Ruthenium-Catalyzed Ring-Opening Addition of Anilides to 7-Azabenzonorbornadienes: A Diastereoselective Route to Hydronaphthylamines

Article abstract of DOI:10.1021/acs.joc.8b00604

The ruthenium(II)-catalyzed direct ring-opening reaction of 7-azabenzonorbornadienes with anilides via C-H activation to access hydronaphthylamines has been developed. The transformation proceeds with a high stereoselectivity to give cis-configuration products under redox-neutral conditions.

Full text of DOI:10.1021/acs.joc.8b00604

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Ruthenium-Catalyzed Ring-Opening Addition
of Anilides to 7- Azabenzonorbornadienes: A
Diastereoselective Route to Hydronaphthylamines
Qiangqiang Yan, Chunhua Xiong, Steven Chu, Zhanxiang Liu, and Yuhong Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00604 • Publication Date (Web): 18 Apr 2018
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Ruthenium-Catalyzed Ring-Opening Addition of Anilides to 7-
Azabenzonorbornadienes: A Diastereoselective Route to
Hydronaphthylamines
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Qiangqiang Yan, † Chunhua Xiong, ‡ Steven Chu, † Zhanxiang Liu, † and
Yuhong Zhang *,†, §
†Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
‡Department of Applied Chemistry, Zhejiang Gongshang University, Hangzhou 310012, China.
§State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
E-mail: yhzhang@zju.edu.cn
NHAc
Boc
N
NHAc
[RuCl2(p-cymene)]2 (5 mol%)
HN
Boc
AgSbF6 (30 mol%), NaOAc (50 mol%)
H
High Eff iciency
Redox-Neutr al Process
Broad Substrate Scope
√
Diastereoselectivity
√
√
√
Abstract
Ruthenium(II)ꢀcatalyzed direct ringꢀopening reaction of 7ꢀazabenzonorbornadienes with
anilides via CꢀH activation to access hydronaphthylamines has been developed. The transformation
proceeds with high stereoselectivity to give cisꢀconfiguration products under redoxꢀneutral
conditions.
Introduction
Hydronaphthylamines are ubiquitous structural motifs that widely exist in natural
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products, pharmaceuticals and biologically active molecules (Figure 1). Over the past
decades, significant advances have been made in the preparation of these important scaffolds.
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Traditional methods to access hydronaphthylamines, such as FriedelꢀCrafts, Haworth and
LeuckartꢀWallach reactions, usually suffer from harsh reaction conditions, multiple steps, and
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narrow substrate scope. In recent years, transition metalꢀcatalyzed ringꢀopening reaction of
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azabicyclic alkenes with aryl halides, 3 amines, 4 phenols 5 and organometallic reagents has
been widely used as reliable approaches for the synthesis of hydronaphthylamines. However,
the prefunctionalization of the substrates is usually inevitable in these transformations with
the undesirable toxic waste. Consequently, the development of more facile and efficient
routes to their preparation is highly desirable.
Figure 1 Representative biologically active molecules featuring hydronaphthylamines.
Transitionꢀmetalꢀcatalyzed direct CꢀH functionalization reactions have emerged as an
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appealing and powerful tool owing to their high stepꢀ and atomꢀeconomy. In particular, the
ringꢀopening addition of a CꢀH bond to strained heterobicyclic alkenes for construction of
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complicated molecules represents an ideal and environmentally attractive strategy. For
instance, Li and coworkers reported rhodium(III)ꢀcatalyzed coupling reaction of
2ꢀarylpyridines and strained 7ꢀoxabenzonorbornadienes via CꢀH activation to afford
orthoꢀnaphthylated arenes under redoxꢀneutral conditions, whereas the coupling reaction with
similar 7ꢀazabenzonorbornadienes only proceeded under oxidative conditions to furnish
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cisꢀfused dihydrocarbazoles.
Later, Miura and Satoh demonstrated the
rhodium(III)ꢀcatalyzed direct coupling of arylphosphine oxides with heterobicyclic alkenes to
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afford functionalized naphthalenes under redoxꢀneutral conditions.
Recently,
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cobalt(III)ꢀcatalyzed direct CꢀH naphthylation of arenes with 7ꢀoxabenzonorbornadienes was
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developed by Li and Cheng groups, independently (Scheme 1a). Furthermore, selective
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alkylation reaction of arenes with heterobicyclic alkenes by Rh(III) or Ru(II)ꢀcatalysis has
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been described by Bolm groups (Scheme 1b). Despite these significant advancements, the
synthetic method to access hydronaphthylamines is still unprecedented. Herein, we disclose a
rutheniumꢀcatalyzed ringꢀopening reaction for the assembly of valuable hydronaphthylamines
from anilides and 7ꢀazabenzonornadiene (Scheme 1c). The reaction proceeded efficiently
under redoxꢀneutral conditions and displayed good functional group compatibility. Notably,
the transformation exhibited high stereoselectivity to afford cisꢀconfiguration products.
7ꢀOxabenzonorbornadienes were compatible with the catalytic system to give functionalized
naphthalenes under the modified reaction conditions.
Scheme 1. Metalꢀcatalyzed CꢀH bond functionalization of oxaꢀ and azabicyclic alkenes
Results and discussion
We initially choose the acetanilide (1a) and 7ꢀaxabenzonorbornadiene (2a) as model
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substrates to start our investigation. The reaction was performed in the presence of 5 mol %
of [RuCl2(pꢀcymene)]2 and 20 mol % of AgSbF6 and PivOH in 1, 2ꢀdichloroethane(DCE) at
100 oC under air atmosphere. Unfortunately, the desired ringꢀopening coupling product could
be obtained in low yield (Table 1, entry 1). Other silver salts were screened and the results
were inferior to that of AgSbF6 (Table 1, entries 2ꢀ3). The yield of the reaction sharply
increased to 62% when NaOAc was used as an additive (Table 1, entries 4ꢀ8). The solvent
effect of the reaction was investigated by the employment of different solvents, and DCE
exhibited the highest efficiency (Table 1, entries 9ꢀ12). To our delight, further optimization of
the reaction conditions gave the ring opening product 3a in 80% yield with 30 mol% AgSbF6
and 50 mol% NaOAc (Table 1, entry 13). In addition, the amount of catalyst had a significant
effect on the reaction efficiency and we found that Cp*Co(CO)I2 failed to promote the
reaction, but [Cp*RhCl2]2 catalyzed the reaction to give the same product in 36% yield (see
Supporting Information). It should be emphasized that the reaction proceeded very efficiently
under redoxꢀneutral conditions.
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Table 1. Optimization of the Reaction Conditions a
Entry Additive (mol %) Base (mol %)
Solvent
Yield b (%)
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1
2
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4
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8
AgSbF6
AgBF4
PivOH
PivOH
PivOH
HOAc
1, 2ꢀDichloroethane
1, 2ꢀDichloroethane
1, 2ꢀDichloroethane
1, 2ꢀDichloroethane
1, 2ꢀDichloroethane
1, 2ꢀDichloroethane
1, 2ꢀDichloroethane
1, 2ꢀDichloroethane
trace
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AgNTf2
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
16
NaHCO3
LiOAc
CsOAc
NaOAc
NR
Trace
Trace
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AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
NaOAc
NaOAc
NaOAc
Toluene
CH3CN
36
NR
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a
DMF
Trace
NR
2, 2, 2ꢀ Trifluoroethanol
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NaOAc
NaOAc
1, 2ꢀDichloroethane
80 c
Reactions were carried out by using 1a (0.2 mmol), 2a (0.3 mmol), Cat. Ru (0. 01 mmol),
b
c
additive (0.04 mmol), base/acid (0.04 mmol), solvent (1.0 mL), 100 °C, air, 8 h. Isolated yield.
Cat. Ru (0. 01 mmol), additive (0.06 mmol), base/acid (0.1 mmol).
With the optimum reaction conditions in hand, we investigated the generality and
limitation of the protocol with diverse 7ꢀaxabenzonorbornadienes (Scheme 2). We found that
the reaction presented broad substrate scope, and a variety of electronꢀdonating or
electronꢀwithdrawing groups were wellꢀtolerated under the standard conditions (3a-3l). It was
worth mentioning that the electronic factors of acetanilide had a distinct influence on the
reaction. The similar reactivity of paraꢀ and metaꢀ substituted anilides (3b-3c) was observed
compared to the orthoꢀsubstituted one (3d), suggesting that steric hindrance exerted
negligible influence on this transformation. In addition, anilides bearing a halogen atom (Cl,
Br, or I) at para position of phenyl ring smoothly survived under the optimized conditions to
deliver hydronaphthylamine products (3j-3l). Unfortunately, the orthoꢀchloro substituted
anilides hampered the reactivity (3m). Other types of amides, including propyl or isopropyl
amides, could be compatible with the reaction to afford the target product in moderate yield
(
3n-3o). It should be noted that the product 3o was obtained in 45% yield along with the
naphthylated product 5p in 30% yield. The substrate bearing the strong electronwithdrawing
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COOMe group could also be involved in the reaction to afford 3n in 41% isolated yield.
Hydronaphthylamine product 3q and 3r were also isolated in moderate yields when
substituted 7ꢀaxabenzonorbornadienes were used.
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Scheme 2. Synthesis of hydronaphthylamines from diverse anilides a,b
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a Reaction conditions:
1 (0.2 mmol), 2 (0.3 mmol), [RuCl2(pꢀcymene)]2 (0.01 mmol), AgSbF6
(0.06 mmol), NaOAc (0.1 mmol), DCE (1 mL), air, 100 °C, 8 h. b Isolated yields
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With the development of dehydrative naphthylation reactions, we next extended the
strained bicyclic alkenes to 7ꢀoxabenzonorbornadienes (Schemec 3). For the reactions, the
conditions are different from the ones in Scheme2. A wide variety of acetanilides bearing
electronꢀdonating (5a–5h) or electronꢀwithdrawing (5i–5n) groups at different positions of
the phenyl ring were subjected to the optimized conditions, and to our satisfaction, moderate
to good yields of the desired naphthylation products were obtained in 48ꢀ82% yields,
showing the good functional group compatibility. It was observed that the electron factors of
acetanilide exerted an obvious effect on the reaction as demonstrated by the higher reactivity
of electronꢀrich substrates. In case of the meta substituted substrates, the reaction occurred at
the less hindered position, indicative of good regioselectivity (5c). The ortho substituted
acetanilide had poor reactivity (5d), revealing that steric hindrance played effect on this
transformation. The reaction showed good tolerance toward halogenated substituents,
including Cl, Br and I groups, allows for further derivatization of the obtained products
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(
5j–5l). It was noteworthy that the acetanilide attached with an acetyl group smoothly
coupled with 4a to afford the corresponding product 5n in reasonable yield. Other types of
amides, such as propyl or isopropyl amides, participated in the reaction successfully to access
the relevant products (5o–5p) in acceptable yields. In addition, the heterobicyclic olefin
substrate is not limited to 4a, other substituted 7ꢀoxabenzonorbornadienes were applicable
under the standard conditions to give the desired compounds (5q–5r). Notably, the addition
of 1a onto unsymmetrically substituted 7ꢀoxabicyclo alkene 4r led to a mixture of
regioisomers 5r and 5r’ in 64% yield.
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Scheme 3. Synthesis of naphthalene derivatives from diverse anilides a,b
5
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7
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O
R2
NH
R1
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H
O
R2
N
[RuCl2(p-cymene)]2 (5 mol %)
R1
AgSbF6 (20 mol%), PivOH (2 eq.)
1,4-dioxane, 100 oC, 8 h
O
R3
5
1
4
R3
O
O
O
O
NH
NH
NH
NH
5c, 72%
5a, 81%
O
5b, 82%
5d, 61%
O
O
O
NH
NH
NH
NH
O
5h, 77%
O
5g, 62%
5f, 61%
5e, 78%
O
O
O
NH
NH
NH
NH
I
Br
F
Cl
5l, 70%
5k, 57%
O
5i, 71%
O
5j, 53%
O
O
NH
NH
NH
NH
O
MeOOC
5p, 44%
5o, 76%
5m, 54%
5n, 48%
O
O
O
NH
NH
NH
Br
Br
5r
5r'
5q, 62%
64%
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a Reaction conditions: 1 (0.2 mmol), 4 (0.3 mmol), [RuCl2(pꢀcymene)]2 (0.01 mmol), AgSbF6
5
6
7
(0.04 mmol), PivOH (2 equiv), 1,4ꢀdioxane (1 mL), air, 100 °C, 8 h. b Isolated yields.
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To gain insight into the reaction mechanism, a series of preliminary experiments were
conducted as outlined in Scheme 4. The kinetic isotope effect (KIE) values of 2.3 were
observed from the competitive reactions of 1a and 1a-d5 with 2a at a low conversion [Scheme
4, Eq. (1)]. Moreover, a similar result was obtained from two parallel reactions [Scheme 4, Eq.
(2)]. The above results indicated that the cleavage of C−H bond might be involved in the
rateꢀdetermining step. Intermolecular competition experiment between 1p and 1g was carried
out, and the more electronꢀdeficient anilide reacted at a higher rate [Scheme 4, Eq. (3)],
suggesting that the C−H activation probably occurs via a concerted metalationꢀdeprotonation
mechanism. 13
Scheme 4. Mechanistic investigations
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On the basis of previous reports 9ꢀ11,14and the results of control experiments, a plausible
catalytic cycle is proposed as shown in Scheme 5. Initially, the active cationic ruthenium
complex is generated from ligand exchange with AgSbF6 or NaOAc. The following directed
CꢀH activation results in the formation of the sixꢀmembered ruthenacycle intermediate
Then, the alkene ꢀbond in 2a coordinates with ruthenacycle and is subsequently inserted
into the RuꢀC bond of the resulting intermediate
intermediate
Protonation of intermediate
and regenerates the active ruthenium catalyst, which initiates the next catalytic cycle. In the
case of the coupling of 7ꢀoxabenzonorbornadiene, intermediate undergoes βꢀoxygen
elimination preferentially to give intermediate . Protonolysis of the RuꢀO bond by AcOH
liberates the dihydronaphthol intermediate
A.
π
A
B
to afford the eightꢀmembered Ru(II)
9,15
C. The subsequent βꢀN elimination leads to the ringꢀopening intermediate D.
D
in the presence of AcOH releases the corresponding product 3a
F
G
H
, which is dehydrated to give the product 5a.
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Scheme 5. Plausible mechanism
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Conclusion
In conclusion, we have developed the rutheniumꢀcatalyzed ringꢀopening reaction of
7ꢀazabenzonorbornadiene with anilides via CꢀH activation. The
concertedꢀmetalationꢀdeprotonation and βꢀnitrogen elimination are supposed to be involved
ꢀ
in the reaction processes. Attractive features of this system include redoxꢀneutral conditions,
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a broad substrate scope and good functional group tolerance, which provides an alternative
avenue for the synthesis of hydronaphthylamines. Naphthlenes were obtained in high yields
by the use of 7ꢀoxabicyclic alkenes as the reaction partners.
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Experiment Section
General Information. All reactions were performed under air atmosphere in a flameꢀdried reaction
flask. The other materials and solvents were purchased from common commercial sources and used
without additional purification, if there is no special version. Starting materials
7ꢀoxa/azabenzonorbornadienes 9, 16 were synthesized according to literature procedures. H NMR
1
spectra were recorded at 400 MHz using TMS as internal standard, 13C NMR spectra were recorded
at 100 MHz using TMS as internal standard. The multiplicities are reported as follows: singlet (s),
doublet (d), doublet of doublets (dd), multiplet (m), triplet (t) and broad resonances (br). Mass
spectroscopy data of the products were collected on an HRMSꢀTOF instrument.
General Procedure for Ruthenium-Catalyzed Ring-Opening Addition of Anilides to 7-
Azabenzonorbornadienes (3). To a flameꢀdried reaction flask, amides 1 (0.2 mmol),
7ꢀaxabenzonorbornadienes 2 (0.3 mmol), [RuCl2(pꢀcymene)]2 (6.1 mg, 0.01 mmol), AgSbF6 (20.6
mg, 0.06 mmol), NaOAc (8.2 mg, 0.1 mmol) and DCE (1 mL) were added under air atmosphere. The
mixture was stirred for 8 h at 100 °C. The mixture was then cooled to room temperature, diluted with
EtOAc, filtered through a celite pad, and concentrated in vacuo. The residue was purified by flash
column chromatography on silica gel (eluent: hexane/EtOAc = 5/1 with triethylamine), to afford the
desired product 3.
tert-butyl (1S,2R)-2-(2-acetamidophenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3a) Light
brown solid; yield: 80% (60.5mg); m.p = 172ꢀ174 °C; 1H NMR (400 MHz, CDCl3, ppm) δ 7.72 (s,
1H), 7.54 (d, J = 8.4 Hz, 1H), 7.30 (dd, J = 6.8, 2.4 Hz, 1H), 7.25ꢀ7.21 (m, 3H), 7.16 (d, J = 6.8 Hz,
1H), 7.10ꢀ7.04 (m, 2H), 6.68 (dd, J = 9.8, 1.4 Hz, 1H), 6.04 (dd, J = 9.8, 4.6 Hz, 1H), 5.29 (t, J = 6.4
Hz, 1H), 4.72 (d, J = 7.6 Hz, 1H), 4.25 (d, J = 7.8 Hz, 1H), 2.21 (s, 3H), 1.32 (s, 9H). 13C NMR
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(100MHz, CDCl3) δ 169.3, 155.9, 135.9, 133.5, 132.9, 132.0, 129.8, 129.7, 128.3, 128.2, 128.0,
127.8, 126.8, 126.3, 126.2, 126.0, 80.0, 51.0, 39.6, 28.3, 23.9.HRMS (EIꢀTOF): Calculated for
C23H26N2O3 [M]+ 378.1943, Found 378.1946.
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tert-butyl(1S,2R)-2-(2-acetamido-5-methylphenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3b)
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White solid; yield: 82% (64.3mg); m.p = 142ꢀ144 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.65 (s,
1H), 7.34 (d, J = 8.0 Hz, 1H), 7.28ꢀ7.23 (m, 3H), 7.15 (d, J = 6.8 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H),
6.91 (s, 1H), 6.66 (dd, J = 9.6, 1.8 Hz, 1H), 6.02 (dd, J = 9.6, 4.0 Hz, 1H) 5.25 (d, J = 8.0 Hz, 1H),
4.75 (d, J = 8.0 Hz, 1H), 4.21 (d, J = 8.0 Hz, 1H), 2.21 (s, 3H), 2.04 (s, 3H), 1.30 (s, 9H). 13C NMR
(100MHz, CDCl3) δ 169.4, 155.6, 135.9, 133.6, 133.3, 132.7, 132.6, 130.6, 129.8, 128.5, 128.2,
128.1, 127.9, 126.7, 126.6, 126.3, 79.7, 50.7, 39.9, 28.2, 23.7, 21.1. HRMS (EIꢀTOF): Calculated for
C24H28N2O3 [M]+ 392.2100, Found 392.2108.
tert-butyl(1S,2R)-2-(2-acetamido-4-methylphenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3c)
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White solid; yield: 78% (61.2mg); m.p = 154ꢀ155 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.60 (s,
1H), 7.37 (s, 1H), 7.27ꢀ7.22 (m, 3H), 7.15 (d, J = 7.2 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.85 (d, J =
7.6 Hz, 1H), 6.66 (d, J = 9.6 Hz, 1H), 6.02 (dd, J = 9.4, 4.6 Hz, 1H), 5.29 (t, J = 8.8 Hz, 1H), 4.71 (d,
J = 8.0 Hz, 1H), 4.19 (d, J = 8.0 Hz, 1H), 2.28 (s, 3H), 2.09 (s, 3H), 1.34 (s, 9H). 13C NMR
(100MHz, CDCl3) δ 169.2, 155.9, 137.7, 135.7, 133.5, 132.9, 129.9, 129.6, 128.7, 128.3, 128.1,
127.9, 127.2, 126.9, 126.7, 125.9, 79.9, 51.1, 39.3, 28.3, 23.9, 21.0. HRMS (EIꢀTOF): Calculated for
C24H28N2O3 [M]+ 392.2100, Found 392.2106.
tert-butyl(1S,2R)-2-(2-acetamido-3-methylphenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3d)
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Light brown solid; yield: 74% (58.1mg); m.p = 105ꢀ106 °C; H NMR (400 MHz, CDCl3, ppm) δ
7.55 (s, 1H), 7.25ꢀ7.19 (m, 3H), 7.11ꢀ7.06 (m, 3H), 6.99 (d, J = 6.0 Hz, 1H), 6.59 (dd, J = 9.6, 2.0 Hz,
1H), 6.01 (dd, J = 9.8, 3.0 Hz, 1H), 5.24 (t, J = 8.6 Hz, 1H), 4.74 (d, J = 8.8 Hz, 1H), 4.22 (d, J = 8.8
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Hz, 1H), 2.19 (s, 3H), 2.11 (s, 3H), 1.22 (s, 9H). C NMR (100MHz, CDCl3) δ 169.4, 155.5, 136.4,
134.6, 133.7, 132.7, 130.4, 130.1, 129.5, 128.3, 128.0, 127.6, 127.5, 127.2, 126.9, 126.5, 79.5, 50.3,
40.5, 28.1, 23.0, 18.5. HRMS (EIꢀTOF): Calculated for C24H28N2O3 [M]+ 392.2100, Found
392.2112.
tert-butyl(1S,2R)-2-(2-acetamido-4,5-dimethylphenyl)-1,2-dihydronaphthalen-1-ylcarbamate
(3e)
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White solid; yield: 85% (69.1mg); m.p = 140ꢀ141 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.49 (s,
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1H), 7.29ꢀ7.23 (m, 4H), 7.15(d, J = 6.8 Hz, 1H), 6.84 (s, 1H), 6.66 (d, J = 9.6 Hz, 1H), 6.03 (dd, J =
9.8, 4.2 Hz, 1H), 5.25 (t, J = 7.8, 1H), 4.72 (d, J = 8.4 Hz, 1H), 4.16 (d, J = 8.2 Hz, 1H), 2.18 (s, 1H),
2.10 (s, 3H), 2.05 (s, 3H), 1.31 (s, 9H). 13C NMR (100MHz, CDCl3) δ 169.4, 155.8, 136.2, 134.8,
133.7, 133.4, 132.9, 130.9, 130.0, 129.8, 128.2, 128.1, 127.8, 127.7, 126.7, 126.2, 79.7, 50.8, 39.7,
28.2, 23.8,19.5. HRMS (EIꢀTOF): Calculated for C25H30N2O3 [M]+ 406.2256, Found 406.2252.
tert-butyl(1S,2R)-2-(2-acetamido-5-isopropylphenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3f)
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Light brown solid; yield: 68% (57.1mg); m.p = 125ꢀ126 °C; H NMR (400 MHz, CDCl3, ppm) δ
7.52 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.30ꢀ7.28 (m, 1H), 7.23 (d, J = 5.6 Hz, 2H), 7.16 (d, J = 7.2
Hz, 1H), 7.09 (dd, J = 8.2, 1.8 Hz, 1H), 6.91 (d, J = 1.6 Hz, 1H), 6.70 (dd, J = 9.6, 1.6 Hz, 1H), 6.07
(dd, J = 9.6, 4.4 Hz, 1H), 5.30 (d, J = 6.4 Hz, 1H), 4.70 (d, J = 8.4 Hz, 1H), 4.20 (d, J = 8.4 Hz, 1H),
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2.77ꢀ2.72 (m,1H), 2.07 (s, 3H), 1.31 (s, 9H), 1.11 (d, J = 9.6 Hz, 3H), 1.09 (d, J = 9.2 Hz, 3H). C
NMR (100MHz, CDCl3) δ 169.4, 155.7, 146.8, 133.8, 133.5, 132.9, 132.2, 129.9, 128.3, 128.1,
127.9, 126.6, 126.5, 126.2, 125.9, 79.8, 50.8, 40.1, 33.6, 28.3, 24.1, 23.8, 23.6. HRMS (EIꢀTOF):
Calculated for C26H32N2O3 [M]+ 420.2413, Found 420.2418.
tert-butyl(1S,2R)-2-(2-acetamido-5-methoxyphenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3g)
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White solid; yield: 67% (54.7mg); m.p = 148ꢀ149 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.55 (s,
1H), 7.32 (d, J = 8.4 Hz, 1H), 7.29ꢀ7.22 (m, 3H), 7.14 (d, J = 6.8 Hz, 1H), 6.76 (dd, J = 8.6, 3.2 Hz,
1H), 6.68ꢀ6.64 (m, 2H), 6.03 (dd, J = 9.6, 4.0 Hz, 1H), 5.27 (t, J = 8.8 Hz, 1H), 4.74 (d, J = 8.8 Hz,
1H), 4.20 (d, J = 8.0 Hz, 1H), 3.63 (s, 3H), 2.09 (s, 3H), 1.32 (s, 9H). 13C NMR (100MHz, CDCl3) δ
169.7, 157.9, 155.7, 134.8, 133.5, 132.8, 129.8, 129.1, 128.7, 128.3, 128.2, 128.1, 126.7, 126.2,
115.1, 112.9, 79.9, 55.2, 50.9, 39.9, 28.2, 23.7. HRMS (EIꢀTOF): Calculated for C24H28N2O4 [M]+
408.2049, Found 408.2056.
tert-butyl (1S,2R)-2-(2-acetamido-5-ethoxyphenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3h)
White solid; yield:52% (43.8mg); 1H NMR (400 MHz, CDCl3, ppm) δ 7.50 (s, 1H), 7.31 (d, J = 9.2
Hz, 1H), 7.29ꢀ7.25 (m, 3H), 7.16 (d, J = 6.8 Hz, 1H), 6.75 (dd, J = 8.8, 2.4 Hz, 1H), 6.68ꢀ6.65 (m,
2H), 6.04 (dd, J = 9.4, 3.8 Hz, 1H), 5.27 (t, J = 8.4 Hz, 1H), 4.74 (d, J = 9.2 Hz, 1H), 4.20 (d, J = 8.0
Hz, 1H), 3.92ꢀ3.86 (m, 2H), 2.10 (s, 3H), 1.33 (s, 9H), 1.29 (t, J = 4.8 Hz, 3H ). 13C NMR (100MHz,
CDCl3) δ 169.6, 157.3, 155.7, 134.9, 133.5, 132.8, 129.8, 128.5, 128.4, 128.3, 128.2, 128.1, 126.7,
126.3, 115.6, 113.5, 79.9, 63.4, 50.8, 39.9, 28.2, 23.7,14.7. HRMS (EIꢀTOF): Calculated for
C25H30N2O4 [M]+ 422.2206, Found 422.2213.
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tert-butyl(1S,2R)-2-(4-acetamidobiphenyl-3-yl)-1,2-dihydronaphthalen-1-ylcarbamate (3i)
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White solid; yield: 58% (52.7mg); m.p = 150ꢀ151 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.66 (s,
1H), 7.62 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 4.0 Hz, 4H), 7.33ꢀ7.26 (m, 5H),
7.18 (d, J = 6.8 Hz, 1H), 6.70 (d, J = 9.6 Hz, 1H), 6.08 (dd, J = 9.6, 3.6 Hz, 1H), 5.33 (t, J = 7.6, 1H),
4.79 (d, J = 7.6 Hz, 1H), 4.29 (s, 1H), 2.13 (s, 3H), 1.27 (s, 9H). 13C NMR (100MHz, CDCl3) δ
169.3, 155.7, 140.5, 138.9, 135.2, 133.4, 132.8, 132.5, 129.7, 128.7, 128.4, 128.4, 128.3, 127.2,
127.0, 126.8, 126.6, 126.5, 126.4, 80.0, 50.9, 40.0, 28.2, 24.0. HRMS (EIꢀTOF): Calculated for
C29H30N2O3 [M]+ 454.2256, Found 454.2246.
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tert-butyl(1S,2R)-2-(2-acetamido-5-chlorophenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3j)
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White solid; yield: 60% (49.4mg); m.p = 171ꢀ173 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.67 (s,
1H), 7.50 (d, J = 8.4 Hz, 1H), 7.33ꢀ7.25 (m, 3H), 7.19 (t, J = 7.2 Hz, 2H), 7.09 (d, J = 2.0 Hz, 1H),
6.70 (dd, J = 9.6, 1.2 Hz, 1H), 5.98 (dd, J = 9.6, 4.0 Hz, 1H), 5.24 (d, J = 8.0 Hz, 1H), 4.74 (d, J =
7.6 Hz, 1H), 4.23 (s, 1H), 2.10 (s, 3H), 1.31 (s, 9H). 13C NMR (100MHz, CDCl3) δ 169.2, 155.7,
134.7, 134.5, 132.9, 132.5, 131.5, 129.8, 128.8, 128.5, 128.5, 127.9, 127.5, 127.0, 126.5, 80.2, 50.6,
39.9, 28.2, 23.9. HRMS (EIꢀTOF): Calculated for C23H25ClN2O3 [M]+ 412.1554, Found 412.1551.
tert-butyl(1S,2R)-2-(2-acetamido-5-bromophenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3k)
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White solid; yield: 57% (51.9mg); m.p = 183ꢀ184 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.66 (s,
1H), 7.44 (d, J = 7.6 Hz, 1H), 7.35(d, J = 7.6 Hz, 1H), 7.30ꢀ7.25 (m, 4H), 7.18 (d, J = 6.8 Hz, 1H),
6.70 (d, J = 9.2 Hz, 1H), 5.98 (dd, J = 9.2, 3.2 Hz, 1H), 5.23 (t, J = 7.6, 1H), 4.74 (d, J = 6.8 Hz, 1H),
4.22 (s, 1H), 2.09 (s, 3H), 1.31 (s, 9H). 13C NMR (100MHz, CDCl3) δ 169.2, 155.8, 135.3, 135.0,
132.9, 132.8, 132.5, 130.9, 128.8, 128.6, 128.5, 127.9, 127.1, 126.6, 119.5, 80.3, 50.6, 40.1, 28.3,
24.0. HRMS (EIꢀTOF): Calculated for C23H25BrN2O3 [M]+ 456.1049, Found 456.1055.
tert-butyl(1S,2R)-2-(2-acetamido-5-iodophenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3l)
White solid; yield: 56% (56.4mg); m.p = 170ꢀ172 °C; 1H NMR (400 MHz, CDCl3, ppm) δ 7.66 (s,
1H), 7.47 (d, J = 6.8 Hz, 1H), 7.37 (s, 1H), 7.25ꢀ7.18 (m, 4H), 7.10 (d, J = 7.2 Hz, 1H), 6.62 (d, J =
9.6 Hz, 1H), 5.89 (dd, J = 9.6, 3.6 Hz, 1H), 5.13 (t, J = 8.2 Hz, 1H), 4.70 (d, J = 7.6 Hz, 1H), 4.11 (d,
J = 7.8 Hz, 1H), 1.99 (s, 3H), 1.23 (s, 9H). 13C NMR (100MHz, CDCl3) δ 169.3, 155.6, 138.8, 136.8,
135.9, 135.3, 132.9, 132.9, 132.4, 128.8, 128.5, 128.1, 127.0, 126.7, 90.9, 80.2, 50.5, 40.1, 28.2, 23.9.
HRMS (EIꢀTOF): Calculated for C23H25IN2O3 [M]+ 504.0910, Found 504.0918.
tert-butyl (1S,2R)-2-(2-butyramidophenyl)-1,2-dihydronaphthalen-1-ylcarbamate(3n)
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White solid; yield: 68% (55.2mg); m.p = 154ꢀ155 °C; 1H NMR (400 MHz, CDCl3, ppm) δ 7.63 (s,
1H), 7.57 (d, J = 7.6 Hz, 1H), 7.30ꢀ7.20 (m, 4H), 7.16 (d, J = 7.2 Hz, 1H), 7.09ꢀ7.03 (m, 2H), 6.68 (d,
J = 9.2 Hz, 1H), 6.04 (dd, J = 9.8, 4.2 Hz, 1H), 5.32 (s, 1H), 4.69 (d, J = 6.8 Hz, 1H), 4.22 (s, 1H),
2.28 (t, J = 7.2 Hz, 2H), 1.79ꢀ1.70 (m, 2H), 1.33 (s, 9H), 0.99 (t, J = 7.4 Hz, 3H). 13C NMR
(100MHz, CDCl3) δ 172.0, 155.8, 135.9, 133.5, 132.9, 131.8, 129.8, 128.3, 128.1, 128.0, 127.8,
126.8, 126.3, 126.1, 126.0, 80.0, 51.1, 39.7, 39.2, 28.3, 19.2, 13.8. HRMS (EIꢀTOF): Calculated for
C25H30N2O3 [M]+ 406.2256, Found 406.2254.
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tert-butyl(1S,2R)-2-(2-isobutyramidophenyl)-1,2-dihydronaphthalen-1-ylcarbamate (3o)
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White solid; yield: 45% (36.5mg); m.p = 166ꢀ167 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.65 (s,
1H), 7.58 (d, J = 6.0 Hz, 1H), 7.28 (t, J = 6.0 Hz, 1H), 7.24ꢀ7.19 (m, 3H), 7.16 (d, J = 6.0 Hz, 1H),
7.10ꢀ7.03 (m, 2H), 6.68 (d, J = 6.8 Hz, 1H), 6.05 (dd, J = 7.8, 3.4 Hz, 1H), 5.32 (s, 1H), 4.66 (s, 1H),
4.18 (s, 1H), 2.53ꢀ2.47 (m, 1H), 1.32 (s, 9H), 1.26 (t, J = 5.2 Hz, 6H). 13C NMR (100MHz, CDCl3) δ
175.8, 155.7, 135.9, 133.6, 132.9, 131.8, 129.8, 129.7, 128.3, 128.2, 128.1, 127.8, 126.7, 126.2,
126.1, 126.0, 80.0, 51.3, 39.8, 36.3, 28.2, 19.8, 19.6. HRMS (EIꢀTOF): Calculated for C25H30N2O3
[M]+ 406.2256, Found 406.2255.
methyl 4-acetamido-3-((1S,2R)-1-(tert-butoxycarbonylamino)-1,2-dihydronaphthalen-2-yl)
benzoate (3p)
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White solid; yield: 41% (35.7mg); m.p = 181ꢀ182 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.90ꢀ7.86
(m, 2H), 7.80 (s, 2H), 7.31ꢀ7.29 (m, 1H), 7.26ꢀ7.25 (d, J = 4.0 Hz, 2H), 7.20 (d, J = 7.2 Hz, 1H),
6.74 (d, J = 9.2 Hz, 1H), 6.01 (dd, J = 9.6, 4.0 Hz, 1H), 5.27 (t, J = 6.8 Hz, 1H), 4.73 (d, J = 6.8 Hz,
1H), 4.27 (s, 1H), 3.83 (s, 3H), 2.07 (s, 3H), 1.27 (s, 9H). 13C NMR (100MHz, CDCl3) δ 168.9,
166.5, 155.7, 140.6, 133.1, 132.5, 131.7, 130.8, 129.2, 128.8, 128.6, 128.5, 127.1, 126.9, 126.3,
124.5, 80.1, 52.0, 50.8, 40.2, 20.2, 24.2. HRMS (EIꢀTOF): Calculated for C25H28N2O5 [M]+
436.1998, Found 436.1992.
tert-butyl (1S,2R)-2-(2-acetamidophenyl) -6,7-difluoro-1,2-dihydronaphthalen-
1-ylcarbamate (3q)
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White solid; yield: 48% (39.7mg); m.p = 133ꢀ135 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.58 (s,
1H), 7.50 (d, J = 6.0 Hz, 1H), 7.24 (t, J = 6.0 Hz, 1H), 7.09ꢀ7.02 (m, 3H), 6.97 (t, J = 7.2 Hz, 1H),
6.57 (d, J = 7.6 Hz, 1H), 6.06 (dd, J = 7.2, 3.2 Hz, 1H), 5.27 (s, 1H), 4.62 (s, 1H), 4.20 (s, 1H), 2.14
(s, 3H), 1.34 (s, 9H). 13C NMR (100MHz, CDCl3) δ 169.2, 155.7, 150.8 (q, JC–F = 3.4 Hz), 148.8 (q,
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JC–F = 4.0 Hz), 135.8, 131.4, 130.7, 130.4, 129.8(q, JC–F = 3.5 Hz), 129.4, 128.2, 126.7, 126.5, 126.3,
115.6 (d, JC–F = 15.2 Hz), 115.4 (d, JC–F = 15.2 Hz), 80.4, 50.5, 38.7, 28.3, 23.9. HRMS (EIꢀTOF):
Calculated for C23H24F2N2O3 [M]+ 414.1755, Found 414.1751.
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(3r)
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White solid; yield: 52% (42.2mg); m.p = 126ꢀ128 °C; H NMR (400 MHz, CDCl3, ppm) δ 7.67 (s,
1H), 7.56 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.11ꢀ7.03 (m, 2H), 6.99 (s, 1H), 6.94 (s, 1H),
6.61 (d, J = 9.2 Hz, 1H), 5.95 (dd, J = 5.4, 4.2 Hz, 1H), 5.23 (s, 1H), 4.65 (s, 1H), 4.22 (s, 1H), 2.25
(s, 3H), 2.24 (s, 3H), 2.09 (s, 3H), 1.33 (s, 9H). 13C NMR (100MHz, CDCl3) δ 169.1, 155.9, 136.7,
136.3, 136.0, 132.2, 130.7, 130.4, 129.9, 128.6, 128.2, 127.8, 127.7, 127.4, 126.1, 79.9, 50.8, 39.9,
28.3, 24.0, 19.8, 19.4. HRMS (EIꢀTOF): Calculated for C25H30N2O3 [M]+ 406.2256, Found
406.2256.
General Procedure for Ruthenium-Catalyzed Ring-Opening Addition of Anilides to 7-
oxabenzonorbornadienes (5). To a flameꢀdried reaction flask, amides 1 (0.2 mmol),
7ꢀoxabenzonorbornadienes 4 (0.3 mmol), [RuCl2(pꢀcymene)]2 (6.1 mg, 0.01 mmol), AgSbF6 (13.7
mg, 0.04 mmol), PivOH (40.8 mg, 0.4 mmol) and 1,4ꢀdioxane (1 mL) were added under air
atmosphere. The mixture was stirred for 8 h at 100 °C. The mixture was then cooled to room
temperature, diluted with EtOAc, filtered through a celite pad, and concentrated in vacuo. The
residue was purified by flash column chromatography on silica gel (eluent: hexane/EtOAc = 10/1), to
afford the desired product 5.
N-(2-(naphthalen-2-yl)phenyl)acetamide (5a)
White solid; yield: 81% (42.3mg); m.p = 144ꢀ146 °C; 1H NMR (400 MHz, CDCl3, ppm) δ 8.15 (d, J
= 8.4 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.28ꢀ7.18
13
(m, 6H), 7.10ꢀ7.05 (m, 4H), 2.56 (s, 3H). C NMR (100 MHz, CDCl3, ppm) δ 157.8, 146.9, 146.8,
138.5, 136.7, 134.1, 130.1, 130.1, 129.3, 128.4, 127.9, 127.7, 127.3, 126.9, 126.7, 126.3, 125.9, 25.3.
HRMS (EIꢀTOF): Calculated for C18H15NO [M]+ 261.1154, found : 261.1153.
N-(4-methyl-2-(naphthalen-2-yl)phenyl)acetamide (5b)
1
Light brown solid; yield: 82% (45.1mg); m.p = 123ꢀ126 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.11 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.91ꢀ7.86 (m, 2H), 7.83 (s, 1H), 7.56ꢀ7.54 (m, 2H),
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7.47 (dd, J = 9.4, 1.2 Hz, 1H), 7.21 (dd, J = 9.6, 1.2 Hz, 1H), 7.16 (s, 1H), 7.07 (s, 1H), 2.37 (s, 3H),
1.98 (s, 3H). 13C NMR (100MHz, CDCl3) δ 168.4, 135.8, 134.2, 133.5, 132.7, 132.4, 132.3, 130.8,
129.1, 128.7, 128.3, 128.0, 127.8, 127.1, 126.7, 126.5, 122.2, 24.5, 20.9. HRMS (EIꢀTOF):
Calculated for C19H17NO [M]+ 275.1310, Found 275.1313.
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N-(5-methyl-2-(naphthalen-2-yl)phenyl)acetamide (5c)
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Light brown solid; yield: 72% (39.6mg); m.p = 141ꢀ142 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.11 (s, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.92ꢀ7.85 (m, 2H), 7.82 (s, 1H), 7.55ꢀ7.53 (m, 2H), 7.46 (dd, J
= 8.4, 1.2 Hz, 1H), 7.22 (d, J = 7.6 Hz, 1H), 7.13 (s, 1H), 7.03 (d, J = 7.6 Hz, 1H), 2.42 (s, 3H), 1.97
(s, 3H). 13C NMR (100MHz, CDCl3) δ 168.4, 138.6, 135.7, 134.6, 133.6, 132.6, 130.1, 129.5, 128.7,
128.3, 128.0, 127.8, 127.2, 126.7, 126.5, 125.4, 122.4, 24.6, 21.5. HRMS (EIꢀTOF): Calculated for
C19H17NO [M]+ 275.1310, Found 275.1311.
N-(2-methyl-6-(naphthalen-2-yl)phenyl)acetamide (5d)
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Light brown solid; yield: 61% (33.5mg); m.p = 145ꢀ146 °C; H NMR (400 MHz, CDCl3, ppm) δ
7.80ꢀ7.75 (m, 3H), 7.70 (s, 1H), 7.44ꢀ7.42 (m, 2H), 7.36 (dd, J = 8.4, 1.2 Hz, 1H), 7.21 (d, J = 5.2 Hz,
2H), 7.19 (t, J = 5.0 Hz, 1H), 6.61 (s, 1H), 2.25 (s, 3H), 1.88 (s, 3H). 13C NMR (100MHz, CDCl3) δ
169.7, 139.6, 137.3, 137.2, 133.6, 133.0, 132.7, 130.5, 128.3, 128.2, 128.0, 127.9, 127.8, 127.3,
126.6, 126.4, 23.3, 18.9. HRMS (EIꢀTOF): Calculated for C19H17NO [M]+ 275.1310, Found
275.1314.
N-(4,5-dimethyl-2-(naphthalen-2-yl)phenyl)acetamide (5e)
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Light brown solid; yield: 78% (45.1mg); m.p = 138ꢀ140 °C; H NMR (400 MHz, CDCl3, ppm) δ
7.99 (s, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.90ꢀ7.86 (m, 2H), 7.82 (s, 1H), 7.55ꢀ7.53 (m, 2H), 7.47 (dd, J
= 8.0, 1.2 Hz, 1H), 7.13 (s, 1H), 7.09 (s, 1H), 2.34 (s, 3H), 2.29 (s, 3H), 1.98 (s, 3H). 13C NMR
(100MHz, CDCl3) δ 168.4, 137.0, 135.8, 133.6, 133.1, 132.6, 132.3, 131.3, 130.3, 128.6, 128.2,
128.0, 127.8, 127.3, 126.6, 126.4, 123.6, 24.5, 19.9, 19.3. HRMS (EIꢀTOF): Calculated for
C20H19NO [M]+ 289.1467, Found 289.1461.
N-(4-tert-butyl-2-(naphthalen-2-yl)phenyl)acetamide (5f)
Light brown solid; yield: 61% (38.7mg); m.p = 83ꢀ84 °C; 1H NMR (400 MHz, CDCl3, ppm) δ 8.14
(d, J = 8.4 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.92ꢀ7.88 (m, 2H), 7.85 (s, 1H), 7.57ꢀ7.54 (m, 2H),
7.49 (dd, J = 9.2, 1.6 Hz, 1H), 7.43 (dd, J = 8.8, 2.4Hz, 1H), 7.33 (d, J = 2.4 Hz, 1H), 7.09 (s, 1H),
1.98 (s, 3H), 1.35 (s, 9H). 13C NMR (100MHz, CDCl3) δ 168.4, 147.6, 136.2, 133.6, 132.6, 132.2,
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132.1, 128.7, 128.3, 128.0, 127.8, 127.2, 126.7, 126.5, 125.5, 121.9, 34.5, 31.4, 24.5. HRMS
(EIꢀTOF): Calculated for C22H23NO [M]+ 317.1780, Found 317.1782.
6-fluoro-2-methyl-3,4-diphenylquinoline(5g)
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Light brown solid; yield: 62% (36.1mg); m.p = 135ꢀ137 °C; H NMR (400 MHz, CDCl3, ppm) δ
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8.02 (d, J = 9.2 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.91ꢀ7.86 (m, 2H), 7.83 (s, 1H), 7.56ꢀ7.53 (m, 2H),
7.47 (dd, J = 8.4, 1.2 Hz, 1H), 6.98 (s, 1H), 6.93 (dd, J = 8.8, 3.2 Hz, 1H), 8.90 (d, J = 2.8 Hz, 1H),
3.82 (s, 1H), 7.96 (s, 3H). 13C NMR (100MHz, CDCl3) δ 168.5, 156.6, 135.7, 134.7, 133.5, 132.7,
128.6, 128.2, 128.0, 127.9, 127.8, 126.9, 126.7, 126.6, 124.5, 115.7, 113.6, 55.6, 24.3. HRMS
(EIꢀTOF): Calculated for C19H17NO2 [M]+ 291.1259, Found 291.1256.
N-(2,2'-binaphthyl-3-yl)acetamide (5h)
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Light brown solid; yield: 77% (47.9mg); m.p = 148ꢀ150 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.85 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.93ꢀ7.87 (m, 4H), 7.77 (d, J = 7.2 Hz, 2H), 7.58ꢀ7.54 (m, 3H),
7.50ꢀ7.41 (m, 2H), 7.32 (s, 1H), 2.01 (s, 3H). 13C NMR (100MHz, CDCl3) δ 168.4, 135.4, 133.6,
133.5, 132.8, 132.7, 132.1, 130.3, 129.5, 128.9, 128.7, 128.1, 127.9, 127.8, 127.5, 127.1, 126.9,
126.8, 126.6, 125.5, 118.3, 24.9. HRMS (EIꢀTOF): Calculated for C22H17NO [M]+ 311.1310, Found
311.1315.
N-(4-fluoro-2-(naphthalen-2-yl)phenyl)acetamide (5i)
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Light brown solid; yield: 71% (39.6mg); m.p = 147ꢀ149 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.07 (dd, J = 8.6, 5.4 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.83ꢀ7.78 (m, 2H), 7.74 (s, 1H), 7.49ꢀ7.46 (m,
2H), 7.36 (d, J = 8.0 Hz, 1H), 7.02ꢀ6.97 (m, 3H), 1.88 (s, 3H). 13C NMR (100MHz, CDCl3) δ 168.5,
159.3(d, JC–F = 243.3 Hz), 134.7, 134.6, 133.5, 132.9, 130.8(d, JC–F = 1.9 Hz), 128.9, 128.3, 128.1,
127.8, 126.9(d, JC–F = 5.3 Hz), 126.6, 124.2(d, JC–F = 7.8 Hz), 116.8(d, JC–F = 22.1 Hz), 115.0(d, JC–F
= 21.9 Hz), 24.4. HRMS (EIꢀTOF): Calculated for C18H14FNO [M]+ 279.1059, Found 279.1056.
N-(4-chloro-2-(naphthalen-2-yl)phenyl)acetamide (5j)
White solid; yield: 53% (31.3mg); m.p = 160ꢀ162 °C; 1H NMR (400 MHz, CDCl3, ppm) δ 8.27 (d, J
= 8.8 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.93ꢀ7.86 (m, 2H), 7.83 (s, 1H), 7.59ꢀ7.56 (m, 2H), 7.44 (dd,
J = 8.4, 1.6 Hz, 1H), 7.36 (dd, J = 8.4, 2.6 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.14 (s, 1H), 1.98 (s,
3H). 13C NMR (100MHz, CDCl3) δ 168.3, 134.2, 133.6, 133.6, 133.5, 132.9, 130.0, 129.4, 129.1,
128.4, 128.1, 127.8, 127.0, 126.9, 126.5, 122.9, 24.6. HRMS (EIꢀTOF): Calculated for C18H14ClNO
[M]+ 295.0764, Found 295.0767.
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N-(4-bromo-2-(naphthalen-2-yl)phenyl)acetamide (5k)
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Light brown solid; yield: 57% (38.6mg); m.p = 158ꢀ160 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.23 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.93ꢀ7.87 (m, 2H), 7.83 (s, 1H), 7.59ꢀ7.56 (m, 2H),
7.52ꢀ7.47 (m, 2H), 7.44 (dd, J = 8.4, 1.2 Hz, 1H), 7.14 (s, 1H), 1.97 (s, 3H). 13C NMR (100MHz,
CDCl3) δ 168.3, 134.1, 133.9, 133.5, 132.9, 132.8, 131.4, 129.1, 128.4, 128.1, 127.9, 127.0, 126.9,
126.5, 123.1, 117.0, 24.7. HRMS (EIꢀTOF): Calculated for C18H14BrNO [M]+ 339.0259, Found
339.0251.
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N-(4-iodo-2-(naphthalen-2-yl)phenyl)acetamide (5l)
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Light brown solid; yield: 70% (54.1mg); m.p = 161ꢀ163 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.13 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.93ꢀ7.87 (m, 2H), 7.83 (s, 1H), 7.69 (dd, J = 8.6,
1.8 Hz, 1H), 7.67 (s, 1H), 7.59ꢀ7.57 (m, 2H), 7.44 (dd, J = 8.4, 1.2 Hz, 1H), 7.13 (s, 1H), 1.98 (s,
3H). 13C NMR (100MHz, CDCl3) δ 168.3, 138.7, 137.4, 134.9, 134.0, 133.9, 133.5, 132.9, 129.1,
128.4, 128.1, 127.9, 127.0, 126.9, 126.5, 123.2, 24.8. HRMS (EIꢀTOF): Calculated for C18H14INO
[M]+ 387.0120, Found 387.0122.
methyl 4-acetamido-3-(naphthalen-2-yl)benzoate (5m)
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Light brown solid; yield: 54% (34.4mg); m.p = 109ꢀ111 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.52 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.6, 2.2 Hz, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.99 (d, J = 8.8 Hz,
1H), 7.95ꢀ7.89 (m, 2H), 7.87 (s, 1H), 7.61ꢀ7.57 (m, 2H), 7.48 (dd, J = 8.2, 1.8 Hz, 1H), 7.42 (s, 1H),
3.91 (s, 3H), 2.02 (s, 3H). 13C NMR (100MHz, CDCl3) δ 168.5, 166.6, 139.2, 134.4, 133.6, 132.9,
131.8, 131.2, 130.2 129.2, 128.6, 128.1, 127.8, 127.0, 126.9, 126.7, 125.5, 120.2, 52.1, 24.9. HRMS
(EIꢀTOF): Calculated for C20H17NO3 [M]+ 319.1208, Found 319.1214.
N-(4-acetyl-2-(naphthalen-2-yl)phenyl)acetamide (5n)
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Light brown solid; yield: 48% (29.1mg); m.p = 134ꢀ135 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.55 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 8.6, 3.8 Hz, 2H), 7.95ꢀ7.89 (m, 3H), 7.87 (s, 1H), 7.61ꢀ7.58 (m,
2H), 7.47 (dd, J = 8.4, 1.6 Hz, 2H), 7.43 (s, 1H), 2.60 (s, 3H), 2.02 (s, 3H). 13C NMR (100MHz,
CDCl3) δ 197.1, 168.5, 139.4, 134.4, 133.6, 132.9, 132.7, 131.3, 130.5 129.3, 129.3, 128.6, 128.1,
127.9, 127.0, 126.9, 126.6, 120.2, 26.5, 24.9. HRMS (EIꢀTOF): Calculated for C20H17NO2 [M]+
303.1259, Found 303.1254.
N-(2-(naphthalen-2-yl)phenyl)butyramide (5o)
Light brown solid; yield: 76% (43.9mg); m.p = 98ꢀ99 °C;1H NMR (400 MHz, CDCl3, ppm) δ 8.33 (d,
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J = 8.4 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.92ꢀ7.89 (m, 1H), 7.88ꢀ7.86 (m, 1H), 7.85 (s, 1H),
7.57ꢀ7.53 (m, 2H), 7.48 (dd, J = 8.4,1.6 Hz, 1H), 7.40 (td, J = 8.8, 1.2 Hz, 1H), 7.33 (d, J = 7.6 Hz,
1H), 7.23ꢀ7.19 (m, 2H), 2.13 (t, 7.6 Hz, 2H ), 1.63ꢀ1.57 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H). 13C NMR
(100MHz, CDCl3) δ 171.4, 135.6, 134.9, 133.5, 132.7, 132.1, 130.3, 128.8, 128.6, 128.4, 128.0,
127.8, 127.1, 126.8, 126.6, 124.4, 121.8, 39.7, 18.9, 13.7. HRMS (EIꢀTOF): Calculated for
C20H19NO [M]+ 289.1467, Found 289.1469.
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N-(2-(naphthalen-2-yl)phenyl)isobutyramide (5p)
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Light brown solid; yield: 44% (25.4mg); m.p = 142ꢀ143 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.35 (d, J = 6.8 Hz, 1H), 7.96 (d, J = 6.8 Hz, 1H), 7.93ꢀ7.90 (m, 1H), 7.88ꢀ7.87 (m, 1H), 7.86 (s, 1H),
7.58ꢀ7.54 (m, 2H), 7.49 (dd, J = 6.8, 1.2 Hz, 1H), 7.41 (dt, J = 6.6, 1.2 Hz, 1H), 7.34 (d, J = 6.0 Hz,
1H), 7.24ꢀ7.19 (m, 2H), 2.32ꢀ2.61(m, 1H), 1.09 (s, 3H), 1.08(s, 3H). 13C NMR (100MHz, CDCl3) δ
175.0, 135.6, 135.0, 133.5, 132.7, 132.1, 130.2, 128.8, 128.6, 128.4, 128.0, 127.8, 127.2, 126.8,
126.6, 124.3, 121.6, 36.7, 19.4. HRMS (EIꢀTOF): Calculated for C20H19NO [M]+ 289.1467, Found
289.1469.
N-(2-(6,7-dimethylnaphthalen-2-yl)phenyl)acetamide (5q)
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Light brown solid; yield: 62% (35.8mg); m.p = 143ꢀ144 °C; H NMR (400 MHz, CDCl3, ppm) δ
8.31 (d, J = 6.4 Hz, 1H), 7.83 (d, J = 6.8 Hz, 1H), 7.72 (s, 1H), 7.66 (s, 1H), 7.62 (s, 1H), 7.40ꢀ7.35
(m, 2H), 7.32 (d, J = 5.6 Hz, 1H), 7.21ꢀ7.18 (m, 2H), 2.47 (s, 3H), 2.46 (s, 3H), 1.97 (s, 3H). 13C
NMR (100MHz, CDCl3) δ 168.3, 136.7, 136.5, 134.9, 134.6, 132.5, 132.3, 131.6, 130.2, 128.4,
127.8, 127.5, 127.3, 127.2, 126.2, 124.3, 121.5, 24.7, 20.3. HRMS (EIꢀTOF): Calculated for
C20H19NO [M]+ 289.1467, Found 289.1461.
N-(2-(7-bromonaphthalen-2-yl)phenyl)acetamide (5r) yield = 22 %
N-(2-(6-bromonaphthalen-2-yl)phenyl)acetamide (5r’) yield = 42 %
1
Light brown solid; yield: 64% (43.4mg); H NMR (400 MHz, CDCl3, ppm) δ 8.25 (d, J = 8.0 Hz,
1H), 8.07 (s, 0.3H), 8.03 (d, J = 1.2 Hz, 0.7H), 7.92 (d, J = 8.0 Hz, 0.7H), 7.86 (d, J = 8.4 Hz, 0.4H),
7.80 (d, J = 10.4 Hz, 0.7H), 7.77 (s, 0.4H), 7.76ꢀ7.74 (m, 1H), 7.62 (dd, J = 8.8, 1.6 Hz, 1H),
7.52ꢀ7.49 (m, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H ), 7.23 (t, J = 7.4 Hz, 1H), 7.10 (s,
1H), 2.00 (s, 2H), 1.99 (s, 1H). 13C NMR (100MHz, CDCl3) δ 168.4, 136.8, 136.1, 134.8, 134.6,
133.7, 132.0, 131.9, 131.9, 131.1, 130.3, 130.2, 130.0, 130.0, 129.9, 129.7, 129.5, 128.8, 128.7,
128.3, 128.1, 127.9, 127.5, 127.3, 124.7, 122.2, 120.8, 120.6, 24.6. HRMS (EIꢀTOF): Calculated for
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C18H14BrNO [M]+ 339.0259, Found 339.0257.
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Procedure of Deuterium Labeling Experiment (Scheme 4, eq 1-2).
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Scheme 4, Eq(1) To a flameꢀdried reaction flask was added substrate 1a (0.1 mmol) and 1a-d5 (0.1
mmol), 2a (0.3 mmol), [RuCl2(pꢀcymene)]2 (6.1 mg, 0.01 mmol), AgSbF6 (20.6 mg, 0.06 mmol),
NaOAc (8.2 mg, 0.1 mmol) and DCE (1 mL). The mixture was stirred for 20 min at 100 °C under air
atmosphere. The mixture was then cooled to room temperature, diluted with EtOAc, filtered through
a celite pad, and concentrated in vacuo. The residue was purified by flash column chromatography
on silica gel (eluent: hexane/EtOAc = 5/1 with triethylamine), to afford the desired product（yield =
33%）. The ratio of product 3a/3a-d4 was analyzed by 1H NMR (400MHz, CDCl3).
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Scheme 4, Eq(2) To a flameꢀdried reaction flask was added substrate 1a (0.2 mmol), 2a (0.3 mmol),
[RuCl2(pꢀcymene)]2 (6.1 mg, 0.01 mmol), AgSbF6 (20.6 mg, 0.06 mmol), NaOAc (8.2 mg, 0.1 mmol)
and DCE (1 mL). The mixture was stirred for 20 min at 100 °C under air atmosphere. The mixture
was then cooled to room temperature, diluted with EtOAc, filtered through a celite pad, and
concentrated in vacuo. The residue was purified by flash column chromatography on silica gel
(eluent: hexane/EtOAc = 5/1 with triethylamine), to afford the desired product 3a（yield = 28.3%）.
To a flameꢀdried reaction flask was added substrate 1a-d5 (0.2 mmol), 2a (0.3 mmol),
[RuCl2(pꢀcymene)]2 (6.1 mg, 0.01 mmol), AgSbF6 (20.6 mg, 0.06 mmol), NaOAc (8.2 mg, 0.1 mmol)
and DCE (1 mL). The mixture was stirred for 20 min at 100 °C under air atmosphere. The mixture
was then cooled to room temperature, diluted with EtOAc, filtered through a celite pad, and
concentrated in vacuo. The residue was purified by flash column chromatography on silica gel
(eluent: hexane/EtOAc = 5/1 with triethylamine), to afford the desired product 3a-d4（yield =
10.3%）.
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Procedure of Competitive Experiment (Scheme 4, eq 3). To a flameꢀdried reaction flask was
added substrate 1n (0.1 mmol) and 1g (0.1 mmol), 2a (0.3 mmol), [RuCl2(pꢀcymene)]2 (6.1 mg, 0.01
mmol), AgSbF6 (20.6 mg, 0.06 mmol), NaOAc (8.2 mg, 0.1 mmol) and DCE (1 mL). The mixture
was stirred for 8 h at 100 °C under air atmosphere. The mixture was then cooled to room temperature,
diluted with EtOAc, filtered through a celite pad, and concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel (eluent: hexane/EtOAc = 5/1), to afford the
separated products 5n（yield = 52.7%）and 5g（yield = 30.5%）. The ratio of product 5n/5g was
determined on the basis of isolated yield by flash column chromatography on silica gel.
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Supporting Information availability statement
1
Details for experiments conditions, copies of H and 13C NMR spectra for all isolated compounds.
This material is available free of charge via the Internet at http://pubs.acs.org.
Author Information
Corresponding Author
*Email: yhzhang@zju.edu.cn
Acknowledgments
Funding from National Basic Research Program of China (21472165, 21672186) and Important
Project of Zhejiang Province (2017C03049) are highly acknowledged. As a summer intern at
Zhejiang University, the coꢀauthor Steven Chu is from JSerra Catholic High School in the USA.
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References
5
6
7
8
9
(1) (a) Sterling, J.; Herzig, Y.; Goren, T. Novel Dual Inhibitors of AChE and MAO Derived from
Hydroxy Aminoindan and Phenethylamine as Potential Treatment for Alzheimer's Disease. J. Med.
Chem. 2002, 45, 5260ꢀ5279. (b) Tangallapally, R. P.; Yendapally, R.; Lee, R. E.; Hevener, K.; Jones,
V. C.; Lenaerts, A. J. M.; McNeil, M. R.; Wang, Y.; Franzblau, S.; Lee, R. E. Synthesis and
Evaluation of Nitrofuranylamides as Novel Antituberculosis Agents. J. Med. Chem. 2004, 47,
5276ꢀ5283.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2) (a) Haworth, R. D. Syntheses of alkylphenanthrenes. Part I. 1ꢀ, 2ꢀ, 3ꢀ, and
4ꢀMethylphenanthrenes. J. Chem. Soc. 1932, 1125ꢀ1133. (b) Moore, M. L. The Leuckart Reaction.
Org. React. 1949, 5, 301ꢀ330. (c) Hulin, B.; Koreeda, M. A Convenient, Mild Method for the
Cyclization of 3ꢀ and 4ꢀArylalkanoic Acids via their Trifluoromethanesulfonic Anhydride
Derivatives. J. Org. Chem. 1984, 49, 207ꢀ209. (d) Mallory, F. B.; Luzik Jr, E. D.; Mallory, C. W.;
Carroll, P. J. Nuclear Spinꢀspin Coupling via Nonbonded Interactions. 7. Effects of Molecular
Structure on Nitrogenꢀfluorine Coupling. J. Org. Chem. 1992, 57, 366ꢀ370. (e) Wempe, M. F.;
Grunwell, J. R. The Transannular Rearrangement of 5ꢀCyclodecynone. J. Org. Chem. 1995, 60,
2714ꢀ2720. (f) Colyer, J. T.; Andersen, N. G.; Tedrow, J. S.; Soukup, T. S.; Faul, M. M. Reversal of
Diastereofacial Selectivity in Hydride Reductions of NꢀtertꢀButanesulfinyl Imines. J. Org. Chem.
2006, 71, 6859ꢀ6862.
(3) (a) Feng, C.ꢀC.; Nandi, M.; Sambaiah, T.; Cheng, C.ꢀH. NickelꢀCatalyzed Highly Stereoselective
Ring Opening of 7ꢀOxaꢀ and Azanorbornenes with Organic Halides. J. Org. Chem. 1999, 64,
3538ꢀ3543. (b) Rayabarapu, D. K.; Shukla, P.; Cheng, C.ꢀH. Cyclization of OxaꢀBicyclic Alkenes
with βꢀIodoꢀ(Z)ꢀpropenoates and oꢀIodobenzoate Catalyzed by Nickel Complexes:ꢁ A Simple
25
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Page 26 of 29
1
2
3
4
Efficient Route to Annulated Coumarins. Org. Lett. 2003, 5, 4903ꢀ4906.
5
6
7
8
9
(4) (a) Lautens, M.; Fagnou, K.; Taylor, M. RhodiumꢀCatalyzed Asymmetric Ring Opening of
Oxabicyclic Alkenes with Phenols. Org. Lett. 2000, 2, 1677ꢀ1679. (b) Cho, Y.ꢀH.; Zunic, V.;
Senboku, H.; Olsen, M.; Lautens, M. RhodiumꢀCatalyzed RingꢀOpening Reactions of
NꢀBocꢀAzabenzonorbornadienes with Amine Nucleophiles. J. Am. Chem. Soc. 2006, 128, 6837ꢀ6846.
(c) Lu, Z.; Wang, J.; Han, B; Li, S.; Zhou, Y.; Fan, B. Palladium-Catalyzed Asymmetric Ring
Opening Reaction of Azabenzonorbornadienes with Aromatic Amines. Adv. Synth. Catal. 2015, 357,
3121ꢀ3125.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(5) Yang, F.; Chen, J.; Xu, J.; Ma, F.; Zhou, Y.; Shinde, M. V.; Fan, B. Palladium/Lewis Acid
Coꢀcatalyzed Divergent Asymmetric RingꢀOpening Reactions of Azabenzonorbornadienes with
Alcohols. Org. Lett. 2016, 18, 4832ꢀ4835.
(6) (a) Lautens, M.; Dockendorff, C. Palladium(II) Catalyst Systems for the Addition of Boronic
Acids to Bicyclic Alkenes:ꢁ New Scope and Reactivity. Org. Lett. 2003, 5, 3695ꢀ3698. (b) Arrayas, R.
G.; Cabrera, S.; Carretero, J. C. CopperꢀCatalyzed AntiꢀStereocontrolled RingꢀOpening of
Azabicyclic Alkenes with Grignard Reagents. Org. Lett. 2005, 7, 219ꢀ221. (c) Ogura, T.; Yoshida, K.;
Yanagisawa, Akira.; Imamoto, T. Optically Active Dinuclear Palladium Complexes Containing a
PdꢀPd Bond: Preparation and Enantioinduction Ability in Asymmetric RingꢀOpening Reactions. Org.
Lett. 2009, 11, 2245ꢀ2248. (d) Zhang, W.; Chen, J.; Zeng, G.; Yang, F.; Xu, J.; Sun, W.; Shinde, M. V.;
Fan, B. Asymmetric RingꢀOpening Reactions of Azaꢀ and Oxaꢀbicyclic Alkenes with Boronic Acids
Using a Palladium/Zinc Coꢀcatalytic System. J. Org. Chem. 2017, 82, 2641ꢀ2647.
(7) For reviews on natural product synthesis by CꢀH activation, see: (a) Colby, D. A.; Tsai, A. S.;
Bergman, R. G.; Ellman, J. A. Rhodium Catalyzed ChelationꢀAssisted CꢀH Bond Functionalization
26
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The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Reactions. Acc. Chem. Res. 2012, 45, 814ꢀ825. (b) Ackermann, L. CarboxylateꢀAssisted
RutheniumꢀCatalyzed Alkyne Annulations by CꢀH/Het–H Bond Functionalizations. Acc. Chem. Res.
2014, 47, 281ꢀ295. For selected reports on ortho functionalization of anilides: (c) Boele, M. D. K.;
van Strijdonck, G. P. F.; de Vries, A. H. M.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N. M.
Selective PdꢀCatalyzed Oxidative Coupling of Anilides with Olefins through CꢀH Bond Activation at
Room Temperature. J. Am. Chem. Soc. 2002, 124, 1586ꢀ1587. (d) Ackermann, L.; Vicente, R.;
Althammer, A. Assisted RutheniumꢀCatalyzed CꢀH Bond Activation: Carboxylic Acids as
Cocatalysts for Generally Applicable Direct Arylations in Apolar Solvents. Org. Lett. 2008, 10,
2299ꢀ2302. (e) Patureau, F. W.; Glorius, F. Rh Catalyzed Olefination and Vinylation of Unactivated
Acetanilides. J. Am. Chem. Soc. 2010, 132, 9982ꢀ9983. (f) Ackermann, L.; Wang, L.; Wolfram. R.;
Lygin, A. V. RutheniumꢀCatalyzed Oxidative CꢀH Alkenylations of Anilides and Benzamides in
Water. Org. Lett. 2012, 14, 728ꢀ731.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
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33
34
35
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8) Wang, F.; Yu, S.; Li, X. Transition MetalꢀCatalysed Couplings between Arenes and Strained or
Reactive Rings: Combination of CꢀH Activation and Ring Scission. Chem. Soc. Rev. 2016, 45,
6462ꢀ6477.
(9) Qi, Z.; Li, X. Rhodium(III)-Catalyzed Coupling of Arenes with 7-Oxa/Azabenzonorbornadienes
by CꢀH Activation. Angew. Chem. Int. Ed. 2013, 52, 8995ꢀ9000.
(10) Unoh, Y.; Satoh, T.; Hirano, K.; Miura, M. Rhodium(III)ꢀCatalyzed Direct Coupling of
Arylphosphine Derivatives with Heterobicyclic Alkenes: A Concise Route to Biarylphosphines and
Dibenzophosphole Derivatives. ACS Catal. 2015, 5, 6634ꢀ6639.
(11) (a) Kong, L.; Yu, S.; Tang, G.; Wang, H.; Zhou, X.; Li, X. Cobalt(III)ꢀCatalyzed CꢀC Coupling
of Arenes with 7ꢀOxabenzonorbornadiene and 2ꢀVinyloxirane via CꢀH Activation. Org. Lett. 2016,
27
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Page 28 of 29
1
2
3
4
5
6
7
8
9
18, 3802ꢀ3805. (b) Muralirajan, K.; Prakash S.; Cheng, C.ꢀH. Cobalt-Catalyzed Mild Ring-Opening
Addition of Arenes CꢀH Bond to 7-Oxabicyclic Alkenes. Adv. Synth. Catal. 2017, 359, 513ꢀ518.
(12) (a) Dong, W.; Parthasarathy, K.; Cheng, Y.; Pan, F.; Bolm, C. Hydroarylations of Heterobicyclic
Alkenes through RhodiumꢀCatalyzed Directed CꢀH Functionalizations of SꢀAryl Sulfoximines.
Chem. Eur. J. 2014, 20, 15732ꢀ15736. (b) Cheng, H.; Dong, W.; Dannenberg, C. A.; Dong, S.; Guo,
Q.; Bolm, C. RutheniumꢀCatalyzed Hydroarylations of Oxaꢀ and Azabicyclic Alkenes. ACS. Catal.
2015, 5, 2770ꢀ2773.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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27
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48
49
50
51
52
53
54
55
56
57
58
59
60
(13) Gorelsky, S. I.; Lapointe, D.; Fagnou, Keith.
Analysis of the Concerted
MetalationꢀDeprotonation Mechanism in PalladiumꢀCatalyzed Direct Arylation Across a Broad
Range of Aromatic Substrates. J. Am. Chem. Soc. 2008, 130, 10848ꢀ10849.
(14) (a) Ackermann, L.; Vicente, R.; Potukuchi, H. K.; Pirovano, V. Mechanistic Insight into Direct
Arylations with Ruthenium(II) Carboxylate Catalysts. Org. Lett. 2010, 12, 5032ꢀ5035. (b) Flegeau, E.
F.; Bruneau, C.; Dixneuf, P. H.; Jutand, A. Autocatalysis for CꢀH Bond Activation by Ruthenium(II)
Complexes in Catalytic Arylation of Functional Arenes. J. Am. Chem. Soc. 2011, 133, 10161ꢀ10170.
(c) Ackermann, L. CarboxylateꢀAssisted TransitionꢀMetalꢀCatalyzed CꢀH Bond Functionalizations:
Mechanism and Scope. Chem. Rev. 2011, 111, 1315ꢀ1345. (d) Sarkar, S. D.; Liu, W.; Kozhushkov, S.
I.; Ackermann, L. Weakly Coordinating Directing Groups for Ruthenium(II)‐Catalyzed CꢀH
Activation. Adv. Synth. Catal. 2014, 356, 1461ꢀ1479. (e) Lanke, V.; Bettadapur, K. R.; Prabhu, K. R.
SiteꢀSelective Addition of Maleimide to Indole at the Cꢀ2 Position: Ru(II)ꢀCatalyzed C–H Activation.
Org. Lett. 2015, 17, 4662ꢀ4664.
(15) Zhang, Y.; Wu, Q.; Cui, S. Rh(III)ꢀCatalyzed CꢀH ActivationꢀDesymmetrization of
Diazabicycles with Arenes: Facile Synthesis of Functionalized Cyclopentenes. Chem. Sci. 2014, 5,
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297ꢀ302.
5
6
7
8
(16) (a) Otani, Y.; Nagae, O.; Naruse, Y.; Inagaki, S.; Ohno, M.; Yamaguchi, K.; Yamamoto, G.;
Uchiyama, M.; Ohwada, T. An Evaluation of Amide Group Planarity in 7ꢀAzabicyclo[2.2.1]heptane
Amides. Low Amide Bond Rotation Barrier in Solution. J. Am. Chem. Soc. 2003, 125, 15191ꢀ15199.
(b) McManus, H. A.; Fleming, M. J.; Lautens, M. Enantioselective Total Synthesis of
9
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(+)-Homochelidonine by
a
PdII-Catalyzed Asymmetric Ring-Opening Reaction of
a
meso-Azabicyclic Alkene with an Aryl Boronic Acid. Angew. Chem. Int. Ed. 2007, 46, 433ꢀ436. (c)
Gandeepan, P.; Rajamalli, P.; Cheng, C.ꢀH. Diastereoselective [3+2] Annulation of Aromatic/Vinylic
Amides with Bicyclic Alkenes through Cobalt-Catalyzed CꢀH Activation and Intramolecular
Nucleophilic Addition. Angew. Chem. Int. Ed. 2016, 55, 4308ꢀ4311.
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