Diastereoselective synthesis of n -aryl tetrahydroquinolines and n -aryl indolines by the tandem reaction of arynes

Article abstract of DOI:10.1021/jo5003399

A tandem reaction of arynes with α- or β-amino ketones has been revealed. Arynes react with β-amino ketones through a cascade insertion-cyclization process to afford N-aryl tetrahydroquinolines in good yield with excellent anti-selectivity. Meanwhile, the coupling of arynes with α-amino ketones produces multisubstituted indolines in high yield with syn-selectivity. A quaternary carbon center can be constructed in this process, and the reaction can be easily scaled up.

Full text of DOI:10.1021/jo5003399

Note
pubs.acs.org/joc
Diastereoselective Synthesis of N‑Aryl Tetrahydroquinolines and
N‑Aryl Indolines by the Tandem Reaction of Arynes
Ji-Xin Pian, Lin He,* Guang-Fen Du, Hao Guo, and Bin Dai*
School of Chemistry and Chemical Engineering, Shihezi University, Xinjiang, Uygur Autonomous Region 832000, China
S
* Supporting Information
ABSTRACT: A tandem reaction of arynes with α- or β-amino
ketones has been revealed. Arynes react with β-amino ketones
through a cascade insertion−cyclization process to afford N-
aryl tetrahydroquinolines in good yield with excellent anti-
selectivity. Meanwhile, the coupling of arynes with α-amino
ketones produces multisubstituted indolines in high yield with
syn-selectivity. A quaternary carbon center can be constructed
in this process, and the reaction can be easily scaled up.
etrahydroquinolines1 and indolines2 are two important
classes of structural motifs in numerous natural and
synthetic compounds with a wide spectrum of biological
of arynes enables them to be used as dienophiles in a series of
pericyclic reactions, such as 1,3-dipolar cycloaddition,11 Diels−
Alder reaction,12 and insertion−cyclization reaction,13 which
facilitate easy access to different types of heterocycles. In
particular, the click rection of arynes and amino-carbonyl
compounds that is triggered by nitrogen insertion leads to the
construction of a large number of pharmaceutically active
heterocycles, including acridones,13a,b acridines,13c,d indoline-
s,13e,f polycyclic indolones,13g,h isatins,13i indoles,13j,k and
quinazolinones.13l Recently, Zhu13m and our group13n
independently reported an efficient method to produce
multisubstituted N-arylindoles from arynes and α-amino
ketones. As a following study, we reasoned that the coupling
of arynes with the readily available β-amino ketones can lead to
the construction of polysubstituted tetrahydroquinolines. In the
present work, we propose a novel approach to the
diastereoselective synthesis of N-aryl tetrahydroquinolines and
indolines involving a tandem insertion−cyclization process of
arynes.
T
activities (Figure 1). The significance of these motifs has led to
Figure 1. Examples of bioactive tetrahydroquinoline and indoline
derivatives.
the development of several efficient methods for the synthesis
of tetrahydroquinolines, such as aza-Michael addition,3 aza-
Diels−Alder reaction (Povarov reaction),4 hydrogenation of
quinolines,5 and other miscellaneous reactions.6 Different
protocols have also been established for the preparation of
indolines.7 However, to the best of our knowledge, information
on the synthesis of tetrahydroquinolines and indolines
containing a quaternary stereocenter is limited. Such
information is essential for studying the bioactivity of these
compounds.8 Therefore, the development of novel and efficient
methods for the synthesis of tetrahydroquinolines and indolines
with a quaternary center is of high importance.
Arynes are highly active intermediates that can be
conveniently generated by the fluoride-induced 1,2-elimination
reaction of o-(trimethylsilyl)-aryl triflates under very mild
conditions, as reported by Kobayashi et al.9 Their findings
paved the way for the dramatic progress of aryne chemistry.
Presently, arynes are an important class of building blocks
widely applied in organic synthesis.10 The high electrophilicity
We began our studies with the commercially available aryne
precursor 1a and β-amino ketone 2a. With 3.0 equiv CsF as
fluoride source, the cascade reaction smoothly proceeded in
acetonitrile at room temperature to furnish the desired
tetrahydroquinoline 3a in 64% yield with excellent diaster-
eoselectivity14 (anti/syn > 25:1; Table 1, entry 1), together with
a small amount of N-phenylation amine 4a. Considering these
successful results, several other fluorides such as KF, NaF, LiF,
and Bu4NF were subsequently tested for the reaction. However,
all the fluorides tested above showed lower efficiency, and most
of the 2a was recovered (Table 1, entries 2−5). Interestingly,
when 3.0 equiv of 18-crown-6 was added as coadditive, the
reaction was finished within a relatively short time, producing
the desired product in 72% yield with excellent diastereose-
lectivity (Table 1, entry 6). A brief screening of the reaction
Received: February 12, 2014
Published: May 21, 2014
© 2014 American Chemical Society
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Note
a
Table 1. Optimization of Reaction Conditions
Scheme 1. Synthesis of N-Aryl Tetrahydroquinolines
b
c
b
entry
additives
solvent
t/h
3a
anti/syn 4a
1
2
3
4
5
6
CsF (3.0 equiv)
KF (3.0 equiv)
NaF (3.0 equiv)
LiF (3.0 equiv)
CH3CN
CH3CN
CH3CN
CH3CN
6
30
30
30
30
2
64
>25:1
−
−
−
>25:1
12
d
d
d
d
6 (90)
4 (91)
0 (93)
10 (67)
72
−
−
−
−
11
Bu4NF (3.0 equiv) THF
KF+18-C-6
(3.0 equiv)
CH3CN
>25:1
7
KF+18-C-6
(3.0 equiv)
THF
4
4
30
>25:1
>25:1
−
51
54
26
31
25
23
−
8
KF+18-C-6
(3.0 equiv)
CH2Cl2
toluene
Et2O
31
d
d
9
KF+18-C-6
(3.0 equiv)
4
0 (44)
0 (43)
55
10
11
12
13
KF+18-C-6
(3.0 equiv)
4
−
KF+18-C-6
(2.0 equiv)
CH3CN
CH3CN
CH3CN
2
>25:1
>25:1
−
KF+18-C-6
(1.0 equiv)
30
30
57
d
no additives
0 (94)
a
b
1a (0.15 mmol), 2a (0.10 mmol), solvent: 2.0 mL, rt. Isolated yields.
c
Determined by 1H NMR analysis of the crude reaction mixture.
d
Recovery yield of 2a.
media proved that acetonitrile was still the best choice with
respect to yields and selectivities (Table 1, entries 6−10).
Reducing the loading of additive reversed the outcomes of 3a
and 4a (Table 1, entries 11 and 12). Finally, the control
experiment indicated that no product was produced in the
absence of additives (Table 1, entry 13).
With the optimized reaction conditions in hand, the scope of
the reaction was subsequently examined, and the results are
summarized in Scheme 1. A range of differently substituted β-
amino ketones underwent the tandem reaction smoothly to
afford the corresponding tetrahydroquinolines with excellent
diastereoselectivity. The electronic properties and varied
positions of the substituted groups on the aromatic ring had
no evident effects on the reaction yields and selectivities
(Scheme 1, 3b to 3g). Aliphatic β-amino ketones were also
proved to be good candidates for the coupling reaction,
producing the corresponding alkyl-substituted tetrahydroquino-
lines in good yield (Scheme 1, 3h and 3i). Surprisingly, when β-
unsubstituted β-amino ketone 2j was employed, a diminished
yield was abserved (Scheme 1, 3j). In addition, the unsym-
metrical aryne derived from the 3-methoxy substituted triflate
precursor 1b smoothly underwent the cascade reaction to yield
58% of the corresponding tetrahydroquinoline with nearly
complete regioselectivity and diastereoselectivity (Scheme 1,
3k).15 More interestingly, the reaction can be easily scaled up
without losing the reaction yield and diastereoselectivity.
To further demonstrate the utility of this protocol, the
tandem insertion−cyclization of arynes and α-amino ketones
was next investigated. In our previous studies of these similar
cascade reactions,13n we showed that the direct acidic workup
of the crude products led to the formation of dehydrated
indoles. However, in this current research, after filtration of the
crude reaction mixture through a basic pad of anhydrous
potassium carbonate, the hydroxy group can be retained, and
indolines were isolated as the major products (Scheme 2). α-
Amino ketones substituted with both electron-donating and
electron-withdrawing groups efficiently coupled with arynes,
producing the corresponding indolines in high yield with
excellent diastereoselectivity14 (Scheme 2, 6a−6d). Addition-
ally, different positions of the substituents only very slightly
affected the reaction. Alkyl-substituted α-amino ketones were
also suitable reactants for the tandem reaction, producing the
corresponding alkyl-substituted indolines in moderate yields
(Scheme 2, 6e and 6f). The symmetric naphthalene can also
undergo annulation with α-amino ketone to yield 75% of
benzindoline 6g (Scheme 2, 6g). The unsymmetric aryne again
reacted with α-amino ketone to afford indoline 6h with nearly
complete regioselectivity (Scheme 2, 6h).15
Two feasible transition states were proposed for current
transformation based on experiment outcomes (see Scheme 3).
For the reaction of β-amino ketones, a six-membered chair
model A was proposed. The bulky phenyl groups sitting at the
equatorial position are more stable than those at the axial
position, which would lead to anti-selectivity of tetrahydroqui-
nolines. On the other hand, a five-membered envelope model B
was proposed for the reaction of α-amino ketones. Two
adjacent phenyl groups adopt anti-positions preferentially,
which can minimize the van der Waals repulsions and lead to
the syn-selectivity of indolines.
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Note
temperature until full consumption of the starting aminoketone
as indicated by TLC. The reaction mixture was then diluted
with ethyl acetate, filtered through a short pad of anhydrous
K2CO3, and concentrated. The crude product was purified by
flash column chromatography on silica gel (PE/EtOAc, 15:1−
10:1) to give the desired product.
Scheme 2. Synthesis of N-Aryl Indolines
Scale-up Experiment. To a solution of β-aminoketone 2a
(1.204 g, 4.0 mmol), KF (232 mg, 4.0 mmol), 18-crown-6
(1.06 g, 4.0 mmol) in anhydrous acetonitrile (8.0 mL) was
added 2-(trimethylsilyl)-aryl triflate 1a (1.2 mL, 5 mmol). The
mixture was stirred for 12 h at room temperature under a
nitrogen atmosphere. The reaction mixture was then filtered
through a short pad of anhydrous K2CO3, washed with ethyl
acetate, and concentrated. The crude product was purified by
flash column chromatography on silica gel (PE/EtOAc, 15:1−
10:1) to give 3a in 73% yield (1.10 g).
1,2,4-Triphenyl-1,2,3,4-tetrahydroquinolin-4-ol (3a). Reac-
tion time: 2 h; 81.5 mg, 72% yield; white solid; mp 58.7−60.4
°C; IR (KBr, cm−1) ν 3449, 1631, 1599, 1485, 1449, 1352,
1
1120, 1095, 1044, 889, 758, 698, 507; H NMR (400 MHz,
CDCl3) δ 7.57−7.53 (m, 2H), 7.36−7.32 (m, 2H), 7.29−7.25
(m, 3H), 7.23−7.18 (m, 2H), 7.15−7.04 (m, 6H), 7.01−6.96
(m, 1H), 6.84−6.81 (m, 1H), 6.64−6.59 (m, 1H), 6.46−6.43
(m, 1H), 5.06 (dd, J = 3.3, 12.1 Hz, 1H), 2.66−2.57 (m, 1H),
2.39−2.32 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 147.71,
147.07, 146.67, 142.21, 129.36, 129.30, 129.05, 128.94, 128.43,
128.14, 128.10, 127.96, 127.14, 126.88, 126.39, 125.92, 118.04,
116.79, 73.51, 60.98, 48.51; HRMS (EI, TOF): m/z calcd for
C27H23NO [M]+ 377.1780, found: 377.1776.
2-(4-Chlorophenyl)-1,4-diphenyl-1,2,3,4-tetrahydroquino-
lin-4-ol(3b). Reaction time: 2 h; 82.8 mg, 67% yield; light-
yellow solid; mp 65.3−66.2 °C; IR (KBr, cm−1) ν 3437, 2912,
2830, 1632, 1593, 1489, 1449, 1350, 1090, 1063, 1043, 1013,
891, 827, 752, 700, 511; 1H NMR (400 MHz, CDCl3) δ 7.57−
7.50 (m, 2H), 7.39−7.32 (m, 2H), 7.31−7.27 (m, 1H), 7.25−
7.19 (m, 4H), 7.14−7.05 (m, 5H), 7.02−6.96 (m, 1H), 6.86−
6.81 (m, 1H), 6.66−6.60 (m, 1H), 6.45−6.40 (m, 1H), 5.05
(dd, J = 2.7, 12.0 Hz, 1H), 2.56 (dd, J = 13.1, 13.1 Hz, 1H),
2.35−2.28 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 147.55,
146.88, 146.46, 140.78, 132.65, 129.43, 129.40, 129.34, 128.96,
128.26, 127.96, 126.93, 126.31, 126.16, 118.21, 116.74, 73.37,
60.39, 48.31; HRMS (MALDI, TOF): m/z calcd for
C27H2235ClNO [M + H − H2O − H2]+ 392.1201, found:
392.1203.
Scheme 3. Proposed Mechanism
In summary, we have described an insertion−cyclization
reaction of arynes with α- or β-amino ketones. The mild
reaction conditions, simple procedure, and excellent diaster-
eoselectivity provided a novel approach to the synthesis of
these versatile nitrogen-containing heterocycles.
1-(4-Chlorophenyl)-2,4-diphenyl-1,2,3,4-tetrahydroquino-
lin-4-ol (3c). Reaction time: 2 h; 82.7 mg, 67% yield; white
solid; mp 60.5−61.8 °C; IR (KBr, cm−1) ν 3447, 2832, 2716,
1631, 1598, 1489, 1450, 1363, 1215, 1090, 1043, 895, 827, 750,
1
EXPERIMENTAL SECTION
700, 569; H NMR (400 MHz, CDCl3) δ 7.56−7.51 (m, 2H),
■
7.38−7.32 (m, 2H), 7.30−7.24 (m, 3H), 7.21−7.08 (m, 5H),
7.05−6.98 (m, 3H), 6.86−6.81 (m, 1H), 6.68−6.62 (m, 1H),
6.45−6.39 (m, 1H), 5.00 (dd, J = 2.8, 12.0 Hz, 1H), 2.60 (dd, J
= 13.3, 13.3 Hz, 1H), 2.38−2.29 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 147.29, 146.83, 145.39, 141.87, 131.31, 130.57,
129.50, 129.03, 128.97, 128.73, 128.25, 128.01, 127.96, 127.33,
126.93, 126.29, 118.45, 116.80, 73.40, 61.04, 48.39; HRMS
(MALDI, TOF): m/z calcd for C27H2235ClNO [M + H − H2O
− H2]+ 392.1201, found: 392.1205.
All reactions were conducted under nitrogen atmosphere in
oven-dried glassware with magnetic stirring bar. Anhydrous
THF, ether, and toluene were distilled from sodium, anhydrous
1
CH2Cl2 and CH3CN were distilled from calcium hydride. H
NMR (400 MHz), 13C NMR (100 MHz, CDCl3) spectra were
recorded using tetramethylsilane as an internal standard and
reported in ppm (δ). α-Aminoketones16 and β-aminoketones17
were prepared according to the literature.
General Procedure for the Tandem Reaction of Aryne
with β-Aminoketone (or α-Aminoketone). To a mixture of
aminoketone 2 (or 5) (0.3 mmol), KF (52 mg, 0.9 mmol), 18-
crown-6 (238 mg, 0.9 mmol) in anhydrous acetonitrile (2.0
mL) was added 2-(trimethylsilyl) aryl triflate 1 (0.45 mmol)
under N2 atmosphere. The mixture was stirred at room
1-(4-Chlorophenyl)-2-(4-methoxyphenyl)-4-phenyl-
1,2,3,4-tetrahydroquinolin-4-ol (3d). Reaction time: 5 h; 70.2
mg, 53% yield; light-yellow solid; mp 73.5−74.8 °C; IR (KBr,
cm−1) ν 3447, 3028, 2930, 2835, 1601, 1512, 1489, 1452, 1352,
1
1311, 1246, 1170, 1089, 978, 829, 756, 700; H NMR (400
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Note
MHz, CDCl3) δ 7.55−7.51 (m, 2H), 7.37−7.32 (m, 2H),
7.30−7.26 (m, 1H), 7.21−7.13 (m, 4H), 7.02−6.97 (m, 3H),
6.84−6.80 (m, 1H), 6.71−6.67 (m, 2H), 6.66−6.60 (m, 1H),
6.37 (d, J = 8.3 Hz, 1H), 4.94 (dd, J = 2.8, 12.1 Hz, 1H), 3.71
(s, 3H), 2.58 (dd, J = 13.5, 13.5 Hz, 1H), 2.34−2.27 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 158.65, 147.43, 146.97, 145.40,
133.79, 131.35, 130.79, 129.51, 129.10, 129.08, 128.92, 128.55,
127.94, 126.88, 126.28, 118.28, 116.68, 113.57, 73.49, 60.34,
55.12, 48.35; HRMS (MALDI, TOF): m/z calcd for
C28H2435ClNO2 [M + H − H2O − H2]+ 422.1306, found:
422.1308.
11.3 Hz, 1H), 2.36−2.17 (m, 2H), 2.09−1.97 (m, 2H), 1.92 (s,
1H), 0.93 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
147.04, 146.83, 142.96, 129.19, 128.58, 128.49, 128.17, 127.92,
127.30, 127.06, 125.56, 125.42, 118.36, 117.36, 70.16, 60.48,
42.78, 33.43, 8.91; HRMS (MALDI, TOF): m/z calcd for
C23H23NO [M + H − H2O − H2]+ 310.1590, found: 310.1587.
2-Isopropyl-4-methyl-1-phenyl-1,2,3,4-tetrahydroquino-
lin-4-ol (3i). Reaction time: 5 h; 45.5 mg, 54% yield; brown oil;
IR (KBr, cm−1) ν 3554, 3433, 3062, 2961, 2872, 1598, 1562,
1492, 1457, 1367, 1300, 1281, 1215, 1164, 1125, 1082, 1023,
1
945, 886, 859, 746, 699, 512; H NMR (400 MHz, CDCl3) δ
7.45−7.39 (m, 3H), 7.30−7.25 (m, 1H), 7.22−7.18 (m, 2H),
6.96−6.90 (m, 1H), 6.73−6.68 (m, 1H), 6.26−6.22 (m, 1H),
3.67 (dt, J = 12, 3.2 Hz, 1H), 2.01−1.96 (m, 1H), 1.94 (s, 1H),
1.88−1.81 (m, 1H), 1.80−1.73 (m, 1H), 1.72 (s, 3H), 0.87 (d, J
= 7.0 Hz, 3H), 0.85 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 147.18, 146.58, 129.78, 129.27, 128.55, 127.85,
126.32, 125.62, 117.80, 117.30, 67.23, 59.04, 36.25, 29.02,
28.18, 19.54, 15.18; HRMS (MALDI, TOF): m/z calcd for
C19H23NO [M + H − H2O − H2]+ 262.1590, found: 262.1600.
1,4-Diphenyl-1,2,3,4-tetrahydroquinolin-4-ol (3j). Reaction
time: 3 h; 36.8 mg, 31% yield; light-brown oil; IR (KBr, cm−1)
ν 3552, 3441, 3060, 3031, 2944, 2857, 1593, 1569, 1494, 1446,
1319, 1271, 1220, 1164, 1120, 1065, 1025, 980, 755, 695, 560;
1H NMR (400 MHz, CDCl3) δ 7.50−7.44 (m, 2H), 7.41−7.31
(m, 4H), 7.30−7.23 (m, 3H), 7.19−7.13 (m, 1H), 7.02−6.92
(m, 2H), 6.77−6.72 (m, 1H), 6.67−6.61 (m, 1H), 3.92−3.83
(m, 1H), 3.52−3.44 (m, 1H), 2.40−2.32 (m, 1H), 2.31 (s, 1H),
2.24−2.16 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 147.83,
147.70, 144.78, 129.65, 129.23, 128.72, 128.48, 127.97, 126.92,
126.48, 125.62, 124.68, 118.26, 115.31, 73.40, 47.43, 39.35;
HRMS (MALDI, TOF): m/z calcd for C21H19NO [M + H −
H2O − H2]+ 282.1277, found: 282.1277.
5-Methoxy-1,2,4-triphenyl-1,2,3,4-tetrahydroquinolin-4-ol
(3k). Reaction time: 4 h; 71.0 mg, 58% yield; white solid; mp
164.8−167.4 °C; IR (KBr, cm−1) ν 3572, 3447, 2926, 2833,
1736, 1601, 1592, 1493, 1466, 1435, 1352, 1234, 1107, 1080,
1055, 986, 910, 889, 761, 698; 1H NMR (400 MHz, CDCl3) δ
7.31−7.24 (m, 2H), 7.21−7.14 (m, 5H), 7.13−7.07 (m, 4H),
7.05−6.96 (m, 5H), 6.30 (d, J = 8.0 Hz, 1H), 6.19 (d, J = 8.5
Hz, 1H), 4.86−4.81 (m, 1H), 3.86 (s, 1H), 3.36 (s, 3H), 2.54−
2.49 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 158.43, 150.83,
148.90, 146.61, 141.19, 129.02, 128.73, 128.63, 128.14, 127.78,
127.52, 126.73, 125.71, 125.43, 124.47, 117.01, 110.39, 102.20,
72.50, 61.00, 55.29, 49.68; HRMS (MALDI, TOF): m/z calcd
for C28H25NO2 [M + H − H2O − H2]+ 388.1696, found:
388.1700.
4-(4-Bromophenyl)-1-(4-chlorophenyl)-2-(p-tolyl)-1,2,3,4-
tetrahydroquin-olin-4-ol (3e). Reaction time: 2 h; 121.2 mg,
80% yield; light-yellow solid; mp 124.4−124.7 °C; IR (KBr,
cm−1) ν 3439, 2832, 1632, 1601, 1489, 1450, 1352, 1215, 1090,
1
1069, 1045, 1011, 816, 756; H NMR (400 MHz, CDCl3) δ
7.48−7.38 (m, 4H), 7.21−7.17 (m, 2H), 7.14−7.09 (m, 2H),
7.03−6.94 (m, 5H), 6.82−6.77 (m, 1H), 6.68−6.62 (m, 1H),
6.42−6.37 (m, 1H), 4.93 (dd, J = 2.6, 11.9 Hz, 1H), 2.52 (dd, J
= 13.3, 13.3 Hz, 1H), 2.32−2.26 (m, 2H), 2.24 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 147.31, 146.16, 145.18, 138.49,
137.01, 131.37, 131.00, 130.60, 129.53, 129.17, 128.99, 128.92,
128.25, 127.97, 127.84, 120.87, 118.43, 116.77, 73.28, 60.57,
48.30, 21.06; HRMS (MALDI, TOF): m/z calcd for
C28H2379Br35ClNO [M + H − H2O − H2]+ 484.0462, found:
484.0436.
2-(3-Bromophenyl)-1-(3,4-dichlorophenyl)-4-(3-methoxy-
phenyl)-1,2,3,4-tetrahydroquinolin-4-ol (3f). Reaction time: 2
h; 116.6 mg, 70% yield; light-yellow solid; mp 72.9−75.2 °C;
IR (KBr, cm−1) ν 3452, 2832, 1593, 1450, 1383, 1352, 1215,
1
1130, 1043, 764, 698; H NMR (400 MHz, CDCl3) δ 7.70 (s,
1H), 7.43−7.38 (m, 2H), 7.30−7.26 (m, 1H), 7.24−7.17 (m,
2H), 7.14−7.04 (m, 2H), 6.96−6.92 (m, 1H), 6.88−6.79 (m,
3H), 6.74−6.66 (m, 2H), 6.54−6.49 (m, 1H), 4.92 (dd, J = 3.1,
11.6 Hz, 1H), 3.73 (s, 3H), 2.51 (dd, J = 13.5, 13.5 Hz, 1H),
2.40−2.33 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 159.61,
149.03, 146.32, 146.28, 143.03, 132.96, 130.83, 130.20, 130.14,
129.57, 129.52, 129.49, 129.45, 129.37, 128.86, 128.60, 128.03,
125.11, 122.33, 120.13, 119.32, 117.31, 113.42, 112.93, 73.04,
60.87, 55.19, 48.20; HRMS (MALDI, TOF): m/z calcd for
C28H2279Br35Cl2NO2 [M + H − H2O − H2]+ 534.0022, found:
534.0003.
1-(4-Chlorophenyl)-4-(4-nitrophenyl)-2-phenyl-1,2,3,4-tet-
rahydroquinolin-4-ol (3g). Reaction time: 6 h; 86.4 mg, 63%
yield; light-yellow solid; mp 79.2−80.3 °C; IR (KBr, cm−1) ν
1
3422, 2816, 1599, 1490, 1450, 1350, 1086, 1015, 853, 756; H
NMR (400 MHz, CDCl3) δ 8.22−8.18 (m, 2H), 7.75−7.71 (m,
2H), 7.25−7.17 (m, 5H), 7.16−7.10 (m, 2H), 7.05−7.01 (m,
3H), 6.75−6.71 (m, 1H), 6.70−6.64 (m, 1H), 6.45−6.41 (m,
1H), 4.99 (dd, J = 3.1, 11.9 Hz, 1H), 2.56 (dd, J = 12.2, 13.9
Hz, 1H), 2.46 (s, 1H), 2.35 (dd, J = 3.2, 13.9 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 154.70, 147.30, 146.99, 144.78,
141.10, 131.70, 130.68, 129.64, 129.59, 128.91, 128.38, 128.03,
127.61, 127.51, 127.02, 123.24, 118.70, 116.89, 73.57, 60.75,
48.01; HRMS (MALDI, TOF): m/z calcd for C27H2135ClN2O3
[M + H − H2O − H2]+ 437.1051, found: 437.1043.
3-(Diphenylamino)-1,3-diphenylpropan-1-one (4a). yellow
solid; mp 139.5−140.6 °C; IR (KBr, cm−1) ν 3061, 3030, 1685,
1
1587, 1496, 1446, 1355, 1272, 1211, 989, 751, 696; H NMR
(400 MHz, CDCl3) δ 7.78−7.72 (m, 2H), 7.53−7.47 (m, 1H),
7.39−7.29 (m, 4H), 7.28−7.19 (m, 3H), 7.19−7.13 (m, 4H),
6.96−6.87 (m, 6H), 6.19 (t, J = 6.8 Hz, 1H), 3.80−3.72 (m,
1H), 3.59−3.50 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
197.83, 146.74, 141.83, 136.87, 133.15, 129.13, 128.51, 128.48,
128.01, 127.22, 127.10, 123.01, 121.90, 58.20, 41.86; HRMS
(EI, TOF): m/z calcd for C27H23NO [M]+ 377.1780, found:
377.1778.
4-Ethyl-1,2-diphenyl-1,2,3,4-tetrahydroquinolin-4-ol (3h).
Reaction time: 5 h; 59.5 mg, 60% yield; brown oil; IR (KBr,
cm−1) ν 3429, 3031, 2967, 2879, 1728, 1593, 1573, 1487, 1452,
1,2,3-Triphenylindolin-3-ol (6a). Reaction time: 1 h; 95.9
mg, 88% yield; white solid; mp 66.7−68.1 °C; IR (KBr, cm−1)
ν 3542, 3058, 3019, 2860, 1587, 1500, 1474, 1361, 1302, 1268,
1
1367, 1302, 1214, 1125, 1068, 1008, 961, 876, 752, 699; H
NMR (400 MHz, CDCl3) δ 7.44−7.40 (m, 1H), 7.30−7.26 (m,
2H), 7.21−7.16 (m, 4H), 7.15−7.10 (m, 1H), 7.05−6.98 (m,
4H), 6.81−6.76 (m, 1H), 6.51−6.47 (m, 1H), 4.88 (dd, J = 3.8,
1
1169, 1030, 917, 751, 698, 652, 513; H NMR (400 MHz,
CDCl3) δ 7.44−7.39 (m, 2H), 7.37−7.29 (m, 3H), 7.27−7.20
5823
dx.doi.org/10.1021/jo5003399 | J. Org. Chem. 2014, 79, 5820−5826

The Journal of Organic Chemistry
Note
(m, 6H), 7.19−7.10 (m, 5H), 7.07 (d, J = 7.4 Hz, 1H), 6.97 (t,
J = 7.2 Hz, 1H), 6.85 (t, J = 7.3 Hz, 1H), 5.30 (s, 1H), 1.99 (s,
1H); 13C NMR (100 MHz, CDCl3)δ 148.82, 144.33, 142.55,
134.30, 133.97, 129.66, 129.03, 128.42, 128.39, 128.17, 127.98,
127.30, 126.50, 125.64, 122.94, 121.52, 120.26, 108.85, 82.05,
80.05; HRMS (MALDI, TOF): m/z calcd for C26H21NO [M +
H − H2O]+ 346.1590, found: 346.1582.
1-(4-Methoxyphenyl)-2,3-diphenylindolin-3-ol (6b). Reac-
tion time: 2 h; 85.9 mg, 72% yield; light-yellow solid; mp
146.6−149.3 °C; IR (KBr, cm−1) ν 3485, 2835, 1599, 1510,
1462, 1354, 1240, 1028, 830, 750, 696, 592, 572, 522; 1H NMR
(400 MHz, CDCl3) δ 7.44−7.40 (m, 2H), 7.38−7.31 (m, 3H),
7.25−7.17 (m, 4H), 7.15−7.10 (m, 4H), 7.05 (d, J = 7.4 Hz,
1H), 6.89 (m, J = 8.1 Hz, 1H), 6.85−6.78 (m, 3H), 5.22 (s,
1H), 3.73 (s, 3H), 2.05 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 156.12, 150.63, 144.00, 135.95, 134.09, 133.32, 129.73,
128.68, 128.19, 128.11, 127.86, 127.24, 126.80, 125.50, 124.65,
119.78, 114.44, 108.79, 82.06, 81.03, 55.34; HRMS (MALDI,
TOF): m/z calcd for C27H23NO2 [M + H − H2O]+ 376.1696,
found: 376.1699.
δ 7.42−7.32 (m, 3H), 7.22−7.07 (m, 4H), 6.83−6.77 (m, 1H),
6.72 (d, J = 8.0 Hz, 1H), 3.80 (q, J = 6.5 Hz, 1H), 1.85 (s, 1H),
1.64 (s, 3H), 1.27 (d, J = 6.5 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 149.27, 142.61, 134.01, 129.51, 129.30, 124.36,
124.28, 123.15, 119.19, 108.59, 68.64, 23.96, 11.55; HRMS
(MALDI, TOF): m/z calcd for C16H17NO [M + Na]+
262.1202, found: 262.1191.
1,2,3-Triphenyl-2,3-dihydro-1H-benzo[f]indol-3-ol (6g).
Reaction time: 15 h; 93.1 mg, 75% yield; brown solid; mp
78.8−80.1 °C; IR (KBr, cm−1) ν 3456, 3048, 1631, 1497, 1447,
1381, 1350, 1235, 1096, 1030, 917, 857, 751, 711, 692, 533; 1H
NMR (400 MHz, CDCl3) δ 7.69−7.60 (m, 2H), 7.54 (s, 1H),
7.48−7.44 (m, 3H), 7.41−7.38 (m, 1H), 7.37−7.34 (m, 2H),
7.33−7.30 (m, 2H), 7.30−7.28 (m, 2H), 7.28−7.24 (m, 5H),
7.19−7.15 (m, 2H), 7.04−6.97 (m, 1H), 5.34 (s, 1H), 2.05 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 146.12, 144.48, 142.37,
137.35, 135.34, 134.75, 129.37, 129.15, 128.59, 128.33, 128.27,
128.14, 127.47, 126.65, 126.47, 126.19, 125.02, 122.94, 122.91,
120.88, 102.80, 81.56, 79.87; HRMS (EI, TOF): m/z calcd for
C30H23NO [M]+ 413.1780, found: 413.1773.
1-Phenyl-2,3-di-p-tolylindolin-3-ol (6c). Reaction time: 2 h;
108.1 mg, 92% yield; light-yellow solid; mp 172.6−174.6 °C; IR
(KBr, cm−1) ν 3552, 3028, 2850, 1589, 1473, 1358, 1329, 1274,
4-Methoxy-1,2,3-triphenylindolin-3-ol (6h). Reaction time:
15 h; 96.8 mg, 82% yield; white solid; mp 135.2−136.8 °C; IR
(KBr, cm−1) ν 3536, 3062, 3035, 2946, 2834, 1593, 1500, 1485,
1
1
1207, 1071, 1045, 920, 837, 783, 752, 696, 657, 582; H NMR
1466, 1358, 1261, 1110, 1030, 926, 771, 702, 621; H NMR
(400 MHz, CDCl3) δ 7.32−7.27 (m, 2H), 7.24−7.19 (m, 3H),
7.18−7.12 (m, 5H), 7.08−7.00 (m, 5H), 6.96 (t, J = 7.2 Hz,
1H), 6.83 (t, J = 7.3 Hz, 1H), 5.27 (s, 1H), 2.37 (s, 3H), 2.28
(s, 3H), 1.97 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.81,
142.64, 141.50, 137.81, 136.83, 134.12, 131.13, 129.51, 129.16,
128.97, 128.63, 128.28, 126.45, 125.63, 122.82, 121.56, 120.13,
108.70, 81.81, 79.80, 21.19, 21.08; HRMS (MALDI, TOF): m/
z calcd for C28H25NO [M + H − H2O]+ 374.1903, found:
374.1890.
3-(3-Bromophenyl)-2-(2-methoxyphenyl)-1-phenylindolin-
3-ol (6d). Reaction time: 2 h; 100.6 mg, 71% yield; light-yellow
solid; mp 168.7−170.3 °C; IR (KBr, cm−1) ν 3536, 3422, 3055,
2954, 1589, 1491, 1462, 1352, 1275, 1244, 1206, 1177, 1111,
1090, 1038, 947, 923, 800, 767, 700, 615; 1H NMR (400 MHz,
CDCl3) δ 7.70 (s, 1H), 7.41−7.37 (m, 1H), 7.31−7.25 (m,
4H), 7.24−7.18 (m, 3H), 7.17−7.08 (m, 4H), 6.96−6.91 (m,
1H), 6.89−6.84 (m, 3H), 5.74 (s, 1H), 3.57 (s, 3H), 2.16 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 157.73, 147.92, 142.62,
133.94, 130.01, 129.71, 129.37, 129.34, 129.22, 129.04, 128.45,
125.63, 124.94, 123.02, 122.35, 122.10, 120.88, 120.40, 119.88,
110.77, 109.33, 81.86, 73.53, 55.15; HRMS (MALDI, TOF):
m/z calcd for C27H2279BrNO2 [M + H − H2O]+ 454.0801,
found: 454.0796.
3-(4-Chlorophenyl)-2-methyl-1-phenylindolin-3-ol (6e).
Reaction time: 2 h; 45.9 mg, 46% yield; light-yellow solid;
mp 125.7−127.4 °C; IR (KBr, cm−1) ν 3056, 2920, 1594, 1556,
1492, 1458, 1371, 1246, 1212, 1087, 1012, 835, 770, 698, 517,
487; 1H NMR (400 MHz, CDCl3) δ 7.58−7.53 (m, 2H), 7.44−
7.39 (m, 2H), 7.38−7.33 (m, 2H), 7.26−7.13 (m, 4H), 7.02−
6.98 (m, 1H), 6.82−6.76 (m, 2H), 4.01 (q, J = 6.5 Hz, 1H),
2.18 (s, 1H), 1.22 (d, J = 6.5 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 150.36, 142.40, 141.91, 133.58, 133.21, 129.96,
129.40, 128.36, 128.06, 124.87, 124.85, 124.79, 119.68, 108.80,
81.40, 71.82, 10.28; HRMS (MALDI, TOF): m/z calcd for
C21H1835ClNO [M]+ 335.1071, found: 335.1063.
(400 MHz, CDCl3) δ 7.42−7.36 (m, 2H), 7.35−7.29 (m, 2H),
7.29−7.24 (m, 4H), 7.23−7.15 (m, 5H), 7.15−7.09 (m, 2H),
6.96−6.83 (m, 2H), 6.44−6.37 (m, 1H), 5.10 (s, 1H), 3.60 (s,
3H), 2.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 157.22,
149.77, 146.54, 142.90, 135.78, 130.99, 128.96, 128.31, 128.15,
128.05, 127.84, 126.90, 125.39, 122.48, 120.47, 103.19, 102.90,
82.02, 80.75, 55.33; HRMS (EI, TOF): m/z calcd for
+
C27H23NO2 [M + Na] 416.1621, found: 416.1632.
1-(4-Bromophenyl)-3-((4-chlorophenyl)amino)-3-(p-tolyl)-
propan-1-one (2e). Reaction time: 20 h; 1.2 g, 70% yield; light-
yellow solid; mp 136.5−137.4 °C; IR (KBr, cm−1) ν 3390,
1670, 1629, 1603, 1584, 1506, 1487, 1397, 1352, 1311, 1280,
1213, 1075,992, 812, 734, 505; 1H NMR (400 MHz, CDCl3) δ
7.73 (d, J = 8.3 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H), 7.26 (d, J =
7.7 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 7.02 (d, J = 8.5 Hz, 2H),
6.47 (d, J = 8.5 Hz, 2H), 4.90 (t, J = 6.3 Hz, 1H), 4.66 (s, 1H),
3.45−3.34 (m, 2H), 2.30 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 197.19, 145.43, 139.14, 137.26, 135.34, 132.00,
129.64, 129.59, 128.92, 128.72, 126.15, 122.49, 114.97, 54.56,
46.09, 21.06; HRMS (MALDI, TOF): m/z calcd for
C22H1981Br35ClNO [M]+ 429.0312, found: 429.0312.
3-(3-Bromophenyl)-3-((3,4-dichlorophenyl)amino)-1-(3-
methoxyphenyl) propan-1-one (2f). Reaction time: 20 h; 1.3
g, 68% yield; light-yellow solid; mp 110.6−111.6 °C; IR (KBr,
cm−1) ν 3387, 1669, 1635, 1604, 1506, 1487, 1400, 1351, 1313,
1
1283, 1214, 1173, 1075, 991, 814, 738, 507; H NMR (400
MHz, CDCl3) δ 7.97 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.70−
7.65 (m, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H),
7.09 (d, J = 8.7 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.91 (s, 1H),
6.81−6.75 (m, 1H), 6.65−6.60 (m, 1H), 6.41−6.35 (m, 1H),
4.88 (t, J = 6.2 Hz, 1H), 4.82 (s, 1H), 3.77 (s, 3H), 3.40 (d, J =
6.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 196.57, 160.11,
146.34, 143.42, 138.16, 136.39, 132.61, 131.23, 130.49, 130.28,
130.12, 126.62, 123.08, 120.52, 118.40, 115.10, 113.37, 112.74,
112.15, 55.22, 54.55, 45.98; HRMS (ESI, TOF): m/z calcd for
C22H1881Br35Cl2NO2 [M + H]+ 479.9950, found: 479.9944.
5-Methyl-4-(phenylamino)hexan-2-one (2i). Reaction
time: 8 h; 319.4 mg, 78%; brown oil; IR (KBr, cm−1) ν
3386, 3053, 2961, 2873, 1711, 1601, 1508, 1468, 1430, 1364,
2,3-Dimethyl-1-phenylindolin-3-ol (6f). Reaction time: 2 h;
65.7 mg, 46% yield; brown oil; IR (KBr, cm−1) ν 3557, 3428,
3047, 2977, 2922, 2859, 1595, 1500, 1477, 1458, 1363, 1285,
1218, 1097, 1015, 919, 724, 698; 1H NMR (400 MHz, CDCl3)
5824
dx.doi.org/10.1021/jo5003399 | J. Org. Chem. 2014, 79, 5820−5826

The Journal of Organic Chemistry
Note
Zhu, Y.; Gao, B.; Liu, X.; Feng, X. Angew. Chem., Int. Ed. 2010, 49,
3799−3802. (e) Shi, F.; Xing, G.-J.; Zhu, R.-Y.; Tan, W.; Tu, S. Org.
Lett. 2013, 15, 128.
1316, 1264, 1180, 1091, 1068, 1031, 991, 869, 750, 691, 502;
1H NMR (400 MHz, CDCl3) δ 7.17−7.11 (m, 2H), 6.69−6.64
(m, 1H), 6.61−6.57 (m, 2H), 3.76−3.71 (m, 1H), 3.66 (s, 1H),
2.65−2.51 (m, 2H), 2.13 (s, 3H), 1.99−1.90 (m, 1H), 0.96 (d, J
= 6.8 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 208.23, 147.51, 129.36, 117.33, 113.33, 54.96, 45.31,
31.46, 30.55, 18.74, 18.61; HRMS (MALDI, TOF): m/z calcd
for C13H19NO [M + H]+ 206.1539, found: 206.1533.
(5) For a recent review, see: (a) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.;
Zhou, Y.-G. Chem. Rev. 2012, 112, 2557. For selected examples, see:
(b) Guo, Q. S.; Du, D. M.; Xu, J. Angew. Chem., Int. Ed. 2008, 47, 759.
(c) Wang, X. B.; Zhou, Y. G. J. Org. Chem. 2008, 73, 5640. (d) Ding,
Z. Y.; Wang, T. L.; He, Y. M.; Chen, F.; Zhou, H. F.; Fan, Q. H.; Guo,
Q. X.; Chan, A. S. C. Adv. Synth. Catal. 2013, 355, 3727−3735.
(e) Liao, H. H.; Hsiao, C. C.; Sugiono, E.; Rueping, M. Chem.
Commun. 2013, 49, 7953−7955.
(6) For selected examples of other indoline synthesis methods, see:
(a) Kang, Y. K.; Kim, D. Y. Adv. Synth. Catal. 2013, 355, 3131−3136.
(b) Rawat, B. V.; Kumar, S.; Sudalai, A. Org. Biomol. Chem. 2013, 11,
3608−3611. (c) Zhang, H. R.; Dong, Z. W.; Yang, Y. J.; Wang, P. L.;
Hui, X. P. Org. Lett. 2013, 15, 4750. (d) Truong, P. M.; Mandler, M.
D.; Zavalij, P. Y.; Doyle, M. P. Org. Lett. 2013, 15, 3278. (e) Sun, M.;
Zhang, T.; Bao, W. J. Org. Chem. 2013, 78, 8155−8160.
1-(3-Bromophenyl)-2-(2-methoxyphenyl)-2-(phenyl-
amino)ethanone (5d). Reaction time: 48 h; 584.9 mg, 82%
yield; yellow solid; mp 114.2−116.4 °C; IR (KBr, cm−1) ν
3396, 3056, 3018, 2939, 2840, 1684, 1601, 1566, 1503, 1465,
1
1431, 1310, 1239, 1092, 1027, 996, 902, 751, 695; H NMR
(400 MHz, CDCl3) δ 8.30 (t, J = 1.8 Hz, 1H), 7.99−7.95 (m,
1H), 7.61−7.57 (m, 1H), 7.24−7.08 (m, 5H), 6.89−6.81 (m,
2H), 6.72−6.63 (m, 3H), 6.43 (s, 1H), 5.41 (s, 1H), 4.04 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 195.90, 156.05, 146.06,
136.62, 136.22, 131.84, 130.11, 129.68, 129.23, 128.19, 127.15,
125.73, 122.68, 121.62, 117.73, 113.41, 111.07, 55.66, 55.15;
HRMS (MALDI, TOF): m/z calcd for C21H1879BrNO2 [M +
H]+ 396.0594, found: 396.0604.
(7) For recent reviews, see (a) Zhou, Y.-G. Acc. Chem. Res. 2007, 40,
1357. (b) Kagan, H. B. Tetrahedron: Asymmetry 2009, 20, 2193−2199.
(c) Liu, D.; Zhao, G.; Xiang, L. Eur. J. Org. Chem. 2010, 3975−3984.
(d) Zhang, D.; Song, H.; Qin, Y. Acc. Chem. Res. 2011, 44, 447−457.
(8) (a) Ori, M.; Toda, N.; Takami, K.; Tago, K.; Kogen, H. Angew.
Chem., Int. Ed. 2003, 42, 2540−2543. (b) Luo, C.; Huang, Y. J. Am.
Chem. Soc. 2013, 135, 8193−8196. (c) Martínez, A.; Webber, M. J.;
ASSOCIATED CONTENT
■
Muller, S.; List, B. Angew. Chem., Int. Ed. 2013, 52, 9486−9490. (d) Ni,
̈
S
* Supporting Information
J.; Wang, H.; Reisman, S. E. Tetrahedron 2013, 69, 5622−5633.
(9) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983,
1211.
1
Copies of H and 13C NMR spectra for 2e, 2f, 2i, 3a−3k, 4a,
5d, 6a−6h; ROESY spectra for 3g and 6a. This material is
available free of charge via the Internet at http://pubs.acs.org.
(10) For recent reviews, see: (a) Bhunia, A.; Yetra, S. R.; Biju, A. T.
Chem. Soc. Rev. 2012, 41, 3140−3152. (b) Bhojgude, S. S.; Biju, A. T.
Angew. Chem., Int. Ed. 2012, 51, 1520−1522. (c) Tadross, P. M.;
Stoltz, B. M. Chem. Rev. 2012, 112, 3550. (d) Dubrovskiy, A. V.;
Markina, N. A.; Larock, R. C. Org. Biomol. Chem. 2013, 11, 191−218.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: helin@shzu.edu.cn (L.H.)
*E-mail: db_tea@shzu.edu.cn (B.D.)
■
(e) Wu, C.; Shi, F. Asian J. Org. Chem. 2013, 2, 116−125. (f) Per
́
ez, D.;
Pena, D.; Guitian, E. Eur. J. Org. Chem. 2013, 27, 5981−6013.
́
̃
Notes
(11) (a) Jin, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46,
3323−3325. (b) Shi, F.; Waldo, J. P.; Chen, Y.; Larock, R. C. Org. Lett.
2008, 10, 2409−2412. (c) Shi, F.; Mancuso, R.; Larock, R. C.
Tetrahedron Lett. 2009, 50, 4067−4070. (d) Wu, C.; Fang, Y.; Larock,
R. C.; Shi, F. Org. Lett. 2010, 12, 2234−2237. (e) Zhao, J.; Wu, C.; Li,
P.; Ai, W.; Chen, H.; Wang, C.; Larock, R. C.; Shi, F. J. Org. Chem.
2011, 76, 6837−6843. (f) Dubrovskiy, A. V.; Larock, R. C. Org. Lett.
2010, 12, 1180. (g) Spiteri, C.; Keeling, S.; Moses, J. E. Org. Lett. 2010,
12, 3368. (h) Lu, C.; Dubrovskiy, A. V.; Larock, R. C. J. Org. Chem.
2012, 77, 2279−2284. (i) Li, P.; Wu, C.; Zhao, J.; Rogness, D. C.; Shi,
F. J. Org. Chem. 2012, 77, 3149−3158. (j) Ikawa, T.; Takagi, A.; Goto,
M.; Aoyama, Y.; Ishikawa, Y.; Itoh, Y.; Fujii, S.; Tokiwa, H.; Akai, S. J.
Org. Chem. 2013, 78, 2965−2983.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (No. 21162022) and the Team
Innovation Project of Shihezi University (No. 2011ZRKXTD-
04, 2012ZRKXJQ06). We thank Dr. Cheng-Zhi Gu for helpful
discussions, we also thank Prof. Wan-Fu Sun of Xinjiang
University for assistance with NMR spectroscopy.
REFERENCES
■
(12) (a) Shou, W.-G.; Yang, Y.-Y.; Wang, Y.-G. J. Org. Chem. 2006,
71, 9241. (b) Xie, C.; Zhang, Y. Org. Lett. 2007, 9, 781. (c) Webster,
(1) For recent reviews, see: (a) Katritzky, A. R.; Rachwal, S.;
Rachwal, B. Tetrahedron 1996, 52, 15031−15070. (b) Sridharan, V.;
Suryavanshi, P. A.; Menendez, J. C. Chem. Rev. 2011, 111, 7157.
(c) Nammalwar, L.; Bunce, R. A. Molecules 2014, 19, 204−232.
(2) For recent reviews, see: (a) Crich, D.; Banerjee, A. Acc. Chem. Res.
2007, 40, 151. (b) Fattorusso, E.; Taglialatela-Scafati, O. Modern
Alkaloids; Wiley-VCH: Weinheim, 2008. (c) Zhang, D.; Song, H.; Qin,
Y. Acc. Chem. Res. 2011, 44, 447−457.
R.; Lautens, R. Org. Lett. 2009, 11, 4688. (d) Criado, A.; Pena, D.;
̃
Cobas, A.; Guitian
́
, E. Chem.Eur. J. 2010, 16, 9736. (e) Ikawa, T.;
Takagi, A.; Kurita, Y.; Saito, K.; Azechi, K.; Egi, M.; Kakiguchi, K.; Kita,
Y.; Akai, S. Angew. Chem., Int. Ed. 2010, 49, 5563. (f) Li, J.; Wang, N.;
Li, C.; Jia, X. Org. Lett. 2012, 14, 4994. (g) Kaicharla, T.; Bhojgude, S.
S.; Biju, A. T. Org. Lett. 2012, 14, 6238. (h) Siyang, H.; Wu, X.; Liu,
H.; Wu, X.; Liu, P. J. Org. Chem. 2014, 79, 1505−1510. (i) Bhojgude,
S. S.; Bhunia, A.; Gonnade, R. G.; Biju, A. T. Org. Lett. 2014, 16, 676−
679. (j) Su, S.; Wang, N.; Li, C.; Song, B.; Jia, X.; Li, J. Asian J. Org.
Chem. 2014, DOI: 10.1002/ajoc.201300247.
(3) For selected examples, see: (a) Fustero, S.; Moscardo,
́ ́
J.; Jimenez,
D.; Perez-Carrion, M. D.; Sanchez-Rosello,
́
́
́
́
M.; del Pozo, C. Chem.
Eur. J. 2008, 14, 9868−9872. (b) Huang, Y. M.; Zheng, C. W.; Zhao,
G. RSC Adv. 2013, 3, 16999−17002. (c) Yang, W.; Du, D. M. Chem.
Commun. 2013, 49, 8842−8844. (d) Mao, H. B.; Lin, A. J.; Tang, Y.;
Shi, Y.; Hu, H. W.; Cheng, Y. X.; Zhu, C. J. Org. Lett. 2013, 15, 4062−
4065.
(13) (a) Zhao, J.; Larock, R. C. J. Org. Chem. 2007, 72, 583−588.
(b) Fang, Y.; Rogness, D. C.; Larock, R. C.; Shi, F. J. Org. Chem. 2012,
77, 6262−6270. (c) Huang, X.; Zhang, T. J. Org. Chem. 2010, 75,
506−509. (d) Rogness, D. C.; Larock, R. C. J. Org. Chem. 2011, 76,
4980−4986. (e) Gilmore, C. D.; Allan, K. M.; Stoltz, B. M. J. Am.
Chem. Soc. 2008, 130, 1558−1559. (f) Okuma, K.; Matsunaga, N.;
Nagahora, N.; Shioji, K.; Yokomori, Y. Chem. Commun. 2011, 47,
5822−5824. (g) Rogness, D. C.; Larock, R. C. Tetrahedron Lett. 2009,
(4) For an excellent review, see: (a) Glushkov, V. A.; Tolstikov, A. G.
Russ. Chem. Rev. 2008, 77, 137. For selected examples, see: (b) Liu,
H.; Dagousset, G.; Masson, G.; Retailleau, P.; Zhu, J. J. Am. Chem. Soc.
2009, 131, 4598−4599. (c) Smith, C. D.; Gavrilyuk, J. I.; Lough, A. J.;
Batey, R. A. J. Org. Chem. 2010, 75, 702−715. (d) Xie, M.; Chen, X.;
5825
dx.doi.org/10.1021/jo5003399 | J. Org. Chem. 2014, 79, 5820−5826

The Journal of Organic Chemistry
Note
50, 4003−4008. (h) Giacometti, R. D.; Ramtohul, Y. K. Synlett 2009,
12, 2010−2016. (i) Rogness, D. C.; Larock, R. C. J. Org. Chem. 2011,
76, 4980−4986. (j) Hong, D.; Chen, Z.; Lin, X.; Wang, Y. Org. Lett.
2010, 12, 4608−4611. (k) McAusland, D.; Seo, S.; Pintori, D. G.;
Finlayson, J.; Greaney, M. F. Org. Lett. 2011, 13, 3667−3669.
(l) Vaidya, S. D.; Argade, N. P. Org. Lett. 2013, 15, 4006−4009.
(m) Bunescu, A.; Piemontesi, C.; Wang, Q.; Zhu, J. Chem. Commun.
2013, 49, 10284−10286. (n) He, L.; Pian, J.-X.; Shi, J.-F.; Du, G.-F.;
Dai, B. Tetrahedron 2014, 70, 2400−2405.
(14) The stereoselectivity was determined by ROESY experiments.
For tetrahydroquinoline, ROESY correlation was observed between
H1 and the proton of hydroxy group. However, for indoline, no
ROESY correlation was observed between H1 and the proton of
hydroxy group.
(15) For similar regioselective reactions of 3-methoxyaryne 1b, see
reference 11j and references cited therein. Zhu and our group also
observed similar regioselectivity of 3-methoxyaryne in the cyclization
reaction with α-amino ketones, which was deduced from HMBC and
HSQC analysis of the products, for details see references 13m and
13n.
(16) (a) Li, G.-Q.; Dai, L.-X.; You, S.-L. Chem. Commun. 2007, 8,
852−854. (b) Kumar, M.-P.; Liu, R.-S. J. Org. Chem. 2006, 71, 4951−
4955. (c) Furstner, A.; Alcarazo, M.; Ces
Commun. 2006, 20, 2176−2178.
́
ar, V.; Lehmann, C.-W. Chem.
̈
(17) (a) Li, H.; Zeng, H.-Y.; Shao, H.-W. Tetrahedron Lett. 2009, 50,
6858−6860. (b) Zhang, M.; Xiong, B.; Yang, W.; Chen, L.; Wu, F.;
Wang, Q.; Ding, Y.-Q. Synth. Commun. 2012, 42, 2831−2843. (c) Xia,
M.; Lu, Y.-D. J. Fluorine. Chem. 2006, 127, 1119−1124. (d) Yi, L.; Zou,
J.-H.; Lei, H.-S.; He, Q.-L. Synth. Commun. 1991, 21, 2109−2117.
(e) Abid, M.; Azam, A. Eur. J. Med. Chem. 2005, 40, 935−942.
5826
dx.doi.org/10.1021/jo5003399 | J. Org. Chem. 2014, 79, 5820−5826