Domino N2-Extrusion-Cyclization of Alkynylarylketone Derivatives for the Synthesis of Indoloquinolines and Carbocycle-Fused Quinolines

Article abstract of DOI:10.1021/acs.joc.8b01851

New synthetic approaches for the synthesis of indoloquinolines and carbocycle-fused quinolines have been developed employing alkynylketone substrates. These synthetic transformations involved the application of N₂-extrusion of azido complexes as a key step to generate carbodiimidium ion and nitrilium ion in situ, which further cyclized intramolecularly with alkyne via a domino process to provide indoloquinolines and carbocycle-fused quinolines, respectively, in moderate to good yields.

Full text of DOI:10.1021/acs.joc.8b01851

Subscriber access provided by - Access paid by the | UCSB Libraries
Article
A domino N2-extrusion-cyclization of alkynylarylketone derivatives
for the synthesis of indoloquinolines and carbocycle-fused quinolines
Bhornrawin Akkachairin, Jumreang Tummatorn, Narumol
Khamsuwan, Charnsak Thongsornkleeb, and Somsak Ruchirawat
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01851 • Publication Date (Web): 07 Aug 2018
Downloaded from http://pubs.acs.org on August 8, 2018
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 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 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.
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 47
The Journal of Organic Chemistry
1
2
3
4
A Domino N2ꢀExtrusionꢀCyclization of Alkynylarylketone Derivatives for
the Synthesis of Indoloquinolines and CarbocycleꢀFused Quinolines
5
6
7
8
9
Bhornrawin Akkachairin,† Jumreang Tummatorn,* †‡ Narumol Khamsuwan‡
Charnsak Thongsornkleeb†‡ and Somsak Ruchirawat†‡
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
†Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental
Health and Toxicology (EHT), Ministry of Education, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210,
Thailand
‡Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi,
Bangkok 10210, Thailand
∗Email: jumreang@cri.or.th
ABSTRACT
R
H
N
R
N
O
O
N
TMSN3, TfOH
C
R
N
H
double cyclization
double N2-extrusion/
double aryl migration
O
up to 86%
Ph
N
N
TMSN3, TfOH
Ph
N2-extrusion/
aryl migration
double cyclization
Ph
up to 95%
Ph
New synthetic approaches for the synthesis of indoloquinolines and carbocycleꢀfused quinolines have been
developed employing alkynylketone substrates. These synthetic transformations involved the application of
N2ꢀextrusion of azido complexes as a key step to generate carbodiimidium ion and nitrilium ion in situ
which further cyclized intramolecularly with alkyne via a domino process to provide indoloquinolines and
carbocycleꢀfused quinolines, respectively, in moderate to good yields.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 47
1
2
■ INTRODUCTION
3
4
5
6
7
8
9
Activation of alkyne by Lewis acids, πꢀelectrophilic Lewis acids or Brønsted acids is very useful in many
organic transformations.1 In addition, when a compound consists of both alkyne and ketone functional
groups placed in proper orientation, the reaction of alkyne could be activated more efficiently under the
assistance of the neighboring ketone moiety, while the electrophilicity of the ketone is also enhanced.2 We
envision that this dual alteration of reactivity can be employed to develop new synthetic methods. As our
research group has been interested in the N2ꢀextrusion of azides for several years.3 We therefore proposed
the conceptually expedient method for the synthesis of indoloquinolines (2),4 a wellꢀestablished core
structure showing a broad range of biological activities such as antibacterial, antifungal, antimicrobial, antiꢀ
HIV, anticancer and antimalarial activities.5 Our method involves with the generation of carbodiimide
intermediates in situ employing neighboring ketone participation to promote double aryl migration
concurrently with N2ꢀextrusion of readily available alkynyl ketone precursor as shown in Scheme 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
Scheme 1. Proposed method for synthesis of indoloquinolines.
In general, carbodiimide is one of the most important functional groups used in several applications in
organic synthesis. The utilization of carbodiimides is very wellꢀknown as a coupling reagents to prepare
amides, esters, acid anhydrides and is also commonly used in peptide synthesis.6 In addition, the synthetic
utility of carbodiimides has great impact in many transformations for the synthesis of Nꢀcontaining
compounds.7 Carbodiimide could normally be prepared and stored for subsequent uses or could be
generated and used in situ in the reactions.8 The common precursors used in the preparation of
ACS Paragon Plus Environment

Page 3 of 47
The Journal of Organic Chemistry
1
2
3
4
carbodiimides are thioureas, ureas, isonitriles and isocyanates under different conditions as shown in
Scheme 2.9
5
6
7
Scheme 2. Previous methods for generation of carbodiimide.
8
9
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
■ RESULTS AND DISCUSSION
In this work, the method for in situ generation of carbodiimides is very advantageous as the ketone
precursors (1) are much more easily prepared and more diverse arrays of the compounds are available
comparing to other precursors aforementioned. We proposed a new and challenging synthetic design to
concisely construct indoloquinolines (2) employing domino reactions in one synthetic operation. A
plausible mechanism is shown in Scheme 3. Under acidic conditions, orthoꢀalkynylarylketone (1) could
undergo a protonation to form oxonium ion intermediate (I)10 which further reacted with hydrazoic acid,
generated in situ from TMSN3/TfOH, to provide ketoꢀnitrilium ion intermediate II via the N2 extrusion and
aryl migration reactions. Next, this intermediate was repeatedly attacked by hydrazoic acid and
subsequently underwent a second N2ꢀextrusion (III) and aryl migration to give the reactive carbodiimidium
ion IV. The intramolecular 5ꢀendoꢀdig cyclization of enol intermediate V to carbodiimidium ion could
ensue to intermediate VI which cyclized again by aromatic nucleophile ring B, followed by dehydrative
rearomatization to obtain indoloquinolines (2).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 47
1
2
3
4
5
6
7
8
Scheme 3. Proposed reaction mechanism.
9
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
Scheme 4. Optimal condition for synthesis of indoloquinolines.
In our study, orthoꢀalkynylarylketones 1a was employed as the screening substrate to optimize reaction
conditions (see Table 1 in the Supporting Information). After screening several conditions, all cases
ACS Paragon Plus Environment

Page 5 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
provided indoloquinoline 2a as a major product along with the formation of compound 3a as a minor
product. The best result was obtained when the reaction was carried out using 3.5 equiv of both TMSN3 and
TfOH in dry DCM at 0.3 M concentration. This condition could provide highest yield (58%) of 2a and
could minimize the formation of side product 3a could be minimized as shown in Scheme 4.
9
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
To explore the scope and limitation of our method for the synthesis of indoloquinolines (2), various orthoꢀ
alkynylarylketones (1) having different substituent groups were applied to the optimal conditions as shown
in Scheme 5. Initially, alkyl substituents were examined. The substrates containing butyl (1a) and isopentyl
(1b) groups provided the desired products in moderate yields (58% and 57% yields, respectively). In
increasing the bulkiness of cyclohexyl substituent, the reaction showed less effectiveness than long linear
side chain offering 2c in 43% yield. However, the reaction of substrate tethering with phenylether side
chain was not compatible with this procedure, the reaction of which led to low yield of indoloquinoline 2d.
Next, the study of substrate scope was extended by switching from alkyl to aryl side chain. The reaction of
substrate bearing phenyl group at R1 position furnished product 2e in 54% yield whereas paraꢀfluorophenyl
substituent could offer desired product 2f in higher yield (73%). In case of compound 1e when the reaction
was carried out in larger scale (1.0200 mmol), the reaction could provide the product 2e in higher yield
(76%). However, when the substrate containing paraꢀmethoxyphenyl group 1g was employed, the reaction
resulted in decomposition and provided none of the desired product. This result demonstrated that the
electronic effect on R1 played an important role towards the reactivity and stability of alkyne under these
reaction conditions. Increasing the electron density of R1 seemed to be nonꢀbeneficial for this
transformation as it could increase the rate of decomposition of alkyne under the strong acidic conditions.
Further study on the substrate scope was investigated by varying the substituent groups on aromatic ring B.
With orthoꢀmethyl group, the reaction gave the desired 2h in low yield whereas the metaꢀmethyl
substituent gave 2i as a regioisomeric mixture in good combined yield. This result implied that the steric
effect of methyl group at the orthoꢀposition played a significant role in hampering the cyclization process.
In addition, we found that increasing the nucleophilicity of aromatic ring B did not significantly affect the
product yields. In case of metaꢀmethoxyphenyl precursor 1j, the reaction provided separable regioisomeric
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 47
1
2
3
4
5
6
7
8
indoloquinolines 2j and 2j’ in 71% combined yield which is comparable to the case of electronically
neutral substituent 1i. However, the reaction of 1k was messy and afforded only 11% yield of the desired
product. One of the possibilities is that the paraꢀmethoxyphenyl group could delocalize electron to the
carbodiimidium intermediate which could undergo undesired reaction pathways. Surprisingly, the paraꢀ
fluorophenyl 1l was smoothly converted to the corresponding product in high yield (86%). In order to gain
more information about the influence of substituents, we then expanded the scope of substrates by varying
the substituents at R3. In case of compound 1m, containing paraꢀmethyl group with respect to aniline
moiety, the reaction provided the desired product in 73% yield. When using paraꢀfluoro (1n) and paraꢀ
chloro (1o) substrates, the reaction in both cases could provide the corresponding products in high yields
while substrate bearing paraꢀmethoxy group 1p gave indoloquinoline product in lower yield. These results
showed that the reactivity of carbonyl group towards nucleophile (HN3) was decreased as the electronꢀ
donating group could delocalize electron into the ketone moiety resulting in lower yield of the desired
product. Moreover, the reaction of compound 1o was also examined in a larger scale which led to the
product in slightly higher yield (77%). In case of substrate 1q, containing a methoxy group at the paraꢀ
position with respect to the alkyne moiety, the reaction gave only 31% yield of the desired product. The
resonace effect of methoxy group directly increased the reactivity of alkyne towards acid leading to a
decomposition. A similar effect of the methoxy group para to alkyne was also observed in substate 1g. In
contrast, the reaction of substrate containing electronꢀwithdrawing substituent 1r (paraꢀfluoro) gave the
corresponding product in good yield. Next, we also investigated the reaction by increasing the
nucleophilicity of aromatic ring B. The reaction of both 1s and 1t were not significantly affected on the
product yields. In both cases, the reactions gave separable regioisomeric products in moderate combined
yields. Notably, the yield was improved dramatically in the case of cyclohexyl substituent, affording the
separable 2u and 2u’ in 62% combined yield. However, increasing the nucleophilicity on aromatic ring B
of substrates 1v, 1w, and 1x provided the corresponding products in slightly lower combined yields
comparing to the substrates containing unsubstituted ring B.
9
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
ACS Paragon Plus Environment

Page 7 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Scheme 5. Substrate scope.a
9
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
b
a Isolated Yields. For examples of reaction carried out in larger scale, compounds 1e and 1o were carried
out at 1.0200 mmol (228.9 mg) and 1.0120 mmol (256.8 mg) scales, respectively.
Furthermore, the effect of neighboring group participation on different structural alignment of alkynyl
ketones was further studied. αꢀAlkynylketone 4a was selected as a screening substrate. If the reaction were
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 47
1
2
3
4
5
6
7
8
to undergo the neighboring group participation mode, the carbonyl moiety would activate the alkyne to
form the oxoꢀpyrylium ion and then reacted with hydrazoic acid as proposed in pathway A of Scheme 6.
However, when compound 4a was treated with 3.5 equiv of TMSN3/TfOH, only carbocycleꢀfused
quinoline 5a was obtained in 58% yield. This result implied that ketone moiety could not participate in this
transformation possibly due to high entropy effect of long linear chain of the substrate.11 We therefore
proposed the mechanism for the formation of compound 5a as presented in pathway B of Scheme 6.
Interestingly in this reaction, ketone moiety efficiently reacted with hydrazoic acid to generate nitrilium ion
while the alkyne moiety still remained intact even though it was engulfed in strong acidic conditions. After
the generation of the nitrilium ion intermediate, the alkyne moiety then underwent a domino cyclization/reꢀ
aromatization to provide fused tricyclic ring as the major product. Using this method, a library of fused
quinolines 4a, whose core structure has been found in compounds possessing various biological activities,12
can be easily synthesized. We therefore optimized the reaction conditions (see Table 2 in the Supporting
Information) and found that employing 1.2 equiv of TMSN3/TfOH in 0.1 M dry DCM was the optimal
condition in this conversion.
9
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
Scheme 6. Synthesis of carbocycleꢀfused quinolines.
The general method for the preparation of substrates 4 and 6 was elustrated in Scheme 7. The alkynyl
alcohol derivatives were converted to aldehydes which were reacted with aryl Grignard or aryllithium
ACS Paragon Plus Environment

Page 9 of 47
The Journal of Organic Chemistry
1
2
reagents without further purification to obtain compounds 8 and 9. Next, these alcohols were oxidized with
3
4
PCC to obtain the corresponding compounds.
5
6
7
8
9
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
Scheme 7. The synthesis of compounds 4 and 6
Next, the generality of the method was studied as shown in Scheme 8. A wide range of substrates with
paraꢀsubstituents on aromatic ring B with functional groups including hydrogen (4a), fluoride (4b),
chloride (4c), and bromide (4d) smoothly converted to the corresponding products in good to excellent
yields. In addition, compound 4a was also carried out at 1.0051 mmol scale which could provide the
desired product in camparable yield. However, the reaction of paraꢀmethoxyphenyl substrate (4e) failed to
give the desired product because the resonance effect of the paraꢀmethoxy group accelerated rate of
protonation of alkyne under this strong acid conditions leading to the decomposition of substrate. In
contrast, the reaction of metaꢀmethoxyphenyl substrate (4f) could provide carbocycleꢀfused quinoline in
good yield. The effect of electron withdrawing groups was also evaluated resulting in lower yields of the
corresponding products; paraꢀnitro substituted substrate gave product in much lower yield comparing to
paraꢀtrifluoromethyl substituent. We next examined the effect of substituent on aromatic ring A. The steric
effect of orthoꢀmethyl group (4i) offered the desired product in lower yield comparing with metaꢀmethyl
group substrate (4j). With other substituents at para position such as fluoro (4k) and chloro (4l)
substituents, the reactions gave the desired products in good yields whereas the substrate containing
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 47
1
2
3
4
5
6
7
8
chlorine at meta position (4m) provided the corresponding product in lower yield. Next study, the
resonance effect was also investigated in this conversion. Compound 4n having paraꢀmethoxy group as the
substituent was employed. The results showed that the resonance effect of methoxy group towards alkyne
was not advantageous in this transformation. In this case, the yield of product was dramatically decreased.
On the other hand, substrates containing metaꢀmethoxy group (4o) efficiently furnished the corresponding
products in good yields while substrates with dimethoxy groups, 4p and 4q, offered the desired products in
moderate yields. Moreover, the reaction of substrate with benzyl protecting group (4r) provided separable
regioisomeric products (5r and 5r’) along with deprotected products (5r” and 5r”’) in good combined yield
(88%). Next, we also studied the effect of length on the side chain of precursor. Substrates 6a and 6b with
one longer methylene unit were investigated. The reactions gave sixꢀmembered fused quinolines in much
lower yields comparing to fiveꢀmembered fused quinolines.
9
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
Scheme 8. Synthesis of carbocycleꢀfused quinolines.a
ACS Paragon Plus Environment

Page 11 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
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 Isolated Yields. bFor examples of reaction carried out in larger scale, compound 4a was carried at 1.0051
mmol (175.7 mg) scale.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 47
1
2
■ CONCLUSIONS
3
4
5
6
7
8
9
In summary, we have developed new methods for the synthesis of indoloquinolines and carbocycleꢀfused
quinolines from alkynyl ketone substrates. Indoloquinolines could be achieved by the domino N2ꢀ
extrusion/aryl migration of orthoꢀalkynylarylketones (1) to obtain the carbodiimidium ion key intermediate,
followed by cyclization to obtain the desired products in moderate to good yields. This method provided a
convenient route to synthesize a library of indoloquinolines from easily accessible precursors. For the
synthesis of carbocycleꢀfused quinolines, linear alkynyl ketone (3) underwent the N2ꢀextrustion/aryl
migration to generate nitrilium ion intermediate, followed by cyclization to give the carbocycleꢀfused
quinolines in moderate to excellent yields.
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
■ EXPERIMENTAL SECTION
General Procedure. The commercial grade chemicals were used without further purification, unless
otherwise specified. All solvents used were purified by the solvent purification system. The ovenꢀdried
glassware (110 °C at least for 2 h) was used for all reactions. Crude reaction mixtures were concentrated
under reduced pressure by removing organic solvent with the rotary evaporator. Column chromatography
was performed using silica gel 60 (particle size 0.06−0.2 mm; 70−230 mesh ASTM). Analytical thin layer
chromatography (TLC) was performed with silica gel 60 F254 aluminum sheets. The nuclear magnetic
resonance (NMR) spectra were recorded in deuterochloroform (CDCl3) and deuterated dimethyl sulfoxide
1
(DMSOꢀd6) with 300, 400 and 600 MHz spectrometers. Chemical shifts for H and 13C NMR spectra were
reported in part per million (ppm, δ), relative to tetramethylsilane (TMS) as the internal reference. Coupling
constants (J) were reported in hertz (Hz). Infrared spectra were measured using an FTꢀIR spectrometer and
were reported in cm−1. High resolution mass spectra (HRMS) were obtained using timeꢀofꢀflight (TOF).
General
procedure
for
the
synthesis
of
orthoꢀalkynylarylketones
(1)
2ꢀ(2ꢀ
iodophenyl)(phenyl)methanone (609.3 mg, 1.9775 mmol, 1.0 equiv) was dissolved in NEt3 (4.0 mL/mmol)
in a sealed tube. A solution mixture was added PdCl2(PPh3)2 (27.8 mg, 0.0396 mmol, 2 mol%), CuI (18.8
mg, 0.0989 mmol, 5 mol%), and PPh3 (25.9 mg, 0.0989 mmol, 5 mol%) at room temperature, followed by
bubbling with argon for 30 min at room temperature. The reaction was then added phenylacetylene (261
ACS Paragon Plus Environment

Page 13 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
µL, 2.3730 mmol, 1.2 equiv) and stirred at 85 °C for 1 day. The reaction was quenched with sat. NH4Cl,
and then extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4,
filtered, and concentrated under reduced pressure to provide crude product which was purified on silica gel
(EtOAc/Hexane: 1:9) to yield product 1e (541.0 mg, 97%). (Note: For the synthesis of compounds 1j, 1m,
1n, 1p, 1r, 1s, 1t, 1u, 1v, 1w and 1x, the reactions employed 2ꢀbromobenzophenone derivatives as starting
material which were conducted in sealed tube at 85 °C for 2 days.)
9
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
(2ꢀ(Hexꢀ1ꢀynꢀ1ꢀyl)phenyl)(phenyl)methanone (1a). Yield 958.0 mg (99%, brown oil); IR (neat): υ max 2932,
1
1663, 1287, 927, 702 cm−1; H NMR (300 MHz, CDCl3) δ 7.83–7.79 (m, 2H), 7.60–7.51 (m, 1H), 7.49–
7.34 (m, 6H), 2.10 (t, 2H, J = 6.9 Hz), 1.24–1.12 (m, 4H), 0.78 (t, 3H, J = 6.9 Hz); 13C{1H} NMR (75
MHz, CDCl3) δ197.4, 141.7, 137.3, 132.9, 132.5, 130.1, 129.9, 128.2, 128.0, 127.3, 122.5, 96.6, 78.6, 30.2,
21.7, 18.9, 13.5;; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C19H19O 263.1430; found 263.1429.
(2ꢀ(5ꢀMethylhexꢀ1ꢀynꢀ1ꢀyl)phenyl)(phenyl)methanone (1b). Yield 320.8 mg (81%, orange oil); IR (neat): υ
max 2956, 2869, 1668, 1316, 1288, 928, 704 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.84–7.80 (m, 2H), 7.56
(tt, 1H, J = 6.6, 1.5 Hz), 7.48–7.33 (m, 6H), 2.10 (t, 2H, J = 7.5 Hz), 1.46–1.33 (m, 1H), 1.15 (q, 2H, J =
13
7.2 Hz), 0.75 (d, 6H, J = 6.6 Hz); C{1H} NMR (75 MHz, CDCl3) δ 197.3, 141.7, 137.3, 132.9, 132.4,
130.1, 129.9, 128.2, 128.0, 127.3, 122.4, 96.6, 78.4, 36.9, 26.8, 22.0, 17.2; HRMS (ESIꢀTOF) m/z: [M +
Na]+ calcd for C20H20ONa 299.1406; found 299.1410.
(2ꢀ(Cyclohexylethynyl)phenyl)(phenyl)methanone (1c). Yield 392.7 mg (83%, brown oil); IR (neat): υ max
2929, 2228, 1666, 1449, 1288, 696 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.82 (dd, 2H, J = 7.7, 1.1 Hz), 7.55
13
(t, 1H, J = 7.4 Hz), 7.47–7.34 (m, 6H), 2.31–2.26 (m, 1H), 1.49–1.38 (m, 5H), 1.17–1.08 (m, 5H); C{1H}
NMR (100 MHz, CDCl3) δ 197.5, 141.8, 137.3, 133.0, 132.4, 130.2, 129.9, 128.2, 128.1, 127.4, 122.5,
100.7, 78.6, 31.9, 29.4, 25.7, 24.5; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C21H20ONa 311.1406;
found 311.1408.
(2ꢀ(3ꢀPhenoxypropꢀ1ꢀynꢀ1ꢀyl)phenyl)(phenyl)methanone (1d). Yield 313.6 mg (86%, yellow oil); IR (neat):
υ
max 2923, 1665, 1597, 1494, 1214, 754 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ 7.80ꢀ7.76 (m, 2H), 7.59ꢀ7.52
53
54
55
56
57
58
59
60
(m, 2H), 7.48ꢀ7.40 (m, 5H), 7.25ꢀ7.19 (m, 2H), 6.94 (tt, 1H, J = 7.2, 0.9 Hz), 6.83ꢀ6.79 (m, 2H), 4.62 (s,
13
2H); C{1H} NMR (75 MHz, CDCl3) δ 196.6, 157.6, 141.8, 137.1, 133.2, 133.1, 130.14, 130.11, 129.3,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 47
128.38, 128.36, 138.32, 121.3, 120.9, 114.8, 89.4, 84.8, 56.2; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for
C22H16O2Na 335.1043; found 335.1037.
1
2
3
4
5
6
7
8
Phenyl(2ꢀ(phenylethynyl)phenyl)methanone (1e). Yield 541.0 mg (97%, brown solid); mp 42−43 °C; IR
(neat): υ max 2216, 1663, 1287, 928, 753 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.90−7.86 (m, 2H), 7.63−7.40
(m, 7H), 7.26−7.16 (m, 3H), 7.06−7.02 (m, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 197.0, 141.5, 137.3,
133.1, 132.5, 131.4, 130.3, 130.2, 128.6, 128.4, 128.1, 128.0, 122.6, 121.8, 95.1, 87.4; HRMS (ESIꢀTOF)
m/z: [M + H]+ calcd for C21H15O 283.1117; found 283.1122.
9
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
(2ꢀ((4ꢀFluorophenyl)ethynyl)phenyl)(phenyl)methanone (1f). Yield 262.9 mg (80%, orange solid); mp 68–
69 °C; IR (neat): υ max 2923, 1665, 1508, 1288, 1232, 836, 701 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.90–
7.86 (m, 2H), 7.62–7.54 (m, 2H), 7.53–7.42 (m, 5H), 7.06–6.99 (m, 2H), 6.89 (tt, 2H, J = 8.7, 2.1 Hz);
13C{1H} NMR (75 MHz, CDCl3) δ 196.6, 162.6 (d, JCF = 248 Hz), 141.5, 137.4, 133.3 (d, JCF = 8 Hz),
133.1, 132.5, 130.3, 130.2, 128.7, 128.4, 128.2, 121.7, 118.7 (d, JCF = 4 Hz), 115.4, (d, JCF = 22 Hz), 94.0,
87.2 (d, JCF = 1 Hz); HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C21H13FONa 323.0843; found 323.0838.
(2ꢀ((4ꢀMethoxyphenyl)ethynyl)phenyl)(phenyl)methanone (1g). Yield 186.0 mg (56%, yellow solid); mp
1
91–92 °C; IR (neat): υ max 2215, 1664, 1511, 1288, 1249, 702 cm−1; H NMR (400 MHz, CDCl3) δ 7.89–
7.87 (m, 2H), 7.60–7.56 (m, 2H), 7.53–7.40 (m, 5H), 6.97 (dt, 2H J = 8.8, 2.4 Hz), 6.73 (dt, 2H, J = 8.8, 2.8
Hz), 3.77 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.2, 159.7, 141.3, 137.4, 133.1, 132.9, 132.3,
130.3, 130.2, 128.7, 128.3, 127.8, 122.2, 114.7, 113.7, 95.4, 86.3, 55.2; HRMS (ESIꢀTOF) m/z: [M + Na]+
calcd for C22H16O2Na 335.1043; found 335.1037.
(2ꢀ(Phenylethynyl)phenyl)(oꢀtolyl)methanone (1h). Yield 243.7 mg (81%, brown oil); IR (neat): υ max 2922,
1622, 1634, 1300, 927, 755 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.61–7.57 (m, 2H), 7.49 (td, 1H, J = 7.5,
1.5 Hz), 7.44–7.34 (m, 3H), 7.29–7.14 (m,7H), 2.51 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 198.8,
142.0, 138.6, 138.3, 133.2, 131.6, 131.4, 131.3, 130.83, 130.76, 129.5, 128.4, 128.10, 128.05, 125.4, 122.7,
122.4, 95.0, 87.3, 20.8; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C22H16ONa 319.1093; found 319.1090.
2ꢀ(Phenylethynyl)phenyl)(mꢀtolyl)methanone (1i). Yield 326.1 mg (78%, brown oil); IR (neat): υ max 2922,
1
1662, 1443, 1291, 755 cm−1; H NMR (300 MHz, CDCl3) δ 7.72–7.70 (m, 1H), 7.64–7.60 (m, 2H), 7.53–
7.43 (m, 3H), 7.41–7.31 (m, 2H), 7.25–7.17 (m, 3H), 7.10–7.06 (m, 2H), 2.39 (s, 3H); 13C{1H} NMR (75
ACS Paragon Plus Environment

Page 15 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
MHz, CDCl3) δ 197.2, 141.8, 138.2, 137.5, 133.9, 132.5, 131.4, 130.4, 130.2, 128.6, 128.3, 128.2, 128.1,
128.0, 127.6, 122.7, 121.8, 94.9, 87.5, 21.3; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H17O 297.1274;
found 297.1273.
7
8
(3ꢀMethoxyphenyl)(2ꢀ(phenylethynyl)phenyl)methanone (1j). Yield 203.3 mg (98%, brown oil); IR (neat): υ
9
1
2940, 2217, 1664, 1289, 756 cm−1; H NMR (300 MHz, CDCl3) δ 7.63–7.59 (m, 1H), 7.53–7.32 (m,
max
10
11
12
13
14
15
16
17
18
19
20
6H), 7.28–7.18 (m, 3H), 7.14–7.09 (m, 3H), 3.83 (s, 3H); C{1H} NMR (75 MHz, CDCl3) δ 196.8, 159.7,
13
141.6, 138.7, 132.5, 131.4, 130.2, 129.3, 128.5, 128.4, 128.08, 128.05, 123.4, 122.7, 121.8, 119.8, 113.9,
94.9, 87.4, 55.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H17O2 313.1223; found 313.1235.
(4ꢀMethoxyphenyl)(2ꢀ(phenylethynyl)phenyl)methanone (1k). Yield 192.1 mg (≥99%, brown oil); IR (neat):
υ
max 2940, 1580, 1412, 1330, 1122, 722 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.87 (dt, 2H, J = 9.0, 2.7 Hz),
7.62–7.59 (m, 1H), 7.51–7.40 (m, 3H), 7.27–7.17 (m, 3H), 7.12–7.08 (m, 2H), 6.94 (dt, 2H, J = 9.0, 2.7
Hz), 3.85 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 195.6, 163.7, 142.1, 132.6, 132.4, 131.4, 130.3,
129.9, 128.3, 128.2, 128.11, 128.06, 122.7, 121.6, 113.6, 94.7, 87.5, 55.5; HRMS (ESIꢀTOF) m/z: [M +
Na]+ calcd for C22H16O2Na 335.1043; found 335.1048.
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
(4ꢀFluorophenyl)(2ꢀ(phenylethynyl)phenyl)methanone (1l). Yield 456.0 mg (97%, brown oil); IR (neat): υ
max 2927, 2217, 1664, 1596, 1235, 755 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.94–7.89 (m, 2H), 7.63–7.61
(m, 1H), 7.53–7.49 (m, 2H), 7.47–7.43 (m, 1H), 7.28–7.20 (m, 3H), 7.14 (tt, 2H, J = 8.8, 2.8 Hz), 7.09–
7.07 (m, 2H); C{1H} NMR (100 MHz, CDCl3) δ 195.4, 165.8 (d, JCF = 254 Hz), 141.2, 133.7 (d, JCF = 3
13
Hz), 132.8 (d, JCF = 9 Hz), 132.5, 131.3, 130.4, 128.5 (d, JCF = 4 Hz), 128.2, 128.1, 122.4, 121.6, 115.6,
115.4, 95.2, 87.2; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C21H13FONa 323.0843; found 323.0847.
(4ꢀMethylꢀ2ꢀ(phenylethynyl)phenyl)(phenyl)methanone (1m). Yield 544.2 mg (≥99%, yellow solid); mp
96–97 °C; IR (neat): υ max 2925, 1662, 1598, 1288, 702 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.88–7.85 (m,
2H), 7.56 (tt, 1H, J = 6.3, 1.5 Hz), 7.47–7.42 (m, 4H), 7.25–7.16 (m, 4H), 7.07–7.02 (m, 2H), 2.42 (s, 3H);
13C{1H} NMR (75 MHz, CDCl3) δ 196.9, 140.8, 138.6, 137.7, 133.1, 132.9, 131.4, 130.2, 129.1, 129.0,
128.3, 128.0, 122.7, 122.0, 94.8, 87.7, 21.2; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C22H16ONa
319.1093; found 319.1091.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 47
1
2
3
4
5
6
(4ꢀFluoroꢀ2ꢀ(phenylethynyl)phenyl)(phenyl)methanone (1n). Yield 524.9 mg (97%, orange solid); mp 87–
88 °C; IR (neat): υ max 2214, 1664, 1600, 1572, 1285, 756 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.82–7.85
(m, 2H), 7.61–7.53 (m, 2H), 7.49–7.46 (m, 2H), 7.31 (dd, 1H, J = 9.2, 2.8 Hz), 7.28–7.19 (m, 3H), 7.15 (td,
7
8
13
1H, J = 8.4, 2.4 Hz), 7.05–7.03 (m, 2H); C{1H} NMR (100 MHz, CDCl3) δ 195.9, 163.4 (d, JCF = 252
9
Hz), 137.6 (d, JCF = 3 Hz), 137.4, 133.2, 131.5, 131.2 (d, JCF = 9 Hz), 130.2, 128.8, 128.4, 128.1, 124.4 (d,
JCF = 10 Hz), 122.1, 119.3 (d, JCF = 23 Hz), 115.6 (d, JCF = 22 Hz), 96.3, 86.4 (d, JCF = 3 Hz); HRMS (ESIꢀ
TOF) m/z: [M + H]+ calcd for C21H14FO 301.1023; found 301.1016.
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
(4ꢀChloroꢀ2ꢀ(phenylethynyl)phenyl)(phenyl)methanone (1o). Yield 371.1 mg (≥99%, orange solid); mp 80–
81 °C; IR (neat): υ max 2218, 1666, 1584, 1285, 929, 690 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.87–7.85 (m,
2H), 7.61–7.57 (m, 2H), 7.49–7.45 (m, 3H), 7.41 (dd, 1H, J = 8.0 , 2.0 Hz), 7.27–7.18 (m, 3H), 7.04–7.02
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 195.9, 139.6, 137.1, 136.4, 133.3, 132.2, 131.5, 130.2, 130.1,
128.8, 128.45, 128.40, 128.1, 123.7, 122.0, 96.4, 86.2; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C21H14ClO (Clꢀ35) 317.0728; found 317.0722.
(4ꢀMethoxyꢀ2ꢀ(phenylethynyl)phenyl)(phenyl)methanone (1p). Yield 162.5 mg (43%, orange solid); mp 68–
1
69 °C; IR (neat): υ max 2938, 1657, 1595, 1234, 691 cm−1; H NMR (400 MHz, CDCl3) δ 7.85 (d, 2H, J =
8.0 Hz), 7.56–7.52 (m, 2H), 7.44 (t, 2H, J = 8.0 Hz), 7.25–7.17 (m, 3H), 7.11 (d, 1H, J = 2.4 Hz), 7.09–7.06
13
(m, 2H), 6.95 (dd, 1H, J = 8.8, 2.4 Hz), 3.87 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 196.3, 161.2,
138.1, 133.6, 132.6, 131.5, 131.4, 130.1, 128.4, 128.2, 128.0, 124.0, 122.5, 117.3, 114.4, 95.1, 87.7, 55.5;
HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C22H16O2Na 335.1043; found 335.1036.
(5ꢀMethoxyꢀ2ꢀ(phenylethynyl)phenyl)(phenyl)methanone (1q). Yield 307.4 mg (95%, orange solid); mp 90–
1
91 °C; IR (neat): υ max 2938, 1664, 1595, 1498, 1230, 756 cm−1; H NMR (400 MHz, CDCl3) δ 7.90 (dd,
2H, J = 8.0, 1.2 Hz), 7.58 (tt, 1H, J = 6.8, 1.2 Hz), 7.54 (dd, 1H, J = 8.0, 0.8 Hz), 7.49–7.45 (m, 2H), 7.23–
7.15 (m, 3H), 7.05–7.02 (m, 2H), 6.99–6.97 (m, 2H), 3.86 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
196.9, 159.4, 143.0, 137.1, 133.9, 133.2, 131.1, 130.3, 128.4, 128.0, 122.9, 116.6, 113.9, 113.5, 93.7, 87.4,
55.5; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C22H16O2Na 335.1043; found 335.1040.
(5ꢀFluoroꢀ2ꢀ(phenylethynyl)phenyl)(phenyl)methanone (1r). Yield 139.8 mg (42%, orange solid); mp 66–
67 °C; IR (neat): υ max 2171, 1668, 1597, 1497, 1289, 689 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.89–7.87
ACS Paragon Plus Environment

Page 17 of 47
The Journal of Organic Chemistry
(m, 2H), 7.61–7.58 (m, 2H), 7.50–7.46 (m, 2H), 7.25–7.17 (m, 5H), 7.02–7.00 (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ 195.5, 162.0 (d, JCF = 252 Hz), 143.5 (d, JCF = 7 Hz), 136.6, 134.5 (d, JCF = 8 Hz),
133.5, 131.3, 130.2, 128.5, 128.4, 128.1, 122.3, 117.9 (d, JCF = 4 Hz), 117.6 (d, JCF = 22 Hz), 115.8, (d, JCF
= 23 Hz), 94.8, 86.3; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C21H13FONa 323.0843; found 323.0855.
(2ꢀ(Hexꢀ1ꢀynꢀ1ꢀyl)phenyl)(3ꢀmethoxyphenyl)methanone (1s). Yield 459.7 mg (93%, brown oil); IR (neat): υ
max 2957, 2229, 1668, 1429, 1287, 755 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.48–7.29 (m, 7H), 7.13–7.09
(m, 1H), 3.84 (s, 3H), 2.14 (t, 2H, J = 6.9 Hz), 1.26–1.16 (m, 4H), 0.79 (t, 3H, J = 6.9 Hz); 13C{1H} NMR
(75 MHz, CDCl3) δ 197.1, 159.6, 141.8, 138.6, 132.5, 129.9, 129.2, 127.9, 127.2, 123.4, 122.5, 119.7,
113.6, 96.4, 78.5, 55.4, 30.3, 21.7, 19.0, 13.5; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C20H20O2Na
315.1356; found 315.1350.
1
2
3
4
5
6
7
8
9
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
(3ꢀMethoxyphenyl)(2ꢀ(5ꢀmethylhexꢀ1ꢀynꢀ1yl)phenyl)methanone (1t). Yield 371.4 mg (86%, brown oil); IR
1
(neat): υ max 2956, 2866, 1668, 1595, 1288, 1266, 756 cm−1; H NMR (300 MHz, CDCl3) δ 7.48–7.29 (m,
7H), 7.14–7.07 (m, 1H), 3.84 (s, 3H), 2.14 (t, 2H, J = 7.2 Hz),148–1.34 (m, 1H), 1.12 (q, 2H, J = 7.2 Hz),
0.76 (d, 6H, J = 6.6 Hz); 13C{1H} NMR (75 MHz, CDCl3) δ 197.0, 159.6, 141.7, 138.5, 132.4, 129.8,
129.1, 127.8, 127.2, 123.3, 122.3, 119.6, 113.6, 96.3, 78.4, 55.2, 37.0, 26.8, 21.9, 17.2; HRMS (ESIꢀTOF)
m/z: [M + H]+ calcd for C21H23O2 307.1693; found 307.1686.
(2ꢀ(Cyclohexylethynyl)phenyl)(3ꢀmethoxyphenyl)methanone (1u). Yield 214.6 mg (40%, yellow oil); IR
1
(neat): υ max 2930, 2229, 1667, 1449, 1288, 756 cm−1; H NMR (300 MHz, CDCl3) δ 7.48–7.28 (m, 7H),
7.14–7.07 (m, 1H), 3.84 (d, 3H, J = 0.9 Hz), 2.33 (br s, 1H), 1.63–1.40 (m, 5H), 1.26–1.13 (m, 5H);
13C{1H} NMR (75 MHz, CDCl3) δ 197.3, 159.7, 141.8, 138.7, 132.5, 129.9, 129.2, 128.0, 127.3, 123.5,
122.5, 119.7, 113.7, 100.5, 78.6, 55.4, 31.9, 29.4, 25.8, 24.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C22H23O2 319.1693; found 319.1688.
(2ꢀ((4ꢀFluorophenyl)ethynyl)phenyl)(3ꢀmethoxyphenyl)methanone (1v). Yield 185.5 mg (65%, yellow
solid); mp 84–85 °C; IR (neat): υ max 2941, 1666, 1508, 1289, 1230, 836 cm−1; 1H NMR (300 MHz, CDCl3)
δ 7.62–7.59 (m, 1H), 7.53–7.32 (m, 6H), 7.14–7.06 (m, 3H), 6.91 (tt, 2H, J = 9.3, 2.7 Hz), 3.83 (s, 3H);
13C{1H} NMR (75 MHz, CDCl3) δ 196.7, 162.5 (d, JCF = 248 Hz), 159.7, 141.5, 138.7, 133.3 (d, JCF = 8
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 47
1
2
3
4
5
6
7
8
Hz), 132.5, 130.3, 129.3, 128.6, 128.1, 123.3, 121.7, 119.7, 118.8 (d, JCF = 4 Hz), 115.4 (d, JCF = 22 Hz),
113.9, 93.8, 87.1, 55.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H16FO2 331.1129; found 331.1131.
(4ꢀFluoroꢀ2ꢀ(phenylethynyl)phenyl)(3ꢀmethoxyphenyl)methanone (1w). Yield 321.4 mg (99%, brown
solid); mp 65–66 °C; IR (neat): υ max 2940, 2214, 1667, 1598, 1288, 757 cm−1; 1H NMR (300 MHz, CDCl3)
δ 7.53 (dd, 1H, J = 8.4, 6.0 Hz), 7.44 (s, 1H), 7.36 (d, 2H, J = 4.7 Hz), 7.33–7.21 (m, 4H), 7.17–7.10 (m,
4H), 3.84 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 195.7, 163.4 (d, JCF = 250 Hz), 159.8, 138.8, 137.7 (d,
JCF = 3 Hz), 131.6, 131.1 (d, JCF = 9 Hz), 129.4, 128.8, 128.1, 124.5 (d, JCF = 10 Hz), 123.3, 122.2, 119.8,
119.3 (d, JCF = 23 Hz), 115.5 (d, JCF = 21 Hz), 113.9, 96.1, 86.4 (d, JCF = 4 Hz), 55.5; HRMS (ESIꢀTOF)
m/z: [M + H]+ calcd for C22H16FO2 331.1129; found 331.1138.
9
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
(4ꢀFluoroꢀ2ꢀ(hexꢀ1ꢀynꢀ1ꢀyl)phenyl)(3ꢀmethoxyphenyl)methanone (1x). Yield 261.5 mg (92%, orange solid);
1
mp 64–65 °C; IR (neat): υ max 2960, 1662, 1582, 1278, 1024, 755 cm−1; H NMR (400 MHz, CDCl3) δ
7.44–7.36 (m, 2H), 7.34–7.27 (m, 2H), 7.18–7.12 (m, 1H), 7.11–7.08 (m, 1H), 7.06–7.03 (m, 1H), 3.86 (s,
13
3H), 2.13 (t, 2H, J = 6.6 Hz), 1.29–1.13 (m, 4H), 0.82–0.78 (m, 3H); C{1H} NMR (75 MHz, CDCl3) δ
196.1, 163.3 (d, JCF = 249 Hz), 159.7, 138.7, 137.9 (d, JCF = 3 Hz), 130.5 (d, JCF = 9 Hz), 129.2, 125.1 (d,
JCF = 10 Hz), 123.3, 119.7, 119.4 (d, JCF = 23 Hz), 114.7 (d, JCF = 22 Hz), 113.7, 97.9, 77.7 (d, JCF = 3 Hz),
55.4, 30.1, 21.8, 19.0, 13.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C20H20FO2 311.1442; found
311.1444.
General
procedure
for
the
synthesis
of
indoloquinolines
(2)
(4ꢀChloroꢀ2ꢀ
(phenylethynyl)phenyl)(phenyl)methanone 1o (90.5 mg, 0.2857 mmol, 1.0 equiv) was dissolved in dry
DCM (3.5 mL/mmol) under argon. A solution was added TMSN3 (88.5 µL, 0.9999 mmol, 3.5 equiv),
followed by TfOH (132.7 µL, 0.9999 mmol, 3.5 equiv). The reaction mixture was stirred at room
temperature overnight. After completion, the reaction was quenched with sat. NaHCO3 and extracted with
EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and
concentrated under reduced pressure to provide crude product which was purified on silica gel
(EtOAc/DCM: 1:9) to yield the corresponding indoloquinoline 2o (69.8 mg, 74%).
11ꢀButylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2a). Yield 48.6 mg (58%, white solid); mp 192–193 °C; IR (neat): υ
max 2955, 1611, 1398, 1231, 741 cm−1; 1H NMR (300 MHz, CDCl3) δ 11.91 (br s, 1H), 8.30–8.16 (m, 3H),
ACS Paragon Plus Environment

Page 19 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
7.79–7.74 (m, 1H), 7.58–7.48 (m, 3H), 7.32–7.27 (m, 1H), 3.69–3.64 (m, 2H), 1.96–1.86 (m, 2H), 1.74–
1.62 (m, 2H), 1.06 (t, 3H, J = 7.2 Hz); 13C{1H} NMR (75 MHz, CDCl3) δ 153.4, 146.3, 144.6, 141.3,
128.7, 127.5, 127.1, 124.1, 123.4, 122.7, 121.4, 120.1, 116.5, 110.9, 31.7, 28.9, 23.4, 14.1; HRMS (ESIꢀ
TOF) m/z: [M + H]+ calcd for C19H19N2 275.1543; found 275.1551.
9
11ꢀIsopentylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2b). Yield 57.8 mg (57%, yellow solid); mp 265–266 °C; IR
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
1
(neat): υ max 2921, 1633, 1471, 1399, 742 cm−1; H NMR (400 MHz, DMSOꢀd6) δ 11.69 (s, 1H), 8.29 (d,
1H, J = 8.4 Hz), 8.17 (d, 1H, J = 7.6 Hz), 7.96 (d, 1H, J = 7.6 Hz), 7.73–7.69 (m, 1H), 7.55–7.49 (m, 3H),
7.32–7.28 (m, 1H), 3.65–3.61 (m, 2H), 2.02–1.92 (m, 1H), 1.68–1.62 (m, 2H), 1.09 (d, 6H, J = 6.8 Hz);
13C{1H} NMR (100 MHz, DMSOꢀd6) δ 152.5, 146.4, 143.4, 141.3, 128.4, 127.7, 127.5, 123.8, 123.1,
122.6, 122.5, 120.3, 119.8, 115.1, 110.9, 38.3, 28.3, 26.3, 22.4; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C20H21N2 289.1699; found 289.1698.
11ꢀCyclohexylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2c). Yield 38.5 mg (43%, yellow solid); mp 241–242 °C; IR
(neat): υ max 2926, 1607, 1400, 1256, 741 cm−1; 1H NMR (400 MHz, CDCl3) δ 12.14 (br s, 1H), 8.62 (br s,
1H), 8.34 (br s, 1H), 8.24 (d, 1H, J = 8.4 Hz), 7.76 (t, 1H, J = 7.6 Hz), 7.59–7.46 (m, 3H), 7.36–7.28 (m,
1H), 4.31 (br s, 1H), 2.53 (br s, 2H), 2.10–1.98 (m, 5H), 1.73–1.64 (m, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 153.7, 149.4, 146.8, 141.5, 128.5, 128.3, 127.4, 127.3, 126.9, 123.8, 123.2, 121.5, 119.7, 116.8,
111.0, 42.8, 31.5, 27.6, 26.2; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C21H21N2 301.1699; found
301.1694.
11ꢀ(Phenoxymethyl)ꢀ6Hꢀindolo[2,3ꢀb]quinoline (2d). Yield 17.1 mg (16%, yellow solid); mp 265–266 °C;
IR (neat): υ max 2924, 1598, 1482, 1233, 751 cmꢀ1; 1H NMR (400 MHz, DMSOꢀd6) δ 11.86 (s, 1H), 8.44 (d,
1H, J = 8.4 Hz), 8.12 (d, 1H, J = 8.0 Hz), 8.03 (d, 1H, J = 8.4 Hz), 7.76 (t, 1H, J = 7.2 Hz), 7.57–7.52 (m,
3H), 7.35 (t, 2H, J = 8.0 Hz), 7.23–7.18 (m, 3H), 7.02 (t, 1H, J = 7.2 Hz), 6.09 (s, 2H) ; 13C{1H} NMR (100
MHz, DMSOꢀd6) δ 158.5, 152.5, 146.3, 141.9, 134.9, 129.7, 128.7, 128.3, 127.6, 124.3, 124.1, 123.2,
122.5, 121.2, 119.8, 119.7, 117.0, 114.8, 111.0, 62.7; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C22H17N2O 325.1335; found 325.1343.
11ꢀPhenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2e). Yield 57.5 mg (54%, yellow solid); mp 259–260 °C; IR (neat):
υ
max 2846, 1611, 1584, 1402, 1250, 743 cm−1; 1H NMR (300 MHz, CDCl3) δ 12.39 (br s, 1H), 8.24 (d, 1H,
58
59
60
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 47
1
2
3
4
J = 8.4 Hz), 7.77–7.69 (m, 2H), 7.67–7.63 (m, 3H), 7.53–7.48 (m, 3H), 7.40–7.33 (m, 2H), 7.05 (d, 1H, J =
13
7.5 Hz), 6.98–6.92 (m, 1H); C{1H} NMR (75 MHz, CDCl3) δ 153.4, 146.2, 142.8, 141.6, 136.4 129.4,
5
6
7
8
128.94, 128.89, 128.5, 127.9, 126.6, 126.4, 123.7, 123.0, 122.8, 121.0, 119.7, 116.8, 110.8; HRMS (ESIꢀ
TOF) m/z: [M + H]+ calcd for C21H15N2 295.1230; found 295.1220.
9
11ꢀ(4ꢀFluorophenyl)ꢀ6Hꢀindolo[2,3ꢀb]quinoline (2f). Yield 72.2 mg (73%, yellow solid); mp 296–297 °C;
IR (neat): υ max 2924, 1607, 1507, 1231, 743 cm−1; 1H NMR (300 MHz, CDCl3) δ 10.21 (br s, 1H), 8.20 (d,
1H, J = 8.3 Hz), 7.80–7.74 (m, 2H), 7.57–7.35 (m, 7H), 7.11–7.00 (m, 2H); 13C{1H} NMR (75 MHz,
CDCl3) δ 163.0 (d, JCF = 246 Hz), 153.1, 146.4, 141.7, 141.4, 132.3 (d, JCF = 3 Hz), 131.2 (d, JCF = 8 Hz),
129.0, 128.1, 126.9, 126.3, 123.9, 123.1 (d, JCF = 11 Hz), 121.1, 120.0, 116.8, 116.3, 116.1, 110.8; HRMS
(ESIꢀTOF) m/z: [M + H]+ calcd for C21H14FN2 313.1136; found 313.1132.
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
4ꢀMethylꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2h). Yield 21.5 mg (20%, yellow solid); mp 165–166 °C;
1
IR (neat): υ max 2974, 1610, 1599, 1396, 1245, 733 cm−1; H NMR (300 MHz, CDCl3) δ 10.50 (br s, 1H),
13
7.69–7.61 (m, 5H), 7.57–7.52 (m, 2H), 7.41–7.27 (m, 3H), 7.04–6.93 (m, 2H), 2.97 (s, 3H); C{1H} NMR
(75 MHz, CDCl3) δ 152.3, 145.4, 143.2, 141.1, 136.8, 134.4, 129.4, 129.3, 128.9, 128.5, 127.7, 124.6,
123.7, 123.1, 122.6, 121.2, 119.9, 116.1, 110.6, 18.9; HRMS (ESIꢀTOF) m/z: [M + H ]+ calcd for C22H17N2
309.1386; found 309.1383.
3ꢀMethylꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2i) and 1ꢀMethylꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline
(2i’). Yield 87.8 mg (68%, ratio 2i:2i’; 1.4:1.0, yellow solid); mp 211–212 °C; IR (neat): υ max 2926, 2853,
1598, 1461, 1394, 1236, 744 cm−1; 1H NMR (300 MHz, CDCl3) δ 12.1 (br s, 1.8H), 8.06 (d, 1.0H, J = 8.4
Hz, minor), 7.84 (s, 1.4H, major), 7.63–7.45 (m, 17.2H), 7.38–7.31 (m, 3H), 7.20–7.15 (m, 2.7H), 7.00–
6.84 (m, 3.9H), 6.40 (d, 1H, J = 7.8 Hz), 2.47 (s, 4.2H, major), 2.17 (s, 3H, minor) ; 13C{1H} NMR (75
MHz, CDCl3) δ 153.4 (major), 152.2 (minor), 147.5, 146.3, 143.6, 142.6, 141.7, 141.6, 140.9, 139.2, 136.8,
136.6, 129.4, 128.9, 128.8, 128.7, 128.4, 128.2, 127.6, 127.5, 126.6, 126.1, 126.0, 125.6, 125.1, 123.2,
122.8, 122.1, 121.7, 121.6, 121.3, 119.6, 118.1, 116.0, 110.8, 110.7; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd
for C22H17N2 309.1386; found 309.1390.
3ꢀMethoxyꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2j). Yield 44.7 mg (47%, yellow solid); mp 233–234 °C;
IR (neat): υ max 2965, 1606, 1391, 1218, 744 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.69–7.59 (m, 4H), 7.55–
ACS Paragon Plus Environment

Page 21 of 47
The Journal of Organic Chemistry
7.50 (m, 4H), 7.41–7.36 (m, 1H), 7.07–6.95 (m, 3H), 3.95 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ
160.6, 153.7, 148.1, 143.0, 141.0, 136.5, 129.3, 128.9, 128.5, 127.6, 127.1, 122.7, 121.6, 119.7, 118.8,
115.8, 114.7, 110.6, 105.0, 55.4; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H17N2O 325.1335; found
325.1339.
1
2
3
4
5
6
7
8
9
1ꢀMethoxyꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2j’). Yield 23.3 mg (24%, yellow solid); mp 218–219
°C; IR (neat): υ max 2834, 1599, 1579, 1395, 1244, 1099, 741 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.86 (d,
1H, J = 8.4 Hz), 7.65 (t, 1H, J = 8.0 Hz), 7.58–7.50 (m, 4H), 7.43–7.35 (m, 3H), 6.94–6.89 (m, 1H), 6.74
(d, 1H, J = 7.8 Hz), 6.57 (d, 1H, J = 7.5 Hz), 3.51 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 158.1, 152.6,
147.5, 143.1, 141.3, 141.2, 129.3, 128.0, 127.6, 127.3, 126.9, 123.4, 121.7, 120.0, 119.4, 117.6, 115.4,
110.7, 103.3, 55.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H17N2O 325.1335; found 325. 1337.
2ꢀMethoxyꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2k). Yield 9.3 mg (11%, yellow solid); mp 208 °C
(decomp); IR (neat): υ max 2956, 1611, 1402, 1227, 1034, 743 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.71 (br
s, 1H), 8.08 (d, 1H, J = 9.3 Hz), 7.71–7.61 (m, 3H), 7.57–7.54 (m, 2H), 7.48–7.39 (m, 3H), 7.06–6.94 (m,
3H), 3.77 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 155.1, 151.6, 142.2, 141.6, 141.0, 136.6, 129.3,
129.1, 128.6, 128.2, 127.9, 124.5, 123.2, 121.2, 121.1, 119.9, 116.6, 110.6, 104.8, 55.4; HRMS (ESIꢀTOF)
m/z: [M + H]+ calcd for C22H17N2O 325.1335; found 325.1346.
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
2ꢀFluoroꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2l). Yield 71.2 mg (86%, yellow solid); mp 261–262 °C;
1
IR (neat): υ max 2928, 1631, 1612, 1403, 1227, 744 cm−1; H NMR (400 MHz, CDCl3) δ 10.50 (br s, 1H),
8.16 (dd, 1H, J = 9.2, 5.6 Hz), 7.71–7.63 (m, 3H), 7.55–7.42 (m, 5H), 7.38 (dd, 1H, J = 10.0, 2.8 Hz), 7.07
(d, 1H, J = 7.6 Hz), 7.02–6.98 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 158.4 (d, JCF = 241 Hz), 152.8,
143.1, 142.0 (d, JCF = 5 Hz), 141.6, 135.9, 129.2, 129.1, 128.8, 128.4 (d, JCF = 9 Hz), 128.2, 124.1, 123.2,
120.6, 119.9, 118.8 (d, JCF = 26 Hz), 117.1, 110.7, 109.6 (d, JCF = 23 Hz); HRMS (ESIꢀTOF) m/z: [M + H]+
calcd for C21H14FN2 313.1136; found 313.1134.
9ꢀMethylꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2m). Yield 62.6 mg (73%, yellow solid); mp 242–243 °C;
1
IR (neat): υ max 2858, 1599, 1484, 1381, 1253, 700 cm−1; H NMR (400 MHz, CDCl3) δ 11.95 (bs s, 1H),
8.24 (d, 1H, J = 8.4 Hz), 7.77–7.72 (m, 2H), 7.67–7.65 (m, 3H), 7.54–7.52 (m, 2H), 7.38 (t, 2H, J = 8.0
Hz), 7.19 (d, 1H, J = 8.0 Hz), 6.83 (s, 1H), 2.27 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 153.6, 146.3,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 47
1
2
3
4
5
6
142.6, 139.5, 136.5, 129.4, 129.0, 128.93, 128.90, 128.8, 128.5, 126.6, 126.5, 123.7, 123.2, 122.7, 121.2,
116.7, 110.4, 21.4; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H17N2 309.1386; found 309.1383.
9ꢀFluoroꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2n). Yield 79.9 mg (81%, yellow solid); mp 278–279 °C;
7
8
1
IR (neat): υ max 2860, 1603, 1486, 1472, 1182, 757 cm−1; H NMR (400 MHz, CDCl3) δ 11.96 (br s, 1H),
9
8.17 (d, 1H, J = 8.4 Hz), 7.75 (t, 2H, J = 8.4 Hz), 7.71–7.64 (m, 3H), 7.51–7.48 (m, 2H), 7.41–7.36 (m,
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
13
2H), 7.09 (td, 1H, J = 8.8, 2.4 Hz), 6.70 (dd, 1H, J = 9.2, 2.4 Hz); C{1H} NMR (100 MHz, CDCl3) δ
157.2 (d, JCF = 236 Hz), 153.7, 146.6, 143.5, 137.6, 135.8, 129.3, 129.2, 129.1, 128.9, 126.9, 126.5, 123.5,
123.1, 121.6 (d, JCF = 10 Hz), 116.3 (d, JCF = 4 Hz), 115.3 (d, JCF = 25 Hz), 111.2 (d, JCF = 9 Hz), 109.2 (d,
JCF = 25 Hz); HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C21H14FN2 313.1136; found 313.1132.
9ꢀChloroꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2o). Yield 69.8 mg (74%, yellow solid); mp 303–304 °C;
IR (neat): υ max 2929, 1600, 1451, 1281, 759 cm−1; 1H NMR (400 MHz, CDCl3) δ 12.38 (br s, 1H), 8.12 (d,
1H, J = 8.4 Hz), 7.73–7.67 (m, 5H), 7.46–7.45 (m, 2H), 7.38 (t, 1H, J = 7.5 Hz), 7.24 (d, 1H, J = 9.2 Hz),
7.16 (d, 1H, J = 8.0), 6.94 (s, 1H); C{1H} NMR (100 MHz, CDCl3) δ 153.1, 146.6, 143.6, 139.6, 135.7,
13
129.4, 129.2, 129.1, 129.0, 127.7, 126.7, 126.4, 125.1, 123.7, 123.2, 122.7, 122.2, 115.7, 111.6; HRMS
(ESIꢀTOF) m/z: [M + H]+ calcd for C21H14ClN2 (Clꢀ35) 329.0840; found 329.0839.
9ꢀMethoxyꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2p). Yield 43.8 mg (51%, yellow solid); mp 225–226 °C;
IR (neat): υ max 2930, 1600, 1588, 1486, 1205, 756 cm−1; H NMR (300 MHz, CDCl3) δ 11.18 (br s, 1H),
1
8.20 (d, 1H, J = 8.4 Hz), 7.80–7.72 (m, 2H), 7.70–7.60 (m, 3H), 7.57–7.54 (m, 2H), 7.41–7.36 (m, 2H),
13
7.03 (dd, 1H, J = 8.7, 2.4 Hz), 6.55 (d, 1H, J = 2.4 Hz), 3.59 (s, 3H); C{1H} NMR (75 MHz, CDCl3) δ
153.7, 153.6, 146.4, 142.8, 136.3, 135.9, 129.5, 128.95, 128.92, 128.6, 126.61, 126.56, 123.5, 122.8, 121.6,
116.8, 116.1, 111.3, 106.9, 55.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H17N2O 325.1335; found
325.1345.
8ꢀMethoxyꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2q). Yield 26.4 mg (31%, yellow solid); mp 223–224 °C;
IR (neat): υ max 2934, 1618, 1602, 1402, 1162, 758 cm−1; H NMR (400 MHz, CDCl3) δ 12.21 (br s, 1H),
1
8.17 (d, 1H, J = 8.4 Hz), 7.71 (d, 1H, J = 8.0 Hz), 7.67–7.60 (m, 4H), 7.50–7.48 (m, 2H), 7.37–7.33 (m,
1H), 6.90 (d, 1H, J = 8.4 Hz), 6.82 (s, 1H), 6.52 (dd, 1H, J = 8.8, 2.0 Hz), 3.70 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 160.3, 153.3, 145.3, 143.1, 140.9, 136.5, 129.5, 128.9, 128.4, 128.3, 126.3, 126.2, 123.83,
ACS Paragon Plus Environment

Page 23 of 47
The Journal of Organic Chemistry
123.80, 122.8, 116.9, 114.3, 107.9, 95.1, 55.3; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H17ON2
325.1335; found 325.1330.
1
2
3
4
5
6
7
8
8ꢀFluoroꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2r). Yield 60.0 mg (68%, yellow solid); mp 245–246 °C;
IR (neat): υ max 2925, 1615, 1604, 1401, 1142, 756 cm−1; 1H NMR (300 MHz, CDCl3) δ 12.67 ( br s, 1H),
8.13 (d, 1H, J = 8.1 Hz), 7.71–7.62 (m, 5H), 7.47–7.44 (m, 2H), 7.40–7.34 (m, 1H), 7.05 (dd, 1H, J = 9.3,
9
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
13
2.1 Hz), 6.92 (dd, 1H, J = 8.7, 5.7 Hz), 6.62 (td, 1H, J = 9.3, 2.4 Hz); C{1H} NMR (75 MHz, CDCl3) δ
162.8 (d, JCF= 244 Hz), 153.6, 145.8, 142.6 (d, JCF= 13 Hz), 142.2 (d, JCF= 2 Hz), 136.2, 129.4, 129.0,
128.7, 126.4, 126.2, 124.0 (d, JCF= 10 Hz), 123.7, 123.2, 117.3 (d, JCF= 2 Hz), 116.1, 107.5 (d, JCF= 23 Hz),
98.0 (d, JCF= 26 Hz); HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C21H14FN2 313.1136; found 313.1136.
11ꢀButylꢀ3ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2s). Yield 58.9 mg (40%, white solid); mp 202–203 °C; IR
(neat): υ max 2922, 1610, 1578, 1457, 1220, 739 cm−1; 1H NMR (300 MHz, CDCl3) δ 10.71 (br s, 1H), 8.17–
8.13 (m, 2H), 7.56–7.46 (m, 3H), 7.33–7.27 (m, 1H), 7.17 (dd, 1H, J = 9.0, 2.4 Hz), 4.00 (s, 3H), 3.65–3.60
(m, 2H), 1.94–1.84 (m, 2H), 1.72–1.60 (m, 2H), 1.05 (t, 3H, J = 7.3 Hz); 13C{1H} NMR (75 MHz, CDCl3)
δ 160.5, 153.6, 148.5, 144.7, 140.5, 126.8, 125.3, 123.0, 121.9, 120.2, 118.6, 115.7, 114.4, 110.7, 105.8,
55.5, 31.8, 29.0, 23.4, 14.1; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C20H21N2O 305.1648; found
305.1641.
11ꢀButylꢀ1ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2s’). Yield 29.2 mg (20%, white solid); mp 227–228 °C;
IR (neat): υ max 2928, 1605, 1581, 1394, 1240, 737 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.19 (d, 1H, J = 7.9
Hz), 7.76 (d, 1H, J = 8.3 Hz), 7.63 (t, 1H, J = 7.9 Hz), 7.55–7.47 (m, 2H), 7.33–7.28 (m,1H), 6.85 (d, 1H, J
= 7.7 Hz), 4.05–3.61 (m, 5H), 1.94 (quint, 2H, J = 7.1 Hz), 1.77–1.65 (m, 2H), 1.10 (t, 3H, J = 7.3 Hz);
13C{1H} NMR (75 MHz, CDCl3) δ 158.8, 152.0, 148.1, 147.4, 140.9, 129.0, 127.3, 123.6, 121.8, 120.4,
119.4, 117.3, 116.0, 111.1, 102.9, 55.6, 32.7, 31.9, 23.6, 14.1; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C20H21N2O 305.1648; found 305.1649.
11ꢀIsopentylꢀ3ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2t). Yield 35.9 mg (32%, white solid); mp 244–245
°C; IR (neat): υ max 2954, 1613, 1590, 1220, 1208, 738 cm−1; H NMR (300 MHz, CDCl3) δ 10.85 (br s,
1
1H), 8.15–8.11 (m, 2H), 7.55–7.46 (m, 3H), 7.30 (t, 1H, J = 7.2 Hz), 7.17 (dd, 1H, J = 9.3, 2.7 Hz), 3.99 (s,
3H), 3.63–3.57 (m, 2H), 2.04–1.91 (m, 1H), 1.83–1.72 (m, 2H), 1.14 (d, 6H, J = 6.6 Hz); C{1H} NMR
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 47
1
2
3
4
5
6
(75 MHz, CDCl3) δ 160.5, 153.6, 148.4, 145.0, 140.5, 126.8, 125.1, 122.9, 121.8, 120.2, 118.4, 115.8,
114.3, 110.7, 105.8, 55.5, 38.5, 29.1, 27.3, 22.6; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C21H23N2O
319.1805; found 319.1801.
7
8
11ꢀIsopentylꢀ1ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2t’). Yield 22.1 mg (19%, white solid); mp 264–265
9
1
°C; IR (neat): υ max 2924, 1606, 1580, 1393, 1242, 736 cm−1; H NMR (600 MHz, CDCl3) δ 10.66 (br s,
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
1H), 8.21 (d, 1H, J = 7.9 Hz), 7.75 (d, 1H, J = 8.3 Hz), 7.62 (t, 1H, J = 8.0 Hz), 7.54–7.49 (m, 2H), 7.31–
7.28 (m, 1H), 6.85 (d, 1H, J = 7.6 Hz), 4.04– 3.45 (m, 5H), 2.02–1.97 (m, 1H), 1.85 (q, 2H, J = 7.2 Hz),
1.15 (d, 6H, J = 6.6 Hz); 13C{1H} NMR (125 MHz, CDCl3) δ 158.8, 152.6, 148.7, 147.4, 140.9, 128.5,
127.1, 123.6, 122.2, 120.3, 120.2, 116.9, 116.2, 110.8, 102.7, 55.4, 38.7, 31.2, 29.5, 22.7; HRMS (ESIꢀ
TOF) m/z: [M + H]+ calcd for C21H23N2O 319.1805; found 319.1808.
11ꢀCyclohexylꢀ3ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2u). Yield 35.2 mg (36%, white solid); mp 229–230
°C; IR (neat): υ max 2923, 1600, 1568, 1464, 1240, 1095, 739 cm−1; 1H NMR (400 MHz, CDCl3) δ 11.60 (br
s, 1H), 8.47 (d, 1H, J = 8.1 Hz), 8.31 (br s, 1H), 7.57–7.55 (m, 1H), 7.50–7.44 (m, 2H), 7.31–7.26 (m, 1H),
7.13 (dd, 1H, J = 9.3, 2.4 Hz), 4.24 (br s, 1H), 3.99 (s, 3H), 2.46 (br s, 2H), 2.10–1.87 (m, 5H), 1.73–1.65
(m, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 160.0, 154.0, 149.7, 149.1, 140.9, 127.9, 126.7, 123.5, 121.9,
119.8, 118.4, 114.7, 110.8, 105.8, 55.4, 42.7, 31.7, 27.6, 26.2; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C22H23N2O 331.1805; found 331.1809.
11ꢀCyclohexylꢀ1ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2u’). Yield 25.6 mg (26%, white solid); mp 226–227
°C; IR (neat): υ max 2919, 1601, 1568, 1464, 1240, 1095, 730 cm−1; 1H NMR (300 MHz, CDCl3) δ 11.01 (br
s, 1H), 8.36 (d, 1H, J = 7.8 Hz), 7.76 (dd, 1H, J = 8.4, 0.9 Hz), 7.63 (t, 1H, J = 7.9 Hz), 7.54–7.46 (m, 2H),
7.33–7.27 (m, 1H), 6.85 (d, 1H, J = 7.1 Hz), 4.40–4.31 (m, 1H), 4.07 (s, 3H), 2.64–2.52 (m, 2H), 2.04–1.89
13
(m, 5H), 1.67–1.56 (m, 3H); C{1H} NMR (75 MHz, CDCl3) δ 157.7, 153.3, 151.4, 148.8, 141.2, 128.3,
127.1, 125.6, 121.8, 120.1, 119.7, 118.0, 116.8, 110.9, 102.7, 54.8, 43.7, 28.6, 27.2, 26.1; HRMS (ESIꢀ
TOF) m/z: [M + H]+ calcd for C22H23N2O 331.1805; found 331.1808.
11ꢀ(4ꢀFluorophenyl)ꢀ3ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2v). Yield 37.7 mg (34%, yellow solid); mp
244–245 °C; IR (neat): υ max 2923, 2853, 1609, 1221, 1029, 800 cm−1; 1H NMR (300 MHz, CDCl3) δ 11.74
(br s, 1H), 7.59 (d, 1H, J = 9.3 Hz), 7.50–7.44 (m, 3H), 7.40–7.31 (m, 4H), 7.07–6.97 (m, 3H), 3.86 (s, 3H);
ACS Paragon Plus Environment

Page 25 of 47
The Journal of Organic Chemistry
13C{1H} NMR (75 MHz, CDCl3) δ 163.0 (d, JCF = 246 Hz), 160.7, 153.5, 148.2, 141.8, 140.9, 132.4 (d, JCF
= 4 Hz), 131.2 (d, JCF = 8 Hz), 127.3, 122.5, 121.4, 119.9, 118.9, 116.2 (d, JCF = 9 Hz), 116.0, 114.8, 110.7,
105.2, 55.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H16FN2O 343.1241; found 343.1240.
11ꢀ(4ꢀFluorophenyl)ꢀ1ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2v’). Yield 32.4 mg (30%, yellow solid); mp
242–243 °C; IR (neat): υ max 2934, 1601, 1582, 1396, 1245, 1100, 743 cm−1; 1H NMR (400 MHz, CDCl3) δ
11.99 (br s, 1H), 7.82 (d, 1H, J = 8,4 Hz), 7.62 (t, 1H, J = 8.0 Hz), 7.49 (d, 1H, J = 8.0 Hz), 7.38–7.35 (m,
3H), 7.82–7.22 (m, 2H), 6.94 (t, 1H, J = 7.4 Hz), 6.72 (d, 1H, J = 7.7 Hz), 6.63 (d, 1H, J = 7.9 Hz), 3.54 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.0 (d, JCF = 245 Hz), 157.8, 152.9, 148.0, 141.5, 141.3, 137.3
(d, JCF = 4 Hz), 129.10, 129.05 (d, JCF = 8 Hz), 127.7, 123.2, 121.5, 119.8, 119.6, 117.6, 115.3, 114.9 (d,
JCF = 21 Hz), 110.8, 103.0, 55.4; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H16FN2O 343.1241; found
343.1254.
1
2
3
4
5
6
7
8
9
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
9ꢀFluoroꢀ3ꢀmethoxyꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2w). Yield 44.1 mg (42%, yellow solid); mp
267–268 °C; IR (neat): υ max 2923, 1608, 1493, 1258, 1142, 803 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.64–
7.60 (m, 4H), 7.45–7.41 (m, 2H), 7.39–7.35 (m, 2H), 7.10–7.02 (m, 2H), 6.65 (dd, 1H, J = 9.3, 2.4 Hz),
3.87 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 161.1, 157.3 (d, JCF = 235 Hz), 153.6, 147.9, 144.0, 137.0,
135.8, 129.09, 129.06, 128.9, 127.9, 122.0 (d, JCF = 10 Hz), 118.5, 116.1, 114.6 (d, JCF = 25 Hz), 111.1 (d,
JC F= 9 Hz), 108.8 (d, JCF = 25 Hz), 104.6, 55.4; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H16FN2O
343.1241; found 343.1249.
9ꢀFluoroꢀ1ꢀmethoxyꢀ11ꢀphenylꢀ6Hꢀindolo[2,3ꢀb]quinoline (2w’). Yield 22.8 mg (22%, yellow solid); mp
291–292 °C; IR (neat): υ max 2933, 1602, 1582, 1471, 1251, 1098, 699 cm−1; 1H NMR (300 MHz, CDCl3) δ
7.77 (d, 1H, J = 7.9 Hz), 7.63 (t, 1H, J = 7.8 Hz), 7.59–7.52 (m, 3H), 7.39–7.34 (m, 3H), 7.08 (td, 1H, J =
8.9, 2.6 Hz), 6.72 (d, 1H, J = 7.3 Hz), 6.19 (dd, 1H, J = 9.6, 2.6 Hz), 3.51 (s, 3H); 13C{1H} NMR (75 MHz,
CDCl3) δ 158.1, 157.2 (d, JC F= 234 Hz), 153.2, 148.3, 143.4, 140.9, 137.2, 129.5, 128.1, 127.2, 127.1,
122.4 (d, JCF = 10 Hz), 119.7, 117.0 (d, JCF = 4 Hz), 115.3, 114.9 (d, JCF = 25 Hz), 110.9 (d, JCF = 9 Hz),
109.6 (d, JCF = 25 Hz), 103.2, 55.5; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C22H16FN2O 343.1241;
found 343.1240.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 47
1
2
3
4
5
6
7
8
11ꢀButylꢀ9ꢀfluoroꢀ3ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2x). Yield 40.9 mg (40%, yellow solid); mp 216–
217 °C; IR (neat): υ max 2957, 1617, 1591, 1478, 1259, 1161, 811 cm−1; 1H NMR (300 MHz, DMSOꢀd6) δ
11.62 (s, 1H), 8.19 (d, 1H, J = 9.3 Hz), 7.86 (dd, 1H, J = 9.6, 2.1 Hz), 7.47 (dd, 1H, J = 8.7, 4.5 Hz), 7.37–
7.31 (m, 2H), 7.13 (dd, 1H, J = 9.0, 2.4 Hz), 3.93 (s, 3H), 3.54 (t, 2H, J = 7.6 Hz), 1.73 (quint, 2H, J = 9.3
Hz), 1.60–1.50 (m, 2H), 0.95 (t, 3H, J = 7.2 Hz); 13C{1H} NMR (75 MHz, DMSOꢀd6) δ 160.0, 156.8 (d, JCF
= 232 Hz), 153.5, 148.8, 144.4, 137.1, 125.6, 121.2 (d, JCF = 9 Hz), 117.7, 115.3, 114.1 (d, JCF = 25 Hz),
113.1 (d, JCF = 3 Hz), 111.5 (d, JCF = 9 Hz), 108.7 (d, JCF = 25 Hz), 106.2, 55.3, 31.7, 27.8, 22.4, 13.9;
HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for C20H20FN2O 323.1554; found 323.1559.
9
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
11ꢀButylꢀ9ꢀfluoroꢀ1ꢀmethoxyꢀ6Hꢀindolo[2,3ꢀb]quinoline (2x’). Yield 18.1 mg (18%, brown solid); mp 223–
224 °C; IR (neat): υ max 2958, 1606, 1582, 1465, 1246, 1159, 765 cm−1; 1H NMR (300 MHz, DMSOꢀd6) δ
11.67 (s, 1H), 7.86 (dd, 1H, J = 10.1, 2.4 Hz), 7.61–7.46 (m, 3H), 7.37 (td, 1H, J = 9.2, 2.4 Hz), 6.92 (dd,
1H, J = 7.6, 1.2 Hz), 3.99–3.55 (m, 5H), 1.80 ( quint, 2H, J = 7.7 Hz), 1.70–1.58 (m, 2H), 1.04 (t, 3H, J =
7.2 Hz); 13C{1H} NMR (75 MHz, DMSOꢀd6) δ 158.2, 156.6 (d, JCF = 232 Hz), 152.6, 149.0, 146.0, 137.6,
128.8, 121.1 (d, JCF = 9 Hz), 120.5, 115.5 (d, JCF = 4 Hz), 115.0, 114.5 (d, JCF = 24 Hz), 111.6 (d, JCF = 9
Hz), 109.2 (d, JCF = 25 Hz), 102.8, 55.7, 31.8, 31.6, 22.8, 13.9; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C20H20FN2O 323.1554; found 323.1560.
1ꢀ(2ꢀBenzoylphenyl)hexanꢀ2ꢀone (3a). Yield 6.4 mg (8%, brown oil); IR (neat): υ max 2958, 1716, 1659,
1447, 1268, 699 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.82–7.78 (m, 2H), 7.60–7.54 (m, 1H), 7.50–7.30 (m,
4H), 7.34–7.26 (m, 2H), 3.95 (s, 2H), 2.45 (t, 2H, J = 7.2 Hz), 1.56–1.46 (m, 2H), 1.31–1.19 (m, 2H), 0.85
(t, 3H, J = 7.5 Hz); 13C{1H} NMR (75 MHz, CDCl3) δ 207.7, 198.2, 138.0, 137.9, 134.5, 132.8, 132.0,
130.9, 130.3, 130.1, 128.3, 126.2, 47.2, 42.3, 25.8, 22.2, 13.8; HRMS (ESIꢀTOF) m/z: [M + H]+ calcd for
C19H21O2 281.1536; found 281.1525.
General procedure for the synthesis of αꢀalkynylalcohols (8) and (9) Method A: 6ꢀphenylhexꢀ5ꢀynꢀ1ꢀol
(401.1 mg, 2.3020 mmol, 1.0 equiv) was dissolved in DCM (AR grade) (3.0 mL/mmol) at room
temperature. The solution was added Celite and PCC (595.5 mg, 2.7624 mmol, 1.2 equiv) and stirred at
room temperature. After completion, the reaction was filtered through Celite and silica gel, followed by
ACS Paragon Plus Environment

Page 27 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
concentration under reduced pressure to obtain crude product aldehyde which was used without further
purification. The crude aldehyde was dissolved in dry THF (2.3 mL/mmol) and cooled to 0 °C under argon
atmosphere. The solution was then added 4ꢀfluorophenylmagnesium bromide (1.3 mL, 2.6415 mmol, 1.2
equiv) and then the reaction was allowed to warm to room temperature. After completion, the reaction was
quenched with sat. NH4Cl and extracted with EtOAc. The combined organic layers were washed with
brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to provide the crude product
which was purified on silica gel (EtoAc/Hexane: 2:8) to yield the product 8k (445.3 mg, 75%).
9
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
Method B: 4ꢀBromoveratrole (109.8 µL, 0.7631 mmol, 1.3 equiv) was dissolved in dry THF (3.4
mL/mmol) and cooled to ꢀ40 °C under argon atmosphere. The solution was then added nꢀBuLi (0.6 mL,
0.7044 mmol, 1.2 equiv) and stirred for 30 min and then cooled to ꢀ78 °C. The reaction mixture was added
with the crude aldehyde in dry THF (3.4 mL/mmol), prepared from the oxidation of alcohol with PCC as
described in method A. After completion, the reaction was quenched with H2O and extracted with EtOAc.
The combined organic layers were then washed with brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure to provide the crude product which was purified on silica gel (EtOAc/Hexane: 3:7)
to yield the ꢀalkynylalcohols 8q (104 mg, 55%). (Note: For the synthesis of comcound 8m which used
iodobenzene derivatives as strating material, the temperature was cooled to ꢀ78 °C throughout the reaction.)
1,6ꢀDiphenylhexꢀ5ꢀynꢀ1ꢀone (8a). Yield 351.5 mg (64 %, colorless oil); IR (neat): υ max 3385, 2935, 1490,
1
1066, 754 cm−1; H NMR (300 MHz, CDCl3) δ 7.39–7.32 (m, 6H), 7.30–7.25 (m, 4H), 4.73 (dd, 1H, J =
13
7.2, 5.7 Hz), 2.44 (t, 2H, J = 6.9 Hz), 2.03–1.48 (m, 4H); C{1H} NMR (75 MHz, CDCl3) δ 144.6, 131.6,
128.5, 128.2, 127.7, 127.6, 125.9, 123.9, 89.8, 81.0,74.2, 38.1, 25.0, 19.3; HRMS (ESIꢀTOF) m/z: [M +
Na]+ calcd for C18H18ONa 273.1250; found 273.1259.
6ꢀ(4ꢀFluorophenyl)ꢀ1ꢀphenylhexꢀ5ꢀynꢀ1ꢀol (8b). Yield 484.9 mg (67%, colorless oil); IR (neat): υ max 3385,
1
2936, 1506, 1454, 1229, 834 cm−1; H NMR (300 MHz, CDCl3) δ 7.36–7.23 (m, 7H), 6.98–6.92 (m, 2H),
4.72–4.67 (m, 1H), 2.40 (t, 2H, J = 6.9 Hz), 2.09 (br s, 1H), 2.00–1.82 (m, 2H), 1.80–1.66 (m, 1H), 1.64–
1.50 (m, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 162.0 (d, JCF = 247 Hz), 144.5, 133.3 (d, JCF = 8 Hz),
128.5, 127.6, 125.8, 119.9 (d, JCF = 4 Hz), 115.3 (d, JCF = 22 Hz), 89.4, 79.9, 74.1, 38.1, 24.9,19.2; HRMS
(ESIꢀTOF) m/z: [M + Na]+ calcd for C18H17FONa 291.1156; found 291.1157.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 47
1
2
3
4
5
6
6ꢀ(4ꢀChlorophenyl)ꢀ1ꢀphenylhexꢀ5ꢀynꢀ1ꢀol (8c). Yield 507.4 mg (65%, colorless oil); IR (neat): υ max 3383,
2936, 2236, 1489, 1090, 826 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.37–7.22 (m, 9H), 4.74 (t, 1H, J = 6.3
13
Hz), 2.43 (t, 2H, J = 6.9 Hz), 2.04–1.59 (m, 5H); C{1H} NMR (75 MHz, CDCl3) δ 144.5, 133.5, 132.8,
7
8
9
128.54, 128.48, 127.7, 125.9, 122.4, 90.9, 79.9, 74.2, 38.1, 24.9, 19.3; HRMS (ESIꢀTOF) m/z: [M + Na]+
calcd for C18H17ClONa (Clꢀ35) 307.0860; found 307.0858.
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
6ꢀ(4ꢀBromophenyl)ꢀ1ꢀphenylhexꢀ5ꢀynꢀ1ꢀol (8d). Yield 513.9 mg (72%, colorless oil); IR (neat): υ max 3369,
2935, 2228, 1485, 823 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.40–7.34 (m, 6H), 7.30–7.20 (m, 3H), 4.72 (t,
1H, J = 6.3 Hz), 2.41 (t, 2H, J = 6.9 Hz), 2.01– 1.80 (m, 3H), 1.77–1.68 (m, 1H), 1.66–1.52 (m, 1H);
13C{1H} NMR (75 MHz, CDCl3) δ 144.5, 133.0, 131.4, 128.5, 127.6, 125.8, 122.8, 121.6, 91.1, 80.0, 74.2,
38.1, 24.8, 19.3; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C18H17BrONa (Brꢀ79) 351.0355; found
351.0350.
6ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀphenylhexꢀ5ꢀynꢀ1ꢀol (8e). Yield 503.0 mg (64%, colorless oil); IR (neat): υ
max
3421, 2935, 1606, 1508, 1244, 831 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.36–7.26 (m, 7H), 6.82–6.77 (m,
2H), 4.73 (dd, 1H, J = 7.2, 6.0 Hz), 3.78 (s, 3H), 2.42 (t, 2H, J = 7.2 Hz), 1.98–1.83(m, 3H), 1.79–1.52 (m,
2H); 13C{1H} NMR (75 MHz, CDCl3) δ 159.0, 144.6, 132.8, 128.5, 127.6, 125.9, 116.0, 113.8, 88.1, 80.7,
74.2, 55.2, 38.1, 25.0, 19.3; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C19H20O2Na 303.1356; found
303.1361.
6ꢀ(3ꢀMethoxyphenyl)ꢀ1ꢀphenylhexꢀ5ꢀynꢀ1ꢀol (8f). Yield 249.3 mg (33%, colorless oil); IR (neat): υ max 3421,
2938, 1598, 1575, 1286, 1043, 687 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.35–7.24 (m, 5H), 7.17 (t, 1H, J =
8.1 Hz), 6.97 (dt, 1H, J = 7.5, 0.9 Hz), 6.91–6.90 (m, 1H), 6.81 (ddd, 1H, J = 8.4, 2.7, 0.9), 4.72 (dd, 1H, J
= 7.2, 5.7 Hz), 3.77 (s, 3H), 2.43 (t, 2H, J = 6.9 Hz), 2.04–1.83 (m, 3H), 1.80–1.47 (m, 2H); 13C{1H} NMR
(75 MHz, CDCl3) δ 159.2, 144.5, 129.2, 128.5, 127.6, 125.8, 124.9, 124.1, 116.4, 114.1, 89.7, 80.9, 74.1,
55.2, 38.1, 24.9, 19.2; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C19H20O2Na 303.1356; found 303.1360.
1ꢀMhenylꢀ6ꢀ(4ꢀ(trifluoromethyl)phenyl)hexꢀ5ꢀynꢀ1ꢀol (8g). Yield 424.7 mg (49%, colorless oil); IR (neat): υ
max 3364, 2937, 2237, 1616, 1321, 1066, 841 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.53 (d, 2H, J = 8.4 Hz),
7.46 (d, 2H, J = 8.4 Hz), 7.40–7.27 (m, 5H), 4.74 (dd, 1H, J = 7.2, 6.0 Hz), 2.46 (t, 2H, J = 7.2 Hz), 2.04–
1.83 (m, 3H), 1.81–1.69 (m, 1H), 1.67–1.57 (m, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 144.5, 131.8,
ACS Paragon Plus Environment

Page 29 of 47
The Journal of Organic Chemistry
1
2
3
4
5
6
129.4 (d, JCF = 33 Hz), 128.6, 127.7, 125.9, 125.1 (d, JCF = 4 Hz), 120.4 (d, JCF = 270 Hz), 92.7, 79.9, 74.2,
38.1, 29.7, 24.8, 19.3; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C19H17F3ONa 341.1124; found
341.1110.
7
8
6ꢀ(4ꢀNitrophenyl)ꢀ1ꢀphenylhexꢀ5ꢀynꢀ1ꢀol (8h). Yield 219.3 mg (37%, brown oil); IR (neat): υ max 3394,
9
1
2933, 2225, 1594, 1516, 1342, 854 cm−1; H NMR (300 MHz, CDCl3) δ 8.14 (d, 2H, J = 9 Hz), 7.49 (d,
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
2H, J = 9 Hz), 7.41–7.28 (m, 5H), 4.76–4.72 (m, 1H), 2.48 (t, 2H, J = 6.9 Hz), 2.04–1.82 (m, 3H), 1.80–
13
1.56 (m, 2H); C{1H} NMR (75 MHz, CDCl3) δ 146.6, 144.4, 132.2, 131.0, 128.6, 127.7, 125.8, 123.5,
96.1, 79.6, 74.1, 38.1, 24.7, 19.4; HRMS (ESIꢀTOF) m/z: [M + NH4]+ calcd for C18H21N2O3 313.1547;
found 313.1550.
6ꢀPhenylꢀ1ꢀ(oꢀtolyl)hexꢀ5ꢀynꢀ1ꢀol (8i). Yield 406.6 mg (55%, brown oil); IR (neat): υ max 3394, 2931, 1598,
1
1489, 1442, 1068, 754 cm−1; H NMR (300 MHz, CDCl3) δ 7.49 (dd, 1H, J = 7.4, 1.3 Hz), 7.40–7.34 (m,
2H), 7.32–7.12 (m, 6H), 5.04–4,99 (m, 1H), 2.48 (td, 2H, J = 7.1, 2.3 Hz), 2.36 (s, 3H), 1.95–1.74 (m, 3H),
1.72–1.63 (m, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 142.8, 134.5, 131.5, 130.4, 128.2, 127.5, 127.2,
126.3, 125.1, 123.9, 89.8, 81.0, 70.3, 37.0, 25.1, 19.3, 19.1; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for
C19H20ONa 287.1406; found 287.1407.
6ꢀPhenylꢀ1ꢀ(mꢀtolyl)hexꢀ5ꢀynꢀ1ꢀol (8j). Yield 435.7 mg (70%, light yellow oil); IR (neat): υ max 3329, 2922,
1
1599, 1490, 1442, 1069, 755 cm−1; H NMR (300 MHz, CDCl3) δ 7.40–7.34 (m, 2H), 7.27–7.20 (m, 4H),
7.16–7.07 (m, 3H), 4.67 (t, 1H, J = 6.4 Hz), 2.42 (t, 2H, J = 6.9 Hz), 2.34 (s, 3H), 2.01 (br s, 1H), 1.99–1.81
13
(m, 2H), 1.79–1.54 (m, 2H); C{1H} NMR (75 MHz, CDCl3) δ 144.5, 138.1, 131.5, 128.4, 128.3, 128.1,
127.5, 126.5, 123.9, 122.9, 89.8, 80.9, 74.2, 38.0, 25.0, 21.4, 19.2; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd
for C19H20ONa 287.1406; found 287.1407.
1ꢀ(4ꢀFluorophenyl)ꢀ6ꢀphenylhexꢀ5ꢀynꢀ1ꢀol (8k). Yield 445.3 mg (75%, light yellow oil); IR (neat): υ max
1
3373, 2936, 1603, 1508, 1490, 1221, 755 cm−1; H NMR (300 MHz, CDCl3) δ 7.39–7.35 (m, 2H), 7.34–
7.24 (m, 5H), 7.02 (tt, 2H, J = 8.7, 2.9 Hz), 4.70 (t, 1H, J = 6.6 Hz), 2.43 (t, 2H, J = 6.9 Hz), 2.03 (br s,1H),
1.98–1.79 (m, 2H), 1.77–1.50 (m, 2H) ; 13C{1H} NMR (75 MHz, CDCl3) δ 162.2 (d, JCF = 244 Hz), 140.3
(d, JCF = 3 Hz), 131.5, 128.2, 127.6, 127.5 (d, JCF = 8 Hz), 123.8, 115.3 (d, JCF = 21 Hz), 89.7, 81.1, 73.5,
38.2, 24.9, 19.2; HRMS (ESIꢀTOF) m/z: [M + NH4]+ calcd for C18H21FNO 286.1602; found 286.1608.
ACS Paragon Plus Environment