = 2.0 Hz, 1 H), 6.27 (dd, J = 6.0, 2.0 Hz, 1 H), 7.14−7.35 (m, 10
H), 8.05 (d, J = 5.6 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 166.7
(Cq), 160.6 (Cq), 148.9 (CH), 145.4 (Cq), 139.4 (Cq), 129.6 (CH ×
2), 128.2 (CH × 2), 127.5 (CH × 2), 126.9 (CH × 2), 126.6 (CH),
125.6 (CH), 101.8 (CH), 93.5 (CH), 54.8 (CH3), 53.7 (CH2); MS
(EI, m/z) 290 (M+, 1), 289 (48), 213 (65), 182 (45); HRMS (EI-
G
DOI: 10.1021/acs.organomet.9b00119
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magnetic sector) m/z [M+] calcd for C19H18N2O 290.1419, found
290.1421.
6.59 (dd, J = 5.7, 2.1 Hz, 1 H), 7.10−7.16 (m, 2 H), 7.22−7.30 (m, 3
H), 8.10 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.0
(CH3 × 3), 55.3 (CH3), 81.9 (Cq), 104.3 (CH), 107.5 (CH), 116.0
(d, JC−F = 20.0 Hz, CH), 124.1 (d, JC−F = 3.6 Hz, CH), 128.6 (d, JC−F
= 7.8 Hz, CH), 129.4 (d, JC−F = 12.8 Hz, Cq), 130.3 (d, JC−F = 0.9 Hz,
CH), 148.8 (CH), 153.0 (Cq), 156.0 (Cq), 158.3 (d, JC−F = 247.9 Hz,
Cq), 166.7 (Cq); MS (EI, m/z) 318 (M+, 2), 217 (22), 199 (100), 57
(38); HRMS m/z calcd for C17H19FN2O3 318.1380, found 318.1380.
tert-Butyl (4-chlorophenyl)(4-methoxypyridin-2-yl)carbamate
(1h). Yellow solid; mp 74−75 °C; Rf = 0.50 (n-hexane/ethyl acetate
tert-Butyl (4-methoxypyridin-2-yl)(phenyl)carbamate (1a).
White solid; mp 66−67 °C; Rf = 0.40 (n-hexane/ethyl acetate = 2/
1); 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9 H), 3.86 (s, 3 H), 6.63
(dd, J = 5.5, 2.5 Hz, 1 H), 7.04 (d, J = 2.5 Hz, 1 H), 7.20−7.25 (m, 3
H), 7.36 (t, J = 8.0 Hz, 2 H), 8.19 (d, J = 6.0 Hz, 1 H); 13C NMR
(125 MHz, CDCl3) δ 28.2 (CH3 × 3), 55.3 (CH3), 81.5 (Cq), 106.4
(CH), 107.6 (CH), 126.2 (CH), 127.5 (CH × 2), 128.7 (CH × 2),
141.8 (Cq), 149.3 (CH), 153.5 (Cq), 156.9 (Cq), 166.8 (Cq); MS (EI,
m/z) 300 (M+, 4); HRMS (EI-magnetic sector) m/z [M+] calcd for
C17H20N2O3 300.1474, found 300.1476.
1
= 2/1); H NMR (300 MHz, CDCl3) δ 1.45 (s, 9 H), 3.86 (s, 3 H),
6.64 (dd, J = 5.5, 2.5 Hz, 1 H), 7.07 (d, J = 2.5 Hz, 1 H), 7.15 (d, J =
6.5 Hz, 2 H), 7.30 (d, J = 8.5 Hz, 2 H), 8.18 (d, J = 5.5 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 28.1 (CH3 × 3), 55.3 (CH3), 81.9 (Cq),
106.3 (CH), 107.8 (CH), 128.8 (CH × 2), 128.9 (CH × 2), 131.8
(Cq), 140.3 (Cq), 149.3 (CH), 153.2 (Cq), 156.5 (Cq), 166.9 (Cq);
MS (EI, m/z) 334 (M+, 3), 233 (65), 57 (100); HRMS m/z calcd for
C17H19ClN2O3 334.1084, found 334.1086.
tert-Butyl (4-bromophenyl)(4-methoxypyridin-2-yl)carbamate
(1i). Orange solid; mp 120−121 °C; Rf = 0.50 (n-hexane/ethyl
acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9 H), 3.87 (s,
3 H), 6.65 (dd, J = 5.7, 2.1 Hz, 1 H), 7.05−7.10 (m, 3 H), 7.45 (d, J =
8.7 Hz, 2 H), 8.18 (d, J = 5.1 Hz, 1 H); 13C NMR (125 MHz, CDCl3)
δ 28.2 (CH3 × 3), 55.4 (CH3), 82.0 (Cq), 106.3 (CH), 107.8 (CH),
119.7 (Cq), 129.1 (CH × 2), 131.8 (CH × 2), 140.9 (Cq), 149.3
(CH), 153.2 (Cq), 156.4 (Cq), 166.9 (Cq); MS (EI, m/z) 378 (M+,
5), 279 (100), 277 (90), 57 (57); HRMS m/z calcd for
C17H19BrN2O3 378.0579, found 378.0580.
tert-Butyl (2-methoxyphenyl)(4-methoxypyridin-2-yl)carbamate
(1b). Yellow solid; mp 72−73 °C; Rf = 0.59 (n-hexane/ethyl acetate =
1
1/1); H NMR (300 MHz, CDCl3) δ 1.41 (s, 9 H), 3.80 (s, 3 H),
3.85 (s, 3 H), 6.55 (dd, J = 5.7, 2.1 Hz, 1 H), 6.93−6.97 (m, 2 H),
7.16−7.30 (m, 3 H), 8.10 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 28.1 (CH3 × 3), 55.2 (CH3), 55.6 (CH3), 81.0 (Cq), 104.1
(CH), 107.0 (CH), 111.7 (CH), 120.6 (CH), 128.4 (CH), 129.7
(CH), 130.7 (Cq), 148.8 (CH), 153.7 (Cq), 155.4 (Cq), 156.8 (Cq),
166.5 (Cq); MS (EI, m/z) 330 (M+, 1), 299 (100), 243 (76), 199
(97), 89 (62), 57 (70); HRMS m/z calcd for C18H22N2O4 330.1580,
found 330.1579.
tert-Butyl (3-methoxyphenyl)(4-methoxypyridin-2-yl)carbamate
(1c). Brown solid; mp 50−51 °C; Rf = 0.56 (n-hexane/ethyl acetate =
1
1/1); H NMR (300 MHz, CDCl3) δ 1.45 (s, 9 H), 3.77 (s, 3 H),
3.85 (s, 3 H), 6.64 (dd, J = 5.4, 1.8 Hz, 1 H), 6.79 (t, J = 7.8 Hz, 3 H),
7.00 (s, 1 H), 7.22 (d, J = 9.0 Hz, 1 H), 8.21 (d, J = 6.0 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 28.2 (CH3 × 3), 55.2 (CH3), 55.3
(CH3), 81.6 (Cq), 106.6 (CH), 107.7 (CH), 111.8 (CH), 113.3
(CH), 119.8 (CH), 129.2 (CH), 142.8 (Cq), 149.4 (CH), 153.4 (Cq),
156.8 (Cq), 159.8 (Cq), 166.8 (Cq); MS (EI, m/z) 330 (M+, 22), 230
(100), 215 (55), 57 (100); HRMS m/z calcd for C18H22N2O4
330.1580, found 330.1578.
tert-Butyl (2-benzoylphenyl)(4-methylpyridin-2-yl)carbamate (3-
1
Me/Boc). White oil; Rf = 0.53 (n-hexane/ethyl acetate = 1/2); H
NMR (400 MHz, CDCl3) δ 1.37 (s, 9 H), 2.21 (s, 3 H), 6.71 (dd, J =
5.2, 0.4 Hz, 1 H), 7.09 (s, 1 H), 7.33−7.57 (m, 8 H), 7.70 (dd, J =
8.0, 0.8 Hz, 1 H), 8.03 (d, J = 4.8 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ 21.0 (CH3), 28.1 (CH3), 81.8 (Cq), 120.6 (CH), 121.1
(CH), 126.5 (CH), 127.9 (CH × 2), 129.5 (CH), 130.0 (CH × 2),
130.7 (CH), 130.9 (CH), 132.7 (CH), 136.9 (Cq), 137.2 (Cq), 139.8
(Cq), 147.2 (CH), 148.2 (Cq), 153.2 (Cq), 154.6 (Cq), 195.7 (Cq);
MS (ESI+, m/z) 389 (M+, 100); HRMS (ESI+) m/z [M + H] calcd
for C24H25N2O3 389.1860, found 389.1865.
tert-Butyl (4-methoxyphenyl)(4-methoxypyridin-2-yl)carbamate
(1d). White solid; mp 108−109 °C; Rf = 0.55 (n-hexane/ethyl acetate
1
= 1/1); H NMR (300 MHz, CDCl3) δ 1.44 (s, 9 H), 3.80 (s, 3 H),
3.85 (s, 3 H), 6.60 (dd, J = 5.7, 2.4 Hz, 1 H), 6.88 (d, J = 6.9 Hz, 2
H), 7.06 (d, J = 2.1 Hz, 1 H), 7.14 (d, J = 8.7 Hz, 2 H), 8.18 (d, J =
6.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.2 (CH3 × 3), 55.3
(CH3), 55.4 (CH3), 81.4 (Cq), 105.9 (CH), 107.4 (CH), 114.0 (CH
× 2), 128.9 (CH × 2), 134.7 (Cq), 149.2 (CH), 153.8 (Cq), 157.0
(Cq), 157.8 (Cq), 166.8 (Cq); MS (EI, m/z) 330 (M+, 8), 230 (100),
215 (60); HRMS m/z calcd for C18H22N2O4 330.1580, found
330.1582.
Methyl (2-benzoylphenyl)(4-methoxypyridin-2-yl)carbamate (3-
1
OMe/Moc). White oil; Rf = 0.59 (n-hexane/ethyl acetate = 1/1); H
NMR (400 MHz, CDCl3) δ 3.63 (s, 3 H), 3.77 (s, 3 H), 6.50 (dd, J =
5.6, 2.4 Hz, 1 H), 7.16 (d, J = 2.0 Hz, 1 H), 7.36−7.45 (m, 5 H),
7.50−7.57 (m, 2 H), 7.75 (td, J = 7.6, 2.0 Hz,, 2 H), 8.01 (d, J = 6.0
Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 53.2 (CH3), 55.2 (CH3),
104.6 (CH), 108.2 (CH), 126.7 (CH), 128.0 (CH × 2), 129.6 (CH),
130.2 (CH × 2), 131.2 (CH), 132.9 (CH), 139.3(Cq), 148.4 (CH),
154.7(Cq), 155.9(Cq), 166.8(Cq), 166.4(Cq), 195.6(Cq); HRMS (EI-
magnetic sector) m/z [M+] calcd for C21H18N2O4 362.1267, found
362.1267.
tert-Butyl (4-fluorophenyl)(4-methoxypyridin-2-yl)carbamate
(1e). Yellow solid; mp 58−59 °C; Rf = 0.31 (n-hexane/ethyl acetate
1
= 2/1); H NMR (300 MHz, CDCl3) δ 1.44 (s, 9 H), 3.87 (s, 3 H),
6.63 (dd, J = 6.0, 2.4 Hz, 1 H), 7.00−7.10 (m, 3 H), 7.17−7.21 (m, 2
H), 8.17 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.2
(CH3 × 3), 55.3 (CH3), 81.8 (Cq), 106.0 (CH), 107.6 (CH), 115.6
(d, JC−F = 22.8 Hz, CH), 129.4 (d, JC−F = 8.3 Hz, CH), 137.7 (d, JC−F
N-(2-Benzoylphenyl)-N-(4-methoxypyridin-2-yl)pivalamide (3-
1
OMe/Piv). White oil; Rf = 0.63 (n-hexane/ethyl acetate = 1/1); H
NMR (400 MHz, CDCl3) δ 0.94 (s, 9 H), 3.79 (s, 3 H), 6.71 (dd, J =
6.0, 2.4 Hz, 1 H), 7.08 (d, J = 2.4 Hz, 1 H), 7.24−7.33 (m, 3 H), 7.44
(t, J = 7.6 Hz, 3 H), 7.56 (tt, J = 9.2, 1.2 Hz, 1 H), 7.85 (dd, J = 8.0,
0.8 Hz, 2 H), 8.22 (d, J = 5.6 Hz, 1 H); 13C NMR (100 MHz, CDCl3)
δ 28.6 (CH3× 3), 41.7 (Cq), 55.4 (CH3), 107.8 (CH), 109.9 (CH),
126.0 (CH), 128.2 (CH × 2), 128.7 (CH), 129.5 (CH), 130.6 (CH ×
2), 131.1 (CH), 133.1 (CH), 136.8 (Cq), 137.7 (Cq), 148.7 (CH),
158.3 (Cq), 167.4 (Cq), 180.7 (Cq), 196.2 (Cq); MS (ESI, m/z) 411
(M+23, 1), 397 (80), 389 (100), 381 (90); HRMS (EI-magnetic
sector) m/z [M+] calcd for C24H24N2O3 388.1787, found 388.1786.
N-(2-Benzoylphenyl)-N-(4-methoxypyridin-2-yl)acetamide (3-
= 2.8 Hz, Cq), 149.2 (CH), 153.5 (Cq), 156.6 (Cq), 160.9 (d, JC−F
=
244.0 Hz, Cq), 166.9 (Cq); MS (EI, m/z) 318 (M+, 4), 230 (48), 217
(100), 57 (54); HRMS m/z calcd for C17H19FN2O3 318.1380, found
318.1377.
tert-Butyl (3-fluorophenyl)(4-methoxypyridin-2-yl)carbamate
(1f). Yellow solid; mp 68−69 °C; Rf = 0.28 (n-hexane/ethyl acetate
1
= 2/1); H NMR (300 MHz, CDCl3) δ 1.45 (s, 9 H), 3.87 (s, 3 H),
6.67 (dd, J = 6.0, 2.4 Hz, 1 H), 6.89−7.03 (m, 4 H), 7.24−7.32 (m, 1
H), 8.21 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.1
(CH3 × 3), 55.4 (CH3), 82.0 (Cq), 106.7 (CH), 108.0 (CH), 113.0
(d, JC−F = 21.0 Hz, CH), 114.6 (d, JC−F = 23.8 Hz, CH), 122.9 (d,
1
OMe/Ac). White oil; Rf = 0.53 (n-hexane/ethyl acetate = 1/2); H
JC−F = 2.8 Hz, CH), 129.6 (d, JC−F = 9.1 Hz, CH), 143.2 (d, JC−F
10.0 Hz, Cq), 149.5 (CH), 153.1 (Cq), 156.4 (Cq), 162.6 (d, JC−F
=
=
NMR (400 MHz, CDCl3) δ 2.07 (s, 3 H), 3.76 (s, 3 H), 6.57 (bs, 1
H), 7.19 (d, J = 2.4 Hz, 1 H), 7.38−7.40 (m, 4 H), 7.49−7.57 (m, 3
H), 7.78 (d, J = 2.8 Hz, 2 H), 8.10 (bs, 1 H); 13C NMR (100 MHz,
CDCl3) δ 29.7 (CH3), 55.2 (CH3), 109.0 (CH), 126.9 (CH), 128.1
(CH × 2), 128.2 (CH), 129.3(CH), 130.4 (CH × 2), 131.3 (CH),
132.9 (CH), 134.4 (Cq), 136.7 (Cq), 137.8 (Cq), 140.1 (Cq), 148.6
245.1 Hz, Cq), 167.0 (Cq); MS (EI, m/z) 318 (M+, 3), 217 (100), 57
(50); HRMS m/z calcd for C17H19FN2O3 318.1380, found 318.1377.
tert-Butyl (2-fluorophenyl)(4-methoxypyridin-2-yl)carbamate
(1g). White solid; mp 61−62 °C; Rf = 0.30 (n-hexane/ethyl acetate
1
= 2/1); H NMR (300 MHz, CDCl3) δ 1.44 (s, 9 H), 3.87 (s, 3 H),
H
DOI: 10.1021/acs.organomet.9b00119
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(CH), 167.0 (Cq), 171.1 (Cq), 195.6 (Cq); MS (EI, m/z) 361 (M+,
1), 340 (30), 177 (41), 86 (58), 84 (100), 70 (28), 61 (44); HRMS
(EI-magnetic sector) m/z [M+] calcd for C21H18N2O3 346.1317,
found 346.1318.
MHz, CDCl3) δ 28.0 (CH3 × 3), 55.2 (CH3), 81.9 (Cq), 103.8 (CH),
107.4 (CH), 116.3 (d, JC−F = 21.5 Hz, CH), 123.6 (d, JC−F = 3.6 Hz,
CH), 126.9 (CH), 127.0 (d, JC−F = 11.4 Hz, Cq), 129.9 (CH), 130.9
(CH), 131.8 (d, JC−F = 11.0 Hz, CH), 133.6 (d, JC−F = 8.8 Hz, CH),
137.1 (Cq), 139.8 (Cq), 148.1 (CH), 153.1 (Cq), 156.1 (Cq), 160.8
(d, JC−F = 256.0 Hz, Cq), 166.5 (Cq), 192.5 (Cq); MS (EI, m/z) 422
(M+, 1), 301 (65), 243 (90), 227 (55), 199 (100), 123 (71); HRMS
m/z calcd for C24H23FN2O4 422.1642, found 422.1642.
(2-(Benzyl(4-methoxypyridin-2-yl)amino)phenyl)(phenyl)-meth-
anone (3-OMe/Bn). White oil; Rf = 0.56 (n-hexane/ethyl acetate = 1/
1); 1H NMR (400 MHz, CDCl3) δ 3.61 (s, 3 H), 4.95 (s, 2 H), 5.78
(s, 1 H), 6.13 (d, J = 5.8 Hz, 1 H), 7.16−7.25 (m, 7 H), 7.30−7.35
(m, 3 H), 7.44−7.51 (m, 3 H), 7.63 (dd, J = 9.2, 0.8 Hz, 1 H), 7.74
(d, J = 3.2 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 173.1 (Cq),
166.6 (Cq), 159.6 (Cq), 148.6 (CH), 144.4 (Cq), 138.8(Cq), 137.4
(Cq), 132.6 (CH), 131.9 (CH), 130.2 (CH), 129.6 (CH), 128.3 (CH
× 2), 127.9 (CH × 2), 127.3 (CH × 2), 126.8 (CH), 125.8 (CH),
101.8 (Cq), 93.5 (CH), 54.8 (CH2), 54.7 (CH3); MS (EI, m/z) 394
(M+, 1), 289 (100), 213 (20); HRMS (EI-magnetic sector) m/z [M+]
calcd for C26H22N2O2 394.1681, found 394.1681.
tert-Butyl (2-(3-fluorobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3g). Yellow solid; mp 76−77 °C; Rf = 0.43 (n-hexane/
1
ethyl acetate = 2/1); H NMR (300 MHz, CDCl3) δ 1.39 (s, 9 H),
3.77 (s, 3 H), 6.46 (dd, J = 3.9, 1.8 Hz, 1 H), 6.98 (s, 1 H), 7.20−7.44
(m, 6 H), 7.50−7.57 (m, 2 H), 7.97 (d, J = 6.0 Hz, 1 H); 13C NMR
(125 MHz, CDCl3) δ 28.0 (CH3 × 3), 55.2 (CH3), 82.0 (Cq), 104.4
(CH), 107.6 (CH), 116.6 (d, JC−F = 22.8 Hz, CH), 119.7 (d, JC−F
=
21.9 Hz, CH), 125.8 (d, JC−F = 3.6 Hz, CH), 126.6 (CH), 129.3
(CH), 129.6 (d, JC−F = 8.1 Hz, CH), 130.6 (CH), 131.3 (CH), 136.6
(Cq), 139.5 (d, JC−F = 6.4 Hz, Cq), 139.9 (Cq), 148.2 (CH), 153.1
(Cq), 156.0 (Cq), 162.3 (d, JC−F = 246.1 Hz, Cq), 166.5 (Cq), 194.4
(Cq); MS (EI, m/z) 422 (M+, 1), 340 (44), 177 (65), 61 (94), 57
(100); HRMS m/z calcd for C24H23FN2O4 422.1642, found
422.1640.
tert-Butyl (2-benzoylphenyl)(4-methoxypyridin-2-)carbamate
(3a). Yellow solid; mp 76−77 °C; Rf = 0.40 (n-hexane/ethyl acetate
1
= 2/1); H NMR (300 MHz, CDCl3) δ 1.38 (s, 9 H), 3.74 (s, 3 H),
6.45 (dd, J = 6.0, 2.4 Hz, 1 H), 6.92 (d, J = 2.1 Hz, 1 H), 7.32−7.58
(m, 7 H), 7.72 (d, J = 7.2 Hz, 2 H), 7.97 (d, J = 5.7 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 28.1 (CH3 × 3), 55.1 (CH3), 81.9 (Cq),
104.6 (CH), 107.6 (CH), 126.6 (CH), 127.9 (CH × 2), 129.5 (CH),
130.1 (CH × 2), 130.7 (CH), 131.0 (CH), 132.7 (CH), 137.0 (Cq),
137.3 (Cq), 139.8 (Cq), 148.2 (CH), 153.1 (Cq), 156.1 (Cq), 166.4
(Cq), 195.7 (Cq); MS (EI, m/z) 405 (M+,1), 275 (43), 243 (64), 227
(53), 99 (100); HRMS m/z calcd for C24H24N2O4 404.1736, found
404.1735.
tert-Butyl (2-(4-fluorobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3h). Yellow solid; mp 84−85 °C; Rf = 0.60 (n-hexane/
1
ethyl acetate = 1/1); H NMR (300 MHz, CDCl3) δ 1.38 (s, 9 H),
3.76 (s, 3 H), 6.46 (dd, J = 5.7, 2.4 Hz, 1 H), 6.98−7.05 (m, 3 H),
7.37−7.43 (m, 3 H), 7.63 (td, J = 8.4, 2.1 Hz, 1 H), 7.76 (t, J = 5.4
Hz, 2 H), 7.96 (d, J = 6.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ
28.1 (CH3 × 3), 55.2 (CH3), 82.0 (Cq), 104.6 (CH), 107.5 (CH),
115.1 (d, JC−F = 21.9 Hz, CH), 126.6 (CH), 129.2 (CH), 130.6
(CH), 131.1 (CH), 133.6 (d, JC−F = 2.8 Hz, Cq), 136.9 (Cq), 139.8
(Cq), 148.2 (CH), 153.1 (Cq), 156.0 (Cq), 164.5 (Cq), 165.5 (d, JC−F
= 242.2 Hz, Cq), 166.5 (Cq), 194.2 (Cq); MS (EI, m/z) 422 (M+, 1),
243 (43), 199 (100), 85 (44), 71 (42), 57 (41); HRMS m/z calcd for
C24H23FN2O4 422.1642, found 422.1645.
tert-Butyl (2-(4-methoxybenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (3b). Yellow solid; mp 122−123 °C; Rf = 0.51 (n-
hexane/ethyl acetate = 1/1); 1H NMR (300 MHz, CDCl3) δ 1.38 (s,
9 H), 3.74 (s, 3 H), 3.84 (s, 3 H), 6.45 (dd, J = 5.7, 2.4 Hz, 1 H), 6.82
(d, J = 9.0 Hz, 2 H), 6.93 (d, J = 2.1 Hz, 1 H), 7.33−7.56 (m, 4 H),
7.70 (d, J = 8.7 Hz, 2 H), 7.98 (d, J = 5.7 Hz, 1 H); 13C NMR (125
MHz, CDCl3) δ 28.1 (CH3 × 3), 55.1 (CH3), 55.4 (CH3), 81.8 (Cq),
104.8 (CH), 107.6 (CH), 113.2 (CH × 2), 126.6 (CH), 129.2 (CH),
130.2 (Cq), 130.6 (CH), 130.7 (CH), 132.4 (CH × 2), 137.4 (Cq),
139.6 (Cq), 148.2 (CH), 153.1 (Cq), 156.2 (Cq), 163.3 (Cq), 166.4
(Cq), 194.4 (Cq); MS (EI, m/z) 434 (M+, 1), 243 (40), 199 (100), 57
(66); HRMS m/z calcd for C25H26N2O5 434.1842, found 434.1844.
tert-Butyl (4-methoxypyridin-2-yl)(2-(4-(trifluoromethyl)-
benzoyl)phenyl)carbamate (3d). Yellow solid; mp 148−149 °C; Rf
= 0.48 (n-hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3)
δ 1.38 (s, 9 H), 3.76 (s, 3 H), 6.47 (dd, J = 5.7, 1.8 Hz, 1 H), 6.99 (s,
1 H), 7.36−7.43 (m, 3 H), 7.56−7.62 (m, 3 H), 7.83 (d, J = 8.1 Hz, 2
H), 7.95 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.0
(CH3 × 3), 55.1 (CH3), 82.1 (Cq), 104.3 (CH), 107.4 (CH), 124.9
(q, JC−F = 4.8 Hz, CH × 2), 126.7 (CH), 129.4 (CH), 130.2 (CH ×
2), 130.7 (CH), 131.5 (CH), 133.8 (Cq), 136.5 (Cq), 139.9 (Cq),
140.3 (Cq), 148.2 (CH), 153.1 (Cq), 155.9 (Cq), 166.5 (Cq), 194.7
(Cq); MS (EI, m/z) 472 (M+, 1), 343 (26), 227 (43), 199 (100);
HRMS m/z calcd for C25H23F3N2O4 472.1610, found 472.1611.
tert-Butyl (2-(4-acetylbenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3e). Yellow solid; mp 118−119 °C; Rf = 0.50 (n-
hexane/ethyl acetate = 1/1); 1H NMR (300 MHz, CDCl3) δ 1.38 (s,
9 H), 2.62 (s, 3 H), 3.75 (s, 3 H), 6.46 (dd, J = 6.0, 2.4 Hz, 1 H), 6.99
(d, J = 2.4 Hz, 1 H), 7.38−7.44 (m, 3 H), 7.58 (td, J = 6.9, 1.8 Hz, 1
H), 7.79 (d, J = 8.1, 2 H), 7.89−7.97 (m, 3 H); 13C NMR (125 MHz,
CDCl3) δ 26.8 (CH3), 28.0 (CH3 × 3), 55.1 (CH3), 82.0 (Cq), 104.3
(CH), 107.4 (CH), 126.7 (CH), 127.8 (CH × 2), 129.4 (CH), 130.1
(CH × 2), 130.7 (CH), 131.4 (CH), 136.7 (Cq), 139.6 (Cq), 139.9
(Cq), 140.9 (Cq), 148.1 (CH), 153.1 (Cq), 155.9 (Cq), 166.5 (Cq),
195.1 (Cq), 197.5 (Cq); MS (EI, m/z) 446 (M+, 1), 345 (61), 317
(81), 243 (92), 227 (88), 199 (100), 147 (76); HRMS m/z calcd for
C26H26N2O5 446.1842, found 446.1840.
tert-Butyl (2-(2-chlorobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3i). Yellow solid; mp 94−95 °C; Rf = 0.40 (n-hexane/
1
ethyl acetate = 2/1); H NMR (300 MHz, CDCl3) δ 1.41 (s, 9 H),
3.81 (s, 3 H), 6.49 (dd, J = 6.0, 2.1 Hz, 1 H), 7.15−7.19 (m, 2 H),
7.29−7.41 (m, 5 H), 7.49 (d, J = 7.2 Hz, 1 H), 7.56 (t, J = 7.5 Hz, 1
H), 7.98 (d, J = 6.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.1
(CH3 × 3), 55.2 (CH3), 81.9 (Cq), 103.5 (CH), 107.4 (CH), 126.2
(CH), 127.1 (CH), 130.2 (CH), 130.7 (CH), 131.3 (CH), 131.4
(CH), 131.5 (CH), 132.1 (Cq), 132.4 (CH), 136.1 (Cq), 138.2 (Cq),
140.3 (Cq), 147.9 (CH), 153.2 (Cq), 156.0 (Cq), 166.5 (Cq), 194.2
(Cq); MS (EI, m/z) 438 (M+, 1), 340 (61), 275 (65), 243 (97), 199
(100), 177 (99), 161 (74); HRMS m/z calcd for C24H23ClN2O4
438.1346, found 438.1347.
tert-Butyl (2-(3-chlorobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3j). Yellow solid; mp 88−89 °C; Rf = 0.45 (n-hexane/
1
ethyl acetate = 2/1); H NMR (300 MHz, CDCl3) δ 1.39 (s, 9 H),
3.77 (s, 3 H), 6.46 (dd, J = 5.7, 2.1 Hz, 1 H), 6.99 (d, J= 1.8 Hz, 1 H),
7.29 (t, J = 7.8 Hz, 1 H), 7.38−7.48 (m, 4 H), 7.54−7.62 (m, 2 H),
7.70 (s, 1 H), 7.96 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 28.1 (CH3 × 3), 55.2 (CH3), 82.1 (Cq), 104.3 (CH), 107.6
(CH), 126.7 (CH), 128.1 (CH), 129.3 (CH), 129.9 (CH), 130.6
(CH), 131.3 (CH), 132.6 (CH), 134.0 (Cq), 136.6 (Cq), 139.0 (Cq),
139.8 (Cq), 148.2 (CH), 153.1 (Cq), 155.9 (Cq), 166.5 (Cq), 194.5
(Cq); MS (EI, m/z) 438 (M+, 1), 309 (40), 227 (78), 199 (100);
HRMS m/z calcd for C24H23ClN2O4 438.1346, found 438.1345.
tert-Butyl (2-(4-chlorobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3k). Yellow solid; mp 106−107 °C; Rf = 0.48 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.38 (s,
9 H), 3.78 (s, 3 H), 6.47 (dd, J = 5.7, 1.8 Hz, 1 H), 6.98 (d, J = 1.8
Hz, 1 H), 7.30−7.43 (m, 5 H), 7.56 (td, J = 7.2, 1.8 Hz, 1 H), 7.67 (d,
J = 8.4 Hz, 2 H), 7.95 (d, J = 6.0 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 28.1 (CH3 × 3), 55.2 (CH3), 82.0 (Cq), 104.5 (CH), 107.5
(CH), 126.6 (CH), 128.3 (CH × 2), 129.2 (CH), 130.7 (CH), 131.2
(CH), 131.4 (CH × 2), 135.7 (Cq), 136.8 (Cq), 139.1 (Cq), 139.8
(Cq), 148.2 (CH), 153.1 (Cq), 156.0 (Cq), 166.5 (Cq), 194.5 (Cq);
tert-Butyl (2-(2-fluorobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3f). Yellow solid; mp 166−167 °C; Rf = 0.54 (n-
hexane/ethyl acetate = 1/1); 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
9 H), 3.79 (s, 3 H), 6.48 (dd, J = 5.7, 2.4 Hz, 1 H), 7.00−7.12 (m, 3
H), 7.34−7.59 (m, 6 H), 7.99 (d, J = 5.7 Hz, 1 H); 13C NMR (125
I
DOI: 10.1021/acs.organomet.9b00119
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
MS (EI, m/z) 438 (M+, 1), 309 (49), 243 (81), 227 (64), 199 (100);
HRMS m/z calcd for C24H2335ClN2O4 438.1346, found 438.1343.
tert-Butyl (2-(3-bromobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3l). Yellow solid; mp 78−79 °C; Rf = 0.43 (n-hexane/
8.00 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.0 (CH3
× 3), 55.0 (CH3), 55.4 (CH3 × 2), 81.6 (Cq), 98.3 (CH), 107.3
(CH), 121.2 (Cq), 126.7 (CH), 129.6 (CH), 130.5 (CH), 131.1
(CH), 134.0 (CH), 139.1 (Cq), 139.2 (Cq), 147.9 (CH), 153.2 (Cq),
156.1 (Cq), 160.5 (Cq), 163.8 (Cq), 166.2 (Cq), 194.0 (Cq); MS (EI,
m/z) 464 (M+, 1), 305 (42), 243 (85), 199 (100), 165 (47), 57 (70);
HRMS m/z calcd for C26H28N2O6 464.1947, found 464.1949.
tert-Butyl (2-(3-formylbenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3r). Yellow solid; mp 88−89 °C; Rf = 0.63 (n-hexane/
1
ethyl acetate = 2/1); H NMR (300 MHz, CDCl3) δ 1.39 (s, 9 H),
3.77 (s, 3 H), 6.46 (dd, J = 5.7, 2.1 Hz, 1 H), 6.99 (s, 1 H), 7.23−7.25
(t, J = 7.8 Hz, 1 H), 7.38−7.43 (m, 3 H), 7.54−7.66 (m, 3 H), 7.84
(s, 1 H), 7.96 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ
28.1 (CH3 × 3), 55.2 (CH3), 82.1 (Cq), 104.3 (CH), 107.6 (CH),
126.7 (CH), 128.5 (CH), 129.5 (CH), 130.6 (CH), 131.3 (CH),
132.8 (CH), 135.5 (CH), 136.6 (Cq), 139.2 (Cq), 139.8 (Cq), 148.2
(CH), 153.1 (Cq), 155.9 (Cq), 166.5 (Cq), 194.4 (Cq); MS (EI, m/z)
482 (M+, 1), 353 (39), 299 (37), 243 (87), 227 (87), 199 (100);
HRMS m/z calcd for C24H23BrN2O4 482.0841, found 482.0843.
tert-Butyl (2-(4-bromobenzoyl)phenyl)(4-methoxypyridin-2-yl)-
carbamate (3m). Yellow solid; mp 82−83 °C; Rf = 0.48 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.38 (s,
9 H), 3.77 (s, 3 H), 6.47 (dd, J = 5.4, 1.8 Hz, 1 H), 6.98 (s, 1 H),
7.37−7.60 (m, 8 H), 7.95 (d, J = 5.7, 1 H); 13C NMR (125 MHz,
CDCl3) δ 28.1 (CH3 × 3), 55.2 (CH3), 82.0 (Cq), 104.5 (CH), 107.5
(CH), 126.7 (CH), 127.8 (Cq), 129.3 (CH), 130.7 (CH), 131.2 (CH
× 2), 131.5 (CH × 2), 136.1 (Cq), 136.7 (Cq), 139.8 (Cq), 148.2
(CH), 153.1 (Cq), 156.0 (Cq), 166.5 (Cq), 194.7 (Cq); MS (EI, m/z)
482 (M+, 1), 355 (27), 227 (52), 199 (100). HRMS m/z calcd for
C24H23BrN2O4 482.0841, found 482.0844.
tert-Butyl (2-(3,5-dimethylbenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (3n). Yellow solid; mp 132−133 °C; Rf = 0.63 (n-
hexane/ethyl acetate = 1/1); 1H NMR (300 MHz, CDCl3) δ 1.37 (s,
9 H), 2.26 (s, 6 H), 3.74 (s, 3 H), 6.44 (dd, J = 5.4, 2.1 Hz, 1 H), 6.95
(d, J = 2.4 Hz, 1 H), 7.12 (s, 1 H), 7.29 (s, 2 H), 7.34−7.46 (m, 3 H),
7.52−7.58 (m, 1 H), 7.98 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 21.1 (CH3 × 2), 28.0 (CH3 × 3), 55.1 (CH3), 81.8 (Cq),
104.6 (CH), 107.6 (CH), 126.6 (CH), 127.8 (CH × 2), 129.4 (CH),
130.7 (CH), 130.8 (CH), 134.5 (CH), 137.4 (Cq), 137.5 (Cq), 137.6
(Cq), 139.6 (Cq), 148.1 (CH), 153.1 (Cq), 156.2 (Cq), 166.3 (Cq),
196.2 (Cq); MS (EI, m/z) 432 (M+, 1), 303 (63), 243 (88), 227 (89),
199 (100); HRMS m/z calcd for C26H28N2O4 432.2049, found
432.2047.
1
ethyl acetate = 1/1); H NMR (300 MHz, CDCl3) δ 1.37 (s, 9 H),
3.75 (s, 3 H), 6.45 (dd, J = 5.7, 2.4 Hz, 1 H), 6.98 (d, J = 2.1 Hz, 1
H), 7.38−7.48 (m, 3 H), 7.55−7.61 (m, 2 H), 7.95 (d, J = 6.0 Hz, 1
H), 8.03 (dd, J = 7.5, 1.5 Hz, 2 H), 8.19 (s, 1 H), 9.98 (s, 1 H); 13C
NMR (125 MHz, CDCl3) δ 28.0 (CH3 × 3), 55.2 (CH3), 82.2 (Cq),
104.5 (CH), 107.4 (CH), 126.8 (CH), 128.8 (CH), 129.3 (CH),
130.6 (CH), 131.5 (CH), 132.2 (CH), 132.3 (CH), 135.4 (CH),
136.1 (Cq), 136.5 (Cq), 138.2 (Cq), 139.9 (Cq), 148.2 (CH), 153.1
(Cq), 155.9 (Cq), 166.5 (Cq), 191.5 (CH), 194.6 (Cq); MS (EI, m/z)
432 (M+, 1), 303 (27), 227 (66), 199 (100), 184 (28); HRMS m/z
calcd for C25H24N2O5 432.1685, found 432.1683.
Methyl (2,6-dibenzoylphenyl)(4-methoxypyridin-2-yl)carbamate
(4-OMe/Moc). White oil; Rf = 0.63 (n-hexane/ethyl acetate = 1/1);
1H NMR (CDCl3, 400 MHz) δ 3.62 (s, 3 H), 3.67 (s, 3 H), 6.32 (dd,
J = 4.4, 2.4 Hz, 1 H), 6.99 (bs, 1 H), 7.35 (td, J = 7.6, 1.2 Hz, 4 H),
7.51 (td, J = 8.4, 1.2 Hz, 3 H), 7.62 (dd, J = 7.2, 0.8 Hz, 2 H), 7.71 (d,
J = 5.6 Hz, 1 H), 7.74−7.77 (m, 4 H); 13C NMR (CDCl3, 100 MHz)
δ 53.2 (CH3), 55.0 (CH3), 102.1 (Cq), 107.7 (CH), 126.5 (CH),
127.9 (CH × 4), 130.0 (CH × 4), 131.2 (CH × 2), 132.9 (CH × 2),
137.1(Cq × 2), 139.3(Cq × 2), 147.1 (CH), 154.4 (Cq), 154.9 (Cq),
166.4 (Cq × 2), 195.2 (Cq); MS (EI, m/z) 466 (M+, 1), 362 (58), 361
(100), 317 (51); HRMS (EI-magnetic sector) m/z [M+] calcd for
C28H22N2O5 466.1529, found 466.1530.
N-(2,6-Dibenzoylphenyl)-N-(4-methoxypyridin-2-yl)pivalamide
(4-OMe/Piv). White oil; Rf = 0.66 (n-hexane/ethyl acetate = 1/1); 1H
NMR (CDCl3, 400 MHz) δ 0.76 (9 H), 3.73 (3 H), 6.52 (dd, J = 3.6,
1.6 Hz, 1 H), 7.01 (d, J = 1.2 Hz, 1 H), 7.39−7.47 (m, 7 H), 7.54 (t, J
= 5.2 Hz, 2 H), 7.83 (d, J = 4.4 Hz, 4 H), 7.90 (d, J = 3.6 Hz, 1 H);
13C NMR (CDCl3, 100 MHz) δ 28.1 (CH3× 3), 41.3 (Cq), 55.2
(CH3), 107.9 (CH), 109.2 (CH), 126.1 (CH), 128.1 (CH × 4),
130.5 (CH × 4), 130.9 (CH × 2), 133.0 (CH × 2), 136.9 (Cq × 2),
139.4 (Cq × 2), 140.2 (Cq), 147.9 (CH), 157.2 (Cq), 167.0 (Cq),
179.7 (Cq), 195.5 (Cq × 2); MS (EI, m/z) 492 (M+, 1), 369 (90), 353
(51), 347 (100), 305 (43); HRMS (EI-magnetic sector) m/z [M+]
calcd for C31H28N2O4 492.2049, found.492.2051.
tert-Butyl (2,6-dibenzoylphenyl)(4-methoxypyridin-2-yl)-
carbamate (4a). White solid; mp 126−127 °C; Rf = 0.48 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.36 (s,
9 H), 3.64 (s, 3 H), 6.28 (dd, J = 5.7, 2.1 Hz, 1 H), 6.81 (bs, 1 H),
7.32 (t, J = 7.5 Hz, 4 H), 7.48 (t, J = 7.8 Hz, 3 H), 7.62 (d, J = 7.5 Hz,
2 H), 7.66 (d, J = 5.7 Hz, 1 H), 7.76 (d, J = 7.2 Hz, 4 H); 13C NMR
(125 MHz, CDCl3) δ 27.9 (CH3 × 3), 54.9 (CH3), 82.2 (Cq), 101.8
(Cq), 107.2 (CH), 126.3 (CH), 127.9 (CH × 4), 130.0 (CH × 4),
131.2 (CH), 132.6 (CH × 2), 137.3 (Cq × 2), 139.2 (Cq × 2), 146.8
(CH), 152.6 (Cq), 155.1 (Cq), 166.1 (Cq), 195.2 (Cq × 2); MS (EI,
m/z) 508 (M+, 1), 331 (39), 303 (100), 213 (21), 105 (22); HRMS
m/z calcd for C31H28N2O5 508.1998, found 508.2000.
tert-Butyl (2-(2,4-dimethylbenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (3o). Yellow solid; mp 90−91 °C; Rf = 0.48 (n-hexane/
1
ethyl acetate = 2/1); H NMR (300 MHz, CDCl3) δ 1.40 (s, 9 H),
2.29 (s, 3 H), 2.31 (s, 3 H), 3.77 (s, 3 H), 6.46 (dd, J = 5.7, 2.1 Hz, 1
H), 6.84−6.90 (m, 2 H), 6.98 (s, 1 H), 7.34 (d, J = 6.6 Hz 1 H),
7.32−7.46 (m, 3 H), 7.51 (td, J = 7.2, 1.5 Hz 1 H), 7.98 (d, J = 5.7
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 20.7 (CH3), 21.3 (CH3),
28.1 (CH3 × 3), 55.1 (CH3), 81.8 (Cq), 104.1 (CH), 107.2 (CH),
125.6 (CH), 126.9 (CH), 130.3 (CH), 131.1 (CH), 131.2 (CH),
131.9 (CH), 132.0 (CH), 134.8 (Cq), 138.1 (Cq), 138.9 (Cq), 139.7
(Cq), 141.6 (Cq), 148.0 (CH), 153.1 (Cq), 156.1 (Cq), 166.3 (Cq),
197.3 (Cq); MS (EI, m/z) 432 (M+, 1), 303 (41), 243 (88), 199
(100), 124 (37); HRMS m/z calcd for C26H28N2O4 432.2049, found
432.2046.
tert-Butyl (2-(3,5-dimethoxybenzoyl)phenyl)(4-methoxypyridin-
2-yl)carbamate (3p). Yellow solid; mp 86−87 °C; Rf = 0.63 (n-
hexane/ethyl acetate = 1/1); 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
9 H), 3.75 (s, 9 H), 6.46 (dd, J = 5.7, 1.8 Hz, 1 H), 6.59 (s, 1 H), 6.82
(d, J = 1.8 Hz, 2 H), 6.92 (s, 1 H), 7.37−7.56 (m, 4 H), 7.98 (d, J =
6.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.0 (CH3 × 3), 55.1
(CH3), 55.5 (CH3 × 2), 81.9 (Cq), 104.7 (CH), 105.5 (CH), 107.5
(CH), 107.6 (CH × 2), 126.6 (CH), 129.5 (CH), 130.8 (CH), 131.0
(CH), 137.0 (Cq), 139.4 (Cq), 139.8 (Cq), 148.1 (CH2), 153.1 (Cq),
156.1 (Cq), 160.3 (Cq × 2), 166.3 (Cq), 195.5 (Cq); MS (EI, m/z)
464 (M+, 1), 335 (38), 227 (100), 199 (91); HRMS m/z calcd for
C26H28N2O6 464.1947, found 464.1950.
tert-Butyl (2,6-bis(4-methoxybenzoyl)phenyl)(4-methoxypyridin-
2-yl)carbamate (4b). Yellow solid; mp 138−139 °C; Rf = 0.49 (n-
hexane/ethyl acetate = 1/1); 1H NMR (300 MHz, CDCl3) δ 1.35 (s,
9 H), 3.66 (s, 3 H), 3.83 (s, 6 H), 6.28 (dd, J = 5.7, 2.1 Hz, 1 H), 6.80
(d, J = 8.7 Hz, 4 H), 6.85−6.93 (m, 1 H), 7.45 (t, J = 6.6 Hz, 1 H),
7.57 (d, J = 7.5 Hz, 2 H), 7.68 (d, J = 7.5 Hz, 1 H), 7.74 (d, J = 8.7
Hz, 4 H); 13C NMR (125 MHz, CDCl3) δ 27.9 (CH3 × 3), 54.9
(CH3), 55.4 (CH3 × 2), 82.0 (Cq), 102.0 (CH), 107.1 (CH), 113.1
(CH × 4), 126.1 (CH), 130.2 (Cq × 2), 130.7 (CH × 2), 132.4 (CH
× 4), 137.4 (Cq), 139.5 (Cq × 2), 147.0 (CH), 152.6 (Cq), 155.4
(Cq), 163.2 (Cq × 2), 166.1 (Cq), 193.9 (Cq × 2); MS (EI, m/z) 568
(M+, 1), 361 (93), 333 (100), 225 (94), 135 (93); HRMS m/z calcd
for C33H32N2O7 568.2210, found 568.2209.
tert-Butyl (2-(2,4-dimethoxybenzoyl)phenyl)(4-methoxypyridin-
2-yl)carbamate (3q). White solid; mp 68−69 °C; Rf = 0.47 (n-
hexane/ethyl acetate = 1/2); 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
9 H), 3.59 (s, 3 H), 3.76 (s, 3 H), 3.80 (s, 3 H), 6.30−6.34 (m, 2 H),
6.46 (dd, J = 5.7, 2.1 Hz, 1 H), 6.96 (d, J = 2.1 Hz,1 H), 7.33 (t, J =
8.1 Hz, 2 H), 7.42 (d, J = 8.1 Hz, 2 H), 7.51 (td, J = 6.8, 1.5 Hz, 1 H),
J
DOI: 10.1021/acs.organomet.9b00119
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
tert-Butyl (2,6-bis(2-fluorobenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (4f). Yellow solid; mp 140−141 °C; Rf = 0.61 (n-
hexane/ethyl acetate = 1/1); 1H NMR (300 MHz, CDCl3) δ 1.38 (s,
9 H), 3.68 (s, 3 H), 6.31 (dd, J = 5.7, 2.1 Hz, 1 H), 6.87 (s, 1 H),
6.95−7.08 (m, 4 H), 7.35−7.43 (m, 2 H), 7.46−7.56 (m, 3 H), 7.67−
7.73 (m, 3 H); 13C NMR (125 MHz, CDCl3) δ 27.9 (CH3 × 3), 55.0
(CH3), 82.3 (Cq), 107.1 (CH), 116.3 (d, JC−F = 21.5 Hz, CH × 2),
123.6 (d, JC−F = 3.6 Hz, CH × 2), 126.7 (d, JC−F = 11.5 Hz, Cq × 2),
127.0 (CH), 131.6 (CH × 2), 131.9 (CH × 2), 133.5 (d, JC−F = 8.6
Hz, CH × 2), 137.3 (Cq), 139.5 (Cq × 2), 146.7 (CH), 152.5 (Cq),
154.6 (Cq), 160.8 (d, JC−F = 256.0 Hz, Cq), 166.1 (Cq × 2), 192.1 (Cq
× 2); MS (EI, m/z) 544 (M+, 1), 321 (78), 264 (31), 158 (100);
HRMS m/z calcd for C31H26F2N2O5 544.1810, found 544.1808.
tert-Butyl (2,6-bis(3-fluorobenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (4g). Yellow solid; mp 128−129 °C; Rf = 0.55 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.37 (s,
9 H), 3.67 (s, 3 H), 6.30 (dd, J = 5.7, 1.2 Hz, 1 H), 6.85 (s, 1 H), 7.17
(t, J = 4.5 Hz, 2 H), 7.26−7.33 (m, 2 H), 7.45 (d, J = 9.0 Hz, 2 H),
7.52−7.54 (m, 3 H), 7.61−7.67 (m, 3 H); 13C NMR (125 MHz,
CDCl3) δ 27.9 (CH3 × 3), 55.0 (CH3), 82.5 (Cq), 101.8 (CH), 107.3
(CH × 2), 116.6 (d, JC−F = 21.9 Hz, CH × 2), 119.7 (d, JC−F = 21.9
Hz, CH × 2), 125.7 (d, JC−F = 2.8 Hz, CH × 2), 126.6 (CH), 129.6
(d, JC−F = 7.3 Hz, CH × 2), 131.1 (CH × 2), 137.6 (Cq), 138.9 (Cq ×
2), 139.4 (d, JC−F = 6.4 Hz, Cq × 2), 146.9 (CH), 152.5 (Cq), 154.8
MHz, CDCl3) δ 21.1 (CH3 × 4), 27.9 (CH3 × 3), 54.9 (CH3), 81.9
(Cq), 107.2 (CH), 126.1 (CH), 127.8 (CH × 4), 131.0 (CH), 134.3
(CH × 2), 137.4 (Cq × 2), 137.5 (Cq × 4), 139.5 (Cq × 2), 146.7
(CH), 152.6 (Cq), 155.2 (Cq), 166.1 (Cq), 195.6 (Cq × 2); MS (EI,
m/z) 564 (M+, 1), 331 (34), 242 (84), 133 (100); HRMS m/z calcd
for C35H36N2O5 564.2624, found 564.2626.
tert-Butyl (2,6-bis(2,4-dimethylbenzoyl)phenyl)(4-methoxypyri-
din-2-yl)carbamate (4o). White solid; mp 156−157 °C; Rf = 0.65
(n-hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.38
(s, 9 H), 2.28 (s, 6 H), 2.40 (s, 6H), 3.67 (s, 3 H), 6.29 (dd, J = 5.7,
2.1 Hz, 1 H), 6.74−6.80 (m, 3 H), 6.97 (s, 2 H), 7.27 (d, J = 8.7 Hz, 2
H), 7.40 (t, J = 7.8 Hz, 1 H), 7.57 (d, J = 7.5 Hz, 2 H), 7.73 (d, J = 5.7
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 20.5 (CH3 × 2), 21.3
(CH3 × 2), 28.0 (CH3 × 3), 54.8 (CH3), 81.9 (Cq), 106.8 (CH),
125.3 (CH × 2), 126.6 (CH × 2), 131.6 (CH), 131.9 (CH × 4),
132.0 (CH), 134.9 (Cq × 2), 137.7 (Cq), 138.7 (Cq), 140.3 (Cq),
141.3 (Cq × 2), 146.7 (CH), 152.9 (Cq), 155.0 (Cq), 166.0 (Cq × 2),
196.9 (Cq × 2); MS (EI, m/z) 564 (M+, 1), 359 (38), 331 (100), 225
(52), 133 (60); HRMS m/z calcd for C35H36N2O5 564.2624, found
564.2626.
tert-Butyl (2,6-bis(2,4-dimethoxybenzoyl)phenyl)(4-methoxypyr-
idin-2-yl)carbamate (4q). Yellow solid; mp 96−97 °C; Rf = 0.30 (n-
hexane/ethyl acetate = 1/2); 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
9 H), 3.61 (s, 6 H), 3.67 (s, 3 H), 3.79 (s, 6 H), 6.26−6.34 (m, 5 H),
6.83 (s, 1 H), 7.37 (t, J = 7.8 Hz, 1 H), 7.46 (d, J = 8.7 Hz, 2 H), 7.56
(d, J = 7.8 Hz, 2 H), 7.67 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 27.9 (CH3 × 3), 54.8 (CH3), 55.3 (CH3 × 2), 55.4 (CH3 ×
2), 81.7 (Cq), 98.2 (CH × 2), 101.4 (CH), 103.8 (CH × 2), 106.7
(CH), 121.2 (Cq), 126.2 (CH), 131.1 (CH × 2), 134.1 (CH × 2),
136.5 (Cq), 141.0 (Cq × 2), 146.3 (CH), 152.6 (Cq), 155.0 (Cq),
160.5 (Cq × 2), 163.6 (Cq × 2), 165.8 (Cq), 193.5 (Cq × 2); MS (EI,
m/z) 628 (M+, 1), 363 (100), 225 (96), 165 (32); HRMS m/z calcd
for C35H36N2O9 628.2421, found 628.2421.
(Cq), 162.3 (d, JC−F = 246.1 Hz, Cq × 2), 166.3 (Cq), 193.8 (d, JC−F
=
1.9 Hz, Cq × 2); MS (EI, m/z) 544 (M+, 1), 340 (62), 177 (100), 161
(72), 57 (61); HRMS m/z calcd for C31H26F2N2O5 544.1810, found
544.1808.
tert-Butyl (2,6-bis(4-fluorobenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (4h). Yellow solid; mp 132−133 °C; Rf = 0.53 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.36 (s,
9 H), 3.67 (s, 3 H), 6.31 (dd, J = 5.4, 1.5 Hz, 1 H), 6.85 (s, 1 H), 6.99
(t, J = 8.4 Hz, 4 H), 7.45 (t, J = 8.1 Hz, 1 H), 7.58−7.61 (m, 2 H),
7.65 (d, J = 5.7 Hz, 1 H), 7.79 (td, J = 5.7, 2.4 Hz, 4 H); 13C NMR
(125 MHz, CDCl3) δ 27.9 (CH3 × 3), 55.0 (CH3), 82.4 (Cq), 107.1
(CH), 115.0 (d, JC−F = 21.9 Hz, CH × 4), 126.5 (CH), 131.0 (CH ×
2), 132.6 (d, JC−F = 9.1 Hz, CH × 4), 133.5 (d, JC−F = 2.8 Hz, Cq ×
2), 137.6 (Cq), 139.1 (Cq × 2), 146.9 (CH), 152.5 (Cq), 155.0 (Cq),
164.5 (Cq), 166.4 (JC−F = 24.6 Hz, Cq × 2), 193.6 (Cq × 2); MS (EI,
m/z) 544 (M+, 1), 349 (49), 321 (100), 123 (36); HRMS m/z calcd
for C31H26F2N2O5 544.1810, found 544.1811.
tert-Butyl (2,6-bis(3-chlorobenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (4j). Yellow solid; mp 138−139 °C; Rf = 0.55 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.38 (s,
9 H), 3.67 (s, 3 H), 6.31 (dd, J = 5.7, 2.1 Hz, 1 H), 6.83 (s,1 H), 7.27
(t, J = 7.8 Hz, 2 H), 7.43 (dd, J = 2.1, 1.2 Hz, 2 H), 7.45−7.54 (m, 1
H), 7.60−7.67 (m, 5 H), 7.73 (s, 2 H); 13C NMR (125 MHz, CDCl3)
δ 27.9 (CH3 × 3), 55.0 (CH3), 82.5 (Cq), 101.6 (Cq), 107.4 (CH),
126.7 (CH), 127.9 (CH × 2), 129.3 (CH × 2), 129.9 (CH × 2),
131.3 (CH), 132.6 (CH × 2), 134.3 (Cq × 2), 137.6 (Cq), 138.9 (Cq
× 2), 146.9 (CH), 152.5 (Cq), 154.7 (Cq), 166.3 (Cq), 193.8 (Cq ×
2); MS (EI, m/z) 576 (M+, 1), 365 (100), 337 (98), 225 (32);
HRMS m/z calcd for C31H26Cl2N2O5 576.1219, found 576.1217.
tert-Butyl (2,6-bis(4-chlorobenzoyl)phenyl)(4-methoxypyridin-2-
yl)carbamate (4k). Yellow solid; mp 180−181 °C; Rf = 0.65 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.36 (s,
9 H), 3.68 (s, 3 H), 6.32 (dd, J = 6.0, 2.1 Hz, 1 H), 6.79 (s, 1 H), 7.29
(d, J = 8.7 Hz, 4 H), 7.50 (t, J = 6.9 Hz, 1 H), 7.62−7.70 (m, 7 H);
13C NMR (125 MHz, CDCl3) δ 27.9 (CH3 × 3), 55.0 (CH3), 82.4
tert-Butyl (2-benzoyl-6-methoxyphenyl)(4-methoxypyridin-2-yl)-
carbamate (5b). White solid; mp 112−113 °C; Rf = 0.45 (n-hexane/
1
ethyl acetate = 1/1); H NMR (300 MHz, CDCl3) δ 1.40 (s, 9 H),
3.72 (s, 3 H), 3.89 (s, 3 H), 6.38 (dd, J = 5.7, 1.8 Hz, 1 H), 6.92 (s, 1
H), 7.00 (d, J = 7.5 Hz, 1 H), 7.13 (d, J = 8.1 Hz, 1 H), 7.30−7.40
(m, 3 H), 7.48 (t, J = 7.2 Hz, 1 H), 7.67 (d, J = 7.5 Hz, 2 H), 7.90 (d,
J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.0 (CH3 × 3),
55.0 (CH3), 56.0 (CH3), 81.2 (Cq), 102.8 (CH), 107.0 (CH), 113.5
(CH), 120.8 (CH), 127.8 (CH × 2), 127.9 (CH), 128.8 (Cq), 129.9
(CH × 2), 132.7 (CH), 137.4 (Cq), 138.4 (Cq), 148.1 (CH), 152.9
(Cq), 155.9 (Cq), 156.1 (Cq), 166.1 (Cq), 195.8 (Cq); MS (EI, m/z)
434 (M+, 1), 329 (36), 273 (100), 257 (31), 229 (100); HRMS m/z
calcd for C25H26N2O5 434.1842, found 434.1844.
tert-Butyl (2-benzoyl-5-methoxyphenyl)(4-methoxypyridin-2-yl)-
carbamate (5c). Yellow solid; mp 68−69 °C; Rf = 0.54 (n-hexane/
1
ethyl acetate = 1/1); H NMR (300 MHz, CDCl3) δ 1.39 (s, 9 H),
3.76 (s, 3 H), 3.87 (s, 3 H), 6.48 (dd, J = 5.7, 2.1 Hz, 1 H), 6.87 (dd, J
= 8.4, 2.4 Hz, 1 H), 6.97 (dd, J = 5.7, 2.1 Hz, 2 H), 7.33−7.43 (m, 3
H), 7.50 (t, J = 7.2 Hz, 1 H), 7.70 (d, J = 7.2 Hz, 2 H), 8.01 (d, J = 5.7
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.1 (CH3 × 3), 55.1
(CH3), 55.5 (CH3), 81.8 (Cq), 104.7 (CH), 107.7 (CH), 112.0
(CH), 116.1 (CH), 127.9 (CH × 2), 129.3 (Cq), 130.0 (CH × 2),
131.8 (CH), 132.3 (CH), 138.1 (Cq), 142.0 (Cq), 148.3 (CH), 153.0
(Cq), 156.2 (Cq), 161.8 (Cq), 166.4 (Cq), 195.0 (Cq); MS (EI, m/z)
434 (M+, 1), 303 (100), 229 (47), 105 (39); HRMS m/z calcd for
C25H26N2O5 434.1842, found 434.1843.
(Cq), 107.1 (CH), 126.6 (CH), 128.2 (CH × 4), 131.0 (CH), 131.3
(CH × 4), 135.6 (Cq × 2), 139.0 (Cq × 2), 139.1 (Cq × 2), 146.8
(CH), 152.5 (Cq), 154.7 (Cq), 166.4 (Cq), 194.0 (Cq × 2); MS (EI,
m/z) 576 (M+, 1), 365 (67), 337 (100), 139 (43); HRMS m/z calcd
for C31H26Cl2N2O5 576.1219, found 576.1216.
tert-Butyl (2,6-bis(3,5-dimethylbenzoyl)phenyl)(4-methoxypyri-
din-2-yl)carbamate (4n). Yellow solid; mp 154−155 °C; Rf = 0.60
(n-hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.36
(s, 9 H), 2.26 (s, 12 H), 3.65 (s, 3 H), 6.27 (dd, J = 5.7, 2.1 Hz, 1 H),
6.90 (m, 1 H), 7.10 (m, 2 H), 7.39 (m, 4 H), 7.46 (t, J = 7.2 Hz, 1 H),
7.60 (d, J = 7.2 Hz, 2 H), 7.66 (d, J = 5.7 Hz, 1 H); 13C NMR (125
tert-Butyl (2-benzoyl-4-methoxyphenyl)(4-methoxypyridin-2-yl)-
carbamate (5d). Yellow solid; mp 128−129 °C; Rf = 0.30 (n-hexane/
1
ethyl acetate = 3/1); H NMR (300 MHz, CDCl3) δ 1.38 (s, 9 H),
3.73 (s, 3 H), 3.82 (s, 3 H), 6.44 (dd, J = 5.7, 1.8 Hz, 1 H), 6.84 (d, J
= 1.8 Hz, 1 H), 6.93 (d, J = 2.7 Hz, 1 H), 7.08 (dd, J = 8.7, 3.0 Hz, 1
H), 7.32−7.37 (m, 3 H), 7.48 (t, J = 7.2 Hz, 1 H), 7.72 (d, J = 7.2 Hz,
2 H), 7.98 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.1
(CH3 × 3), 55.1 (CH3), 55.6 (CH3), 81.7 (Cq), 104.5 (CH), 107.5
(CH), 114.2 (CH), 116.6 (CH), 128.0 (CH × 2), 130.0 (CH × 2),
131.9 (CH), 132.4 (Cq), 132.8 (CH), 137.1 (Cq), 137.9 (Cq), 148.2
(CH), 153.3 (Cq), 156.2 (Cq), 157.8 (Cq), 166.3 (Cq), 195.6 (Cq);
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MS (EI, m/z) 434 (M+, 1), 273 (39), 257 (23), 229 (100), 105 (26),
57 (37); HRMS m/z calcd for C25H26N2O5 434.1842, found
434.1844.
tert-Butyl (2,6-dibenzoyl-4-methoxyphenyl)(4-methoxypyridin-
2-yl)carbamate (6d). Yellow solid; mp 164−165 °C; Rf = 0.40 (n-
hexane/ethyl acetate = 3/1); 1H NMR (300 MHz, CDCl3) δ 1.36 (s,
9 H), 3.62 (s, 3 H), 3.84 (s, 3 H), 6.27 (dd, J = 5.7, 2.1 Hz, 1 H), 6.72
(s, 1 H), 7.12 (s, 2 H), 7.32 (t, J = 7.5 Hz, 4 H), 7.47 (t, J = 7.5 Hz, 2
H),7.66 (d, J = 5.7 Hz, 1 H), 7.77 (d, J = 7.2 Hz, 4 H); 13C NMR
(125 MHz, CDCl3) δ 27.9 (CH3 × 3), 54.9 (CH3), 55.8 (CH3), 82.0
(Cq), 102.0 (Cq), 107.1 (CH), 116.4 (CH × 2), 127.9 (CH × 4),
130.0 (CH × 4), 132.6 (CH × 2), 137.2 (Cq × 2), 140.2 (Cq × 2),
146.8 (CH), 152.9 (Cq), 155.2 (Cq), 157.3 (Cq), 166.1 (Cq), 195.0
(Cq × 2); MS (EI, m/z) 538 (M+, 1), 333 (100), 105 (39), 77 (30),
57 (32); HRMS m/z calcd for C32H30N2O6 538.2104, found
538.2101.
tert-Butyl (2,6-dibenzoyl-4-fluorophenyl)(4-methoxypyridin-2-
yl)carbamate (6e). White solid; mp 148−149 °C; Rf = 0.60 (n-
hexane/ethyl acetate = 3/1); 1H NMR (300 MHz, CDCl3) δ 1.40 (s,
9 H), 3.65 (s, 3 H), 6.30 (d, J = 4.2 Hz, 1 H), 6.79 (s, 1 H), 7.35 (t, J
= 7.2 Hz, 6 H), 7.51 (t, J = 7.2 Hz, 2 H), 7.67 (d, J = 5.4 Hz, 1 H),
7.78 (d, J = 7.5 Hz, 4 H); 13C NMR (125 MHz, CDCl3) δ 27.9 (CH3
× 3), 55.0 (CH3), 82.4 (Cq), 107.3 (CH), 117.9 (d, JC−F = 23.8 Hz,
CH), 128.0 (CH × 4), 129.9 (CH × 4), 132.9 (CH × 2), 136.7 (Cq ×
2), 141.1 (d, JC−F = 6.0 Hz, Cq), 146.7 (CH), 152.6 (Cq), 154.8 (Cq),
159.9 (d, JC−F = 249.6 Hz, Cq), 166.2 (Cq × 2), 193.8 (Cq × 2); MS
(EI, m/z) 526 (M+, 1), 349 (41), 321 (100), 57 (36); HRMS m/z
calcd for C31H27FN2O5 526.1904, found 526.1902.
tert-Butyl (2,6-dibenzoyl-4-chlorophenyl)(4-methoxypyridin-2-
yl)carbamate (6h). Yellow solid; mp 121−122 °C; Rf = 0.68 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.37 (s,
9 H), 3.62 (s, 3 H), 6.29 (dd, J = 5.7, 2.1 Hz, 1 H), 6.76 (s, 1 H), 7.33
(t, J = 7.5 Hz, 4 H), 7.49 (t, J = 7.2 Hz, 2 H), 7.58 (s, 2 H), 7.65 (d, J
= 5.7 Hz, 1 H), 7.75 (d, J = 7.5 Hz, 4 H); 13C NMR (125 MHz,
CDCl3) δ 27.9 (CH3 × 3), 55.0 (CH3), 82.6 (Cq), 101.8 (Cq), 107.3
(CH), 128.1 (CH × 5), 129.9 (CH × 5), 130.8 (CH), 132.4 (Cq),
132.9 (CH × 2), 136.7 (Cq × 2), 140.7 (Cq × 2), 146.8 (CH), 152.3
(Cq), 154.7 (Cq), 166.2 (Cq), 193.7 (Cq × 2); MS (EI, m/z) 542 (M+,
1), 365 (84), 337 (100), 105 (82), 77 (49), 57 (71); HRMS m/z
calcd for C31H27ClN2O5 542.1608, found 542.1607.
(2-Aminophenyl)(phenyl)methanone (7). Yellow solid; Rf = 0.63
(n-hexane/ethyl acetate = 4/1); 1H NMR (400 MHz, CDCl3) δ 6.08
(bs, 2 H), 6.60 (td, J = 4.8, 0.8 Hz, 1 H), 6.73 (dd, J = 5.6, 0.8 Hz, 1
H), 7.29 (td, J = 4.8, 0.8 Hz, 1 H), 7.44 (tt, J = 4.4, 0.8 Hz, 3 H), 7.51
(tt, J = 4.4, 0.8 Hz, 1 H), 7.62−7.64 (m, 2 H); 13C NMR (100 MHz,
CDCl3) δ 115.5 (CH), 117.0 (CH), 118.2 (Cq), 128.1 (CH × 2),
129.1 (CH × 2), 131.0 (CH), 134.2 (CH), 134.5 (CH), 140.1 (Cq),
150.9 (Cq), 199.0 (Cq); MS (EI, m/z) 197 (M+, 1), 196 (100), 120
(21); HRMS (EI-magnetic sector) m/z [M+] calcd for C13H11NO
197.0841, found 197.0840.
tert-Butyl (2-benzoyl-4-fluorophenyl)(4-methoxypyridin-2-yl)-
carbamate (5e). Yellow solid; mp 132−133 °C; Rf = 0.50 (n-
hexane/ethyl acetate = 3/1); 1H NMR (300 MHz, CDCl3) δ 1.38 (s,
9 H), 3.73 (s, 3 H), 6.45 (dd, J = 5.7, 1.8 Hz, 1 H), 6.93 (d, J = 1.2
Hz, 1 H), 7.13 (dd, J = 8.1, 2.7 Hz, 1 H), 7.24−7.25 (m, 1 H), 7.33−
7.43 (m, 3 H), 7.51 (t, J = 4.5 Hz, 1 H), 7.70 (d, J = 7.8 Hz, 2 H),
7.94 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.1 (CH3
× 3), 55.1 (CH3), 82.1 (Cq), 104.3 (CH), 107.6 (CH), 116.1 (d, JC−F
= 23.6 Hz, CH), 117.8 (d, JC−F = 22.4 Hz, CH), 128.1 (CH × 2),
130.0 (CH × 2), 132.6 (d, JC−F = 8.1 Hz, CH), 133.0 (CH), 135.6 (d,
JC−F = 3.3 Hz, Cq), 136.7 (Cq), 138.7 (d, JC−F = 6.9 Hz, Cq), 148.1
(CH), 153.0 (Cq), 155.8 (Cq), 160.1 (d, JC−F = 247.4 Hz, Cq), 166.4
(Cq), 194.3 (Cq); MS (EI, m/z) 422 (M+, 1), 293 (35), 261 (45), 245
(44), 217 (100), 57 (44); HRMS m/z calcd for C24H23FN2O4
422.1642, found 422.1642.
tert-Butyl (2-benzoyl-5-fluorophenyl)(4-methoxypyridin-2-yl)-
carbamate (5f). Yellow solid; mp 132−133 °C; Rf = 0.53 (n-
hexane/ethyl acetate = 3/1); 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
9 H), 3.75 (s, 3 H), 6.47 (dd, J = 5.7, 2.4 Hz, 1 H), 6.93 (d, J = 2.4
Hz, 1 H), 7.07 (td, J = 8.1, 2.4 Hz, 1 H), 7.17 (dd, J = 9.3, 2.4 Hz, 1
H), 7.33−7.54 (m, 4 H), 7.69 (d, J = 7.2 Hz, 2 H), 7.97 (d, J = 5.7
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.1 (CH3 × 3), 55.2
(CH3), 82.3 (Cq), 104.6 (CH), 107.8 (CH), 113.8 (d, JC−F = 21.1 Hz,
CH), 118.0 (d, JC−F = 21.9 Hz, CH), 128.0 (CH × 2), 130.0 (CH ×
2), 131.3 (d, JC−F = 9.1 Hz, CH), 132.8 (CH), 133.2 (d, JC−F = 3.6
Hz, Cq), 137.3 (Cq), 142.0 (d, JC−F = 11.0 Hz, Cq), 148.2 (CH),
152.7 (Cq), 155.7 (Cq), 163.7 (d, JC−F = 250.0 Hz, Cq), 166.5 (Cq),
194.6 (Cq); MS (EI, m/z) 422 (M+, 2), 217 (100); HRMS m/z calcd
for C24H23FN2O4 422.1642, found 422.1643.
tert-Butyl (2-benzoyl-6-fluorophenyl)(4-methoxypyridin-2-yl)-
carbamate (5g). Yellow solid; mp 78−79 °C; Rf = 0.48 (n-hexane/
1
ethyl acetate = 3/1); H NMR (300 MHz, CDCl3) δ 1.42 (s, 9 H),
3.73 (s, 3 H), 6.41 (dd, J = 6, 2.4 Hz, 1 H), 6.99 (d, J = 1.5 Hz, 1 H),
7.24 (t, J = 6.9 Hz, 1 H), 7.26−7.43 (m, 4 H), 7.50 (t, J = 7.2 Hz, 1
H), 7.67 (d, J = 7.5 Hz, 2 H), 7.89 (d, J = 5.7 Hz, 1 H); 13C NMR
(125 MHz, CDCl3) δ 27.9 (CH3 × 3), 55.1 (CH3), 82.2 (Cq), 102.9
(CH), 107.4 (CH), 117.9 (d, JC−F = 21.0 Hz, CH), 124.5 (d, JC−F
=
3.6 Hz, CH), 127.9 (CH), 128.3 (d, JC−F = 8.1 Hz, CH × 2), 129.8
(CH × 2), 132.9 (CH), 137.0 (Cq), 139.0 (Cq), 148.0 (CH), 152.3
(Cq), 155.2 (Cq), 159.0 (d, JC−F = 249.3 Hz, Cq), 166.3 (Cq), 194.6
(d, JC−F = 2.8 Hz, Cq); MS (EI, m/z) 422 (M+, 2), 303 (71), 245
(69), 217 (100); HRMS m/z calcd for C24H23FN2O4 422.1642, found
422.1642.
tert-Butyl (2-benzoyl-4-chlorophenyl)(4-methoxypyridin-2-yl)-
carbamate (5h). Yellow solid; mp 130−131 °C; Rf = 0.60 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
9 H), 3.74 (s, 3 H), 6.45 (dd, J = 5.7, 2.1 Hz, 1 H), 6.90 (d, J = 1.5
Hz, 1 H), 7.34−7.40 (m, 4 H), 7.51 (d, J = 8.1 Hz, 2 H), 7.70 (d, J =
7.5 Hz, 2 H), 7.95 (d, J = 5.7 Hz, 1 H); 13C NMR (125 MHz, CDCl3)
δ 28.1 (CH3 × 3), 55.1 (CH3), 82.3 (Cq), 104.4 (CH), 107.7 (CH),
128.1 (CH × 2), 129.2 (CH), 130.0 (CH × 2), 130.9 (CH), 132.1
(CH), 132.4 (Cq), 133.1 (CH), 136.6 (Cq), 138.3 (Cq), 138.4 (Cq),
148.2 (CH), 155.8 (Cq), 155.7 (Cq), 166.4 (Cq), 194.2 (Cq); MS (EI,
m/z) 309 (M+, 1), 277 (62), 261 (63), 105 (54), 57 (73); HRMS m/
z calcd for C24H23ClN2O4 438.1346, found 438.1345.
9(10H)-Acridanone (8). Yellow solid; Rf = 0.43 (n-hexane/ethyl
1
acetate = 2/1); H NMR (400 MHz, DMSO-d6) δ 7.25 (td, J = 6.8,
1.2 Hz, 2 H), 7.54 (d, J = 8.4 Hz, 2 H), 7.73 (td, J = 7.2, 1.6 Hz, 2 H),
8.23 (dd, J = 8.0, 1.6 Hz, 2 H), 11.73 (d, J = 0.4 Hz, 1 H); 13C NMR
(100 MHz, DMSO-d6) δ 117.3 (CH × 2), 120.5 (Cq × 2), 121.0 (CH
× 2), 126.0 (CH × 2), 133.4 (CH × 2), 140.9 (Cq × 2), 176.8 (Cq);
MS (EI, m/z) 196 (M+, 1); HRMS (EI-magnetic sector) m/z [M+]
calcd for C13H9NO 195.0684, found 195.0686.
tert-Butyl (2-benzoyl-4-bromophenyl)(4-methoxypyridin-2-yl)-
carbamate (5i). Yellow solid; mp 125−126 °C; Rf = 0.60 (n-
hexane/ethyl acetate = 2/1); 1H NMR (300 MHz, CDCl3) δ 1.39 (s,
9 H), 3.74 (s, 3 H), 6.45 (d, J = 5.1 Hz, 1 H), 6.90 (s, 1 H), 7.30−
7.39 (m, 3 H), 7.52−7.55 (m, 2 H), 7.65−7.71 (m, 3 H), 7.95 (d, J =
7.8 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 28.1 (CH3 × 3), 55.2
(CH3), 82.3 (Cq), 104.5 (CH), 107.7 (CH), 120.3 (Cq), 128.1 (CH
× 2), 130.0 (CH × 2), 132.1 (CH), 132.4 (CH), 133.1 (CH), 133.9
(CH), 136.6 (Cq), 138.7 (Cq), 138.8 (Cq), 148.2 (CH), 152.8 (Cq),
155.7 (Cq), 166.5 (Cq), 194.1 (Cq); MS (EI, m/z) 482 (M+, 1), 353
(53), 321 (51), 305 (43), 277 (96), 105 (75), 57 (100); HRMS m/z
calcd for C24H23BrN2O4 482.0841, found 482.0841.
10-(4-Methoxypyridin-2-yl)acridin-9(10H)-one (9). White oil; Rf =
0.43 (n-hexane/ethyl acetate = 1/2); 1H NMR (400 MHz, CDCl3) δ
3.95 (s, 3 H), 6.69 (d, J = 5.6 Hz, 2 H), 6.97 (d, J = 1.2 Hz, 1 H), 7.12
(dd, J = 4.0, 1.6 Hz, 1 H), 7.29 (td, J = 4.8, 0.8 Hz, 2 H), 7.52 (td, J =
4.4, 0.8 Hz, 2 H), 8.58 (dd, J = 5.2, 0.8 Hz, 2 H), 8.68 (d, J = 4.0 Hz,
1 H); 13C NMR (100 MHz, CDCl3) δ 55.9 (CH3), 111.2 (CH),
116.2 (CH × 2), 121.8 (CH × 2), 127.5 (CH × 2), 130.0 (CH),
133.3 (CH × 2), 152.3 (CH), 142.2 (Cq × 2), 153.9 (Cq), 169.1
(Cq), 173.2 (Cq × 2), 178.2 (Cq); MS (EI, m/z) 302 (M+, 1), 88
(43), 70 (64), 61 (100); HRMS (EI-magnetic sector) m/z [M+] calcd
for C19H14N2O2 302.1055, found 302.1054.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.9b00119.
■
S
Optimization of reaction conditions, synthesis and
characterization of starting substrates, preparation of
deuterium-labeled substrates 1a-D1 and 1a-D5, and KIEs
operation and calculation, H, 13C and DEPT (90° and
1
135°) NMR spectra of new and known compounds
(PDF)
Accession Codes
CCDC 1897991−1897993 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: j_hchu@nttu.edu.tw.
*E-mail: mijuwu@faculty.nsysu.edu.tw.
ORCID
Jean-Ho Chu: 0000-0003-3366-2126
Ming-Jung Wu: 0000-0002-5507-1848
Notes
■
The authors declare no competing financial interest.
(2) Selected reviews: (a) Brady, P. B.; Bhat, V. Recent Applications
of Rh- and Pd-Catalyzed C(sp3)−H Functionalization in Natural
Product Total Synthesis. Eur. J. Org. Chem. 2017, 2017, 5179−5190.
(b) Nairoukh, Z.; Cormier, M.; Marek, I. Merging C−H and C−C
Bond Cleavage in Organic Synthesis. Nat. Rev. Chem. 2017, 1, 0035.
(c) Shi, X.; Sasmal, A.; Soule, J. F.; Doucet, H. Metal-Catalyzed C−H
Bond Activation of 5-Membered Carbocyclic Rings: A Powerful
Access to Azulene, Acenaphthylene and Fulvene Derivatives. Chem. -
Asian J. 2018, 13, 143−157.
ACKNOWLEDGMENTS
■
We thank the Ministry of Science and Technology of the
Republic of China (MOST 104-2113-M-143-002-MY2 and
MOST 106-2113-M-143-001-MY2) for financial support and
Mr. Min-Yuan Hung for his technical support and services in
GC−MS, Center for Research Resources and Development of
Kaohsiung Medical University (Taiwan).
̈
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N
DOI: 10.1021/acs.organomet.9b00119
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Organometallics
Article
reacts with the palladium center, the ortho steric hindrance might
suppress the reactivity. By contrast, the starting substrates 1b and 1g
bearing an ortho-substituent might cause the steric hindrance between
the pyridine and aniline to form an orthogonal molecular geometry,
which might promote the ease of the formation of the palladium
complex I or II. The phenomenon may eventually result in the
observation of the excellent yield.
(12) Copies of the deposited crystallographic data CCDC-1897993
(4a), CCDC-1897992 (5h), and CCDC-1897991 (I) can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
(13) These results are consistent with that of our previous study, the
palladium-catalyzed ortho-C−H bond aroylation of 2-phenoxypyr-
idines, see ref 5a. In the radical reactions, large kH/kD values are often
observed because of the quantum tunneling effect, see: (a) Lewis, E.
S.; Funderburk, L. H. Rates and Isotope Effects in the Proton
Transfers from 2-Nitropropane to Pyridine Bases. J. Am. Chem. Soc.
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A.; Borden, W. T.; Mayer, J. M. Nitroxyl Radical Plus Hydroxylamine
Pseudo Self-Exchange Reactions: Tunneling in Hydrogen Atom
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Free Radical Chain Oxidations. J. Am. Chem. Soc. 2014, 136, 838−
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(15) The synthetic conditions was followed by the literature
reported, see ref 6a.
(16) For the synthesis and characterization of substrates 1-H/H, 1-
Me/H, and 1-OMe/H, see ref 5b.
O
DOI: 10.1021/acs.organomet.9b00119
Organometallics XXXX, XXX, XXX−XXX