Synthesis of Chiral Cleft C,N-Palladium and Iridium Complexes from 2,3:6,7-Dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione and Their Synthetic Applications

Article abstract of DOI:10.1021/acs.organomet.7b00024

A transition-metal-mediated functionalization of 2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione is reported. By the use of the corresponding imine, iridium or palladium complexes were prepared, and they were well characterized by NMR and single-cry

Full text of DOI:10.1021/acs.organomet.7b00024

Article
pubs.acs.org/Organometallics
Synthesis of Chiral Cleft C,N-Palladium and Iridium Complexes from
2
,3:6,7-Dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione and Their
Synthetic Applications
Congfa He, Bin Wang, Mingli Gao,* and Zhenhua Gu*
Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, People’s Republic
of China
*
S Supporting Information
ABSTRACT: A transition-metal-mediated functionalization of 2,3:6,7-
dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione is reported. By the use
of the corresponding imine, iridium or palladium complexes were
prepared, and they were well characterized by NMR and single-crystal
X-ray crystallographic analysis. The catalytic activity of these two metal
complexes was briefly investigated in hydrogenation and 1,2-addition
reactions. Finally, the catalytic bromination of 2,3:6,7-
dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione was realized in the presence of NBS and Pd(OAc) . Subsequently a new class
2
of V-shaped molecules with biphenanthridine skeletons were synthesized.
1
1
INTRODUCTION
were observed (Scheme 1a,b). The amino alcohol derivative
■
2
was also applied in the addition of Et Zn to aromatic aldehydes,
Cleftlike molecules, such as 2,3:6,7-dibenzobicyclo[3.3.1]nona-
3
2
1
2
̈
,6-diene-4,8-dione 1, Troger base 2 and Kagan’s ether 3,
Scheme 1. Applications of Tro
̈
ger Base Analogues in
represent a class of unique chiral molecules (Chart 1). The
Asymmetric Catalysis
Chart 1. Cleftlike Molecules
bridged systems lead these molecules to be highly rigid, where
two phenyl groups are almost perpendicular to each other.
Tro
̈
ger base 2 was an excellent module that could be used in
4
5
,
6
host−guest as well as “molecular torsion balance” studies.
7
Compound 2 was synthesized as early as 1887, and it contains
two nitrogen chiral centers stabilized by the rigid skeleton. Its
enantiomers were easily obtained via dynamic kinetic resolution
with (−)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate as the
8
chiral reagent. Recently, we reported a practical resolution of
diketone 1 by the use of commercially available optically pure
9
[
1,1′-binaphthalene]-2,2′-diol (BINOL). Multiple grams of
optically pure 1 were obtained from 2-phenylacetonitrile
without column chromatography, and BINOL was recovered
over 95% yield. Despite these successes in the preparation of
optically pure cleftlike molecules, there have only been a few
studies on the catalytically asymmetric reactions by the use of
12
with up to 86% ee being achieved (Scheme 1c). Herein we
report our efforts on the synthesis and applications of C,N-
palladium and iridium complexes based on chiral diketone 1.
10
these V-shaped chiral skeletons as ligands or catalysts. As an
example, optically active Troger bases were used as ligands or
̈
catalysts in Michael addition and aziridination of unsaturated
carbonyl compounds, and moderate asymmetric inductions
Received: January 12, 2017
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.7b00024
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Article
RESULTS AND DISCUSSION
■
Synthesis of Iridium and Palladium Complexes. The
diketone compound has a rigid dihedral angle of around 100°.
The chirality of 1 is more stable than that of Tro
̈
ger base, which
undergoes racemization via acid-mediated ring-opening and
13
ring-closing processes. As a synthetic organic research group,
we have given our attention to the structures and catalytic
activity of 1-based metal complexes. It was anticipated that the
highly rigid structure of these V-shaped molecules was
beneficial for asymmetric induction. Furthermore, C,N-metal-
lacycles, particularly for palladium complexes, have additional
electronic advantages for minimizing transition states: neutral
substrates bind trans to the N atom, and anionic ligands prefer
14
the position trans to the C donor. With this hypothesis in
mind, the diketone (S,S)-1 was converted to monoimine 4
along with 26% of diimine 5 under the catalysis of titanium
tetrachloride. The monoimine 4 was usually contaminated with
Figure 1. ORTEP drawing of iridium complex 6.
16
structure (Figure 2). The dimer 7 was dissociated to
monomer 8 by the treatment of 2.0 equiv of triphenylphos-
9% of starting material (S,S)-1 after purification, however,
which did not affect the further synthesis of the metal
complexes. The treatment of 4 and [Cp*IrCl ] with NaOAc
17
phine ligand.
2
2
Synthetic Applications of Metal Complexes. Iridium
in CH Cl successfully gave complex 6 in 70% yield (Scheme
18
2
2
and palladium complexes are widely used in reduction,
2). Single crystals were obtained by slow volatilization of a
19
20
oxidation, and C−C bond formation reactions. With the
Scheme 2. Synthesis of Ir and Pd Complexes
15
solution of 6 in acetone (Figure 1). It should be noted that
the existence of diimine 5 and diketone 1 did not affect the
reaction between imine 4 and [Cp*IrCl ] . The reaction
2
2
uneventfully delivered the pure monometalated product 6 after
column chromatographic purification on silica gel. The
treatment of the crude imine 4 with Li PdCl in the presence
2
4
of NaOAc gave palladium dimer 7 in 58% overall yield.
Pleasingly, single crystals that were suitable for X-ray analysis
were obtained and the palladium dimer manifests a “Π-shaped”
Figure 2. Structure of palladium dimer 7.
B
DOI: 10.1021/acs.organomet.7b00024
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Article
24
metal complexes 6 and 7 in hand, we briefly investigated their
catalytic activity. In the presence of 1 mol % of iridium complex
acetic acid. Finally, the exploration of 13 to HCl(c) delivered
the dibrominated compound 14 in excellent yield.
6
, β-naphthaldehyde-derived imine 9a was efficiently reduced
Consequently, we proceeded to explore the feasibility of
Suzuki cross-coupling with various substituted (2-
aminophenyl)boronic esters (Scheme 5). The reactions
21
to amine with HCO Na as the reagent (Scheme 3). Under
2
Scheme 3. Synthetic Applications of Metal Complexes
Scheme 5. Phenanthridine-Based V-Shaped Molecule
Synthesis
identical conditions, the cyclic ketone imine 9b was reduced to
the corresponding amine in 82% yield. Under 1 atm of
hydrogen gas, acetophenone-derived imine 9c was converted to
1
0c in excellent yield, whereas only a low level of asymmetric
induction was observed. A cationic palladium species from
complex 7 was able to catalyze the 1,2-addition of aryl boronic
acid to imines. For example, the reaction of 9d with (4-
methoxyphenyl)boronic acid in the presence of dimer 7 and
AgBF4 gave 10d in quantitative yield with moderate
2
2
enantioselectivity.
Synthesis of Phenanthridine-Based V-Shaped Mole-
cules. The synthesis of diketone 1 has poor functional group
tolerance, since it requires a formidable amount of concentrated
sulfuric acid in the acylation step. Thus, only extremely limited
analogues of the diketone 1 have been synthesized until now.
The synthesis of iridium and palladium complexes clearly
indicated that the imines were promising directing groups for
the C−H functionalization of the phenyl ring. Thus, the
treatment of (S,S)-1 with hydroxylamine hydrochloride in
heated EtOH/PhMe afforded a quantitative yield of dioxime 11
proceeded uneventfully, and the products spontaneously
aromatized to phenanthridine rings in good to excellent yields.
Functional groups, such as methyl, tert-butyl, methyl ester,
trifluoromethyl, trifluoromethoxyl, and nitrile, in (2-
aminophenyl)boronic ester components were well tolerated.
Single crystals for compounds 15g,h were obtained, and an X-
ray crystallographic analysis was performed. The structure
clearly manifested that the dihedral angles of the two
23
with perfect E selectivity, which was subsequently methylated
to form 12 (Scheme 4). Bromination of O-methyl oxime was
successfully realized with a catalytic amount of Pd(OAc) in hot
2
25,26
phenanthridine moieties were around 105−110°.
Scheme 4. Synthesis of Dibromo Ketone
CONCLUSION
■
In summary, we performed studies on the functionalization
reactions of the optically active V-shaped molecule 1. Metal
complexes, such as iridium compound 6 and palladium
complexes 7 and 8, were prepared from the imine derivatives.
The first two metal complexes were further characterized by X-
ray crystallographic analysis and displayed moderate to
excellent activity and selectivity in hydrogenations and 1,2-
addition reactions. Finally, the direct bromination reaction of
O-methyl oxime realized the functionalization of (S,S)-1 to
dibromo compound 14, which provided an entry for the
C
DOI: 10.1021/acs.organomet.7b00024
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1
synthesis of phenanthridine-based V-shaped molecules 15 in
good to excellent yields.
mg, 65%). H NMR (400 MHz, CDCl
7
(
3
): δ 7.93−7.91 (m, 2 H), 7.32−
.26 (m, 4 H), 7.24−7.16 (m, 2 H), 7.12−6.89 (m, 12 H), 6.41−6.39
m, 2 H), 4.41 (t, J = 2.8 Hz, 2 H), 3.91 (s, 6 H), 3.82 (t, J = 2.8 Hz, 2
H), 2.71 (dt, J = 13.2, 3.2 Hz, 2 H), 2.66 (dt, J = 13.6, 2.8 Hz, 2 H).
C NMR (100 MHz, CDCl ): δ 193.6, 181.4, 158.5, 141.4, 139.9,
3
EXPERIMENTAL SECTION
13
■
General Information. All reactions were carried out under a
nitrogen atmosphere in flame-dried glassware, unless the reaction
procedure states otherwise. Anhydrous toluene was obtained by
138.6, 138.1, 134.0, 133.2, 132.0, 129.2, 128.9, 128.5, 127.2, 124.2,
123.9, 114.3, 113.8, 55.5, 47.9, 37.7, 33.3. HRMS (ESI): calcd for
+
C
H36ClN
O
4
Pd
[M − Cl] 951.0433, found 951.0513.
48
2
2
distillation from CaH , and anhydrous methanol was obtained by
Synthesis of Monomer 8. A mixture of Pd complex 7 (24.7 mg,
2
distillation from Mg powder. Other solvents were used without any
further purification. Room-temperature reactions were carried out
between 20 and 25 °C. Flash column chromatography was performed
using 40−63 μm silica gel as the stationary phase. H and C NMR
spectra were referenced by using the solvent residue as an internal
reference ( H NMR, 7.26 ppm for CDCl ; C NMR, 77.00 ppm for
CDCl ). Electron spray inization (ESI) mass spectrometry data were
acquired by using an LTQ analyzer type instrument.
0.025 mmol) and PPh (13.1 mg, 0.050 mmol) in chloroform (1.25
3
mL) was stirred at room temperature for 10 h. The solvent was
removed, and the residue was purified by flash chromatography on
1
13
silica gel (dichloromethane/methanol 100/1) to afford 8 (24.3 mg,
1
64%) as a yellow solid. H NMR (400 MHz, CDCl
): δ 8.04−7.95 (m,
3
1
13
1 H), 7.70−7.66 (m, 6 H), 7.41−7.26 (m, 11 H), 7.18 (d, J = 8.4 Hz, 1
H), 7.08 (d, J = 8.4 Hz, 1 H), 7.01 (d, J = 8.8 Hz, 1 H), 6.99−6.91 (m,
2 H), 6.68−6.62 (m, 1 H), 6.54 (t, J = 7.6 Hz, 1 H), 6.37 (t, J = 6.8 Hz,
1 H), 4.66 (s, 1 H), 4.09−3.63 (m, 1 H), 3.84 (s, 3 H), 2.85−2.68 (m,
3
3
Synthesis of Ir Complex (S,S)-6. A solution of titanium(IV)
chloride in dichloromethane (1.0 M, 4.0 mL) was added to a mixture
of (S,S)-1 (2.00 g, 8.06 mmol), 4-methoxyaniline (2.38 g, 19.3 mmol,
2 H). 13C NMR (100 MHz, CDCl
): δ 194.3, 181.4, 161.0, 157.8,
3
143.1, 140.7, 139.6, 138.5, 138.4, 137.9, 135.5, 135.4, 134.1, 131.52,
131.47, 131.2, 130.7, 130.60, 130.58, 129.4, 129.2, 128.6, 128.3, 128.0,
127.8, 124.0, 123.6, 113.5, 113.3, 55.4, 48.7, 38.2, 33.0. 31P NMR (162
2
0
.4 equiv), triethylamine (2.80 mL), and dichloromethane (40 mL) at
°C dropwise. After 10 h, the reaction mixture was quenched with
water and extracted with dichloromethane. The combined organic
layers were washed with brine, dried over Na SO , and concentrated.
MHz, CDCl
Cl] 720.1284, found 720.1302.
3
): δ 42.95. HRMS (ESI): calcd for C42
H33NO PPd [M −
2
+
2
4
The residue was purified by column chromatography on neutral
alumina (hexane/ethyl acetate 5/1) to afford a yellow solid.
Recrystallization of the above crude material was carried out in hot
methanol, and the solid was collected by filtration to give pure bis-
imine 5 (0.97 g, 15%). The filtrate was concentrated to afford the
4-Methoxy-N-(naphthalen-2-ylmethyl)aniline (10a). A mix-
ture of 9a (52.2 mg, 0.2 mmol), (S,S)-6 (1.4 mg, 1 mol %), and
sodium formate (68.0 mg, 1.0 mmol) in TFE (1.0 mL) was stirred at
80 °C for 90 min. The mixture was purified by column
chromatography on silica gel (hexane/ethyl acetate 10/1) to afford
10a as a solid (51.0 mg, 94%).
N-Cyclohexyl-4-methoxyaniline (10b). A mixture of 9b (34.7
mg, 0.2 mmol), (S,S)-6 (1.4 mg, 1 mol %), and sodium formate (68.0
mg, 1.0 mmol) in TFE (1.0 mL) was stirred at 80 °C for 90 min. The
mixture was purified by column chromatography on silica gel (hexane/
ethyl acetate 10/1) to afford 10b (28.6 mg, 82%).
crude product imine (1.67 g, 50% of 4 and 9% of diketone 1).
1
Analytical Data for Compound 4. H NMR (400 MHz, CDCl ): δ
3
8
7
7
.21 (dd, J = 7.6, 1.2 Hz, 1 H), 7.92 (dd, J = 8.0, 1.6 Hz, 1 H), 7.43−
.37 (m, 2 H), 7.35−7.30 (m, 2 H), 7.26 (td, J = 7.6, 1.2 Hz, 1 H),
.03 (d, J = 8.8 Hz, 2 H), 6.85−6.80 (m, 3 H), 4.70 (t, J = 2.8 Hz, 1
H), 4.00 (t, J = 2.8 Hz, 1 H), 3.88 (s, 3 H), 2.81 (dt, J = 13.2, 3.2 Hz, 1
H), 2.75 (dt, J = 13.2, 3.2 Hz, 1H). 13C NMR (100 MHz, CDCl ): δ
4-Methoxy-N-(1-phenylethyl)aniline (10c). A mixture of 9c
(22.5 mg, 0.10 mmol) and (S,S)-6 (0.70 mg, 1 mol %) was dissolved in
trifluoroethanol, bubbled with hydrogen gas for 10 min, an then stirred
3
1
1
3
95.2, 163.4, 156.1, 144.0, 141.8, 136.2, 133.9, 131.5, 131.4, 129.4,
28.8, 128.6, 128.3, 128.04, 128.02, 127.1, 120.7, 114.6, 55.5, 48.6,
+
6.5, 31.9. HRMS (ESI): calcd for C H NO [M + H] 354.1494,
at 85 °C under an H atmosphere (1 atm) for 4 h. The mixture was
24
20
2
2
found 354.1505.
purified by column chromatography on silica gel (hexane/ethyl acetate
10/1) to afford 10c (22.0 mg, 96%, 17% ee) as a solid. HPLC (Daicel
Chiracel OD-H column, column temperature 25 °C, n-hexane/2-
1
Analytical Data for Compound 5. H NMR (400 MHz, CDCl ): δ
3
8
.16−8.12 (m, 2 H), 7.25−7.20 (m, 4 H), 7.03 (d, J = 8.8 Hz, 4 H),
−
1
6
.87−6.82 (m, 6 H), 4.65 (t, J = 2.8 Hz, 2 H), 3.88 (s, 6 H), 2.60 (t, J
propanol 95/5, flow rate 1.0 mL min ): 9.17 min (major
enantiomer), 10.39 min (minor enantiomer).
=
2.8 Hz, 2 H). 13C NMR (100 MHz, CDCl ): δ 164.9, 156.0, 144.2,
3
1
38.5 131.9, 131.0, 128.5, 127.7, 127.0, 120.9, 114.6, 55.5, 36.4, 31.9.
N-((4-Chlorophenyl)(4-methoxyphenyl)methyl)-4-methyl-
benzenesulfonamide (10d). A mixture of 9d (29.3 mg, 0.1 mmol),
(4-methoxyphenyl)boronic acid (30.4 mg, 0.2 mmol), (R,R)-7 (4.9
+
HRMS (ESI): calcd for C H N O [M + H] 459.2073, found
31
27
2
2
4
59.2084.
A mixture of the above crude 4 (70.7 mg, ∼ 0.178 mmol),
mg, 5 mol %), AgBF (2.0 mg, 10 mol %), and K PO (64.0 mg, 0.3
4
3
4
[
Cp*IrCl ] (79.7 mg, 0.10 mmol), and NaOAc (82.0 mg, 1.0 mmol)
mmol) in toluene (1.0 mL) was stirred at room temperature for 8 h.
The mixture was purified by column chromatography on silica gel
(hexane/ethyl acetate 5/1) to afford 10d (40.0 mg, 99%, 61% ee) as a
solid. HPLC (Daicel Chiracel OD column, column temperature 25 °C,
2
2
in dichloromethane (4.0 mL) was stirred at room temperature for 10 h
in air. The residue was purified by column chromatography on silica
gel (hexane/ethyl acetate 3/1) to afford (S,S)-6 as a red solid (0.131 g,
1
−1
7
7
7
7
0%). H NMR (400 MHz, CDCl ): δ 7.93 (dd, J = 8.8, 2.4 Hz, 1 H),
n-hexane/2-propanol 80/20, flow rate 1.0 mL min ): 10.99 min
3
.86 (dd, J = 6.4, 2.8 Hz, 1 H), 7.66 (dd, J = 7.2, 0.4 Hz, 1 H), 7.22−
.19 (m, 2 H), 7.5 (t, J = 7.2 Hz, 1 H), 7.12 (dd, J = 8.8, 3.2 Hz, 1 H),
.02 (d, J = 6.4 Hz, 2 H), 6.96 (dd, J = 8.4, 2.4 Hz, 1 H), 6.43−6.41
(minor enantiomer), 14.21 min (major enantiomer).
Synthesis of Dibromo Ketone 14. A mixture of (S,S)-1 (3.72 g,
15.0 mmol, 1.0 equiv), NH OH·HCl (3.13 g, 45.0 mmol, 3.0 equiv),
2
(
m, 1 H), 4.61 (t, J = 2.8 Hz, 1 H), 3.93 (s, 3 H), 3.91 (t, J = 2.8 Hz, 1
and pyridine (7.5 mL) in ethanol and toluene (60 mL, 1/1 v/v) was
stirred at 80 °C for 4 h. After it was cooled to room temperature, the
mixture was added to ethyl acetate (200 mL) and extracted with HCl
(1 N, 50 mL × 3). The organic layer was washed with brine and dried
over Na SO . After filtration, the solvent was removed to obtain 11
H), 2.78 (dt, J = 13.6, 3.2 Hz, 1 H), 2.73 (dt, J = 13.2, 2.8 Hz, 1 H),
1
.42 (s, 15 H). 13C NMR (100 MHz, CDCl ): δ 194.9, 180.8, 169.4,
3
1
1
3
58.1, 143.1, 142.2, 141.5, 137.4, 134.7, 133.8, 132.7, 129.1, 128.4,
28.3, 128.2, 126.2, 123.4, 121.1, 115.2, 112.6, 89.2, 55.6, 48.5, 37.4,
2
4
+
23
1
3.2, 8.6. HRMS (ESI): calcd for C H IrNO [M − Cl] 680.2141,
(4.17 g, >99%) as a white solid. [α]D = −496 (c 0.63, EtOAc). H
NMR (400 MHz, DMSO): δ 11.53 (s, 2 H), 7.82 (dd, J = 8.0, 0.8 Hz,
2 H), 7.59 (dd, J = 7.6, 0.8 Hz, 2 H), 7.28 (td, J = 7.2, 1.2 Hz, 2 H),
7.18 (td, J = 8.0, 1.2 Hz, 2 H), 4.91 (t, J = 2.8 Hz, 2 H), 2.17 (t, J = 2.8
34
33
2
found 680.2144.
Synthesis of Palladium Complex 7. A mixture of PdCl (88.7
2
mg, 0.50 mmol) and LiCl (43.0 mg, 1.0 mmol) in methanol (5.0 mL)
was stirred at room temperature for 24 h, and then a solution of crude
Hz, 2 H). 13C NMR (100 MHz, DMSO-d ): δ 152.0, 137.5, 129.6,
6
(
0
R,R)-4 (0.177 g, ∼0.445 mmol) in methanol and NaOAc (45.1 mg,
.55 mmol) was added to the mixture and stirred for another 12 h.
The mixture was purified by column chromatography on silica gel
dichloromethane/methanol 50/1) to afford 7 as a yellow solid (143.5
129.1, 128.9, 127.0, 123.5, 31.2, 28.0.
Potassium hydroxide (8.0 g, 140 mmol, 14 equiv) was added to a
solution of 11 (2.78 g, 10 mmol) in DMSO/H O (1/1 v/v, 100 mL).
After the mixture was stirred for 15 min, CH I (4.4 mL, 70.0 mmol,
2
(
3
D
DOI: 10.1021/acs.organomet.7b00024
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7
.0 equiv) was added and this mixture was stirred overnight. The
Characterization Data of Compound 15d. White solid (41.1 mg,
99%). [α]2 = −386 (c 1.15, CH Cl ). H NMR (400 MHz, CDCl ): δ
3
1
reaction mixture was quenched by the addition of water and extracted
with ethyl acetate (100 mL × 3). The combined organic layers were
washed with brine, dried over Na SO , and concentrated. The residue
D
2
2
3
9.18 (d, J = 1.6 Hz, 2 H), 8.52 (d, J = 8.0 Hz, 2 H), 8.31 (dd, J = 8.8,
2.0 Hz, 2 H), 8.20 (d, J = 8.4 Hz, 2 H), 8.07 (d, J = 7.6 Hz, 2 H), 7.82
2
4
was purified by column chromatography on silica gel (hexane/ethyl
(t, J = 8.0 Hz, 2 H), 5.06 (t, J = 2.8 Hz, 2 H), 3.99 (s, 6 H), 3.13 (t, J =
2
3
13
acetate 50/1) to afford 12 (2.20 g, 73%) as a white solid. [α] = −571
2.8 Hz, 2 H). C NMR (100 MHz, CDCl
3
): δ 166.8, 162.4, 146.4,
D
1
(c 0.87, CH Cl ). H NMR (400 MHz, CDCl ): δ 7.94 (dd, J = 8.0,
139.2, 133.4, 131.7, 129.7, 128.7, 127.8, 127.7, 124.9, 123.6, 121.5,
2
2
3
120.5, 52.3, 45.3, 31.0. HRMS (ESI): calcd for C33
H N O
23 2 4
[M + H]+
1
.2 Hz, 2 H), 7.55 (dd, J = 7.6, 1.2 Hz, 2 H), 7.26 (td, J = 7.2, 1.2 Hz, 2
5
8
11.1658, found 511.1663.
Characterization Data of Compound 15e. White solid (35.8 mg,
H), 7.16 (td, J = 8.0, 1.2 Hz, 2 H), 4.91 (t, J = 2.8 Hz, 2 H), 4.08 (s, 6
H), 2.27 (t, J = 2.8 Hz, 2 H). 13C NMR (100 MHz, CDCl ): δ 153.2,
3
2
3
1
6%). [α] = −371 (c 0.635, CH Cl ). H NMR (400 MHz, CDCl ):
1
37.4, 129.6, 129.5, 128.4, 127.1, 124.4, 62.1, 32.1, 28.8. HRMS (ESI):
D
2
2
3
+
δ 8.33 (d, J = 8.4 Hz, 2 H), 8.22−8.19 (m, 4 H), 8.06 (d, J = 7.2 Hz, 2
calcd for C H N O [M + H] 307.1447, found 307.1443.
19
19
2
2
H), 7.79 (t, J = 7.6 Hz, 2 H), 7.57 (dd, J = 8.8, 2.0 Hz, 2 H), 5.04 (t, J
A mixture of 12 (1.0 g, 3.26 mmol, 1.0 equiv), N-bromosuccinimide
=
2.8 Hz, 2 H), 3.11 (t, J = 2.8 Hz, 2 H). 13C NMR (100 MHz,
(
1.22 g, 6.85 mmol, 2.1 equiv), and Pd(OAc) (36.6 mg, 5 mol %) in
2
CDCl ): δ 160.6, 147.2, 142.2, 139.4, 132.7, 131.5, 131.4, 128.0, 124.9,
AcOH (20 mL) was heated to 100 °C and stirred for 90 min. After the
mixture was cooled to room temperature, the solvent was removed
and the residue was purified by chromatography on silica gel (hexane/
ethyl acetate 40/1) to afford 13 (1.36 g, 90%). [α] = −507 (c 0.87,
CH Cl ). H NMR (400 MHz, CDCl ): δ 7.50 (dd, J = 8.0, 1.6 Hz, 2
H), 7.38 (dd, J = 8.0, 1.6 Hz, 2 H), 7.03 (t, J = 8.0 Hz, 2 H), 5.17 (t, J
=
MHz, CDCl ): δ 153.4, 140.0, 135.0, 129.6, 129.0, 127.9, 120.6, 62.5,
3
4
3
1
9
1
22.1, 121.3, 120.5 (q, JC−F = 256 Hz), 120.3, 114.0, 45.1, 30.9.
F
NMR (376 MHz, CDCl ): δ −57.68. HRMS (ESI): calcd for
3
+
2
3
C H N O F [M + H] 563.1194, found 563.1199.
3
1
17
2
2 6
D
1
Characterization Data of Compound 15f. White solid (29.4 mg,
2
2
3
2
3
1
9
0%). [α]D = −327 (c 0.28, CH Cl ). H NMR (400 MHz, CDCl ): δ
2
2
3
3.2 Hz, 2 H), 4.13 (s, 6 H), 2.28 (t, J = 3.2 Hz, 2 H). 13C NMR (100
8.76 (d, J = 2.0 Hz, 2 H), 8.38 (d, J = 8.0 Hz, 2 H), 8.23 (d, J = 8.8 Hz,
H), 8.09 (d, J = 6.8 Hz, 2 H), 7.89 (dd, J = 8.4, 1.6 Hz, 2 H), 7.84 (t,
2
3
+
J = 8.0 Hz, 2 H), 5.06 (t, J = 2.8 Hz, 2 H), 3.13 (t, J = 3.2 Hz, 2 H).
3.0, 29.4. HRMS (ESI): calcd for C H N O Br [M + H]
19 17 2 2 2
13
C NMR (100 MHz, CDCl ): δ 163.1, 145.7, 139.2, 132.23, 132.15,
3
62.9657, found 462.9655.
A mixture of 13 (1.00 g, 2.15 mmol, 1.0 equiv) and HCl (12 N, 10
1
30.9, 130.4, 128.6, 127.9, 124.2, 121.3, 120.6, 119.0, 109.9, 45.2, 30.8.
+
HRMS (ESI): calcd for C H N [M + H] 445.1453, found
31
17
4
mL, 60 equiv) in dioxane (6 mL) was stirred at reflux for 36 h. After
the mixture was cooled to room temperature, water (50 mL) was
added and the resulting mixture was extracted with dichloromethane
4
45.1456.
Characterization Data of Compound 15g. White solid (28.1 mg,
3
1
9
0%). [α]2 = −398 (c 0.583, CH Cl ), H NMR (400 MHz, CDCl ):
D
2
2
3
(
30 mL × 3). The combined organic layers were washed with brine,
δ 8.36 (d, J = 8.0 Hz, 2 H), 8.20 (s, 2 H), 8.05 (d, J = 8.4 Hz, 2 H),
dried over Na SO , and concentrated. The residue was purified by
2
4
7
1
(
1
2
4
.99 (d, J = 7.2 Hz, 2 H), 7.71 (t, J = 8.0 Hz, 2 H), 7.52 (dd, J = 8.4,
chromatography on silica gel (hexane/ethyl acetate 10/1) to afford 14
.6 Hz, 2 H), 5.00 (t, J = 2.8 Hz, 2 H), 3.08 (t, J = 2.8 Hz, 2 H), 2.56
as a white solid (0.86 g, 99%). [α]2 = −658 (c 0.92, CH Cl ). H
3
D
1
2
2
13
s, 6 H). C NMR (100 MHz, CDCl ): δ 159.4, 142.2, 139.5, 136.2,
3
NMR (400 MHz, CDCl ): δ 7.65 (dd, J = 7.6, 0.8 Hz, 2 H), 7.46 (dd,
3
33.0, 130.7, 130.3, 129.3, 127.0, 123.9, 121.8, 120.9, 120.4, 45.4, 31.2,
J = 7.6, 1.2 Hz, 2 H), 7.30 (t, J = 7.6 Hz, 2 H), 4.10 (t, J = 2.8 Hz, 2
+
1.8. HRMS (ESI): calcd for C H N [M + H] 423.1861, found
H), 2.95 (t, J = 3.2 Hz, 2 H). 13C NMR (100 MHz, CDCl ): δ 192.1,
31
23
2
3
23.1867.
Characterization Data of Compound 15h. White solid (37.7 mg,
1
42.5, 136.5, 134.2, 128.8, 126.4, 123.6, 51.0, 30.7. HRMS (ESI): calcd
+
for C H O Br [M + H] 404.9126, found 404.9124.
23
1
17
11
2
2
9
6%). [α]D = −428 (c 0.925, CH Cl ). H NMR (400 MHz, CDCl ):
2
2
3
General Procedure for Synthesis of Phenanthridine-Based
V-Shaped Molecules. Preparation of 15a. A mixture of 14 (30.0
mg, 0.074 mmol, 1.0 equiv), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
δ 8.68 (s, 2 H), 8.40 (d, J = 8.0 Hz, 2 H), 8.26 (d, J = 8.4 Hz, 2 H),
8
7
.07 (d, J = 7.2 Hz, 2 H), 7.90 (dd, J = 8.8, 1.6 Hz, 2 H), 7.80 (t, J =
13
.6 Hz, 2 H), 5.06 (t, J = 2.8 Hz, 2 H), 3.13 (t, J = 2.8 Hz, 2 H).
C
2
-yl)aniline (56.7 mg, 0.26 mmol, 3.5 equiv), PdCl (PPh ) (3.6 mg, 7
2 3 2
NMR (100 MHz, CDCl ): δ 162.3, 145.5, 139.3, 133.0, 131.7, 130.6,
3
mol %), and NaO-t-Bu (35.6 mg, 0.37 mmol) in toluene (5.0 mL) was
refluxed for 3 h. After it was cooled to room temperature, the mixture
was directly submitted to column chromatography on silica gel
1
28.3 (q, JC−F = 32.2 Hz), 128.1, 124.8 (q, JC−F = 3.2 Hz), 124.3 (q,
JC−F = 270 Hz), 123.7, 121.3, 120.6, 120.0 (q, J = 4.0 Hz), 45.3,
C−F
19
3
0.9. F NMR (376 MHz, CDCl ): δ −61.83. HRMS (ESI): calcd for
C H N F [M + H] 531.1296, found 531.1293.
3
(
8
hexane/ethyl acetate/dichloromethane 5/1/1) to give 15a (24.0 mg,
+
3
1
17
2 6
2%) as a white solid. [α] 2D 3 = −670 (c 0.575, CH Cl ). H NMR (400
1
2
2
MHz, CDCl ): δ 8.40 (d, J = 8.0 Hz, 2 H), 8.36 (d, J = 7.6 Hz, 2 H),
3
ASSOCIATED CONTENT
■
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.7b00024.
8
8
.17 (dd, J = 8.4, 0.8 Hz, 2 H), 8.02 (d, J = 7.2 Hz, 2 H), 7.73 (d, J =
.0 Hz, 2 H), 7.70 (td, J = 8.4, 1.6 Hz, 2 H), 7.56 (td, J = 7.2, 1.6 Hz, 2
S
13
H), 5.03 (t, J = 2.8 Hz, 2 H), 3.11 (t, J = 2.8 Hz, 2 H). C NMR (100
MHz, CDCl ): δ 160.3, 143.9, 139.4, 133.3, 131.0, 129.6, 128.7, 127.2,
3
1
26.5, 124.1, 122.2, 121.1, 120.3, 45.3, 31.1. HRMS (ESI): calcd for
+
C H N [M + H] 395.1548, found 395.1551.
2
9
19
2
1
13
Characterization Data of Compound 15b. White solid (22.1 mg,
H and C NMR spectra of new compounds and HPLC
1%). [α]2 = −820 (c 1.06, CH Cl ). H NMR (400 MHz, CDCl ): δ
3
D
1
7
8
2
2
3
traces for 10c,d (PDF)
Crystallographic data of 6, 7, and 15g,h (CIF)
.34 (d, J = 8.0 Hz, 2 H), 8.30 (d, J = 8.4 Hz, 2 H), 7.98−7.96 (m, 4
H), 7.70 (t, J = 8.4 Hz, 2 H), 7.40 (dd, J = 8.4, 1.6 Hz, 2 H), 5.00 (t, J
2.8 Hz, 2 H), 3.09 (t, J = 2.8 Hz, 2 H), 2.57 (s, 6 H). 13C NMR (100
MHz, CDCl ): δ 160.3, 144.0, 139.5, 138.8, 133.3, 130.9, 129.2, 128.1,
=
3
AUTHOR INFORMATION
1
26.6, 122.0, 121.8, 120.8, 120.0, 45.4, 31.2, 21.5. HRMS (ESI): calcd
■
+
for C H N [M + H] 423.1861, found 423.1864.
31
23
2
Corresponding Authors
Characterization Data of Compound 15c. White solid (31.0 mg,
*
*
E-mail for M.G.: gaoml@ustc.edu.cn.
E-mail for Z.G.: zhgu@ustc.edu.cn.
3%). [α]2 = −458 (c 0.95, CH Cl ). H NMR (400 MHz, CDCl ): δ
3
D
1
8
8
2
2
3
.43−8.41 (m, 4 H), 8.13 (d, J = 8.4 Hz, 2 H), 8.00 (d, J = 7.2 Hz, 2
H), 7.79 (dd, J = 8.4, 2.0 Hz, 2 H), 7.72 (t, J = 8.4 Hz, 2 H), 5.03 (t, J
2.8 Hz, 2 H), 3.10 (t, J = 2.8 Hz, 2 H), 1.44 (s, 18 H). 13C NMR
100 MHz, CDCl ): δ 159.7, 149.4, 142.0, 139.5, 133.4, 130.8, 129.1,
ORCID
=
(
1
Zhenhua Gu: 0000-0001-8168-2012
3
Notes
27.0, 123.5, 120.9, 120.4, 117.8, 45.3, 35.1, 31.4, 31.1. HRMS (ESI):
+
calcd for C H N [M + H] 507.2800, found 507.2803.
The authors declare no competing financial interest.
37
35
2
E
DOI: 10.1021/acs.organomet.7b00024
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(
16) CCDC 1525023 contains supplementary crystallographic data
ACKNOWLEDGMENTS
■
2
for compound 7. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre.
This work was supported by the NSFC (21472179 and
1622206), Strategic Priority Research Program of the Chinese
(17) Weiss, M. E.; Fischer, D. F.; Xin, Z.-Q.; Jautze, S.; Schweizer, W.
Academy of Sciences (XDB20000000), and the “973” project
from the MOST of China (2015CB856600).
B.; Peters, R. Angew. Chem., Int. Ed. 2006, 45, 5694−5698.
(18) (a) Crabtree, R. H. Acc. Chem. Res. 1979, 12, 331−337.
(b) Church, T. L.; Andersson, P. G. Coord. Chem. Rev. 2008, 252,
5
13−531.
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F
DOI: 10.1021/acs.organomet.7b00024
Organometallics XXXX, XXX, XXX−XXX