Intramolecular dehydrogenative coupling of biaryl tertiary amines promoted with t-BuOK/DMF: A convenient synthesis of 6-aryl-5,6-dihydrophenanthridines

Article abstract of DOI:10.24820/ark.5550190.p010.000

A number of 6-aryl-5,6-dihydrophenanthridines were prepared in good yields via an intramolecular dehydrogenative coupling of biaryl tertiary amines promoted by t-BuOK/DMF. A reaction mechanism involving a-aminoalkyl radical intermediates is suggested.

Full text of DOI:10.24820/ark.5550190.p010.000

The Free Internet Journal
for Organic Chemistry
Paper
Archive for
Organic Chemistry
Arkivoc 2017, part iv, 174-183
Intramolecular dehydrogenative coupling of biaryl tertiary amines promoted
with t-BuOK/DMF: A convenient synthesis of 6-aryl-5,6-dihydrophenanthridines
Ting Zhang, Lu Qian, Zhen-yu Chen, Yong Zou, Xue-jing Zhang,* and Ming Yan*
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences,
Sun Yat-sen University, Guangzhou 510006, China
Email: zhangxj33@mail.sysu.edu.cn
Received 12-24-2016
Accepted 01-22-2017
Published on line 05-14-2017
Abstract
A number of 6-aryl-5,6-dihydrophenanthridines were prepared in good yields via an intramolecular
dehydrogenative coupling of biaryl tertiary amines promoted by t-BuOK/DMF. A reaction mechanism involving
-aminoalkyl radical intermediates is suggested.
Ar1
Ar1
t-BuOK (3.0 equiv.)
DMF,150 °C, 3 h
16 examples
up to 83% yield
N
R
N
R
Ar2
Ar2
Keywords: Tertiary amine, -aminoalkyl radical, cross-dehydrogenative coupling, dihydrophenanthridine
DOI: https://doi.org/10.24820/ark.5550190.p010.000
Page 174
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
Introduction
Recently, the construction of carbon-carbon bonds via cross-dehydrogenative coupling (CDC) from two simple
C−H bonds has made great progress.1-10 This strategy, introduced by Li and other researchers, is demonstrated
to be a superior alternative to classic coupling procedures using prefunctionalized starting materials. CDC
reactions are generally achieved in the presence of transition-metal catalysts and sacrificial oxidants or H-
acceptors. In recent years, transition-metal-free CDC reactions have also been developed.11-16 In 2015, Wu and
co-workers developed a t-BuOLi-promoted CDC reaction of quinolone N-oxides and 1,3-azoles without
external oxidants.17 A t-BuOK/DMSO mediated intermolecular CDC reaction of nitroarenes and indoles in an
open flask was also reported.18 These transformations usually proceed via oxidative SET (single electron
transfer) C−H activation and the subsequent generation of radical intermediates.
Recently, our group has developed a series of t-BuOK/DMF promoted coupling reactions of tertiary amines,
amides and diphenylmethanes with alkenes, alkynes and ketones.19-25 The formation of α-amino alkyl radicals
or diphenylmethyl radicals initiated by t-BuOK/DMF was proposed. We speculated that α-amino alkyl radicals
would also react with arenes which could provide a new entry to the preparation of polycyclic heterocyclic
compounds, such as 5,6-dihydrophenanthridine derivatives. Dihydrophenanthridine derivatives are present in
the skeleton of a wide number of biologically active compounds, natural products and materials,26-29 however,
only a few synthetic methods for this class of compounds have been reported.30-35 Furthermore, the reported
methods generally suffer from limited functional group tolerance and undesired in situ oxidation. Herein, we
report an intramolecular dehydrogenative coupling of biaryl tertiary amines promoted by t-BuOK/DMF. The
reaction provides a new synthetic approach to 6-aryl-5,6-dihydrophenanthridines (Scheme 1).
1) Previous work
t-BuOK (1.5 equiv.)
N
N
DMF, 90 °C, 3 h
t-BuOK (1.2 equiv.)
DMF, 90 °C, 3 h
N
N
O
R
R
2) This work
t-BuOK (3.0 equiv.)
DMF,150 °C, 3 h
N
N
Scheme 1. t-BuOK /DMF promoted carbon–carbon bond formations.
Page 175
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
Results and Discussion
Initially, we examined the reaction of 1a in DMF with 3.0 equiv. of t-BuOK at 120 °C. To our delight, 2a was
obtained in a moderate yield. Furthermore, a number of bases and reaction solvents were examined and the
results are summarized in Table 1. t-BuONa, t-BuOLi, and K2CO3 were tested, however, no 2a was obtained
(Table 1, entries 2-4). The reaction in DMSO was also applicable, but a lower yield was observed (Table 1, entry
5). THF was found to be incompatible with the reaction and no product 2a was obtained. The effect of t-BuOK
loading was also examined and the best yield was obtained with 3.0 equiv. of t-BuOK (Table 1, entries 7-8).
The reaction was tested at 90, 150 and 180 °C respectively. The reaction at 150 °C gave the best result (Table
1, entries 9-11).
Table 1. Optimization of reaction conditionsa
Base (n equiv.)
Solvent, T °C, 3 h
N
N
1a
2a
Yield (%)b
50
Entry Solvent Base
n (equiv.)
T (°C)
120
120
120
120
120
reflux
120
120
90
1
DMF
DMF
DMF
DMF
t-BuOK
t-BuONa
t-BuOLi
K2CO3
3
3
3
3
3
3
2
4
3
3
3
2
n.d.c
n.d.c
n.d.c
15
3
4
5
DMSO t-BuOK
6
THF
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
n.d.c
34
7
DMF
DMF
DMF
DMF
DMF
8
47
9
17
10
11
150
180
64 (68)
55
a Reaction conditions: 1a (0.2 mmol, 1.0 equiv.), base (n equiv.), solvent (2.0 mL), at the indicated temperature
b
for 3 hours under nitrogen atmosphere. Yields were obtained by GC with n-dodecane as the internal
standard. The value in the parentheses is the isolated yield after column chromatography.c Not detected.
Page 176
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
Scheme 2. Intramolecular cyclization of biaryl tertiary amines 1a-1q promoted by t-BuOK/DMF.
Reaction conditions: 1a-1q (0.2 mmol), t-BuOK (0.6 mmol), DMF (2.0 mL), nitrogen atmosphere, 150 °C, 3 h. Isolated
yields.
With the optimal reaction conditions in hand, the reaction was extended to a variety of biaryl tertiary
amines, and the results are summarized in Scheme 2. Substrates with electron-donating groups such as
methoxyl and methyl groups on the aryl amine motif were well tolerated. Substrates with single and double
methoxyl substitutions gave the products 2b–2e in good yields. The substrates with a methyl substitution gave
the products 2f–2h in lower yields. Radical delocalization between the methyl group and amino alkyl group
accounts for the poor yield of products. The ortho-methyl substituted substrate 1h gave a poor yield which
Page 177
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
implies that this transformation is sensitive to steric hindrance. Substitution with an electron-withdrawing CF3
group showed a detrimental effect. Although complete consumption of 1i was observed, no expected product
2i could be isolated. A substrate with a naphthyl group was also examined and the product 2j was obtained in
a moderate yield. The 2-thienyl substituted substrate 1k was found to be unreactive.
The effect of the substitutions on the biaryl motif was also examined. The replacement of biaryl group with
a naphthyl group (1l) led to the loss of the reactivity. The substrates with a methyl substitution gave the
products 2m–2n in poor yields. However, the substrate with a pyridyl group (1o) gave a 68% yield. When the
methyl group on the nitrogen was changed to ethyl, the product 2p was obtained in a 68% yield. However, the
benzyl replacement (1q) proved to inhibit the reaction.
To have a better understanding of the mechanism, radical trapping experiments were performed (Scheme
3). The reaction was totally inhibited in the presence of oxygen and butylated hydroxytoluene (BHT). The
results implicate a radical reaction pathway.
Scheme 3. Radical trapping experiments.
Based on our previous studies and the present results, a tentative reaction mechanism is proposed (Scheme
3). DMF is deprotonated by t-BuOK to give the carbamoyl radical A. After a single-electron transfer (SET) step,
the α-amino alkyl radical B is generated. B then undergoes an intramolecular radical addition to the phenyl
ring. The resulting aryl radical C transfers an electron to DMF and is subsequently deprotonated by t-BuOK to
give 2a.
Page 178
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
O
O
t-BuOK
t-BuOH
K
H
N
N
K
N
O
SET
DMF
H
O
N
N
N
A
B
1a
N
2a
H
H
H
N
N
DMF
D
C
Scheme 4. Proposed reaction mechanism.
Conclusions
In summary, we have developed an intramolecular dehydrogenative coupling of biaryl tertiary amines
promoted by t-BuOK/DMF. A number of 6-aryl-5,6-dihydrophenanthridines were prepared in good yields. A
radical reaction pathway is proposed. The finding provides
dihydrophenanthridine derivatives.
a
new synthetic approach to
Experimental Section
1
General. H NMR and 13C NMR spectra were recorded on Bruker AVANCE 400 spectrometer. Chemical shifts of
protons are reported in parts per million downfield from tetramethylsilane and are referenced to residual
protium in the NMR solvent (CDCl3: δ 7.26). Chemical shifts of carbon are referenced to the carbon resonances
of the solvent (CDCl3: δ 77.0) unless otherwise stated. Peaks are labeled as singlet (s), broad singlet (br),
doublet (d), triplet (t), double doublet (dd), multiplet (m). Melting points were measured on a WRS-2A melting
Page 179
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
point apparatus and are uncorrected. GC spectra were taken on an Agilent-6890A instrument. All products
were further characterized by HRMS (high resolution mass spectra). The t-BuOK was purchased from Alfa Aesar
chemical company and used without further purification. THF, DMF were dried and redistilled according to
standard methods. DMSO was dried over 4Å molecular sieves.
General procedure for intramolecular dehydrogenative coupling. To a dried 10 mL reaction tube was added
1a (54.3 mg, 0.2 mmol), t-BuOK (67.4 mg, 0.6 mmol) and DMF (2 mL). The mixture was stirred at 150 °C for 3 h
under nitrogen atmosphere. Water (20.0 mL) was then added and the mixture was extracted with CH2Cl2 (15
mL × 2). The combined organic layer was dried over anhydrous Na2SO4. After the solvent was removed, the
crude product was obtained which was purification by column chromatography to give the product 2a (36.9
mg, 68%) as a colorless oil.
5-Methyl-6-phenyl-5,6-dihydrophenanthridine (2a).36 Colorless oil. 1H NMR (400 MHz, DMSO-d6): δ 7.54 (d, J
7.9 Hz, 1H), 7.48 (dd, J 7.7, 1.3 Hz, 1H), 6.99–6.94 (m, 1H), 6.90–6.77 (m, 8H), 6.49–6.39 (m, 1H), 6.29 (d, J 8.1
Hz, 1H), 5.20 (s, 1H), 3.02 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 149.9, 146.8, 140.7, 135.3, 134.8, 133.6,
132.8, 132.6, 132.6, 132.2, 131.6, 128.29, 127.5, 126.5, 122.6, 117.4, 71.0, 41.9. HRMS (ESI) calculated for
C20H18N (M+H)+: 272.1434, found: 272.1433.
1
6-(4-Methoxyphenyl)-5-methyl-5,6-dihydrophenanthridine (2b).36 White solid, M.p. (153.4–156.6 °C). H
NMR (400 MHz, CDCl3): δ 7.81 (d, J 7.5 Hz, 1H), 7.76 (dd, J 7.7, 1.4 Hz, 1H), 7.28 (td, J 7.7, 1.4 Hz, 1H), 7.22–
7.15 (m, 2H), 7.06–7.02 (m, 3H), 6.83 (td, J 7.5, 1.0 Hz, 1H), 6.71–6.67 (m, 2H), 6.59 (d, J 8.1 Hz, 1H), 5.31 (s,
1H), 3.69 (s, 3H), 2.87 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 159.0, 144.8, 136.0, 133.9, 130.6, 129.4, 128.0,
127.5, 127.3, 127.0, 123.1, 122.5, 122.0, 117.7, 113.8, 112.5, 67.2, 55.1, 37.0. HRMS (ESI) calculated for
C21H20NO (M+H)+: 302.1539, found: 302.1554.
1
6-(3-Methoxyphenyl)-5-methyl-5,6-dihydrophenanthridine (2c).36 White solid, M.p. (133.4–146.2 °C). H
NMR (400 MHz, CDCl3): δ 7.80 (d, J 7.5 Hz, 1H), 7.75 (dd, J 7.7, 1.4 Hz, 1H), 7.30–7.25 (m, 1H), 7.22–7.14 (m,
2H), 7.10–7.05 (m, 2H), 6.82 (td, J 7.5, 1.1 Hz, 1H), 6.73 (dd, J 7.7, 1.1 Hz, 1H), 6.71–6.66 (m, 2H), 6.61 (d, J 8.2
Hz, 1H), 5.32 (s, 1H), 3.60 (s, 3H), 2.88 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 159.6, 145.0, 143.2, 135.6, 130.65,
129.5, 127.7, 127.3, 127.0, 123.2, 122.5, 122.0, 119.1, 117.8, 112.8, 112.5, 112.4, 67.9, 55.0, 37.2. HRMS (ESI)
calculated for C21H20NO (M+H)+: 302.1539, found: 302.1550.
6-(3,4-Dimethoxyphenyl)-5-methyl-5,6-dihydrophenanthridine (2d). Colorless oil. 1H NMR (400 MHz, CDCl3):
δ 7.81 (d, J 7.9 Hz, 1H), 7.76 (dd, J 7.7, 1.5 Hz, 1H), 7.29 (td, J 7.7, 1.4 Hz, 1H), 7.23–7.20 (m, 1H), 7.19–7.16 (m,
1H), 7.09–7.06 (m, 1H), 6.83 (td, J 7.5, 1.1 Hz, 1H), 6.71 (dd, J 8.2, 1.9 Hz, 1H), 6.69–6.66 (m, 1H), 6.63 (d, J 1.6
Hz, 1H), 6.61 (d, J 0.6 Hz, 1H), 5.27 (s, 1H), 3.77 (s, 3H), 3.58 (s, 3H), 2.88 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
148.9, 148.6, 145.1, 136.2, 134.3, 130.6, 129.5, 127.6, 127.3, 126.9, 123.1, 122.5, 122.3, 119.0, 117.8, 112.6,
111.0, 109.9, 67.6, 55.8, 55.6, 37.1. HRMS (ESI) calculated for C22H22NO2 (M+H)+: 332.1645, found: 332.1643.
6-(2,5-Dimethoxyphenyl)-5-methyl-5,6-dihydrophenanthridine (2e). Colorless oil. 1H NMR (400 MHz, CDCl3):
δ 7.78 (d, J 7.8 Hz, 1H), 7.74 (dd, J 7.7, 1.4 Hz, 1H), 7.19 (m, 4H), 6.83–6.80 (m, 1H), 6.78 (s, 1H), 6.73–6.64 (m,
1H), 6.62 (m, 1H), 6.57 (d, J 3.1 Hz, 1H), 6.05 (s, 1H), 3.86 (s, 3H), 3.40 (s, 3H), 2.87 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 153.6, 149.7, 145.5, 136.2, 131.5, 130.8, 129.4, 127.4, 127.2, 126.8, 123.1, 122.4, 122.0, 117.5, 113.4,
113.4, 112.1, 111.9, 58.9, 56.2, 55.2, 36.8. HRMS (ESI) calculated for C22H22NO2 (M+H)+: 332.1645, found:
332.1639.
5-Methyl-6-p-tolyl-5,6-dihydrophenanthridine (2f).36 Colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.81 (t, J 6.5
Hz, 1H), 7.75 (dd, J 7.7, 1.4 Hz, 1H), 7.29–7.25 (m, 1H), 7.23–7.18 (m, 1H), 7.18–7.14 (m, 1H), 7.07–7.04 (m,
1H), 7.02 (dd, J 6.6, 4.8 Hz, 2H), 6.96 (d, J 8.1 Hz, 2H), 6.84–6.80 (m, 1H), 6.59 (d, J 8.0 Hz, 1H), 5.32 (s, 1H),
2.87 (s, 3H), 2.22 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.9, 138.6, 137.2, 135.9, 130.7, 129.4, 129.2, 128.3,
Page 180
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
127.5, 127.3, 127.0, 126.7, 123.1, 122.5, 117.6, 112.4, 67.6, 37.1, 21.0. HRMS (ESI) calculated for C21H20N
(M+H)+: 286.1590, found: 286.1603.
5-Methyl-6-m-tolyl-5,6-dihydrophenanthridine (2g). Colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.83–7.72 (m,
2H), 7.27 (d, J 7.3 Hz, 1H), 7.19 (m, 2H), 7.04 (m, 2H), 6.98–6.89 (m, 3H), 6.83 (dd, J 11.8, 7.7 Hz, 1H), 6.63–6.57
(m, 1H), 5.32 (s, 1H), 2.87 (s, 3H), 2.21 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 145.0, 141.6, 138.0, 135.8, 130.6,
129.5, 128.5, 128.4, 127.6, 127.5, 127.3, 127.1, 123.9, 123.2, 122.5, 121.9, 117.6, 112.4, 67.9, 37.2, 21.6.
HRMS (ESI) calculated for C21H20N (M+H)+: 286.1590, found: 286.1585.
1
5-Methyl-6-o-tolyl-5,6-dihydrophenanthridine (2h). Colorless oil. H NMR (400 MHz, CDCl3): δ 7.81 (d, J 7.5
Hz, 1H), 7.76 (dd, J 7.7, 1.4 Hz, 1H), 7.23–7.20 (m, 1H), 7.20–7.16 (m, 1H), 7.16–7.11 (m, 2H), 7.11–7.06 (m,
2H), 7.00 (dd, J 7.2, 6.0 Hz, 1H), 6.81 (dd, J 10.7, 4.3 Hz, 2H), 6.62 (d, J 7.9 Hz, 1H), 5.82 (s, 1H), 2.73 (s, 3H),
2.48 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 145.6, 141.0, 136.1, 134.7, 130.9, 130.8, 129.5, 128.8, 127.5, 127.4,
127.2, 126.8, 126.6, 123.1, 122.1, 121.4, 117.5, 112.1, 63.5, 36.3, 20.1. HRMS (ESI) calculated for C21H20N
(M+H)+: 286.1590, found: 286.1580.
5-Methyl-6-(naphthalen-2-yl)-5,6-dihydrophenanthridine (2j). Colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.84
(d, J 7.8 Hz, 1H), 7.79 (dd, J 7.7, 1.4 Hz, 1H), 7.75–7.71 (m, 1H), 7.71–7.68 (m, 1H), 7.63–7.58 (m, 2H), 7.39 (m,
2H), 7.31–7.26 (m, 1H), 7.24–7.19 (m, 2H), 7.17–7.13 (m, 1H), 7.08 (dd, J 7.6, 1.1 Hz, 1H), 6.85 (td, J 7.6, 1.0 Hz,
1H), 6.61 (d, J 8.0 Hz, 1H), 5.52 (s, 1H), 2.89 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 145.0, 139.3, 135.5, 133.2,
133.0, 130.8, 129.6, 128.6, 128.1, 127.7, 127.6, 127.3, 126.1, 125.8, 125.2, 125.2, 123.2, 122.5, 121.82, 117.8,
112.4, 68.1, 37.1. HRMS (ESI) calculated for C24H20N (M+H)+: 322.1590, found: 322.1592.
5,10-Dimethyl-6-phenyl-5,6-dihydrophenanthridine (2m). Colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J
7.9 Hz, 1H), 7.77 (d, J 7.7 Hz, 1H), 7.24–7.13 (m, 4H), 7.12–7.07 (m, 2H), 7.00 (t, J 7.2 Hz, 1H), 6.83 (t, J 7.6 Hz,
2H), 6.62 (d, J 8.2 Hz, 1H), 5.82 (s, 1H), 2.74 (s, 3H), 2.49 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 145.6, 141.0,
136.1, 134.7, 131.8, 130.9, 129.5, 128.7, 127.5, 127.5, 127.2, 126.8, 126.6, 123.1, 122.2, 121.4, 117.5, 112.1,
63.4, 36.3, 20.2. HRMS (ESI) calculated for C21H20N (M+H)+: 286.1590, found: 286.1580.
5,8-Dimethyl-6-phenyl-5,6-dihydrophenanthridine (2n). Colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.75–7.68
(m, 2H), 7.20–7.14 (m, 4H), 7.13–7.08 (m, 3H), 6.88 (s, 1H), 6.82 (td, J 7.5, 1.0 Hz, 1H), 6.57 (d, J 8.0 Hz, 1H),
5.30 (s, 1H), 2.86 (s, 3H), 2.27 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.6, 141.7, 137.1, 135.6, 129.0, 128.6,
128.5, 128.0, 127.6, 127.6, 126.8, 122.8, 122.5, 122.1, 117.6, 112.3, 68.0, 37.1, 21.2. HRMS (ESI) calculated for
C21H20N (M+H)+: 286.1590, found: 286.1583.
1
6-Methyl-5-phenyl-5,6-dihydrobenzo[c][2,7]naphthyridine (2o). Yellow oil. H NMR (400 MHz, CDCl3): δ 8.45
(d, J 5.4 Hz, 1H), 8.32 (s, 1H), 7.75 (dd, J 7.8, 1.3 Hz, 1H), 7.58 (d, J 5.3 Hz, 1H), 7.33–7.28 (m, 1H), 7.19 (dd, J
6.3, 3.6 Hz, 3H), 7.14 (dd, J 6.6, 3.1 Hz, 2H), 6.84 (dd, J 10.9, 4.1 Hz, 1H), 6.65 (d, J 8.2 Hz, 1H), 5.45 (s, 1H), 2.92
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 148.6, 148.4, 146.0, 141.2, 137.9, 131.9, 130.1, 128.8, 128.0, 126.4, 124.1,
118.8, 117.7, 116.0, 112.6, 65.1, 37.2. HRMS (ESI) calculated for C19H17N2 (M+H)+: 273.1386, found: 273.1364.
1
5-Ethyl-6-phenyl-5,6-dihydrophenanthridine (2p). Yellow oil. H NMR (400 MHz, CDCl3): δ 7.81–7.71 (m, 2H),
7.27–7.23 (m, 1H), 7.21–7.17 (m, 3H), 7.14 (m, 3H), 7.10–7.01 (m, 2H), 6.79 (m, 1H), 6.72 (d, J 8.2 Hz, 1H), 5.49
(s, 1H), 3.47 (m, 1H), 3.25 (m, 1H), 1.17 (t, J 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 144.2, 143.6, 135.7,
130.6, 129.4, 128.5, 127.5, 127.4, 127.1, 127.0, 126.6, 123.5, 122.5, 121.7, 117.2, 112.4, 65.5, 44.1, 12.6.
HRMS (ESI) calculated for C21H20N (M+H)+: 286.1517 286.1590, found: 286.1611.
Page 181
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
Acknowledgements
We thank the National Natural Science Foundation of China (No. 21472248), the Guangdong Engineering
Research Center of Chiral Drugs and the Innovative Scientific Research Team Introducing Project of Zhongshan
City (No. 2015-224) for the financial support of this study.
References
1. Girard, S. A.; Knauber, T.; Li, C. J. Angew. Chem. Int. Ed. 2014, 53, 74.
https://doi.org/10.1002/anie.201304268
2. Shi, Z.; Glorius F. Angew. Chem. Int. Ed. 2012, 51, 9220.
https://doi.org/10.1002/anie.201205079
3. Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215.
https://doi.org/10.1021/cr100280d
4. Li, C. J. Acc. Chem. Res. 2009, 42, 335.
https://doi.org/10.1021/ar800164n
5. Wu, C. J.; Meng, Q. Y.; Lei, T.; Zhong, J. J.; Liu, W. Q.; Zhao, L. M.; Li, Z. J.; Chen, B.; Tung, C. H.; Wu. L. Z. ACS Catal.
2016, 6, 4635.
https://doi.org/10.1021/acscatal.6b00917
6. Mei, S. T.; Liang, H. W.; Teng, B.; Wang, N. J.; Shuai. L.; Yuan, Y.; Chen, Y. C.; Wei, Y. Org. Lett. 2016, 18, 1088.
https://doi.org/10.1021/acs.orglett.6b00197
7. Cambeiro, X. C.; Ahlsten, N.; Larrosa, I. J. Am. Chem. Soc. 2015, 137,15636.
https://doi.org/10.1021/jacs.5b10593
8. Wang, J.; Liu, C.; Yuan, J. W.; Lei, A. W. Angew. Chem. Int. Ed. 2013, 52, 2256.
https://doi.org/10.1002/anie.201208920
9. Kuhl, N.; Hopkinson, M. N.; Glorius, F. Angew. Chem. Int. Ed. 2012, 51, 8230.
https://doi.org/10.1002/anie.201203792
10. Zhang, G.; Zhang, Y. H.; Wang, R. Angew. Chem. Int. Ed. 2011, 50, 10429.
https://doi.org/10.1002/anie.201105123
11. Volvoikar, P. S.; Tilve, S. G. Org. Lett. 2016, 18, 892.
https://doi.org/10.1021/acs.orglett.5b03392
12. Martínez, C.; Bosnidou, A. E.; Allmendinger, S.; Muñiz, K. Chem. Eur. J. 2016, 22, 1.
https://doi.org/10.1002/chem.201504553
13. Liu, J.; Zhang, H.; Yi, H.; Liu, C.; Lei, A. W. Sci. China Chem. 2015, 58, 1323.
https://doi.org/10.1007/s11426-015-5381-2
14. Laha, J. K.; Tummalapalli, K. S. S.; Nair, A.; Patel, N. J. Org. Chem. 2015, 80, 11351
https://doi.org/10.1021/acs.joc.5b01872
15. Sun, X.; Hu, Y.; Nie, S. Z.; Yan, Y. Y.; Zhang, X. J.; Yan, M. Adv. Synth. Catal. 2013, 355, 2179
https://doi.org/10.1002/adsc.201300455
16. Kim, H. J.; Kim, J. Y.; Cho, S. H.; Chang, S. J. Am. Chem. Soc. 2011, 133, 16382.
https://doi.org/10.1021/ja207296y
17. Chen, X. P.; Cui, X. L.; Yang, F. F.; Wu, Y. J. Org. Lett. 2015, 17, 1445.
https://doi.org/10.1021/acs.orglett.5b00330
Page 182
©ARKAT USA, Inc

Arkivoc 2017, iv, 174-183
Zhang, T. et al
18. Kumar, S.; Rathore, V.; Verma, A.; Prasaad, C. D.; Kumar, A.; Yadav, A.; Jana, S.; Sattar, M.; Meenakshi, S.; Kumar, S.
Org. Lett. 2015, 17, 82.
https://doi.org/10.1021/ol503274z
19. Chen, Y. Y.; Chen, J. H.; Zhang, N. N.; Ye, L. M.; Zhang X. J.; Yan, M. Tetrahedron Lett. 2015, 56, 478.
https://doi.org/10.1016/j.tetlet.2014.12.002
20. Wei, W. T.; Liu, Y.; Ye, L. M.; Lei, R. H.; Zhang X. J.; Yan, M. Org. Biomol. Chem. 2015, 13, 817.
https://doi.org/10.1039/C4OB01948B
21. Chen, Y. Y.; Zhang, X. J.; Yuan, H. M.; Wei, W. T.; Yan, M. Chem. Commun. 2013, 49, 10974.
https://doi.org/10.1039/c3cc46340k
22. Wei, W. T.; Dong, X. J.; Nie, S. Z.; Chen, Y. Y.; Zhang, X. J.; Yan, M. Org. Lett. 2013, 15, 6018.
https://doi.org/10.1021/ol402908m
23. Wang, W. J.; Zhao, X.; Tong, L.; Chen, J. H.; Zhang, X. J.; Yan, M. J. Org. Chem. 2014, 79, 8557.
https://doi.org/10.1021/jo501179t
24. Chen, Y. Y.; Chen, Z. Y.; Zhang, N. N.; Chen, J. H.; Zhang X. J.; Yan, M. Eur. J. Org. Chem. 2016, 2016, 599.
25. Chen, Y. Y.; Zhang, N. N.; Ye, L. M.; Chen, J. H.; Sun, X.; Zhang X. J.; Yan, M. RSC Adv. 2015, 5, 48046.
https://doi.org/10.1039/C5RA07188G
26. Pegoraro, S.; Lang, M.; Dreker, T.; Kraus, J.; Hamm, S.; Meere, C.; Feurle, J.; Tasler, S.; Pruetting, S.; Kuras, Z.; Visan,
V.; Grissmer, S. Bioorg. Med. Chem. Lett. 2011, 21, 5647.
https://doi.org/10.1016/j.bmcl.2011.07.013
27. Miao, F.; Yang, X.-J.; Zhou, L.; Hu, H.-J.; Zheng, F.; Ding, X.-D.; Sun, D.-M.; Zhou, C.-D.; Sun, W. Nat. Prod. Res. 2011,
25, 863.
https://doi.org/10.1080/14786419.2010.482055
28. Fotie, J.; Bohle, D. S.; Olivier, M.; Gomez, M. A.; Nzimiro, S. J. Nat. Prod. 2007, 70, 1650.
https://doi.org/10.1021/np0702281
29. Kundu, K.; Knight, S. F.; Lee, S.; Taylor, W. R.; Murthy N. Angew. Chem. Int. Ed. 2010, 49, 6134.
https://doi.org/10.1002/anie.201002228
30. Ye, J.; Limouni, A.; Zaichuk, S.; Lautens M. Angew. Chem. Int. Ed. 2015, 54, 3116.
https://doi.org/10.1002/anie.201411276
31. Augustine, J. K.; Bombrun, A.; Alagarsamy, P.; Jothi, A. Tetrahedron Lett. 2012, 53, 6280.
https://doi.org/10.1016/j.tetlet.2012.09.034
32. Meseroll, L. M. N.; McKee, J. R.; Zanger, M. Synth. Commun. 2011, 41, 2557.
https://doi.org/10.1080/00397911.2010.515329
33. Mandadapu, A. K.; Saifuddin, M.; Agarwal, P. K.; Kundu, B. Org. Biomol. Chem. 2009, 7, 2796.
https://doi.org/10.1039/b905696c
34. Pegoraro, S.; Lang, M.; Dreker, T.; Kraus, J.; Hamm, S.; Meere, C.; Feurle, J.; Tasler, S.; Pruetting, S.; Kuras, Z.; Visan,
V.; Grissmer, S. Bioorg. Med. Chem. Lett. 2009, 19, 2299.
https://doi.org/10.1016/j.bmcl.2009.02.077
35. Castillo, J. C.; Quiroga, J.; Abonia, R.; Rodriguez, J.; Coquerel, Y. J. Org. Chem. 2015, 80, 9767.
https://doi.org/10.1021/acs.joc.5b01564
36. Zhu, X. Q.; Li, X. T.; Han, S. H.; Mei L. R. J. Org. Chem. 2012, 77, 4774.
https://doi.org/10.1021/jo3005952
Page 183
©ARKAT USA, Inc