Catalytic Intramolecular Wittig Reaction Based on a Phosphine/Phosphine Oxide Catalytic Cycle for the Synthesis of Heterocycles

Article abstract of DOI:10.1002/ejoc.201601628

The catalytic intramolecular Wittig reactions of carbonyl-containing bromides are reported. The R₃PO byproducts participate in the catalytic cycle; therefore, the Wittig reaction can be accomplished with only a catalytic amount of organophosphorus reagent. The reaction has also been applied to the efficient and selective synthesis of isoquinolin-1(2H)-ones, indoles, 2,3-dihydro-1H-2-benzazepin-1-ones, benzofurans, and 1,2-dihydroquinolines with a catalytic amount of phosphine oxide (0.1 equiv.) and a tetramethyldisiloxane/titanium isopropoxide [TMDS/Ti(OiPr)₄] reductant system (yields: 35–88 %).

Full text of DOI:10.1002/ejoc.201601628

A Journal of
Accepted Article
Title: Catalytic Intramolecular Wittig Reaction Based on Phosphine/
Phosphine Oxide Catalytic Cycle for Synthesis of Heterocycles
Authors: Long Wang, Mei Sun, and Ming-Wu Ding
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601628
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601628
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10.1002/ejoc.201601628
European Journal of Organic Chemistry
FULL PAPER
Catalytic Intramolecular Wittig Reaction Based on
Phosphine/Phosphine Oxide Catalytic Cycle for Synthesis of
Heterocycles
Long Wang,[a,b] Mei Sun,[a] and Ming-Wu Ding*[a]
Abstract: The catalytic intramolecular Wittig reaction starting from
the carbonyl-containing bromides is reported. The byproduct R3PO
participate in the catalytic cycle so that the Wittig reaction can
accomplish only in catalytic amount of organophosphorus reagent.
Meanwhile, the reaction also has been demonstrated in the efficient
and selective synthesis of isoquinolin-1(2H)-ones, indoles, 2,3-
acceptors and acyl chlorides have also been described.[12]
However, the catalytic intramolecular Wittig reaction starting
from the carbonyl-containing bromides has not been reported
previously. We have disclosed a catalytic aza-Wittig reaction by
utilizing inexpensive tetramethyldisiloxane (TMDS, Me2HSi-O-
SiMe2H) as reductant and its application in preparation of 4(3H)-
quinazolinones and natural product vasicinone.[7] Herein we wish
to report the catalytic intramolecular Wittig reaction starting from
the carbonyl-containing bromides, based on phosphine/
phosphine oxide catalytic cycle with the TMDS/Ti(Oi-Pr)4 as
dihydro-1H-2-benzazepin-1-ones,
benzofurans,
and
1,2-
dihydroquinolines by using catalytic amount of phosphine oxide
(10%) and TMDS/Ti(Oi-Pr)4 reductant system (35-88% yields).
reductant system.
a) Classical intramolecular Wittig reaction
Introduction
waste
P+R3 Br-
Br
R3P
Base
The Wittig reaction of phosphorus ylide with carbonyl compound
provides a powerful method to construct C=C double bond via
inter- or intramolecular fashion under mild reaction condition.[1]
Intramolecular Wittig reaction has become a useful tool in
construction of various five, six, seven and large membered N-
heterocycles through intramolecular cyclization with a wide
variety of carbonyl groups, such as aldehyde, ketone, ester,
amide and imide carbonyl groups (Scheme 1a).[2] A series of
natural products have also been prepared by using the
intramolecular Wittig reaction as the key step.[3] Nevertheless,
the intramolecular Wittig reaction produces triphenylphosphine
oxide as a waste, which is a stoichiometric quantities of high
weight molecular and results in low atom efficiency of the
O
O
+
R3PO
X
R1
X
X
R1
R1
X = C, O, NR2, S
R1 = H, alkyl, aryl
b) This work: catalytic intramolecular Wittig reaction
R3P (Cat.)
R3PO
Br
O
Base
X
R1
X
R1
Scheme 1. Synthesis of cycloalkenes by classical and phosphine-catalyzed
intramolecular Wittig reaction.
reaction. Therefore, the development of
a
catalytic
intramolecular Wittig reaction with recycling of the byproduct
phosphine oxide is highly desirable (Scheme 1b).
Results and Discussion
Recently, the catalytic Wittig,[4-7] Appel,[8] Staudinger
reaction,[9] reduction of silyl peroxides,[10] cyclization reactions
between the Huisgen zwitterion and carbonyl substrates[11]
based on phosphine/phosphine oxide catalytic cycle have
attracted significant attention. In 2009, the group of O’Brien
disclosed the first catalytic Wittig reaction by employing Ph2SiH2
as reductant.[4] Later, some other catalytic Wittig reactions were
achieved with PhSiH3 or (MeO)3SiH used as reductant instead.
The catalytic umpolung addition/intramolecular Wittig reaction
and phosphine catalyzed reaction between some Michael
The imides 2, obtained by reaction of amide 1 with 2-
methylbenzoyl chloride in the presence of NEt3, was converted
to the required bromides 3 via treatment with NBS in CCl4.[2h,13]
Compounds 3 contain an imide carbonyl group, which may
participate in intramolecular Wittig reaction to produce
isoquinolin-1(2H)-ones 4.
O
Cl
R3
O
O
O
CH3
N
R1
R3
R1
NHR2
R2
NEt3
CH3
[a]
Long Wang, Mei Sun, Prof. Ming-Wu Ding
Key Laboratory of Pesticide & Chemical Biology of Ministry of
Education,
1
2
O
O
Central China Normal University,
Wuhan, Hubei 430079, China
E-mail: mwding@mail.ccnu.edu.cn
http://chem.ccnu.edu.cn/info/1057/2693.htm
Long Wang
R1
NBS
CCl4
N
R2
R3
Br
[b]
3
College of Materials and Chemical Engineering,
China Three Gorges University
Yichang, Hubei 443002, China
Scheme 2. Synthesis of the bromides 3.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201601628
European Journal of Organic Chemistry
FULL PAPER
Initially, we selected the bromide 3a as model substrate to
study the catalytic intramolecular Wittig reaction. When a
mixture of the bromide 3a, catalytic amount of the commercially
available cyclic phosphine oxide A (20% equiv), NEt3, TMDS
and Ti(Oi-Pr)4 (100% equiv) was refluxed in toluene, we were
pleased to find that the isoquinolin-1(2H)-one 4a was obtained
(Table 1, entry 1) in 85% yield. The amount of the Ti(Oi-Pr)4 had
a remarkable effect on this reaction. In case that the amount of
Ti(Oi-Pr)4 was reduced from 100% to 20% equiv, satisfactory
yields (84-87%, Table 1, entry 1-3) were also reached as the
reaction time was increased from 2 h to 9 h. However, as the
amount of Ti(Oi-Pr)4 was deminished further to 10% and 5%, the
yields of the product were decreased to 71% and 25% (Table 1,
entry 4, 5). The best result was obtained (88%, Table 1, entry 6)
when the amount of catalyst A was decreased to 10% equiv in
the presence of Ti(Oi-Pr)4 (20% equiv). The change of the
solvent from toluene to dioxane or CH3CN gave the product in
relatively lower yields (32-77%, Table 1, entry 8, 9). While the
base was replaced by K2CO3 or Na2CO3, moderate yields were
also resulted (47-53%, Table 1, entry 10, 11). In the absence of
catalyst A, no isoquinolin-1(2H)-one 4a was produced (Table 1,
entry 12). It has been reported that a phosphine oxide can be
reduced to a phosphine by using TMDS with a metallic additive
Cu(OTf)2.[14] However, as Cu(OTf)2 was used to replace Ti(Oi-
Pr)4 as catalyst, a dark solution was resulted and no product 4a
was obtained (Table 1, entry 13) probably due to the side
reaction of the bromide 3a with Cu(OTf)2 catalyst.
(Table 2). In the absence of Ti(Oi-Pr)4, no isoquinolin-1(2H)-one
4a was produced when TMDS or Et3SiH was used as reductant
(Table 2, entry 1, 2). However, while Ph2SiH2 was uitilized, good
yield of the product was obtained as the cyclic phosphine oxide
A was used (86%, Table 2, entry 3). But no product was
produced as Ph2SiH2/Ph3PO was used (Table 2, entry 4). This
implies that Ph2SiH2 is only a good reducing agent for cyclic
phosphine oxide A.[15] In the presence of catalyst Ti(Oi-Pr)4,
isoquinolin-1(2H)-one 4a was obtained in moderate yields (36-
57%, Table 2, entry 5, 6) as Ph3PO, Ph2MePO and TMDS were
used. However, good yield was also reached as cyclic
phosphine oxide B was utilized (87%, Table 2, entry 7).
Table 2. Optimization of the reaction conditions.
O
O
O
O
P
R2
(Cat.)
R1
R3
N
Ph
N
Silane, NEt3
Toluene, Reflux
Ph
Br
4a
3a
O
Reaction Yield[a]
Time (h) (%)
R1
R3
P
R2
Entry Silane
Ti(Oi-Pr)4
1
TMDS
0
24
0
P
Ph
O
(A)
(10%)
Table 1. Optimization of the reaction conditions.
2
3
4
5
6
Et3SiH
0
(A) (10%)
24
24
24
24
0
86
0
Ph2SiH2
Ph2SiH2
TMDS
0
(A) (10%)
(Cat.)
O
O
P
Ph
(A)
O
O
0
Ph3PO (10%)
Ph3PO (10%)
N
Ph
N
20%
20%
36
TMDS/(i-PrO)4Ti
Solvent, Reflux
base
Ph
TMDS
Ph2MePO
(10%)
Br
24
57
87
4a
3a
7
TMDS
20%
P
24
Ph
O
Yield[a]
(%)
(B)
Entry Ti(Oi-Pr)4
Base
t (h)
Solvent
(10%)
P
Ph
(A)
O
[a] isolated yields.
1
2
3
4
5
6
7
8
100%
50%
20%
10%
5%
20%
10%
20%
20%
20%
20%
20%
Cu(OTf)2
(10%)
20%
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
K2CO3
Na2CO3
NEt3
2
2
9
toluene 85
toluene 84
toluene 87
toluene 71
toluene 25
toluene 88
toluene 68
dioxane 77
CH3CN 32
toluene 47
toluene 53
Having established the optimal conditions, we explored the
scope of the catalytic intramolecular Wittig reaction and the
results were summarized in Scheme 3. All of the the reactions
were carried out smoothly to give the corresponding isoquinolin-
1(2H)-one derivatives 4 in toluene at reflux temperature, and
good yields were obtained regardless of the electronic properties
and steric hindrance of the substituents on bromides 3 (Scheme
3). Many isoquinolin-1(2H)-ones are found in a wide variety of
biologically active substances, which exhibit antitumor,[16]
anticancer,[17] histamine-3 receptor antagonistical,[18] poly(ADP-
ribose)polymerase[19] and c-Jun N-terminal protein kinase
inhibitive activities.[20] Isoquinolinone skeleton is also an
important segment in many significant natural products, such as
oxyisoterihanine[21] and gusanlung D.[22] The above catalytic
intramolecular Wittig reaction provides an efficient synthesis of
20%
20%
20%
20%
10%
10%
10%
10%
10%
10%
0
24
24
24
24
24
24
24
24
24
9
10
11
12
13
toluene
0
10%
NEt3
12
toluene
0
[a] Isolated yields.
The influence of both the silane and phosphine oxide on the
catalytic intramolecular Wittig reaction was also investigated
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10.1002/ejoc.201601628
European Journal of Organic Chemistry
FULL PAPER
isoquinolin-1(2H)-ones by merely using catalytic amount of
organophosphorus reagent, campared with the traditional
intramolecular Wittig reaction.[2h,i]
Cl
Br
N
N
N
O
O
O
6a, 86%
6b, 83%
6c, 74%
Br
Cl
Cl
(10%)
P
Ph
(A)
O
O
O
Cl
O
Cl
F
R2
R1
N
R2
R1
R3
N
O
N
R3
(i-PrO)4Ti (20%)
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
N
O
N
O
Br
4
3
6d, 75%
6f, 79%
Cl 6e, 67%
F
Cl
Cl
Cl
Cl
O
O
F
O
CH3
N
N
N
N
O
N
O
N
O
CH3
4c, 78%
6h, 82%
Cl
6i, 80%
6g, 78%
4a, 88%
4b, 80%
F
Cl
O
N
O
Cl
O
N
CH3
CH3
N
N
N
N
O
O
O
H3C
4d, 84%
4e, 83%
4f, 71%
6k, 77%
6l, 85%
6j, 71%
O
N
O
N
O
N
Scheme 4. Preparation of N-acyl indoles 6 by catalytic intramolecular Wittig
reaction.
On the basis of the above experimental results, the catalytic
intramolecular Wittig reaction involving ketone carbonyl group
was also explored. The required bromides 9 were obtained
directly from the reaction of secondary amine 7 with 2-
(bromomethyl)benzoyl chloride 8. The catalytic intramolecular
Wittig reactions of 7 took place successfully as the cyclic
phosphine oxide A (10% equiv), NEt3, TMDS and Ti(Oi-Pr)4
(20% equiv) were utilized. The 2,3-dihydro-1H-2-benzazepin-1-
ones 10 were obtained in 70-82% yields and the results were
Cl
Cl
4g, 72%
4h, 82%
4i, 87%
O
N
O
N
O
N
4j, 83%
4k, 73%
4l, 75%
O
summarized in scheme 5.
O
O
Br
N
N
Cl
O
NEt3
Cl
NHR2
+
R1
0 °C
CH2Br
4m, 79%
4n, 76%
7
8
Scheme 3. Preparation of isoquinolin-1(2H)-ones 4 by catalytic intramolecular
Wittig reaction.
(10%)
P
O
The above catalytic intramolecular Wittig reaction involving
imide carbonyl group was further utilized for preparation of N-
acyl indoles 6 starting from the bromides 5.[23] As indicated in
Scheme 4, the reaction took place smoothly and various N-acyl
indoles 6 can be obtained in 67-86% yields as R2 is aryl
(compounds 6b-6i), alkyl (compounds 6j, 6k) or cyclic
(compounds 6a, 6l) groups.
O
R2
R1
Ph
O
O
(A)
N
N
R2 R1
(i-PrO)4Ti (20%)
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
Br
9
10
O
R2
O
(Cat. A) (10%)
(i-PrO)4Ti (20%)
R2
R2
N
R2
N
R1
R1
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
O
Br
6
5
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10.1002/ejoc.201601628
European Journal of Organic Chemistry
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A was used, only the 1,2-dihydroquinoline 14a was obtained in
86% yield via intramolecular Wittig cyclization through the
ketone carbonyl group. However, utilizing triphenylphosphine
oxide as the organophosphorus reagent resulted in solely
formation of indole 15a (64%) through the amide carbonyl group
cyclization. A mixture of 14a and 15a was reached in case that
CH3
Cl
O
O
O
N
N
N
diphenylmethyl phosphine oxide was applied.
Ph
R3P=O (10%)
Ph
O
Ph
O
O
O
10a, 78%
10b, 74%
10c, 79%
(i-PrO)4Ti (20%)
N
+
N
N
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
Ph
Ph
Br
Ph
O
O
N
13a
14a
15a
N
CH3
R3P=O = Cat. A
Ph3P=O
Ph2MeP=O
86%
0%
57%
0%
64%
14%
Cl
Scheme 7. Reaction selectivity of the catalytic intramolecular Wittig reaction.
10d, 70%
10e, 82%
The above reaction selectivity of the catalytic intramolecular
Wittig reaction was further utilized in preparing other
dihydroquinolines 14 or indoles 15.[25] As the catalyst A was
used, the 1,2-dihydroquinolines 14 was obtained in 73-87%
yields (Scheme 8). The indoles 15 were reached in moderate
yields (35-68%) when triphenylphosphine oxide was utilized
Scheme 5. Preparation of 2,3-dihydro-1H-2-benzazepin-1-ones 10 by catalytic
intramolecular Wittig reaction.
The catalytic intramolecular Wittig reaction involving ester
carbonyl group was also investigated. As the bromides 11 were
treated with the cyclic phosphine oxide A (10% equiv), NEt3,
TMDS and Ti(Oi-Pr)4 (20% equiv), benzofurans 12 were
obtained in 73-87% yields (Scheme 6).[24] The investigated
functional groups (Cl, Br, OCH3, CH=CH, CN, OAc, NO2) are all
tolerant for the one-pot method due to the mild reaction
condition.
(Scheme 9).
R2
O
(Cat. A) (10%)
R2
O
O
(i-PrO)4Ti (20%)
N
N
R1
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
R1
Br
13
14
O
R
(Cat. A) (10%)
(i-PrO)4Ti (20%)
O
O
R
Cl
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
OCH3
O
Ph
O
Br
O
N
12
11
N
N
Ph
O
O
O
Ph
Ph
Ph
OCH3
14a, 86%
H3CO
Cl
14b, 73%
14c, 78%
Cl
12a, 78%
12c, 82%
12b, 87%
H3CO
O
O
O
O
O
CN
N
N
N
12e, 81%
12d, 73%
Ph
O
14d, 87%
Cl
14f, 85%
Cl
14e, 80%
O
CH3
O
NO2
O
Cl
Ph
O
N
O
N
12f, 76%
12g, 78%
Scheme 6. Preparation of benzofurans 12 by catalytic intramolecular Wittig
reaction.
Br
14g, 82%
Br
14h, 75%
It’s speculated that if the bromides involving two different
carbonyl groups were used, the reaction selectivity will resulted
which may be related to the organophosphorus reagents. Indeed,
when the bromide 13a was treated with different phosphine
oxide under the above catalytic Wittig reaction condition,
dissimilar products were produced (Scheme 7). As the catalyst
Scheme 8. Preparation of 1,2-dihydroquinolines 14 by selective catalytic
intramolecular Wittig reaction.
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10.1002/ejoc.201601628
European Journal of Organic Chemistry
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R1
N
Experimental Section
Ph3P=O (10%)
R2
O
O
O
(i-PrO)4Ti (20%)
N
All reactions were performed in round-bottom flasks under an
atmosphere of air. Unless otherwise noted, materials were purchased
from commercial suppliers and used without further purification. Toluene
was distilled from Na, and stored over 4A molecular sieves. Column
chromatography purifications were performed under “flash” conditions
using 400-630 mesh silica gel. Analytical thin-layer chromatography
(TLC) was carried out on silica gel 60 F254 plates, which were visualized
by exposure to ultraviolet light. Melting points were uncorrected. HRMS
were measured on Angilent 6224 TOF LC/MS spectrometer. 1H NMR
were recorded in CDCl3 on a Varian Mercury 400 or 600 spectrometer
and resonances relative to TMS. Data are reported as follows: chemical
shift, multiplicity (s = single, d = doublet, t = triplet, q = quartet, m =
multiplet), coupling constants (Hz) and integration. 13C NMR spectra
were recorded on Varian Mercury 400/600 (100/150 MHz) with complete
proton decoupling spectrophotometers (CDCl3: 77.0 ppm).
R1
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
R2
Br
15
13
O
O
N
O
N
Ph
Ph
Ph
N
Ph
Cl
H3CO
15a, 64%
15b, 51%
Cl
15c, 35%
O
O
Cl
N
N
General procedure for preparation of isoquinolin-1(2H)-ones 4: To a
solution of phosphine oxide (A) (0.052 g, 0.2 mmol) in anhydrous toluene
(10 mL) was added Ti(O-i-Pr)4 (0.106 g, 0.4 mmol) and TMDS (0.54 g, 4
mmol). After the reaction mixture was stirred at 110 °C for 30 min,
bromide 3[2h] (2 mmol) and NEt3 (0.24 g, 2.4 mmol) were added
sequentially. The reaction mixture was then stirred at 110 °C and
monitored by TLC. After the reaction was completed (16-24 h), the
solvent was removed under reduced pressure and the residue was
purified by flash chromatography on silica gel (ether/petroleum ether =
1:4, V/V) to give isoquinolin-1(2H)-ones 4.
OCH3
Cl
15d, 60%
15e, 43%
O
O
O
N
Br
Br
Ph
N
N
Ph
Cl
OCH3
15g, 62%
15f, 57%
15h, 68%
3-phenyl-2-propylisoquinolin-1(2H)-one (4a)
Light yellow oil (Lit26 pale yellow oil); 1H NMR (CDCl3, 400 MHz) δ (ppm)
8.45 (d, J = 8.4 Hz, 1H, Ar-H), 7.63 (t, J = 7.2 Hz, 1H, Ar-H), 7.57-7.34 (m,
7H, Ar-H), 6.40 (s, 1H, =CH), 3.91 (t, J = 7.6 Hz, 2H, NCH2), 1.64-1.55
(m, 2H, CH2), 0.73 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ
(ppm) 162.7, 143.6, 136.2, 132.1, 128.9, 128.7, 128.3, 127.8, 126.4,
125.6, 107.7, 47.0, 22.0, 11.1.
Scheme 9. Preparation of indoles 15 by selective catalytic intramolecular
Wittig reaction.
With this methodology in hand, a scale-up experiment was
tested to evaluate the applicability of the new technique. We
successfully prepared 4a in gram quantity with a satisfactory
yield of 86% (Scheme 10).
3-(4-chlorophenyl)-2-methylisoquinolin-1(2H)-one (4b)
White solid, mp 144-146 °C (Lit27 mp 142-143 C); H NMR (CDCl3, 600
MHz) δ (ppm) 8.45 (d, J = 8.4 Hz, 1H, Ar-H), 7.65 (t, J = 7.8 Hz, 1H, Ar-
H), 7.55-7.43 (m, 4H, Ar-H), 7.36 (d, J = 7.2 Hz, 2H, Ar-H), 6.45 (s, 1H,
=CH), 3.42 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ (ppm) 163.1,
142.5, 136.0, 134.9, 134.4, 132.2, 130.0, 128.8, 127.7, 126.7, 125.7,
124.8, 107.6, 33.9.
o
1
O
O
O
(Cat. A) (10%)
(i-PrO)4Ti (20%)
N
N
TMDS (2 equiv)
NEt3 (1.2 equiv)
Toluene, reflux
Br
3-methyl-2-phenylisoquinolin-1(2H)-one (4c)
White solid, mp 134-135 °C (Lit28 mp 133-134 C); H NMR (CDCl3, 400
MHz) δ (ppm) 8.37 (d, J = 8.0 Hz, 1H, Ar-H), 7.65-7.24 (s, 8H, Ar-H),
6.44 (s, 1H, =CH), 2.00 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ (ppm)
172.9, 152.3, 132.6, 132.6, 129.6, 128.5, 128.4, 128.1, 127.7, 126.2,
126.1, 125.1, 105.5, 21.6.
o
1
3a, 30mmol
4a
86%, 6.79g
Scheme 10. The synthesis of isoquinolin-1(2H)-one 4a in gram-scale.
2-isopropyl-3-phenylisoquinolin-1(2H)-one (4d)
White solid, mp 131-133 °C (Lit 29); 1H NMR (CDCl3, 400 MHz) δ (ppm)
8.42 (d, J = 7.6 Hz, 1H, Ar-H), 7.61-7.39 (m, 8H, Ar-H), 6.34 (s, 1H, =CH),
4.25-4.18 (m, 1H, NCH), 1.57 (d, J = 6.8 Hz, 6H, 2CH3); 13C NMR (CDCl3,
100 MHz) δ (ppm) 163.2, 144.2, 137.2, 136.0, 132.1, 128.6, 128.5, 128.4,
127.5, 126.5, 126.4, 125.4, 107.9, 53.0, 19.6.
Conclusions
In summary, the catalytic intramolecular Wittig reaction starting
from the carbonyl-containing bromides has been developed
based on phosphine(III)/phosphine(V) oxide catalytic cycle. A
variety of isoquinolin-1(2H)-ones, indoles, 2,3-dihydro-1H-2-
benzazepin-1-ones, benzofurans, and 1,2-dihydroquinolines
were obtained efficiently or selectively via the catalytic
intramolecular Wittig reaction with organophosphorus reagent
used in catalytic amount, and the air-stable and inexpensive
tetramethyldisiloxane (TMDS)/Ti(OiPr)4 used as reductant.
8,9,10,11-tetrahydroazepino[1,2-b]isoquinolin-5(7H)-one (4e)
White solid, mp 96-97 °C (Lit30 mp 99-101 oC); 1H NMR (CDCl3, 400 MHz)
δ (ppm) 8.37 (d, J = 8.0 Hz, 1H, Ar-H), 7.57 (d, J = 7.2 Hz, 1H, Ar-H),
7.41-7.38 (m, 2H, Ar-H), 6.32 (s, 1H, =CH), 4.42 (s, 2H, NCH2), 2.93-2.72
(m, 2H, CH2), 1.78 (s, 6H, 3CH2); 13C NMR (CDCl3, 100 MHz) δ (ppm)
162.8, 145.5, 136.8, 132.0, 128.1, 125.7, 125.1, 124.2, 104.5, 43.3, 35.0,
29.5, 28.5, 28.1.
2-methyl-3-phenylisoquinolin-1(2H)-one (4f)
White solid, mp 56-58 °C (Lit26 mp 58-60 °C); 1H NMR (CDCl3, 600 MHz)
δ (ppm) 8.46 (d, J = 7.8 Hz, 1H, Ar-H), 7.64 (t, J = 7.2 Hz, 1H, Ar-H),
7.50-7.41 (m, 7H, Ar-H), 6.47 (s, 1H, =CH), 3.43 (s, 3H, CH3); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 163.3, 143.8, 136.3, 136.0, 132.2, 128.9,
128.7, 128.6, 128.4, 127.7, 126.6, 125.7, 107.6, 36.1.
2,3-dihydropyrrolo[1,2-b]isoquinolin-5(1H)-one (4g)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601628
European Journal of Organic Chemistry
FULL PAPER
Yellow solid, mp 92-94 °C (Lit31 mp 104-105 oC); 1H NMR (CDCl3, 400
MHz) δ (ppm) 8.39 (d, J = 8.0 Hz, 1H, Ar-H), 7.59 (t, J = 7.2 Hz, 1H, Ar-
H), 7.47-7.38 (m, 2H, Ar-H), 6.42 (s, 1H, =CH), 4.19 (t, J = 7.2 Hz, 2H,
NCH2), 3.10 (t, J = 7.6 Hz, 2H, CH2), 2.24-2.17 (m, 2H, CH2); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 161.4, 143.6, 140.0, 131.8, 127.1, 125.4,
125.4, 124.5, 100.2, 47.8, 31.0, 21.8.
7.45 (d, J = 7.8 Hz, 1H, Ar-H), 7.34 (t, J = 6.0 Hz, 1H, Ar-H), 7.28 (t, J =
7.8 Hz, 1H, Ar-H), 7.15 (t, J = 7.2 Hz, 1H, Ar-H), 6.61 (s, 1H, indole-3-H);
13C NMR (CDCl3, 100 MHz) δ (ppm) 162.3, 138.5, 134.3, 134.3, 133.5,
133.4, 133.3, 128.5, 126.0, 124.9, 123.6, 122.1, 121.0, 113.0, 103.3; MS
(EI, 70 eV): m/z (%) = 219 (100) [M+], 190 (37), 163 (8), 109 (11).
(4-chlorophenyl)(2-(4-chlorophenyl)-1H-indol-1-yl)methanone (6b)
White solid, mp 116-117 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.63 (d,
J = 6.6 Hz, 1H, Ar-H), 7.63 – 7.51 (m, 3H, Ar-H), 7.32 – 7.26 (m, 4H, Ar-
H), 7.24 – 7.15 (m, 4H, Ar-H), 6.79 (s, 1H, indole-3-H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 168.6, 139.6, 139.5, 138.0, 133.6, 133.1, 131.5, 131.2,
129.3, 129.0, 128.7, 128.5, 124.5, 123.3, 120.9, 113.9, 110.1; MS (EI, 70
eV): m/z (%) = 365 (22) [M+], 139 (100), 111 (34). Anal. Calcd for
C21H13Cl2NO: C, 68.87; H, 3.58; N, 3.82. Found: C, 68.97; H, 3.44; N,
3.60.
3-(4-chlorophenyl)-2-ethylisoquinolin-1(2H)-one (4h)
White solid, mp 107-109 °C (Lit 29); 1H NMR (CDCl3, 600 MHz) δ (ppm)
8.45 (d, J = 7.8 Hz, 1H, Ar-H), 7.64-7.36 (m, 7H, Ar-H), 6.38 (s, 1H, =CH),
3.99 (q, J = 6.0 Hz, 2H, NCH2), 1.15 (t, J = 7.2 Hz, 3H, CH3); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 162.5, 142.2, 136.0, 135.0, 134.6, 132.3,
130.3, 128.7, 127.9, 126.7.6, 125.7, 125.3, 107.9, 40.6, 14.2.
3-(4-chlorophenyl)-2-propylisoquinolin-1(2H)-one (4i)
1
White solid, mp 91-93 °C; H NMR (CDCl3, 600 MHz) δ (ppm) 8.45 (d, J
(4-bromophenyl)(2-(4-bromophenyl)-1H-indol-1-yl)methanone (6c)
White solid, mp 135-136 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.64 (d,
J = 8.4 Hz, 1H, Ar-H), 7.58 (d, J = 7.2 Hz, 1H, Ar-H), 7.51 (d, J = 8.4 Hz,
1H, Ar-H), 7.46 (d, J = 8.4 Hz, 1H, Ar-H), 7.36 (d, J = 8.4 Hz, 1H, Ar-H),
7.31 – 7.24 (m, 3H, Ar-H), 7.16 (d, J = 8.4 Hz, 1H, Ar-H), 6.79 (s, 1H,
indole-3-H); 13C NMR (CDCl3, 150 MHz) δ (ppm) 168.7, 139.7, 138.0,
133.5, 131.8, 131.6, 131.4, 129.5, 129.0, 128.2, 124.6, 123.4, 121.9,
120.9, 113.9, 110.2; MS (EI, 70 eV): m/z (%) = 455 (16) [M+], 183 (100),
155 (20). Anal. Calcd for C21H13Br2NO: C, 55.42; H, 2.88; N, 3.08. Found:
C, 55.37; H, 2.76; N, 3.22.
= 7.8 Hz, 1H, Ar-H), 7.64 (t, J = 7.2 Hz, 1H, Ar-H), 7.50-7.45 (m, 4H, Ar-
H), 7.35 (d, J = 8.4 Hz, 2H, Ar-H), 6.37 (s, 1H, =CH), 3.89 (t, J = 7.8 Hz,
2H, NCH2), 1.60-1.56 (m, 2H, CH2), 0.75 (t, J = 7.2 Hz, 3H, CH3); 13C
NMR (CDCl3, 100 MHz) δ (ppm) 162.7, 142.4, 136.0, 134.9, 134.6, 132.3,
130.3, 128.6, 127.9, 126.7, 125.7, 125.3, 107.9, 47.0, 22.1, 11.1; HRMS
Calculated for [C18H16ClNO+H]+: 298.0999, Found: 298.0993.
2-propyl-3-(p-tolyl)isoquinolin-1(2H)-one (4j)
1
Light yellow oil; H NMR (CDCl3, 400 MHz) δ (ppm) 8.44 (d, J = 8.0 Hz,
1H, Ar-H), 7.62 (t, J = 7.2 Hz, 1H, Ar-H), 7.48-7.27 (m, 4H, Ar-H), 6.38 (s,
1H, =CH), 3.91 (t, J = 8.0 Hz, 2H, NCH2), 2.44 (s, 3H, CH3), 1.62-1.58 (m,
2H, CH2), 0.74 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ
(ppm) 162.8, 143.8, 138.7, 136.3, 133.4, 132.1, 129.0, 128.9, 127.9,
127.8, 126.4, 125.6, 107.7, 47.1, 22.1, 21.3, 11.2; HRMS Calculated for
[C19H19NO+H]+: 278.1545, Found: 278.1541.
(4-fluorophenyl)(2-(4-fluorophenyl)-1H-indol-1-yl)methanone (6d)
o
1
White solid, mp 141-142 C; H NMR (CDCl3, 600 MHz) δ (ppm) 7.67 (t,
J = 4.8 Hz, 1H, Ar-H), 7.66 – 7.59 (m, 3H, Ar-H), 7.30 – 7.24 (m, 4H, Ar-
H), 6.96 (t, J = 8.4 Hz, 2H, Ar-H), 6.91 (t, J = 8.4 Hz, 2H, Ar-H), 6.75 (s,
1H, indole-3-H); 13C NMR (CDCl3, 150 MHz) δ (ppm) 168.6, 166.6, 164.0,
163.3, 160.8, 139.8, 138.0, 132.8, 132.7, 131.1, 129.9, 129.8, 129.0,
124.4, 123.3, 120.7, 115.7, 115.5, 115.2, 113.9, 109.6; MS (EI, 70 eV):
m/z (%) = 333 (35) [M+], 123 (100), 95 (22). Anal. Calcd for C21H13F2NO:
C, 75.67; H, 3.93; N, 4.20. Found: C, 75.90; H, 3.78; N, 4.43.
2-ethyl-3-phenylisoquinolin-1(2H)-one (4k)
Light yellow solid, mp 76-79 °C (Lit32 mp 78-81 °C); 1H NMR (CDCl3, 400
MHz) δ (ppm) 8.48 (d, J = 8.0 Hz, 1H, Ar-H), 7.65 (t, J = 7.6 Hz, 1H, Ar-
H), 7.51-7.42 (m, 7H, Ar-H), 6.43 (s, 1H, =CH), 4.01 (q, J = 7.2 Hz, 2H,
NCH2), 1.16 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ (ppm)
162.6, 143.5, 136.2, 136.1, 132.2, 128.9, 128.8, 128.4, 127.8, 126.5,
125.7, 125.1, 107.8, 40.7, 14.1.
(2-chlorophenyl)(2-(2-chlorophenyl)-1H-indol-1-yl)methanone (6e)
1
White solid, mp 64-65 oC; H NMR (CDCl3, 600 MHz) δ (ppm) 8.16 (d, J
= 6.0 Hz, 1H, Ar-H), 7.62 (d, J = 7.8 Hz, 1H, Ar-H), 7.49 (d, J = 6.0 Hz,
1H, Ar-H), 7.38 (t, J = 7.2 Hz, 2H, Ar-H), 7.33 (t, J = 7.2 Hz, 1H, Ar-H),
7.15 – 7.00 (m, 6H, Ar-H), 6.66 (s, 1H, indole-3-H); 13C NMR (CDCl3, 100
MHz) δ (ppm) 167.0, 137.0, 136.5, 135.0, 133.9, 132.0, 131.8, 131.3,
129.8, 129.6, 129.5, 129.4, 129.2, 128.9, 126.4, 126.2, 125.3, 123.9,
120.7, 115.6, 112.9; MS (EI, 70 eV): m/z (%) = 365 (12) [M+], 330 (53),
139 (100), 111 (35). Anal. Calcd for C21H13Cl2NO: C, 68.87; H, 3.58; N,
3.82. Found: C, 68.79; H, 3.40; N, 4.02.
2-benzyl-3-phenylisoquinolin-1(2H)-one (4l)
1
White solid, mp 103-104 °C (Lit33 mp 104-105 °C); H NMR (CDCl3, 400
MHz) δ (ppm) 8.50 (d, J = 8.0 Hz, 1H, Ar-H), 7.64 (t, J = 7.2 Hz, 1H, Ar-
H), 7.49 (d, J = 6.6 Hz, 2H, Ar-H), 7.37 (d, J = 6.6 Hz, 1H, Ar-H), 7.32 (t,
J = 6.6 Hz, 2H, Ar-H), 7.19-7.15 (m, 5H, Ar-H), 6.90 (d, J = 5.4 Hz, 2H,
Ar-H), 6.44 (s, 1H, =CH), 5.25 (s, 2H, NCH2); 13C NMR (CDCl3, 100 MHz)
δ (ppm) 163.1, 143.8, 137.6, 136.4, 135.7, 132.4, 129.1, 128.8, 128.2,
128.1, 126.8, 126.8, 126.6, 125.8, 125.1, 108.0, 48.5.
(3-chlorophenyl)(2-(3-chlorophenyl)-1H-indol-1-yl)methanone (6f)
7-bromo-3-phenyl-2-propylisoquinolin-1(2H)-one (4m)
1
White solid, mp 67-70 oC; H NMR (CDCl3, 600 MHz) δ (ppm) 7.86 (d, J
White solid, mp 108-109 °C; 1H NMR (CDCl3, 400 MHz) δ (ppm) 8.57 (s,
1H, Ar-H), 7.66 (d, J = 8.4 Hz, 1H, Ar-H), 7.47-7.31 (m, 6H, Ar-H), 6.34 (s,
1H, =CH), 3.89 (t, J = 6.8 Hz, 2H, NCH2), 1.61-1.55 (m, 2H, CH2), 0.71 (t,
J = 7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ (ppm) 161.4, 144.1,
135.7, 135.2, 134.8, 130.4, 128.9, 128.7, 128.3, 127.3, 126.4, 119.9,
106.9, 47.1, 21.9, 11.0; HRMS Calculated for [C18H16BrNO+Na]+:
364.0313, Found: 364.0308.
= 8.4 Hz, 1H, Ar-H), 7.65 (d, J = 6.6 Hz, 1H, Ar-H), 7.53 – 7.44 (m, 2H,
Ar-H), 7.38 – 7.28 (m, 3H, Ar-H), 7.25 (s, 1H, Ar-H), 7.21 (t, 3H, Ar-H) ,
7.15 – 7.07 (m, 3H, Ar-H), 6.70 (s, 1H, indole-3-H); 13C NMR (CDCl3, 100
MHz) δ (ppm) 168.2, 139.1, 138.1, 136.5, 134.5, 134.3, 134.1, 132.5,
129.9, 129.5, 129.4, 128.9, 128.3, 127.9, 127.6, 126.4, 125.0, 123.7,
120.9, 114.3, 110.7; MS (EI, 70 eV): m/z (%) = 365 (29) [M+], 190 (6),
139 (100), 111 (37). Anal. Calcd for C21H13Cl2NO: C, 68.87; H, 3.58; N,
3.82. Found: C, 68.62; H, 3.43; N, 4.01.
3-(2-chlorophenyl)-2-propylisoquinolin-1(2H)-one (4n)
1
Light yellow oil; H NMR (CDCl3, 400 MHz) δ (ppm) 8.47 (d, J = 8.0 Hz,
(5-chloro-2-(4-chlorophenyl)-1H-indol-1-yl)(4-
chlorophenyl)methanone (6g)
1H, Ar-H), 7.64 (t, J = 7.2 Hz, 1H, Ar-H), 7.52-7.38 (m, 6H, Ar-H), 6.39 (s,
1H, =CH), 4.27-4.20 (m, 1H, NCH2a), 3.41-3.34 (m, 1H, NCH2b), 1.69-
1.44 (m, 2H, CH2), 0.72 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100
MHz) δ (ppm) 162.4, 140.4, 136.1, 134.8, 134.0, 132.1, 131.3, 130.4,
129.5, 127.8, 126.7, 126.7, 125.8, 125.4, 107.8, 46.9, 21.9, 11.2; HRMS
Calculated for [C18H16ClNO+H]+: 298.0999, Found: 298.0994.
White solid, mp 141-142 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.60 (d,
J = 1.8 Hz, 1H, Ar-H), 7.57 (d, J = 9.0 Hz, 1H, Ar-H), 7.53 (d, J = 8.4 Hz,
2H, Ar-H), 7.28 (d, J = 8.4 Hz, 2H, Ar-H), 7.25 – 7.21 (m, 1H, Ar-H), 7.20
(s, 4H, Ar-H), 6.71 (s, 1H, indole-3-H); 13C NMR (CDCl3, 100 MHz) δ
(ppm) 168.0, 140.9, 139.8, 136.4, 134.1, 132.7, 131.5, 130.7, 130.1,
129.3, 128.9, 128.8, 128.6, 124.7, 120.3, 115.0, 109.0; MS (EI, 70 eV):
m/z (%) = 399 (14) [M+], 190 (5), 139 (100), 111 (32). Anal. Calcd for
C21H12Cl3NO: C, 62.95; H, 3.02; N, 3.50. Found: C, 63.10; H, 2.95; N,
3.67.
General procedure for preparation of N-acyl indoles 6: To a solution
of phosphine oxide (A) (0.052 g, 0.2 mmol) in anhydrous toluene (10 mL)
was added Ti(O-i-Pr)4 (0.106 g, 0.4 mmol) and TMDS (0.54 g, 4 mmol).
After the reaction mixture was stirred at 110 °C for 30 min, bromide 5 (2
mmol) and NEt3 (0.24 g, 2.4 mmol) were added sequentially. The
reaction mixture was then stirred at 110 °C and monitored by TLC. After
the reaction was completed (16-24 h), the solvent was removed under
reduced pressure and the residue was purified by flash chromatography
on silica gel (ether/petroleum ether = 1:5, V/V) to give N-acyl indoles 6.
(5-chloro-2-phenyl-1H-indol-1-yl)(phenyl)methanone (6h)
White solid, mp 102-103 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.64 (d,
J = 9.0 Hz, 1H, Ar-H), 7.62 – 7.55 (m, 3H, Ar-H), 7.39 (t, J = 7.2 Hz, 1H,
Ar-H), 7.32 – 7.11 (m, 8H, Ar-H), 6.71 (s, 1H, indole-3-H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 169.8, 142.5, 136.5, 134.6, 133.0, 132.5,
130.3, 130.2, 128.6, 128.3, 128.3, 128.2, 127.8, 124.3, 120.1, 115.1,
108.4; MS (EI, 70 eV): m/z (%) = 331 (24) [M+], 190 (3), 105 (100), 77
(23). Anal. Calcd for C21H14ClNO: C, 76.02; H, 4.25; N, 4.22. Found: C,
76.25; H, 4.09; N, 4.40.
6H-isoindolo[2,1-a]indol-6-one (6a)34
Yellow solid, mp 152-153 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.90 (d,
J = 7.8 Hz, 1H, Ar-H), 7.76 (d, J = 7.2 Hz, 1H, Ar-H), 7.52 (s, 2H, Ar-H),
(5-chloro-2-(4-fluorophenyl)-1H-indol-1-yl)(4-
fluorophenyl)methanone (6i)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601628
European Journal of Organic Chemistry
FULL PAPER
White solid, mp 146-147 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.64 (d,
J = 8.4 Hz, 1H, Ar-H), 7.62 – 7.55 (m, 3H, Ar-H), 7.26 – 7.21 (m, 3H, Ar-
H), 6.95 (t, J = 8.4 Hz, 2H, Ar-H), 6.90 (t, J = 8.4 Hz, 2H, Ar-H), 6.68 (s,
1H, indole-3-H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 168.3, 166.6, 164.1,
163.4, 160.9, 141.0, 136.3, 132.7, 130.6, 130.0, 129.9, 128.7, 128.5,
124.4, 120.2, 115.7, 115.5, 115.3, 114.9, 108.5; MS (EI, 70 eV): m/z (%)
White solid, mp 187-188 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 8.17 (d,
J = 7.8 Hz, 1H, Ar-H), 7.54 (t, J = 7.2 Hz, 1H, Ar-H), 7.46 (t, J = 7.2 Hz,
1H, Ar-H), 7.41-7.20 (m, 10H, Ar-H), 7.13 (s, 1H, =CH), 4.38 (s, 2H, CH2),
2.19 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz) δ (ppm) 167.6, 142.7,
142.2, 138.8, 135.5, 135.4, 134.3, 131.2, 131.0, 130.6, 129.1, 129.0,
128.8, 128.6, 128.0, 127.8, 127.7, 127.2, 127.0, 125.7, 125.6, 51.1, 18.2;
MS (EI, 70 eV): m/z (%) = 325 (M+, 99), 308 (100), 218 (18), 178 (27).
Anal. Calcd for C23H19NO: C, 84.89; H, 5.89; N, 4.30. Found: C, 84.67; H,
5.65; N, 4.53.
=
367 (21) [M+], 208 (3), 123 (100), 95 (22). Anal. Calcd for
C21H12ClF2NO: C, 68.58; H, 3.29; N, 3.81. Found: C, 68.77; H, 3.17; N,
3.92.
1-(2-ethyl-1H-indol-1-yl)propan-1-one (6j)34
4-(4-chlorophenyl)-2-phenyl-2,3-dihydro-1H-2-benzazepin-1-one
(10e)
Yellow oil; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.83 (d, J = 7.8 Hz, 1H,
Ar-H), 7.49 (d, J = 7.2 Hz, 1H, Ar-H), 7.25 – 7.18 (m, 2H, Ar-H), 6.43 (s,
1H, indole-3-H), 3.06 (q, J = 7.2 Hz, 4H, 2CH2), 1.42 – 1.29 (m, 6H,
2CH3); 13C NMR (CDCl3, 100 MHz) δ (ppm) 174.3, 144.5, 136.1, 129.9,
123.3, 122.7, 120.1, 114.8, 107.1, 32.4, 24.0, 13.2, 9.2; MS (EI, 70 eV):
m/z (%) = 201 (40) [M+], 145 (100), 130 (85), 115 (9).
White solid, mp 159-161 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 8.14 (d,
J = 7.8 Hz, 1H, Ar-H), 7.53 (t, J = 7.2 Hz, 1H, Ar-H), 7.46 (t, J = 7.8 Hz,
1H, Ar-H), 7.41-7.23 (m, 10H, Ar-H), 7.13 (s, 1H, =CH), 4.42 (s, 2H, CH2);
13C NMR (CDCl3, 150 MHz) δ (ppm) 167.9, 142.7, 141.2, 137.0, 135.1,
134.6, 133.8, 131.3, 131.1, 130.6, 129.8, 129.6, 129.3, 129.1, 129.0,
128.7, 127.9, 127.1, 126.9, 126.4, 126.2, 51.0; MS (EI, 70 eV): m/z (%) =
345 (M+, 100), 242 (13), 208 (52), 176 (22). Anal. Calcd for C22H16ClNO:
C, 76.41; H, 4.66; N, 4.05. Found: C, 76.59; H, 4.57; N, 4.24.
1-(2-methyl-1H-indol-1-yl)ethanone (6k)34
Yellow oil; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.98 (d, J = 8.4 Hz, 1H,
Ar-H), 7.45 (d, J = 7.8 Hz, 1H, Ar-H), 7.25 – 7.20 (m, 2H, Ar-H), 6.37 (s,
1H, indole-3-H), 2.73 (s, 3H, COCH3), 2.63 (s, 3H, CH3); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 170.4, 137.2, 136.4, 129.7, 123.5, 123.1,
119.8, 111.2, 109.8, 27.2, 17.6; MS (EI, 70 eV): m/z (%) = 173 (51) [M+],
130 (100), 103 (18).
General procedure for preparation of benzofurans 12: To a solution
of phosphine oxide (A) (0.052 g, 0.2 mmol) in anhydrous toluene (10 mL)
was added Ti(O-i-Pr)4 (0.106 g, 0.4 mmol) and TMDS (0.54 g, 4 mmol).
After the reaction mixture was stirred at 110 °C for 30 min, bromide 11 (2
mmol) and NEt3 (0.24 g, 2.4 mmol) were added sequentially. The
reaction mixture was then stirred at 110 °C and monitored by TLC. After
the reaction was completed (16-24 h), the solvent was removed under
reduced pressure and the residue was purified by flash chromatography
on silica gel (ether/petroleum ether = 1:5, V/V) to give furans 12.
7-chloro-1H-pyrrolo[1,2-a]indol-3(2H)-one (6l)
1
White solid, mp 84-87 oC; H NMR (CDCl3, 600 MHz) δ (ppm) 7.96 (d, J
= 8.4 Hz, 1H, Ar-H), 7.46 (d, J = 1.8 Hz, 1H, Ar-H), 7.22 (dd, J = 8.4 Hz, J
= 1.8 Hz, 1H, Ar-H), 6.22 (s, 1H, indole-3-H), 3.20 – 3.13 (m, 2H,
COCH2), 3.12 – 3.04 (m, 2H, CH2); 13C NMR (CDCl3, 100 MHz) δ (ppm)
171.4, 145.0, 136.4, 129.5, 128.6, 123.3, 120.2, 114.3, 99.8, 34.5, 19.6;
MS (EI, 70 eV): m/z (%) = 205 (100) [M+], 177 (35), 163 (23), 115 (10).
Anal. Calcd for C11H8ClNO: C, 64.25; H, 3.92; N, 6.81. Found: C, 64.47;
H, 3.77; N, 6.99.
2-phenylbenzofuran (12a)
White solid, mp 114-116 °C, lit.35 118-120 °C; 1H NMR (CDCl3, 400 MHz)
δ (ppm) 7.87 (d, J = 7.6 Hz, 2H, Ar-H), 7.58 (d, J = 7.6 Hz, 1H, Ar-H),
7.52 (d, J = 8.0 Hz, 1H, Ar-H), 7.44 (t, J = 7.6 Hz, 2H, Ar-H), 7.35 (t, J =
7.6 Hz, 1H, Ar-H), 7.31-7.20 (m, 2H, Ar-H), 7.02 (s, 1H, furan-3-H); 13C
NMR (CDCl3, 100 MHz) δ (ppm) 155.9, 154.8, 130.4, 129.2, 128.7, 128.5,
124.9, 124.2, 122.9, 120.9, 111.1, 101.3; MS (EI, 70 eV): m/z (%) = 194
(M+, 100), 165 (38).
General procedure for preparation of 2,3-dihydro-1H-2-benzazepin-
1-ones 10: To a solution of phosphine oxide (A) (0.052 g, 0.2 mmol) in
anhydrous toluene (10 mL) was added Ti(O-i-Pr)4 (0.106 g, 0.4 mmol)
and TMDS (0.54 g, 4 mmol). After the reaction mixture was stirred at 110
°C for 30 min, bromide 9 (2 mmol) and NEt3 (0.24 g, 2.4 mmol) were
added sequentially. The reaction mixture was then stirred at 110 °C and
monitored by TLC. After the reaction was completed (16-24 h), the
solvent was removed under reduced pressure and the residue was
purified by flash chromatography on silica gel (ether/petroleum ether =
1:3, V/V) to give 2,3-dihydro-1H-2-benzazepin-1-ones 10.
2-(4-chlorophenyl)benzofuran (12b)
White solid, mp 139-141 °C, lit.36 135-138 °C; 1H NMR (CDCl3, 400 MHz)
δ (ppm) 7.77 (d, J = 8.4 Hz, 2H, Ar-H), 7.57 (d, J = 7.6 Hz, 1H, Ar-H),
7.51 (d, J = 8.0 Hz, 1H, Ar-H), 7.44-7.37 (m, 2H, Ar-H), 7.34-7.19 (m, 2H,
Ar-H), 6.99 (s, 1H, furan-3-H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 154.8,
154.7, 134.2, 129.0, 128.9, 128.9, 126.0, 124.5, 123.0, 121.0, 111.1,
101.7; MS (EI, 70 eV): m/z (%) = 228 (M+, 100), 165 (28), 114 (12), 82
(11).
2,4-diphenyl-2,3-dihydro-1H-2-benzazepin-1-one (10a)
White solid, mp 129-131 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 8.13 (d,
J = 7.2 Hz, 1H, Ar-H), 7.51 (t, J = 7.2 Hz, 1H, Ar-H), 7.43 (t, J = 7.2 Hz,
1H, Ar-H), 7.39-7.24 (m, 11H, Ar-H), 7.14 (s, 1H, =CH), 4.45 (s, 2H, CH2);
13C NMR (CDCl3, 100 MHz) δ (ppm) 168.1, 142.8, 142.5, 138.6, 135.5,
134.6, 131.2, 130.5, 129.4, 129.2, 128.9, 128.7, 128.0, 127.6, 126.9,
126.4, 125.7, 51.2; HRMS Calculated for [C22H17NO+H]+: 312.1388,
Found: 312.1383.
2-(4-methoxyphenyl)benzofuran (12c)
White solid, mp 144-146 °C, lit.36 147-148 °C; 1H NMR (CDCl3, 400 MHz)
δ (ppm) 7.79 (d, J = 8.8 Hz, 2H, Ar-H), 7.55 (d, J = 7.2 Hz, 1H, Ar-H),
7.49 (d, J = 7.6 Hz, 1H, Ar-H), 7.30-7.15 (m, 2H, Ar-H), 7.13-6.93 (m, 2H,
Ar-H), 6.87 (s, 1H, furan-3-H), 3.85 (s, 3H, CH3); 13C NMR (CDCl3, 100
MHz) δ (ppm) 159.9, 156.0, 154.6, 129.5, 126.4, 123.7, 123.3, 122.8,
120.5, 114.2, 110.9, 99.6, 55.3; MS (EI, 70 eV): m/z (%) = 224 (M+, 100),
209 (72), 181 (37), 152 (18).
4-phenyl-2-(p-tolyl)-2,3-dihydro-1H-2-benzazepin-1-one (10b)
White solid, mp 116-117 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 8.13 (d,
J = 7.8 Hz, 1H, Ar-H), 7.51 (t, J = 7.2 Hz, 1H, Ar-H), 7.43 (t, J = 7.2 Hz,
1H, Ar-H), 7.37-7.15 (m, 10H, Ar-H), 7.14 (s, 1H, =CH), 4.42 (s, 2H, CH2),
2.35 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ (ppm) 168.3, 142.7,
140.2, 138.9, 136.8, 135.6, 134.8, 131.3, 130.6, 129.9, 129.5, 129.0,
128.8, 128.1, 127.7, 126.3, 125.9, 51.4, 21.1; HRMS Calculated for
[C23H19NO+H]+: 326.1545, Found: 326.1538.
(E)-2-styrylbenzofuran (12d)
White solid, mp 121-123 °C, lit.37 125-126 °C; 1H NMR (CDCl3, 400 MHz)
δ (ppm) 7.52 (d, J = 7.6 Hz, 3H, Ar-H), 7.47 (d, J = 8.0 Hz, 1H, Ar-H),
7.43-7.33 (m, 3H, Ar-H), 7.30-7.18 (m, 3H, Ar-H), 7.00 (d, J = 16.0 Hz,
1H, =CH), 6.67 (s, 1H, furan-3-H); 13C NMR (CDCl3, 100 MHz) δ (ppm)
155.0, 154.8, 136.5, 130.2, 129.1, 128.7, 128.1, 126.6, 124.6, 122.8,
120.8, 116.3, 110.8, 105.2; MS (EI, 70 eV): m/z (%) = 220 (M+, 100), 191
(32), 165 (11).
2-(4-chlorophenyl)-4-phenyl-2,3-dihydro-1H-2-benzazepin-1-one
(10c)
White solid, mp 191-192 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 8.12 (d,
J = 7.8 Hz, 1H, Ar-H), 7.54 (t, J = 7.2 Hz, 1H, Ar-H), 7.45 (t, J = 7.2 Hz,
1H, Ar-H), 7.39-7.31 (m, 8H, Ar-H), 7.25 (d, J = 6.0 Hz, 2H, Ar-H), 7.15 (s,
1H, =CH), 4.44 (s, 2H, CH2); 13C NMR (CDCl3, 150 MHz) δ (ppm) 168.1,
142.2, 141.3, 138.4, 135.4, 134.3, 132.3, 131.3, 131.2, 130.8, 129.6,
129.4, 129.2, 129.0, 128.8, 128.3, 127.8, 127.7, 125.8, 125.6, 51.0; MS
(EI, 70 eV): m/z (%) = 345 (M+, 100), 242 (33), 219 (17), 178 (25). Anal.
Calcd for C22H16ClNO: C, 76.41; H, 4.66; N, 4.05. Found: C, 76.56; H,
4.47; N, 4.31.
4-(benzofuran-2-yl)benzonitrile (12e)38
White solid, mp 140-142 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.94 (d,
J = 8.4 Hz, 2H, Ar-H), 7.72 (d, J = 8.4 Hz, 2H, Ar-H), 7.62 (d, J = 7.8 Hz,
1H, Ar-H), 7.54 (d, J = 8.4 Hz, 1H, Ar-H), 7.35 (t, J = 7.8 Hz, 1H, Ar-H),
7.27 (d, J = 8.4 Hz, 1H, Ar-H), 7.17 (s, 1H, furan-3-H).
4-(benzofuran-2-yl)phenyl acetate (12f)39
White solid, mp 135-138 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.87 (d,
J = 9.0 Hz, 2H, Ar-H), 7.58 (d, J = 7.2 Hz, 1H, Ar-H), 7.51 (d, J = 8.4 Hz,
1H, Ar-H), 7.29 (t, J = 7.8 Hz, 1H, Ar-H), 7.23 (t, J = 7.8 Hz, 1H, Ar-H),
7.18 (d, J = 9.0 Hz, 2H, Ar-H), 6.99 (s, 1H, furan-3-H), 2.33 (s, 3H, CH3).
2-(4-nitrophenyl)benzofuran (12g)40
4-phenyl-2-(o-tolyl)-2,3-dihydro-1H-2-benzazepin-1-one (10d)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601628
European Journal of Organic Chemistry
FULL PAPER
White solid, mp 180-182 °C; 1H NMR (CDCl3, 600 MHz) δ (ppm) 8.29 (d,
J = 8.4 Hz, 2H, Ar-H), 7.98 (d, J = 9.0 Hz, 2H, Ar-H), 7.64 (d, J = 7.8 Hz,
1H, Ar-H), 7.55 (d, J = 8.4 Hz, 1H, Ar-H), 7.37 (t, J = 7.2 Hz, 1H, Ar-H),
7.28 (t, J = 7.2 Hz, 1H, Ar-H), 7.23 (s, 1H, furan-3-H).
Ar-H), 6.60 (t, J = 7.8Hz, 1H, Ar-H), 4.94 (s, 2H, CH2), 3.77 (s, 3H, CH3);
13C NMR (CDCl3, 150 MHz) δ (ppm) 169.3, 161.3, 137.4, 137.2, 137.0,
131.2, 130.4, 128.7, 128.2, 127.2, 126.7, 126.6, 125.0, 124.7, 124.3,
121.6, 113.2, 55.2, 45.3; MS (EI, 70 eV): m/z (%) = 341 (20) [M+], 135
(100), 77 (15), 206 (13). Anal. Calcd for C23H19NO2: C, 80.92; H, 5.61; N,
4.10. Found: C, 80.67; H, 5.66; N, 4.27.
General
procedure
for
selective
preparation
of
1,2-
(3-(4-bromophenyl)quinolin-1(2H)-yl)(phenyl)methanone (14g)
dihydroquinolines 14: To a solution of phosphine oxide (A) (0.052 g,
0.2 mmol) in anhydrous toluene (10 mL) was added Ti(O-i-Pr)4 (0.106 g,
0.4 mmol) and TMDS (0.54 g, 4 mmol). After the reaction mixture was
stirred at 110 °C for 30 min, bromide 13 (2 mmol) and NEt3 (0.24 g, 2.4
mmol) were added sequentially. The reaction mixture was then stirred at
110 °C and monitored by TLC. After the reaction was completed (16-24
h), the solvent was removed under reduced pressure and the residue
was purified by flash chromatography on silica gel (ether/petroleum ether
= 1:4, V/V) to give 1,2-dihydroquinolines 14.
1
Yellow solid, mp 140-141 oC; H NMR (CDCl3, 600 MHz) δ (ppm) 7.67 –
7.48 (m, 4H, Ar-H), 7.43 (d, J =8.4 Hz, 2H, Ar-H), 7.36 (t, J = 7.8 Hz, 3H,
Ar-H), 7.21 (d, J = 7.2Hz, 1H, Ar-H), 7.04 (t, J = 7.8Hz, 1H, Ar-H), 6.97 (s,
1H, Ar-H), 6.86 (t, J = 7.2Hz, 1H, Ar-H), 6.58 (s, 1H, =CH), 4.91(s, 2H,
CH2); 13C NMR (CDCl3, 150 MHz) δ (ppm) 169.7, 136.5, 136.2, 136.0，
135.0, 131.8, 130.5, 128.9, 128.5, 128.1, 126.8, 126.8，126.6, 125.1,
124.4, 122.2, 122.1, 44.8; MS (EI, 70 eV): m/z (%) = 389 (12) [M+], 105
(100), 204 (17), 284 (12). Anal. Calcd for C22H16BrNO: C, 67.71; H, 4.13;
N, 3.59. Found: C, 67.82; H, 4.05; N, 3.75.
(3-(4-bromophenyl)quinolin-1(2H)-yl)(4-chlorophenyl)methanone
(14h)
White solid, mp 147-148 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.54 (d,
J = 8.4 Hz, 2H, Ar-H), 7.44(d, J = 8.4 Hz, 2H, Ar-H), 7.30(d, J = 8.4 Hz,
2H, Ar-H), 7.24 (d, J = 8.4 Hz, 3H, Ar-H), 7.08(t, J = 7.8 Hz, 1H, Ar-H),
6.97(s, 1H, =CH), 6.90 (t, J = 7.8 Hz, 1H, Ar-H), 6.54(d, J = 3.6 Hz, 1H,
Ar-H), 4.91(s, 2H, CH2); 13C NMR (CDCl3, 150 MHz) δ (ppm) 168.5,
136.6, 136.4, 136.2, 135.9, 133.4, 131.9, 130.5, 128.6, 128.4, 126.9,
126.6, 125.4, 124.3, 122.3, 122.0, 119.0, 44.8; MS (EI, 70 eV): m/z (%) =
425 (17) [M+], 139 (100), 141 (33), 204 (25). Anal. Calcd for
C22H15BrClNO: C, 62.21; H, 3.56; N, 3.30. Found: C, 62.03; H, 3.70; N,
3.23
phenyl(3-phenylquinolin-1(2H)-yl)methanone (14a)
White solid, mp 139-140 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.59 (d,
J = 7.2 Hz, 2H, Ar-H), 7.47 – 7.32 (m, 6H, Ar-H), 7.27 (d, J = 7.8 Hz, 2H,
Ar-H), 7.23 (d, J = 7.2 Hz, 1H, Ar-H), 7.06 (t, J = 7.2 Hz, 1H, Ar-H), 6.99
(s, 1H, Ar-H), 6.86 (t, J = 7.2 Hz, 1H, Ar-H), 6.60 (s, 1H, Ar-H), 4.96 (s,
2H, CH2); 13C NMR (CDCl3, 100 MHz) δ (ppm) 169.7, 137.4, 137.1, 136.4,
135.1, 130.4, 128.9, 128.8, 128.7, 128.2, 128.0, 126.7, 126.5, 125.0,
125.0, 124.3, 121.5, 45.1; MS (EI, 70 eV): m/z (%) = 311 (44) [M+], 105
(100), 206 (50), 178 (8), 128 (5). Anal. Calcd for C22H17NO: C, 84.86; H,
5.50; N, 4.50. Found: C, 85.02; H, 5.39; N, 4.33.
(4-chlorophenyl)(3-phenylquinolin-1(2H)-yl)methanone (14b)
White solid, mp 137-138 oC; 1H NMR (CDCl3, 400 MHz) δ (ppm) 7.58 (d,
J = 8.4 Hz, 2H, Ar-H), 7.51 – 7.20 (m, 8H, Ar-H), 7.07 (t, J = 7.2 Hz, 1H,
Ar-H), 6.98 (s, 1H, Ar-H), 6.89 (t, J = 7.6 Hz, 1H, Ar-H), 6.56 (d, J = 7.2
Hz, 1H, CH), 4.95 (s, 2H, CH2); 13C NMR (CDCl3, 100 MHz) δ (ppm)
168.4, 137.5, 137.0, 136.5, 136.2, 133.6, 130.5, 128.8, 128.7, 128.4,
128.3, 126.8, 126.7, 125.2, 125.0, 124.2, 121.5, 45.1; MS (EI, 70 eV):
m/z (%) = 345 (38) [M+], 139 (100), 206 (76), 111 (27). Anal. Calcd for
C22H16ClNO: C, 76.41; H, 4.66; N, 4.05. Found: C, 76.66; H, 4.57; N,
4.30.
(2-methoxyphenyl)(3-phenylquinolin-1(2H)-yl)methanone (14c)
Yellow oil; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.70-7.26 (m, 7H, Ar-H),
7.24-6.42 (m, 7H, Ar-H), 5.56-5.22 (m, 0.8H, CH2), 4.85-4.43 (m, 1.2H,
CH2), 3.42 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz) δ (ppm) 168.3,
137.4, 131.2, 129.6, 129.4, 128.7, 128.1, 128.0, 127.4, 126.3, 126.2,
125.4, 125.2, 121.4, 121.3, 120.7, 120.6, 114.8, 110.8, 55.1, 43.6; MS
(EI, 70 eV): m/z (%) = 341 (21) [M+], 135 (100), 77 (18), 136 (9). Anal.
Calcd for C23H19NO2: C, 80.92; H, 5.61; N, 4.10. Found: C, 81.06; H,
5.71; N, 4.04.
General procedure for selective preparation of indoles 15: To a
solution of triphenylphosphine oxide (0.056 g, 0.2 mmol) in anhydrous
toluene (10 mL) was added Ti(O-i-Pr)4 (0.106 g, 0.4 mmol) and TMDS
(0.54 g, 4 mmol). After the reaction mixture was stirred at 110 °C for 30
min, bromide 13 (2 mmol) and NEt3 (0.24 g, 2.4 mmol) were added
sequentially. The reaction mixture was then stirred at 110 °C and
monitored by TLC. After the reaction was completed (24-48 h), the
solvent was removed under reduced pressure and the residue was
purified by flash chromatography on silica gel (ether/petroleum ether =
1:5, V/V) to give indoles 15.
1-phenyl-2-(2-phenyl-1H-indol-1-yl)ethanone (15a)
White solid, mp 152-153 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.96 (d,
J = 6.0 Hz, 2H, Ar-H), 7.72 – 7.58 (m, 2H, Ar-H), 7.54 – 7.32 (m, 7H, Ar-
H), 7.22 – 7.06 (m, 3H, Ar-H), 6.66 (s, 1H, indole-3-H), 5.50 (s, 2H, CH2);
13C NMR (CDCl3, 100 MHz) δ (ppm) 193.7, 141.6, 138.2, 134.5, 133.9,
132.3, 129.1, 128.8, 128.6, 128.2, 128.1, 127.9, 122.0, 120.7, 120.3,
109.4, 102.6, 50.7; MS (EI, 70 eV): m/z (%) = 311 (31) [M+], 206 (100),
178 (13), 128 (5). Anal. Calcd for C22H17NO: C, 84.86; H, 5.50; N, 4.50.
Found: C, 84.97; H, 5.26; N, 4.52.
(3-(4-chlorophenyl)quinolin-1(2H)-yl)(4-methoxyphenyl)methanone
(14d)
White solid, mp 169-170 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.50 (d,
J = 8.4 Hz, 2H, Ar-H), 7.35 (q, J = 8.4 Hz, 4H, Ar-H), 7.21 (d, J = 7.8 Hz,
1H, Ar-H), 7.04 (t, J = 7.8 Hz, 1H, Ar-H), 6.95 (s, 1H, =CH), 6.88 (t, J =
7.8 Hz, 1H, Ar-H), 6.76 (d, J = 8.4 Hz, 2H, Ar-H), 6.60 (d, J = 7.8 Hz, 1H,
Ar-H), 4.90 (s, 2H, CH2), 3.78 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz) δ
(ppm) 169.3, 161.3 137.0, 136.2, 135.7, 133.9, 131.2, 128.8, 128.4,
127.1, 126.9, 126.8, 126.3, 124.8, 124.3, 122.0, 113.3, 55.2, 45.1; MS
(EI, 70 eV): m/z (%) = 375 (9) [M+], 135 (100), 91.95 (7), 136 (8). Anal.
Calcd for C23H18ClNO2: C, 73.50; H, 4.83; N, 3.73. Found: C, 73.37; H,
4.67; N, 3.94.
2-(2-(4-chlorophenyl)-1H-indol-1-yl)-1-phenylethanone (15b)
White solid, mp 136-137 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.97 (d,
J = 7.8 Hz, 2H, Ar-H), 7.66 (q, J = 7.8 Hz, 2H, Ar-H), 7.51 (t, J = 7.8 Hz,
2H, Ar-H), 7.36 (s, 4H, Ar-H), 7.22 – 7.13 (m, 2H, Ar-H), 7.09 (d, J = 7.8
Hz, 1H, Ar-H), 6.65 (s, 1H, indole-3-H), 5.47 (s, 2H, CH2); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 193.6, 140.3, 138.3, 134.4, 134.2, 134.1,
130.8, 130.3, 128.9, 128.9, 128.1, 127.9, 122.3, 120.8, 120.5, 109.4,
103.0, 50.6; MS (EI, 70 eV): m/z (%) = 345 (56) [M+], 205 (100), 139 (71),
240 (38). Anal. Calcd for C22H16ClNO: C, 76.41; H, 4.66; N, 4.05. Found:
C, 76.26; H, 4.52; N, 4.22.
2-(2-(2-methoxyphenyl)-1H-indol-1-yl)-1-phenylethanone (15c)
White solid, mp 189-190 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.74-
7.26 (m, 7H, Ar-H), 7.25-6.42 (m, 7H, Ar-H), 5.58-5.38 (m, 0.8H, CH2),
4.66-4.36 (m, 1.2H, CH2), 3.64-3.24 (m, 3H, CH3); 13C NMR (CDCl3, 150
MHz) δ (ppm) 166.5, 154.8, 138.1, 137.2, 136.1, 133.8, 132.5, 129.8,
128.7, 128.2, 127.4, 126.3, 126.2, 125.5, 125.2, 124.9, 122.4, 121.3,
112.6, 55.3, 43.7; MS (EI, 70 eV): m/z (%) = 341 (1) [M+], 213 (100), 215
(97), 216 (9). Anal. Calcd for C23H19NO2: C, 80.92; H, 5.61; N, 4.10.
Found: C, 80.89; H, 5.42; N, 4.23.
(4-chlorophenyl)(3-(4-chlorophenyl)quinolin-1(2H)-yl)methanone
(14e)
1
White solid, mp 122-123oC; H NMR (CDCl3, 600 MHz) δ (ppm) 7.50 (d,
J = 8.4Hz, 2H, Ar-H), 7.38 (d, J = 7.8Hz, 2H, Ar-H), 7.30 (d, J = 7.8Hz,
2H, Ar-H), 7.24 (q, 3H, J =8.4Hz, Ar-H), 7.08 (t, 1H, J = 7.2Hz, Ar-H),
6.96 (s, 1H, =CH), 6.89 (t, 1H, J = 7.2Hz, Ar-H), 6.54 (t, 1H, J = 7.2Hz,
Ar-H), 6.90 (s, 2H, CH2); 13C NMR (CDCl3, 150 MHz) δ (ppm) 168.5,
136.6, 136.3, 136.2, 135.5, 134.1, 133.4, 130.5, 129.3, 128.9, 128.6,
128.4, 126.9, 126.3, 125.4, 124.3, 121.9, 44.9; MS (EI, 70 eV): m/z (%) =
379 (13) [M+], 139 (100), 141 (33), 240 (30). Anal. Calcd for
C22H15Cl2NO: 69.49; H, 3.98; N, 3.68. Found: C, 69.72; H, 3.84; N, 3.62.
(4-methoxyphenyl)(3-phenylquinolin-1(2H)-yl)methanone (14f)
1-(4-chlorophenyl)-2-(2-(4-methoxyphenyl)-1H-indol-1-yl)ethanone
(15d)
Yellow solid, mp 136-137 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.58 (d,
J = 7.8Hz, 2H, Ar-H), 7.41 (t, J = 7.8Hz,，2H, Ar-H), 7.34 (q, J = 7.8Hz，
3H, Ar-H), 7.21 (d, J = 7.2Hz, 1H, Ar-H), 7.03 (t, J = 7.2Hz, 1H, Ar-H),
6.97 (s, 1H, =CH), 6.87 (t, J = 7.8Hz , 1H, Ar-H), 6.75 (d, J = 8.4Hz, 2H,
White solid, mp 127-128 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.84 (d,
J = 8.4Hz, 2H, Ar-H), 7.64 (d, J = 7.2Hz, 1H, Ar-H), 7.43 (d, J = 7.8Hz,
2H, Ar-H), 7.32 (d, J = 8.4Hz, 2H, Ar-H), 7.15 (t, 2H, J = 8.4Hz, Ar-H),
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601628
European Journal of Organic Chemistry
FULL PAPER
7.06 (d, J = 7.8 Hz, 1H, Ar-H), 6.91 (d, 2H, J = 8.4Hz, Ar-H), 6.58 (s, 1H,
indole-3-H), 5.40 (s, 2H, CH2), 3.81 (s, 3H, CH3); 13C NMR (CDCl3, 150
MHz) δ (ppm) 192.8, 159.6, 141.4, 140.4, 137.9, 132.9, 130.5, 129.4,
129.2, 128.3, 124.6, 121.9, 120.7, 120.3, 114.1, 109.3, 102.3, 55.3, 50.7;
MS (EI, 70 eV): m/z (%) = 375 (23) [M+], 236 (100), 205 (16), 192 (14).
Anal. Calcd for C23H18ClNO2: C, 73.50; H, 4.83; N, 3.73. Found: C, 73.74;
H, 4.72; N, 3.59.
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1-(4-chlorophenyl)-2-(2-(4-chlorophenyl)-1H-indol-1-yl)ethanone
(15e)
White solid, mp 130-131 oC; 1H NMR (CDCl3, 400 MHz) δ (ppm) 7.82 (d,
J = 8.4 Hz, 2H, Ar-H), 7.64 (d, J = 7.8 Hz, 1H, Ar-H), 7.43 (d, J = 8.4 Hz,
2H, Ar-H), 7.32 (q, J = 11.4 Hz, 4H, Ar-H), 7.20 – 7.11 (m, 2H, Ar-H),
7.05 (d, J = 7.8 Hz, 1H, Ar-H), 6.62 (s, 1H, indole-3-H), 5.36 (s, 2H, CH2);
13C NMR (CDCl3, 150 MHz) δ (ppm) 192.6, 140.6, 140.2, 138.2, 134.3,
132.7, 130.7, 130.3, 129.3, 129.3, 128.9, 128.2, 122.4, 120.9, 120.6,
109.4, 103.2, 50.6; MS (EI, 70 eV): m/z (%) = 379 (23) [M+], 205 (100),
240 (58), 204 (56). Anal. Calcd for C22H15Cl2NO: C, 69.49; H, 3.98; N,
3.68. Found: C, 69.57; H, 3.81; N, 3.51.
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2-(2-(4-methoxyphenyl)-1H-indol-1-yl)-1-phenylethanone (15f)
White solid, mp 182-183 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 8.16-
6.78 (m, 13H, Ar-H), 6.58 (s, 1H, indole-3-H), 5.44 (s, 2H, CH2), 3.79 (s,
3H, CH3); 13C NMR (CDCl3, 150 MHz) δ (ppm) 193.8, 159.6, 141.5, 138.0,
134.7, 133.9, 130.5, 128.9, 128.3, 128.0, 124.7, 121.8, 120.6, 120.2,
114.1, 109.3, 102.1, 55.3, 50.7; MS (EI, 70 eV): m/z (%) = 341 (39) [M+],
236 (100), 237 (17), 205 (16). Anal. Calcd for C23H19NO2: C, 80.92; H,
5.61; N, 4.10. Found: C, 80.70; H, 5.77; N, 4.05.
1-(4-bromophenyl)-2-(2-phenyl-1H-indol-1-yl)ethanone (15g)
White solid, mp 143-144 oC; 1H NMR (CDCl3, 600 MHz) δ (ppm) 7.71 (d,
J = 8.4Hz, 2H, Ar-H), 7.64 (d, J = 6.6Hz, 1H, Ar-H), 7.56 (d, J = 8.4Hz,
2H, Ar-H), 7.36(t, 5H, J = 8.4Hz, Ar-H), 7.14 (t, 2H, J = 7.8Hz, Ar-H), 7.05
(d, J = 6.6Hz, 1H, Ar-H), 6.63 (s, 1H, indole-3-H), 5.36 (s, 2H, CH2); 13C
NMR (CDCl3, 150 MHz) δ (ppm) 192.9, 141.5, 138.1, 133.2, 132.2, 132.2,
129.4, 129.2, 129.1, 128.7, 128.3, 128.2, 122.2, 120.8, 120.4, 109.4,
102.8, 50.6; MS (EI, 70 eV): m/z (%) = 389 (12) [M+], 206 (100), 204 (22),
207 (17). Anal. Calcd for C22H16BrNO: C, 67.71; H, 4.13; N, 3.59. Found:
C, 67.82; H, 4.31; N, 3.70.
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1-(4-bromophenyl)-2-(2-(4-chlorophenyl)-1H-indol-1-yl)ethanone
(15h)
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o
1
White solid, mp 127-128 C; H NMR (CDCl3, 600 MHz) δ (ppm) 7.73(d,
J =8.4 Hz, 2H, Ar-H), 7.64 (d, J =7.8 Hz, 1H, Ar-H), 7.59 (d, J =8.4 Hz,
2H, Ar-H), 7.37-7.26 (m, 4H, Ar-H), 7.21-7.10 (m, 2H, Ar-H), 7.04 (d, J =
7.8Hz, 1H, Ar-H), 6.62 (s, 1H, indole-3-H), 5.35 (s, 2H, CH2); 13C NMR
(CDCl3, 150 MHz) δ (ppm) 192.8, 140.2, 138.2, 134.3, 133.1, 132.3,
130.7, 130.3, 129.4, 128.9, 128.2, 122.4, 120.9, 120.1, 109.4, 103.2,
122.2, 50.6; MS (EI, 70 eV): m/z (%) = 425 (19) [M+], 205 (100), 240 (63),
204 (56). Anal. Calcd for C22H15BrClNO: C, 62.21; H, 3.56; N, 3.30.
Found: C, 62.10; H, 3.77; N, 3.14.
Preparation of isoquinolin-1(2H)-one 4a in gram quantity: To a
solution of phosphine oxide (A) (0.576 g, 3.0 mmol) in anhydrous toluene
(100 mL) was added Ti(O-i-Pr)4 (1.59 g, 6 mmol) and TMDS (8.10 g, 60
mmol). After the reaction mixture was stirred at 110 °C for 30 min,
bromide 3a (10.77 g, 30 mmol) and NEt3 (3.64 g, 36 mmol) were added
sequentially. The reaction mixture was then stirred at 110 °C and
monitored by TLC. After the reaction was completed (24 h), the solvent
was removed under reduced pressure and the residue was purified by
flash chromatography on silica gel (ether/petroleum ether = 1:4, V/V) to
give isoquinolin-1(2H)-one 4a (6.79 g, 86% yield).
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Acknowledgements
We gratefully acknowledge financial support of this work by the
National Natural Science Foundation of China (No. 21572075,
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Keywords: Catalytic Intramolecular Wittig Reaction • Phosphine
Oxide • Isoquinolin-1(2H)-one • indole • 2,3-dihydro-1H-2-
benzazepin-1-one
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FULL PAPER
FULL PAPER
Long Wang, Mei Sun, and Ming-Wu
Ding*
R3P
Page No. – Page No.
Br
NEt3
Catalytic Intramolecular Wittig
Reaction Based on
Phosphine/Phosphine Oxide Catalytic
Cycle for Synthesis of Heterocycles
O
X
R1
X
R1
X= CON, O, CH2, NR
35-88% yield
R3PO(10%)
Text for Table of Contents
TMDS/Ti(i-PrO)4
The catalytic intramolecular Wittig reaction starting from the carbonyl-containing bromides is reported.
The byproduct R3PO participate in the catalytic cycle so that the Wittig reaction can accomplish only in
catalytic amount of organophosphorus reagent.
a Key Topic for the Table of Contents: Organophosphorus Catalysis
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