Electrophilic Cyclization of Aryl Propargylic Alcohols: Synthesis of Dihalogenated 6,9-Dihydropyrido[1,2-a]indoles via a Cascade Iodocyclization

Article abstract of DOI:10.1021/acs.joc.6b02013

A strategy for the synthesis of 6,9-dihydropyrido[1,2-a]indoles through a cascade iodocyclization of 4-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol derivatives is presented. This reaction was conducted under very mild conditions and in a short time. The reactions are metal-free, are environmentally friendly and give up to 94% yield. Moreover, the obtained halides allow functional group diversification by palladium-catalyzed coupling reactions, which could act as potential intermediates for the synthesis of valuable compounds.

Full text of DOI:10.1021/acs.joc.6b02013

Subscriber access provided by University of Illinois at Urbana-Champaign Library
Article
Electrophilic Cyclization of Aryl Propargylic
Alcohols: Synthesis of Dihalogenated 6,9-
dihydropyrido[1,2-a]indoles via a Cascade Iodocyclization
Jia Wang, Hai-Tao Zhu, Si Chen, Yu Xia, Dong-Po Jin, Yi-Feng Qiu, Ying-Xiu Li, and Yong-Min Liang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02013 • Publication Date (Web): 11 Oct 2016
Downloaded from http://pubs.acs.org on October 12, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Electrophilic Cyclization of Aryl Propargylic
Alcohols: Synthesis of Dihalogenated
6
,9-dihydropyrido[1,2-a]indoles via a Cascade
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Iodocyclization
†
‡
†
†
†
†
Jia Wang, Hai-Tao Zhu, Si Chen, Yu Xia, Dong-Po Jin, Yi-Feng Qiu,
†
,†
Ying-Xiu Li, and Yong-Min Liang*
†
State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, P.R. China.
‡
Shannxi Key Laboratory of Phytochemistry, Baoji University of Arts and
Sciences, Baoji 721013, China.
liangym@lzu.edu.cn
ABSTRACTꢀ
ꢀ
A strategy for the synthesis of 6,9-dihydropyrido[1,2-a]indoles through a
cascade
iodocyclization
of
4
-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol derivatives is presented.
This reaction is conducted under very mild condition and in a short time. The
reactions are metal-free, environmental friendly and up to 94% yield. Moreover,
the obtained halides allow functional group diversification by
palladium-catalyzed coupling reactions, which could act as potential
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
intermediates for the synthesis of valuable compounds.
INTRODUCTION
Nitrogen-containing heterocycles are ubiquitous structural units in significant
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
natural products and biologically active molecules.
Synthesis of
nitrogen-containing heterocycles has been the force of considerable attention
for a long time. Meanwhile, a variety of well-established methods have been
2
reported. Among multifarious N-heterocycles, indoles are well known to exert
3
biological activity in many medicinally important ingredients. Furthermore, the
pyridoindoles have unique nitrogen-containing tricyclic structures which
derived from indoles. The pyridoindoles are important heterocycles which
4
essentially contribute to the biological activities. As a result of the remarkable
pharmacological activities, much attention has been paid to the exploration
5
mild and efficient preparative protocols for building pyridoindoles. In recent
years, the electrophilic cyclization, especially iodocyclization, has been a
6
prominent research objective in organic chemistry. Many important
carbocycles and heterocycles have been produced based on the efficient
7
iodocyclizations. What’s more, the iodocyclizations are considered to be mild,
8
metal-free and environmental friendly. Although great achievements have
been made to iodocyclization, few examples of sequential cascade
iodocyclization to form pyridoindoles have been reported until now. Therefore,
seeking
alternative
methods
for
the
construction
of
6
,9-dihydropyrido[1,2-a]indoles based on iodocyclization is indeed desirable.
ACS Paragon Plus Environment

Page 3 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Scheme 1. Iodine-promoted Cascade Carbocyclization
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Recently, methods involving iodonium-induced activation of propargylic
alcohol substrates have offered the opportunity to construct diiodinated
9
10
11
carbocycles by Yamamoto, Wang, and our group. This reaction is
generally believed to proceed through a cascade process. Initial activation of
the propargyl hydroxyl group of A with a Lewis acidic iodine leads to the
propargyl carbocation intermediate B, which could resonate with allene
carbocation C. The intermediate C is reacted with an iodide anion to give D,
which can be activated by an iodide cation. Subsequent intramolecular
Friedel–Craft type reaction of the aromatic ring with the activated allene forms
the product E (Scheme 1a). Encouraged by these achievements and in
continuing our interest in the electrophilic cyclization of alkynols, we
envisioned that the substrates 1 containing an indole moiety could undergo the
identical isomerization process in the presence of electrophilic reagents and
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
then cyclize to afford dihalogenated 6,9-dihydropyrido[1,2-a]indoles (Scheme
1b). Herein, we report an effective method for the synthesis of a variety of
dihalogenated 6,9-dihydropyrido[1,2-a]indoles via sequential cascade
iodocyclization under mild reaction conditions.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
RESULTS AND DISCUSSION
Table 1. Optimization of Reaction Conditions for the Formation of 2a, 3a
a
or 4a with different electrophiles
ꢀ
b
entry
solvent
DCE
electrophile (equiv)
yield (%)
88
1
2
3
4
5
6
7
8
9
I
I
I
I
I
I
I
I
I
I
I
I
I
2
2
2
(1.0)
(1.2)
(1.5)
(1.2)
(1.2)ꢀ
(1.2)ꢀ
(1.2)ꢀ
(1.2)ꢀ
(1.2)ꢀ
(1.2)ꢀ
(1.2)ꢀ
(1.2)ꢀ
(1.2)ꢀ
DCE
94
DCE
94
CH
CH
CH
THF
Et
2
Cl
CN
NO
2
2
2
92
3
88
3
2
2
2
2
2
2
2
2
2
83
69
2
O
65
acetone
MeOH
toluene
DCE
84
1
0
80
11
88
c
1
1
2
3
83
d
DCE
92
14
DCE
IBr (1.2)
ICl (1.2)
83
81
1
5
DCE
a
All reactions were run under the following conditions, unless otherwise
indicated: 0.20 mmol of 1a, 1.2 equiv of electrophile in 4 mL of solvent were
ACS Paragon Plus Environment

Page 5 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
b
c
stirred at room temperature for 10 min. Yields of isolated products. The
d
reaction was run at 0 °C. The reaction was run at 40 °C.
At the onset of our investigation, we examined the reaction of
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1a) with 1.0 equiv of I
1,2-dichloroethane (DCE) at room temperature. The desired product
,8-diiodo-10-methyl-9,9-diphenyl-6,9-dihydropyrido[1,2-a]indole (2a) was
isolated in 88% yield after 10 min (Table 1, entry 1). An increase in the amount
of I to 1.2 equiv afforded 2a in 94% yield. The yield of 2a equaled to 94% by
increasing the amount of I to 1.5 equiv. After screening a series of solvents
such as CH Cl , CH CN, CH NO , THF, Et O, CH COCH , MeOH, and
2
in
7
2
2
2
2
3
3
2
2
3
3
toluene, we found that DCE was better than other solvents (entries 2 and 4-11).
However, an unsatisfactory yield of 2a was obtained when the reaction was
performed at 0 °C (entry 12). In addition, increasing the temperature to 40 °C
could not give a superior yield (entry 13). The reactions of 1a with IBr (1.2
equiv)
gave
the
expected
product
7
-bromo-8-iodo-10-methyl-9,9-diphenyl-6,9-dihydropyrido[1,2-a]indole (3a) in
83%
yield
(entry
14).
The
desired
product
7
-chloro-8-iodo-10-methyl-9,9-diphenyl-6,9-dihydropyrido[1,2-a]indole
(4a)
was obtained in the presence of ICl (1.2 equiv) (entry 15). From a series of
detailed investigations mentioned above, the combination of 1.0 equiv of 1a,
1
.2 equiv of electrophile in DCE at room temperature for 10 min was
determined as the optimum reaction conditions.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
Table 2. Electrophilic Iodocyclization for the Formation of 2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
All reactions were run under the following conditions, unless otherwise
2
indicated: 0.20 mmol of 1, 1.2 equiv of I in 4 mL of DCE were stirred at room
b
temperature for 10 min. The reaction was run for 30 min. Yields are given for
isolated products.
ACS Paragon Plus Environment

Page 7 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
After having established the optimized conditions for the present reaction,
various 4-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol derivatives were
subjected to the above conditions, as summarized in Table 2. The structure of
the representative product 2a was determined by X-ray crystallographic
analysis. The reactions of substrates 1b and 1c bearing double
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2
electron-donating groups (R and R ) on the para-position of the aromatic ring
resulted in the corresponding products 2b and 2c in excellent yields. The
yields of 2d and 2e decreased with the increase of electronegativity on the
1
2
substituent R and R groups. Subsequently, compounds 1f-1n with
2
electron-donating or electron-withdrawing substituents (R ) on different
positions of the aromatic ring were designed. The corresponding products
2
f-2n were obtained in good yields. In the meantime, the reactions also
worked well with the substrates 1o and 1p which had two substituents on the
same aryl group, furnishing the expected products 2o and 2p in good yields.
Afterwards, the huge steric hindrance substrate 1q with the 1-naphthyl group
was attempted and afforded the product 2q in 71% yield. It is noteworthy that
the corresponding product 2r was obtained in good yield when the substrate
had a cyclic substituent. Substrate 1s with both strong electron-rich and
electron-withdrawing substituent groups worked well and gave the product 2s
in a surprisingly high yield of 92%. The transformation proceeded smoothly for
the substrate 1t with a heterocyclic 2-thienyl group. Although the substrate 1y
with secondary alcohol failed to afford the corresponding product 2y, products
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
u-2x with alkyl groups were gained in good yields. This might be attributed to
theꢀ fact that one aryl group could not adequately stabilize the allene
1
2
carbocation generated by the propargylic alcohol substrate. Substrate 1z
with a phenyl group on the 3-position of indole also worked well and afforded
product 2z in 86% yield. It is noteworthy that when the methyl group was
absent from the 3-position of indole ring, the yield of 2aa was significantly
reduced. This might be due to the presence of a methyl group at the 3-position
of indole, which activated the indole ring system, facilitating the intramolecular
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
cyclization. Meanwhile, the substrates with substituents on different positions
of the indole rings gave the products 2ab-2ae in moderate to good yields. Due
to the fact that the electron cloud of indole could be influenced by the
substituents on it, the subsequent cyclization process was potentially affected.
As a strong electron-donating group, a methoxy group showed more
remarkable influence on the product yield. In particular, the substrate 1af with
two methyl groups instead of the hydrogens on the methylene was attempted
under the standard conditions. In this reaction, more reaction time was needed
for a full conversion of the substrate. A relative lower yield was obatined due to
steric effect. Neither the substrate 1ag with imidazole nor substrate 1af with
benzimidazole gave the desired products as our expectation.
ACS Paragon Plus Environment

Page 9 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Table 3. Synthesis of Dihalogenated 6,9-dihydropyrido[1,2-a]indoles with
a
IBr and ICl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ
a
All reactions were run under the following conditions, unless otherwise
indicated: 0.20 mmol of 1, 1.2 equiv of IBr or ICl in 4 mL of DCE were stirred at
room temperature for 10 min. Yields are given for isolated products.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
To explore the scope of the iodine-containing electrophiles and the
mechanism
of
this
electrophilic
cyclization,
the
reactions
of
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol derivatives with IBr and
ICl were tested, as depicted in Table 3. The product 3a was achieved in 83%
yield. The structure of the representative product 3a was determined by X-ray
crystallographic analysis. Similarly, other typical substrates also gave the
corresponding bromine-containing products in good yields. Meanwhile, in the
presence of ICl, the desired products 4a and 4b were gained in good yields.
For an increasing electronegativity of halogen anion, the yields of 3a and 4a
were progressively decreased due to an unstable intermediate C compared
with 2a.
Scheme 2. Proposed Reaction Mechanism
ꢀ
On the basis of the above observations, a plausible mechanism is
proposed in Scheme 2. First, in the presence of Lewis acidic iodine,
propargylic alcohol 1 was converted to the intermediate A along with an
unstable hypoiodous acid (HOI) and an iodine anion. The rapid
ACS Paragon Plus Environment

Page 11 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
tautomerization of A formed intermediate allene carbocation B. At the same
time, the halogen anion captured the allene carbocation to give the
halogenated intermediate C, which reacted with hypoiodous acid to form an
iodonium intermediate D. Subsequently, the activated allene intermediate D
was attacked by the 2-position of the indole ring to give the intermediate E,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
3
which delivered the products 2, 3 or 4 by deprotonation.
Scheme 3. Palladium-Catalyzed Coupling Reactions
ꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
As shown in Scheme 3, the compounds 2b, 3b, and 4b can be further
elaborated by using various palladium-catalyzed processes. The Suzuki
1
4
coupling of 2b and 3b afforded the same product 5b in 57% and 71% yields,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
respectively. In the meantime, the Suzuki coupling of 4b furnished the product
1
5
6b in 62% yield. The Sonagashira coupling of 2b gave the corresponding
product 7b in 36% yield and 30% of 2b was recovered.
CONCLUSION
In conclusion, a new and mild protocol for the synthesis of dihalogenated
6
,9-dihydropyrido[1,2-a]indoles has been established. This method adds
interest to this clean process and also relates to the incorporation of iodine,
which opens broad perspectives for future research. Noteworthily, the resulting
halogenated 6,9-dihydropyrido[1,2-a]indoles are readily elaborated to more
products by using known organopalladium chemistry, which may be essential
intermediates for building delicate and sophisticated natural products. Further
studies on expanding this strategy are in progress in our laboratory.
EXPERIMENTAL SECTION
General
procedure
for
synthesis
of
4
-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol derivatives (1a-1ae)
To a solution of indole derivatives (100 mmol) in DMF (250 mL) was
o
added NaH (60%, 2.0 equiv) slowly at 0 C, The resulting solution was stirred
o
1
h at 0 C, Then, the propargylic bromide (2.0 equiv) was added dropwise
through a syringe. The reaction mixture was stirred at room temperature for
ACS Paragon Plus Environment

Page 13 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
another 2h. When the reaction was considered complete as determined by
TLC analysis, the mixture was quenched by water (200 mL) and extracted by
ethyl acetate (3 x 150 mL). The combined organic layer was dried over
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2 4 2 4
anhydrous Na SO , the Na SO was removed by decantation and the organic
phase was concentrated under reduced pressure and purified by silica gel
flash column chromatography (petroleum ether/EtOAc = 30/1) in 70-90%
1
6
yields. A solution of the above 1-(prop-2-yn-1-yl)-1H-indole derivatives (5
mmol) in THF (20 mL) with Ar was cooled to −40°C and n-BuLi (2.4 mol/L in
o
THF, 1.1 equiv) was added dropwise. After stirring 30 minutes at −40 C, the
solution of ketone C (1.5 equiv) in THF (5 mL) was added to the reaction via
syringe and the resulting mixture was removed to room temperature. After 2h,
the mixture was quenched by water, and extracted with ethyl acetate (3 x 40
mL). The combined organic layers were washed with water, brine, dried over
2 4 2 4
Na SO , the Na SO was removed by decantation and the organic phase was
concentrated under reduced pressure. The crude material was purified by
flash column chromatography (petroleum ether/EtOAc = 10/1) in 65-85%
1
7
yields to give the substrate 1.
Synthesis of 1af
To a solution of 3-methyl-1H-indole (30 mmol) in DMF (100 mL) was
o
added NaH (60%, 2.0 equiv) slowly at 0 C, The resulting solution was stirred
o
2
h at 0 C, Then, the 3-chloro-3-methylbut-1-yne (2.0 equiv) was added
dropwise through a syringe. The reaction mixture was stirred at room
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
temperature for another 12h. When the reaction was considered complete as
determined by TLC analysis, the mixture was quenched by water and
extracted by ethyl acetate (3 x 60 mL). The combined organic layer was dried
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2 4 2 4
over anhydrous Na SO , the Na SO was removed by decantation and the
organic phase was concentrated under reduced pressure and purified by silica
gel flash column chromatography (petroleum ether/EtOAc = 30/1) in 15% yield
(887
mg)
to
provide
desired
product
1
8
3-methyl-1-(2-methylbut-3-yn-2-yl)-1H-indole.
The substrate 1af was
synthesized from 3-methyl-1-(2-methylbut-3-yn-2-yl)-1H-indole according to
general procedure as mentioned above.
Synthesis of 1ag and 1ah
To a solution of imidazole (28.0 mmol) in THF (30 mL) was added NaOH (28.0
o
mmol). The resulting mixture was stirred at 50 C for 1h before it was coold to
room temperature. Subsenquently, 3-bromopropyne (30.8 mmol, 1.1 equiv)
was added and the solution stirred for another 12h. After filtration, the resulting
solution was concentrated under reduced pressure and purified by silica gel
flash column chromatography (petroleum ether/EtOAc = 2/1) in 70% yield to
1
9
provide 1-(prop-2-yn-1-yl)-1H-imidazole. The substrate 1ag was synthesized
from 1-(prop-2-yn-1-yl)-1H-imidazole according to general procedure as
mentioned above. The substrate 1ah which was synthesized from
benzimidazole was similar to general procedure for the synthesis of substrate
1
ag.
ACS Paragon Plus Environment

Page 15 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
General
6,9-dihydropyrido[1,2-a]indoles
To a solution of 1 (0.20 mmol) in DCE (4.0 mL) was added I
0.24 mmol, 1.2 equiv) at room temperature. When the reaction was
Procedure
for
Synthesis
of
halogenated
2
, IBr or ICl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(
considered complete as determined by TLC analysis, the reaction mixture was
quenched by addition of saturated aqueous sodium thiosulfate and diluted with
ethyl acetate (3 x 15 mL), washed with water, saturated brine, dried over
2 4 2 4
Na SO , the Na SO was removed by decantation and the organic phase was
concentrated under reduced pressure. The residue was purified by
chromatography on silica gel (petroleum ether/EtOAc = 30/1) to afford
corresponding halogenated 6,9-dihydropyrido[1,2-a]indoles derivatives 2, 3 or
4
.
2
To a solution of 1af (0.20 mmol) in DCE (4.0 mL) was added I (0.24 mmol,
1.2 equiv) at room temperature. When the reaction was considered complete
as determined by TLC analysis, the reaction mixture was evaporated under
reduced pressure. The residue was purified by chromatography on silica gel
(petroleum ether/EtOAc = 30/1) to afford corresponding product 2af.
Typical Procedure for 5b (synthesis from 2b): To a solution of
7
,8-diiodo-10-methyl-9,9-di-p-tolyl-6,9-dihydropyrido[1,2-a]indole 2b (123.0
mg, 0.20 mmol) in dioxane/H (2:0.5 mL) was added
-Methoxyphenylboronic acid (121.6 mg, 4.0 equiv), Pd(PPh (46.2 mg, 20
2
O
4
3 4
)
mol % ), Na
2
CO
3
(212 mg, 10.0 equiv). The reaction vial was flushed with Ar
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
and the reaction mixture was stirred at 80 °C for 12h. On completion, the
reaction mixture was quenched with H
ether (3 x 10 mL). The combined organic layers were washed with water, brine,
dried over Na SO , the Na SO was removed by decantation and the organic
2
O (10 mL) and extracted with ethyl
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
4
2
4
phase was concentrated under reduced pressure. The crude material was
purified by flash column chromatography (petroleum ether/EtOAc = 20/1) to
1
4a
give 5b.
Typical Procedure for 5b (synthesis from 3b): To a solution of
-bromo-8-iodo-10-methyl-9,9-di-p-tolyl-6,9-dihydropyrido[1,2- a]indole 3b
113.6 mg, 0.20 mmol) in dioxane/H (2:0.5 mL) was added
4-Methoxyphenylboronic acid (121.6 mg, 4.0 equiv), Pd(PPh (46.2 mg, 20
mol % ), Na CO (212 mg, 10.0 equiv). The reaction vial was flushed with Ar
and the reaction mixture was stirred at 80 °C for 12h. On completion, the
reaction mixture was quenched with H O (10 mL) and extracted with ethyl
ether (3 x 10 mL). The combined organic layers were washed with water, brine,
dried over Na SO , the Na SO was removed by decantation and the organic
7
(
2
O
3 4
)
2
3
2
2
4
2
4
phase was concentrated under reduced pressure. The crude material was
purified by flash column chromatography (petroleum ether/EtOAc = 20/1) to
14a
give 5b.
Typical
-chloro-8-iodo-10-methyl-9,9-di-p-tolyl-6,9-dihydropyrido[1,2-a]indole
104.7 mg, 0.20 mmol) in dioxane/H
Procedure
for
6b:
To
a
solution
of
7
4b
(
2
O
(2:0.5 mL) was added
ACS Paragon Plus Environment

Page 17 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
4
3 4
-Methoxyphenylboronic acid (60.8 mg, 2.0 equiv), Pd(PPh ) (23.1 mg, 10
mol % ), Na
and the reaction mixture was stirred at 80 °C for 12h. On completion, the
reaction mixture was quenched with H O (10 mL) and extracted with ethyl
ether (3 x 10 mL). The combined organic layers were washed with water, brine,
dried over Na SO , the Na SO was removed by decantation and the organic
2 3
CO (106 mg, 5.0 equiv). The reaction vial was flushed with Ar
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
2
4
2
4
phase was concentrated under reduced pressure. The crude material was
purified by flash column chromatography (petroleum ether/EtOAc = 20/1) to
1
4a
give 6b.
Typical Procedure for 7b: To a soluton of 2b (123.0 mg, 0.2 mmol) in
anhydrous CH CN (4 mL) was added K CO (55.2 mg, 2.0 equiv),
PdCl (PPh (11.2 mg, 8 mol%), CuI (1.5 mg, 4 mol%) and
-ethynyl-4-methoxybenzene (79.2 mg, 3.0 equiv). The reaction vial was
3
2
3
2
3 2
)
1
flushed with Ar and the reaction mixture was stirred for 48h at 50°C. Then, the
mixture was quenched slowly by addition of aqueous 1M HCl (4 mL) and
extracted with ethyl ether (3 x 20 mL). The combined organic layers were
2 4 2 4
washed with water, brine, dried over Na SO , the Na SO was removed by
decantation and the organic phase was concentrated under reduced pressure.
The crude material was purified by flash column chromatography
1
5c
(petroleum ether/EtOAc = 20/1) to give 7b.
Characterization Data of 1a−1ah
4
-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1a): Pale yellow solid,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
H NMR (400 MHz, CDCl
3
) δ ppm 7.55 (d, J = 8.0 Hz, 1H), 7.50-7.47 (m, 4H),
7.33 (d, J = 8.0 Hz, 1H), 7.26-7.18 (m, 7H), 7.12 (t, J = 8.0 Hz, 1H), 6.89 (s,
1
3
1
H), 4.83 (s, 2H), 2.81 (s, 1H), 2.28 (s, 3H). C NMR (100 MHz, CDCl
3
) δ ppm
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
44.4, 136.1, 129.2, 128.2, 127.7, 125.9, 124.9, 121.7, 119.1, 111.2, 109.3,
87.5, 81.8, 74.3, 35.9, 9.6.
4
-(3-methyl-1H-indol-1-yl)-1,1-di-p-tolylbut-2-yn-1-ol (1b): Pale yellow oil,
1
3
H NMR (400 MHz, CDCl ) δ ppm 7.56 (d, J = 7.6 Hz, 1H), 7.39-7.34 (m, 5H),
7.22 (t, J = 7.6 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.0 Hz, 4H), 6.93
1
3
(
s, 1H), 4.88 (s, 2H), 2.70 (s, 1H), 2.30 (s, 3H), 2.29 (s, 6H). C NMR (100
MHz, CDCl ) δ ppm 141.8, 137.4, 136.1, 129.1, 128.9, 125.8, 124.9, 121.7,
119.1, 111.1, 109.3, 87.8, 81.4, 74.1, 35.9, 21.0, 9.6.
3
1
,1-bis(4-methoxyphenyl)-4-(3-methyl-1H-indol-1-yl)but-2-yn-1-ol
(1c):
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.55 (d, J = 7.6 Hz, 1H), 7.37
(d, J = 8.8 Hz, 4H), 7.33 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.12 (t, J =
7
.6 Hz, 1H), 6.90 (s, 1H), 6.76 (d, J = 8.8 Hz, 4H), 4.84 (s, 2H), 3.71 (s, 6H),
13
2
3
.88 (s, 1H), 2.29 (s, 3H). C NMR (100 MHz, CDCl ) δ ppm 158.9, 137.0,
136.1, 129.1, 127.2, 124.9, 121.7, 119.1, 113.4, 111.1, 109.3, 87.9, 81.3, 73.6,
5
5.2, 35.9, 9.6.
1
,1-bis(4-fluorophenyl)-4-(3-methyl-1H-indol-1-yl)but-2-yn-1-ol (1d): Pale
1
yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.56 (d, J = 8.0 Hz, 1H), 7.41-7.38
(m, 4H), 7.31 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 7.2 Hz, 1H), 7.13 (t, J = 7.2 Hz,
1
H), 6.92 (t, J = 8.4 Hz, 4H), 6.88 (s, 1H), 4.87 (s, 2H), 2.82 (s, 1H), 2.29 (s,
ACS Paragon Plus Environment

Page 19 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
3
1
3
H). C NMR (100 MHz, CDCl
3
) δ ppm 162.2 (d, JC-F = 245 Hz), 140.1, 136.1,
3
2
129.2, 127.7 (d, JC-F = 8 Hz), 124.9, 121.8, 119.2, 115.1 (d, JC-F = 21 Hz),
1
11.4, 190.2, 87.0, 82.3, 73.4, 35.8, 9.5.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
,1-bis(4-chlorophenyl)-4-(3-methyl-1H-indol-1-yl)but-2-yn-1-ol (1e): Pale
1
yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.54 (d, J = 8.0 Hz, 1H), 7.32-7.29
(m, 5H), 7.19-7.15 (m, 5H), 7.13-7.09 (m, 1H), 6.84 (s, 1H), 4.82 (s, 2H), 2.86
1
3
3
(s, 1H), 2.27 (s, 3H). C NMR (100 MHz, CDCl ) δ ppm 142.5, 136.0, 133.8,
129.2, 128.4, 127.3, 124.9, 121.8, 119.2, 111.4, 109.2, 86.4, 82.6, 73.4, 35.8,
9
.5.
4
-(3-methyl-1H-indol-1-yl)-1-phenyl-1-(o-tolyl)but-2-yn-1-ol
(1f):
Pale
1
yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.86-7.84 (m, 1H), 7.56 (d, J = 7.2
Hz, 1H), 7.38 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.4 Hz, 1H), 7.25-7.18 (m, 6H),
.12 (t, J = 7.6 Hz, 1H), 7.08-7.06 (m, 1H), 6.89 (s, 1H), 4.85 (s, 2H), 2.68 (s,
7
1
3
1H), 2.30 (s, 3H), 1.99 (s, 3H). C NMR (100 MHz, CDCl
3
) δ ppm 143.5, 141.0,
36.2, 136.1, 132.0, 129.1, 128.3, 128.1, 127.9, 126.3, 126.0, 125.5, 124.9,
21.7, 119.1, 111.2, 109.2, 86.6, 82.2, 74.0, 35.9, 20.9, 9.6.
1
1
4-(3-methyl-1H-indol-1-yl)-1-phenyl-1-(m-tolyl)but-2-yn-1-ol (1g): Pale
1
yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.57-7.55 (m, 1H), 7.51-7.48 (m,
2H), 7.36-7.31 (m, 2H), 7.27-7.21 (m, 5H), 7.14-7.11 (m, 2H), 7.02 (d, J = 6.8
1
3
Hz, 1H), 6.91 (s, 1H), 4.85 (s, 2H), 2.83 (s, 1H), 2.29 (s, 3H), 2.24 (s, 3H). C
NMR (100 MHz, CDCl ) δ ppm 144.5, 144.4, 137.9, 136.1, 129.1, 128.5, 128.2,
28.1, 127.7, 126.5, 125.9, 124.9, 123.0, 121.7, 119.1, 111.1, 109.3, 87.6,
3
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
8
1.7, 74.3, 35.9, 21.4, 9.6.
4-(3-methyl-1H-indol-1-yl)-1-phenyl-1-(p-tolyl)but-2-yn-1-ol
(1h): Pale
1
yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.56 (d, J = 8.0 Hz, 1H), 7.49 (d, J
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
=
7.2 Hz, 2H), 7.38-7.33 (m, 3H), 7.27-7.19 (m, 4H), 7.15-7.10 (m, 1H), 7.06 (d,
J = 8.0 Hz, 2H), 6.91 (s, 1H), 4.85 (s, 2H), 2.81 (s, 1H), 2.29 (s, 3H), 2.28 (s,
1
3
3H). C NMR (100 MHz, CDCl
3
) δ ppm 144.6, 141.6, 137.5, 136.1, 129.1,
1
28.9, 128.2, 127.6, 125.8, 124.9, 121.7, 119.1, 111.1, 109.3, 87.6, 81.6, 74.2,
35.8, 21.0, 9.6.
1
-(4-methoxyphenyl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol (1i):
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.54 (d, J = 7.6 Hz, 1H), 7.47
(d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 1H), 7.26-7.17
(m, 4H), 7.14-7.09 (m, 1H), 6.88 (s, 1H), 6.73 (d, J = 8.8 Hz, 2H), 4.82 (s, 2H),
13
3
3.67 (s, 3H), 2.87 (s, 1H), 2.28 (s, 3H). C NMR (100 MHz, CDCl ) δ ppm
159.0, 144.7, 136.8, 136.1, 129.2, 128.1, 127.6, 127.3, 125.9, 124.9, 121.7,
1
19.1, 113.5, 111.1, 109.3, 87.8, 81.5, 74.0, 55.1, 35.8, 9.5.
1
-(2-chlorophenyl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol (1j):
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.83 (d, J = 7.2 Hz, 1H), 7.55
(d, J = 8.0 Hz, 1H), 7.40 (s, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.29-7.17 (m, 7H),
7.11 (t, J = 6.8 Hz, 1H), 6.92 (s, 1H), 4.84 (s, 2H), 3.17 (s, 1H), 2.29 (s, 3H).
1
3
3
C NMR (100 MHz, CDCl ) δ ppm 142.7, 140.3, 136.1, 132.3, 131.1, 129.3,
1
8
29.1, 128.2, 128.0, 127.9, 126.6, 126.5, 125.0, 121.7, 119.0, 111.0, 109.3,
5.5, 82.1, 73.7, 35.9, 9.6.
ACS Paragon Plus Environment

Page 21 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
-(3-chlorophenyl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol (1k):
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.56-7.53 (m, 2H), 7.46 (d, J
=
6
6.8 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.26-7.20 (m, 4H), 7.18-7.10 (m, 3H),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
3
3
.89 (s, 1H), 4.87 (s, 2H), 2.82 (s, 1H), 2.29 (s, 3H). C NMR (100 MHz, CDCl )
δ ppm 146.4, 143.8, 136.1, 134.1, 129.5, 129.2, 128.4, 128.0, 127.9, 126.1,
1
25.8, 124.9, 124.1, 121.9, 119.2, 111.3, 109.2, 86.8, 82.3, 73.9, 35.8, 9.6.
1
-(4-chlorophenyl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol (1l):
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.55 (d, J = 8.0 Hz, 1H), 7.44
(
d, J = 6.8 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.27-7.18
m, 6H), 7.12 (t, J = 8.0 Hz, 1H), 6.88 (s, 1H), 4.86 (s, 2H), 2.82 (s, 1H), 2.29 (s,
(
1
3
3H). C NMR (100 MHz, CDCl
3
) δ ppm 144.0, 143.0, 136.1, 133.6, 129.2,
28.3, 128.3, 128.0, 127.4, 125.8, 124.9, 121.8, 119.2, 111.3, 109.2, 86.9,
2.2, 73.9, 35.8, 9.6.
1
8
1-(4-fluorophenyl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol (1m):
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.55 (d, J = 8.0 Hz, 1H),
7
.46-7.40 (m, 4H), 7.33 (d, J = 8.0 Hz, 1H), 7.27-7.18 (m, 4H), 7.15-7.10 (m,
1
3
1H), 6.92-6.88 (m, 3H), 4.85 (s, 2H), 2.81 (s, 1H), 2.28 (s, 3H). C NMR (100
1
MHz, CDCl
3
) δ ppm 162.1 (d, JC-F = 245 Hz), 144.3, 140.3, 136.1, 129.2,
2
1
28.8, 127.9, 127.8, 127.8, 125.8, 124.9, 121.8, 119.2, 115.0 (d, JC-F = 22 Hz),
111.3, 109.2, 87.2, 82.0, 73.9, 35.8, 9.6.
1
-([1,1'-biphenyl]-4-yl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol
1
(
1n): Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.56-7.50 (m, 7H), 7.46
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
d, J = 8.0 Hz, 2H), 7.39-7.34 (m, 3H), 7.31-7.19 (m, 5H), 7.14-7.11 (m, 1H),
1
3
6.90 (s, 1H), 4.85 (s, 2H), 2.82 (s, 1H), 2.29 (s, 3H). C NMR (100 MHz, CDCl
δ ppm 144.3, 143.4, 140.6, 140.4, 136.1, 129.2, 128.7, 128.3, 127.8, 127.3,
27.0, 126.9, 126.4, 125.9, 124.9, 121.8, 119.1, 111.2, 109.3, 87.4, 81.9, 74.2,
35.9, 9.6.
3
)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
1
-(3,4-dimethylphenyl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol
1
(
1o): Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.56-7.51 (m, 3H), 7.35
(s, 1H), 7.25-7.21 (m, 6H), 7.13-7.12 (m, 1H), 7.01 (s, 1H), 6.91 (s, 1H), 4.83 (s,
1
3
2
H), 2.80 (s, 1H), 2.31 (s, 3H), 2.17 (s, 6H). C NMR (100 MHz, CDCl
3
) δ ppm
1
44.6, 142.0, 136.4, 136.2, 136.1, 129.4, 129.2, 128.2, 127.6, 127.1, 125.9,
124.9, 123.3, 121.7, 119.1, 111.1, 109.3, 87.8, 81.5, 74.2, 35.9, 19.8, 19.4,
9
.6.
1
-(3,4-dichlorophenyl)-4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol
1
(1p): Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.60 (s, 1H), 7.55 (d, J
=
8.0 Hz, 1H), 7.45-7.43 (m, 2H), 7.34 (d, J = 8.4 Hz, 1H), 7.29-7.19 (m, 6H),
.13 (t, J = 8.0 Hz, 1H), 6.89 (s, 1H), 4.89 (s, 2H), 2.83 (s, 1H), 2.29 (s, 3H).
7
1
3
3
C NMR (100 MHz, CDCl ) δ ppm 144.7, 143.5, 136.1, 132.3, 131.8, 130.1,
1
8
29.2, 128.5, 128.2, 127.9, 125.8, 125.4, 124.9, 121.9, 119.2, 111.5, 109.2,
6.4, 82.6, 73.5, 35.8, 9.6.
4-(3-methyl-1H-indol-1-yl)-1-(naphthalen-1-yl)-1-phenylbut-2-yn-1-ol (1q):
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 8.00-7.94 (m, 2H), 7.80-7.77
(m, 2H), 7.54 (d, J = 7.6 Hz, 1H), 7.45-7.39 (m, 3H), 7.34 (t, J = 7.6 Hz, 1H),
ACS Paragon Plus Environment

Page 23 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
7
.26-7.15 (m, 6H), 7.10 (t, J = 7.6 Hz, 1H), 6.79 (s, 1H), 4.77 (s, 2H), 2.89 (s,
1
3
1H), 2.25 (s, 3H). C NMR (100 MHz, CDCl
3
) δ ppm 144.1, 138.3, 136.2,
34.5, 129.8, 129.5, 129.2, 128.6, 128.4, 128.0, 126.6, 126.3, 125.5, 125.3,
25.0, 124.6, 124.5, 121.7, 119.1, 119.1, 111.1, 109.2, 87.5, 82.9, 74.4, 35.9,
1
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
9.5.
-(3-(3-methyl-1H-indol-1-yl)prop-1-yn-1-yl)-2,3-dihydro-1H-inden-1-ol (1r):
1
1
Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.52 (d, J = 7.6 Hz, 1H), 7.37
(d, J = 6.4 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 7.22-7.16 (m, 4H), 7.11-7.08 (m,
1H), 6.86 (s, 1H), 4.73 (s, 2H), 3.02-2.95 (m, 1H), 2.80 (s, 1H), 2.46-2.39 (m,
1
3
2
3
H), 2.31-2.29 (m, 1H), 2.27 (s, 3H). C NMR (100 MHz, CDCl ) δ ppm 145.2,
142.8, 136.0, 129.0, 128.9, 127.0, 124.9, 124.8, 123.1, 121.6, 119.0, 119.0,
1
10.9, 109.2, 86.9, 79.2, 76.1, 42.9, 35.7, 29.4, 9.5.
1
-(4-fluorophenyl)-1-(4-methoxyphenyl)-4-(3-methyl-1H-indol-1-yl)but-2-y
1
n-1-ol (1s): Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.55 (d, J = 8.0
Hz, 1H), 7.43-7.39 (m, 2H), 7.35-7.31 (m, 3H), 7.20 (t, J = 7.6 Hz, 1H), 7.12 (t,
J = 7.6 Hz, 1H), 6.93-6.87 (m, 3H), 6.74 (d, J = 8.0 Hz, 2H), 4.83 (s, 2H), 3.69
1
3
(s, 3H), 3.04 (s, 1H), 2.28 (s, 3H). C NMR (100 MHz, CDCl
3
) δ ppm 162.0 (d,
1
3
J
C-F = 245 Hz), 159.0, 140.5, 136.6, 136.0, 129.1, 127.7 (d, JC-F = 8 Hz),
2
1
27.2, 124.9, 121.7, 119.1, 114.9 (d, JC-F = 21 Hz), 111.2, 109.2, 87.4, 81.7,
73.4, 55.1, 35.8, 9.5.
1
-(4-fluorophenyl)-4-(3-methyl-1H-indol-1-yl)-1-(thiophen-2-yl)but-2-yn-1-
1
ol (1t): Pale yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.57-7.51 (m, 3H),
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
7
.34 (d, J = 8.4 Hz, 1H), 7.23-7.19 (m, 2H), 7.13 (t, J = 7.6 Hz, 1H), 6.98-6.91
1
3
(m, 4H), 6.85-6.83 (m, 1H), 4.88 (s, 2H), 3.00 (s, 1H), 2.30 (s, 3H). C NMR
1
(100 MHz, CDCl
3
) δ ppm 162.4 (d, JC-F = 246 Hz), 149.4, 139.5, 136.1, 129.1,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
2
1
27.6 (d, JC-F = 9 Hz), 126.5, 126.1, 125.5, 124.9, 121.8, 119.2, 115.0 (d, JC-F
= 21 Hz), 111.3, 109.2, 86.6, 81.4, 71.3, 35.8, 9.6.
1
5
-(3-methyl-1H-indol-1-yl)-2-phenylpent-3-yn-2-ol (1u): Pale yellow oil, H
3
NMR (400 MHz, CDCl ) δ ppm 7.54-7.51 (m, 3H), 7.32-7.18 (m, 5H), 7.10 (t, J
= 7.6 Hz, 1H), 6.88 (s, 1H), 4.78 (s, 2H), 2.54 (s, 1H), 2.28 (s, 3H), 1.68 (s, 3H).
1
3
C NMR (100 MHz, CDCl
24.8, 121.7, 119.1, 119.0, 111.0, 109.2, 88.2, 79.2, 69.8, 35.7, 33.0, 9.5.
5-(3-methyl-1H-indol-1-yl)-2-(p-tolyl)pent-3-yn-2-ol (1v): Pale yellow oil, H
NMR (400 MHz, CDCl ) δ ppm 7.55 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 7.6 Hz,
H), 7.33 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.15-7.09 (m, 3H), 6.91
3
) δ ppm 145.1, 136.1, 129.1, 128.2, 127.7, 124.8,
1
1
3
2
1
3
(s, 1H), 4.81 (s, 2H), 2.51 (s, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 1.69 (s, 3H). C
NMR (100 MHz, CDCl ) δ ppm 142.2, 137.4, 136.0, 129.0, 128.9, 124.8, 124.7,
21.7, 119.1, 119.0, 111.0, 109.2, 88.3, 79.0, 69.7, 35.7, 32.9, 21.0, 9.6.
3
1
2-(4-chlorophenyl)-5-(3-methyl-1H-indol-1-yl)pent-3-yn-2-ol (1w): Pale
1
yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.54 (d, J = 7.6 Hz, 1H), 7.41 (d, J
=
8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz, 1H), 7.24-7.18 (m, 3H), 7.11 (t, J = 7.6 Hz,
1
3
1H), 6.88 (s, 1H), 4.81 (s, 2H), 2.56 (s, 1H), 2.29 (s, 3H), 1.64 (s, 3H). C NMR
100 MHz, CDCl ) δ ppm 143.5, 136.0, 133.4, 129.0, 128.3, 126.3, 124.8,
21.7, 119.2, 119.1, 111.2, 109.1, 87.6, 79.6, 69.4, 35.7, 33.0, 9.6.
(
3
1
ACS Paragon Plus Environment

Page 25 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
6
-(3-methyl-1H-indol-1-yl)-3-phenylhex-4-yn-3-ol (1x): Pale yellow oil, H
NMR (400 MHz, CDCl ) δ ppm 7.56 (d, J = 7.6 Hz, 1H), 7.41 (d, J = 7.2 Hz,
H), 7.36 (d, J = 8.4 Hz, 1H), 7.31-7.19 (m, 4H), 7.13 (t, J = 7.2 Hz, 1H), 6.95
s, 1H), 4.87 (s, 2H), 2.46 (s, 1H), 2.31 (s, 3H), 1.96-1.82 (m, 2H), 0.88 (t, J =
3
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(
1
3
7.2 Hz, 3H). C NMR (100 MHz, CDCl
3
) δ ppm 143.9, 136.0, 129.1, 128.1,
27.6, 125.4, 124.9, 121.7, 119.1, 119.0, 111.1, 109.2, 87.1, 80.3, 73.8, 38.11,
5.7, 9.6, 9.0.
1
3
1
4-(3-methyl-1H-indol-1-yl)-1-phenylbut-2-yn-1-ol (1y): Pale yellow oil, H
NMR (400 MHz, CDCl ) δ ppm 7.54 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 6.4 Hz,
H), 7.31-7.26 (m, 4H), 7.21-7.18 (m, 1H), 7.14-7.09 (m, 1H), 6.86 (s, 1H),
3
2
1
3
5.30 (s, 1H), 4.75 (s, 2H), 2.50 (s, 1H), 2.28 (s, 3H). C NMR (100 MHz, CDCl
δ ppm 140.1, 136.0, 129.1, 128.5, 128.3, 126.5, 124.9, 121.7, 119.1, 119.1,
11.1, 109.2, 84.5, 81.0, 64.3, 35.6, 9.5.
1,1-diphenyl-4-(3-phenyl-1H-indol-1-yl)but-2-yn-1-ol (1z): Yellow oil, H
NMR (400 MHz, CDCl ) δ ppm 7.93 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.0 Hz,
H), 7.51-7.49 (m, 4H), 7.42-7.38 (m, 3H), 7.29 (s, 1H), 7.27-7.17 (m, 9H),
3
)
1
1
3
2
1
3
4.89 (s, 2H), 2.81 (s, 1H). C NMR (100 MHz, CDCl
3
) δ ppm 144.4, 136.6,
35.2, 128.7, 128.3, 127.8, 127.3, 126.7, 125.9, 125.9, 124.9, 122.3, 120.4,
20.1, 117.6, 109.7, 88.3, 81.2, 74.4, 36.2.
1
1
1
4-(1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1aa): Pale yellow oil, H NMR
400 MHz, CDCl ) δ ppm 7.60 (d, J = 7.6 Hz, 1H), 7.48-7.46 (m, 4H), 7.35 (d, J
8.0 Hz, 1H), 7.25-7.17 (m, 7H), 7.12-7.08 (m, 2H), 7.47 (d, J = 3.2 Hz, 1H),
(
3
=
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
4
.84 (s, 2H), 2.83 (s, 1H). C NMR (100 MHz, CDCl
3
) δ ppm 144.4, 135.7,
128.8, 128.2, 127.7, 127.2, 125.9, 121.8, 121.0, 119.8, 109.4, 101.9, 87.9,
8
1.4, 74.3, 36.1.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
-(4-chloro-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1ab): Pale yellow oil,
1
H NMR (400 MHz, CDCl
3
) δ ppm 7.49-7.47 (m, 4H), 7.27-7.20 (m, 7H), 7.16
(
d, J = 3.2 Hz, 1H), 7.13-7.07 (m, 2H), 6.60 (s, 1H), 4.88 (s, 2H), 2.81 (s, 1H).
1
3
3
C NMR (100 MHz, CDCl ) δ ppm 144.3, 136.5, 128.3, 127.8, 127.6, 126.2,
125.9, 122.4, 119.6, 108.2, 100.7, 88.3, 80.9, 74.4, 36.5.
4
-(5-methoxy-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1ac): Pale yellow
1
oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.49 (d, J = 7.2 Hz, 4H), 7.26-7.16 (m,
7H), 7.09 (d, J = 2.8 Hz, 1H), 7.05 (s, 1H), 6.85 (d, J = 8.8 Hz, 1H), 6.39 (s, 1H),
1
3
4
.83 (s, 2H), 3.77 (s, 3H), 3.01 (s, 1H). C NMR (100 MHz, CDCl
3
) δ ppm
1
5.42, 144.5, 131.1, 129.3, 128.2, 127.8, 127.7, 125.9, 112.1, 110.2, 102.8,
101.5, 87.9, 81.4, 74.3, 55.8, 36.3.
4
-(6-chloro-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1ad): Pale yellow oil,
1
3
H NMR (400 MHz, CDCl ) δ ppm 7.49-7.47 (m, 5H), 7.40 (s, 1H), 7.28-7.19
(m, 6H), 7.09-7.07 (m, 2H), 6.43 (d, J = 3.2 Hz, 1H), 4.80 (s, 2H), 2.85 (s, 1H).
1
3
C NMR (100 MHz, CDCl
3
) δ ppm 144.3, 136.1, 128.3, 128.1, 127.8, 127.4,
1
25.9, 121.9, 120.6, 109.6, 102.1, 88.4, 80.8, 74.4 , 36.3.
4-(7-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1ae): Pale yellow
1
solid, H NMR (400 MHz, CDCl
3
) δ ppm 7.44-7.41 (m, 5H), 7.23-7.16 (m, 6H),
7
.04 (d, J = 3.2 Hz, 1H), 6.98 (t, J = 7.2 Hz, 1H), 6.91 (d, J = 7.2 Hz, 1H), 6.45
ACS Paragon Plus Environment

Page 27 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
3
(
d, J = 2.8 Hz, 1H), 5.10 (s, 2H), 2.76 (s, 1H), 2.73 (s, 3H). C NMR (100 MHz,
CDCl ) δ ppm 144.4, 134.8, 130.0, 129.0, 128.2, 127.7, 125.8, 124.8, 120.9,
20.2, 119.2, 102.6, 88.4, 82.9, 74.3, 38.8, 19.4.
3
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
-methyl-4-(3-methyl-1H-indol-1-yl)-1,1-diphenylpent-2-yn-1-ol (1af): Pale
1
yellow oil, H NMR (400 MHz, CDCl
3
) δ ppm 7.75 (s,1H), 7.54-7.52 (m, 5H),
7
.28-7.22 (m, 6H), 7.09-7.05 (m, 3H), 2.78 (s, 1H), 2.29 (s, 3H), 1.95 (s, 6H).
1
3
3
C NMR (100 MHz, CDCl ) δ ppm 144.6, 135.2, 130.1, 128.2, 127.7, 126.0,
121.9, 121.1, 119.0, 118.8, 112.9, 110.0, 89.9, 86.2, 74.4, 52.0, 30.0, 9.6.
1
4
-(1H-imidazol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1ag): White solid, H NMR
(400 MHz, DMSO) 7.75 (s, 1H), 7.55 (d, J = 7.2 Hz, 4H), 7.32 (t, J = 7.2 Hz,
1
3
4H), 7.28 (s, 1H), 7.23 (d, J = 7.2 Hz, 2H), 6.96 (s, 2H), 5.12 (s, 2H). C NMR
100 MHz, DMSO) δ ppm 146.0, 137.0, 128.7, 128.0, 127.1, 125.6, 119.3, 88.7,
0.4, 72.8, 35.8.
(
8
4-(1H-benzo[d]imidazol-1-yl)-1,1-diphenylbut-2-yn-1-ol (1ah): White solid,
1
H NMR (400 MHz, DMSO) 8.36 (s, 1H), 7.78-7.71 (m, 2H), 7.54 (d, J = 6.8 Hz,
13
4
H), 7.29-7.21 (m, 8H), 6.95 (s, 1H), 5.42 (s, 2H). C NMR (100 MHz, DMSO)
δ ppm 146.0, 143.5, 143.5, 133.5, 128.0, 127.2, 125.6, 122.6, 121.9, 119.6,
10.9, 88.8, 80.1, 72.9, 34.3.
1
Characterization Data of products 2, 3, and 4
7,8-diiodo-10-methyl-9,9-diphenyl-6,9-dihydropyrido[1,2-a]indole
(2a):
) δ
1
Yellow solid (110.4 mg, 94%), mp: 198-200 °C, H NMR (400 MHz, CDCl
3
ppm 7.49 (d, J = 7.6 Hz, 1H), 7.30-7.28 (m, 10H), 7.20-7.18 (m, 2H), 7.14-7.09
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 50
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
(
m, 1H), 4.89 (s, 2H), 1.57 (s, 3H). C NMR (100 MHz, CDCl
3
) δ ppm 144.2,
134.5, 133.8, 129.4, 129.1, 128.0, 127.4, 125.1, 121.8, 119.6, 118.7, 108.3,
-
1
1
07.4, 105.7, 61.4, 55.0, 10.1. IR (neat, cm ): 2919, 1491, 1466, 1443, 1239,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
8
08, 761, 701. HRMS (ESI) m/z Calcd for C25
H
20
I
2
N: [M+H] = 587.9680.
Found: 587.9675.
7
,8-diiodo-10-methyl-9,9-di-p-tolyl-6,9-dihydropyrido[1,2-a]indole
(2b):
) δ
1
Yellow solid (113.2 mg, 92%), mp: 100-102 °C, H NMR (400 MHz, CDCl
3
ppm 7.47 (d, J = 8.0 Hz, 1H), 7.20-7.18 (m, 6H), 7.10-7.08 (m, 5H), 4.89 (s,
1
3
2
H), 2.33 (s, 6H), 1.58 (s, 3H). C NMR (100 MHz, CDCl
3
) δ ppm 137.0, 134.7,
1
33.8, 130.2, 129.3, 129.3, 128.7, 125.9, 121.7, 119.5, 118.7, 108.3, 107.3,
-
1
105.1, 61.0, 55.0, 21.1, 10.1. IR (neat, cm ): 2917, 1508, 1467, 1448, 1236,
+
8
13, 738, 671. HRMS (ESI) m/z Calcd for C27
H
24
I
2
N: [M+H] = 615.9993.
Found: 615.9997.
7,8-diiodo-9,9-bis(4-methoxyphenyl)-10-methyl-6,9-dihydropyrido[1,2-a]i
1
ndole (2c): White solid (112.6 mg, 87%), mp: 102-104 °C, H NMR (400 MHz,
CDCl
3
) δ ppm 7.49 (d, J = 8.0 Hz, 1H), 7.21-7.16 (m, 6H), 7.13-7.09 (m, 1H),
1
3
6.82 (d, J = 7.2 Hz, 4H), 4.88 (s, 2H), 3.79 (s, 6H), 1.60 (s, 3H). C NMR (100
MHz, CDCl
3
) δ ppm 158.5, 136.7, 134.8, 133.8, 130.5, 129.2, 126.5, 121.7,
-1
1
19.5, 118.7, 113.2, 108.3, 107.1, 104.9, 60.3, 55.2, 54.9, 10.1. IR (neat, cm ):
2928, 1606, 1508, 1466, 1251, 826, 789, 739. HRMS (ESI) m/z Calcd for
+
C
27
H
24
I
2
NO
2
: [M+H] = 647.9891. Found: 647.9886.
9
,9-bis(4-fluorophenyl)-7,8-diiodo-10-methyl-6,9-dihydropyrido[1,2-a]ind
ACS Paragon Plus Environment

Page 29 of 50
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
ole (2d): Yellow solid (82.2 mg, 66%), mp: 86-88 °C, H NMR (400 MHz,
CDCl ) δ ppm 7.50 (d, J = 8.0 Hz, 1H), 7.27-7.22 (m, 6H), 7.16-7.11 (m, 1H),
3
.00 (t, J = 8.4 Hz, 4H), 4.90 (s, 2H), 1.59 (s, 3H). C NMR (100 MHz, CDCl )
3
1
3
7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
4
δ ppm 161.9 (d, JC-F = 246 Hz), 140.0 (d, JC-F = 3 Hz), 134.1, 133.8, 131.0 (d,
3
2
J
C-F = 8 Hz), 129.0, 124.8, 122.1, 119.8, 118.9, 115.0 (d, JC-F = 22 Hz), 108.4,
-
1
1
07.3, 106.1, 60.3, 55.0, 10.1. IR (neat, cm ): 2920, 1601, 1504, 1467, 1232,
+
8
29, 806, 740. HRMS (ESI) m/z Calcd for C25
H
18
F
2
I
2
N: [M+H] = 623.9491.
Found: 623.9487.
9
,9-bis(4-chlorophenyl)-7,8-diiodo-10-methyl-6,9-dihydropyrido[1,2-a]ind
1
ole (2e): Yellow solid (95.6 mg, 73%), mp: 102-104 °C, H NMR (400 MHz,
CDCl
H), 7.14-7.10 (m, 1H), 4.89 (s, 2H), 1.59 (s, 3H). C NMR (100 MHz, CDCl
δ ppm 142.4, 133.9, 133.6, 133.5, 130.7, 129.1, 128.4, 123.8, 122.2, 119.9,
3
) δ ppm 7.48 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.4 Hz, 4H), 7.22-7.20 (m,
1
3
6
3
)
-
1
118.9, 108.5, 107.6, 106.4, 60.5, 55.1, 10.3. IR (neat, cm ): 2918, 1488, 1467,
+
1
6
094, 1013, 820, 739, 663. HRMS (ESI) m/z Calcd for C25
H17Cl
2
I
2
N: [M] =
54.8822. Found: 654.8822.
7,8-diiodo-10-methyl-9-phenyl-9-(o-tolyl)-6,9-dihydropyrido[1,2-a]indole
1
(
2f): Pale yellow solid (107.0 mg, 89%), mp: 216-218 °C, H NMR (400 MHz,
CDCl
3
) δ ppm 7.51 (d, J = 8.0 Hz, 1H), 7.41 (s, 2H), 7.30-7.22 (m, 4H),
7.20-7.17 (m, 3H), 7.14-7.06 (m, 2H), 6.77 (d, J = 7.6 Hz, 1H), 5.26 (d, J = 17.2
1
3
Hz, 1H), 4.33 (d, J = 16.8 Hz, 1H), 1.94 (s, 3H), 1.54 (s, 3H). C NMR (100
MHz, CDCl
3
) δ ppm 146.7, 141.6, 139.4, 133.8, 132.8, 132.1, 129.2, 129.0,
ACS Paragon Plus Environment