Cascade annulations of aryldiazonium salts, nitriles and halo-alkynes leading to 3-haloquinolines

Article abstract of DOI:10.1016/j.tet.2017.05.085

A regiospecific access to 3-haloquinolines has been developed via a three-component annulation of aryldiazonium salts, nitriles and haloalkynes. This reaction proceeds through an initial formation of reactive nitrilium ion and further cascade annulation with haloalkynes. This method provides a straightforward access to a diverse array of functionalized quinolones (28 examples) under mild conditions and exhibits broad functional group tolerance. Applications of this method in a gram scale reaction and a formal synthesis of Pitavastatin are illustrated.

Full text of DOI:10.1016/j.tet.2017.05.085

Accepted Manuscript
Cascade annulations of aryldiazonium salts, nitriles and halo-alkynes leading to 3-
haloquinolines
Mani Ramanathan, Shiuh-Tzung Liu
PII:
S0040-4020(17)30594-X
10.1016/j.tet.2017.05.085
TET 28751
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 April 2017
Revised Date: 23 May 2017
Accepted Date: 28 May 2017
Please cite this article as: Ramanathan M, Liu S-T, Cascade annulations of aryldiazonium salts, nitriles
and halo-alkynes leading to 3-haloquinolines, Tetrahedron (2017), doi: 10.1016/j.tet.2017.05.085.
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Cascade Annulations of Aryldiazonium
Salts, Nitriles and Halo-alkynes Leading to
3-Haloquinolines
Mani Ramanathan and Shiuh-Tzung Liu
*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan

ACCEPTED MANUSCRIPT
Tetrahedron
1
TETRAHEDRON
Pergamon
Cascade Annulations of Aryldiazonium Salts, Nitriles and Halo-
alkynes Leading to 3-Haloquinolines
Mani Ramanathan and Shiuh-Tzung Liu*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Abstract—A regiospecific access to 3-haloquinolines has been developed via a three-component annulation of aryldiazonium salts,
nitriles and haloalkynes. This reaction proceeds through an initial formation of reactive nitrilium ion and further cascade annulation with
haloalkynes. This method provides a straightforward access to a diverse array of functionalized quinolones (28 examples) under mild
conditions and exhibits broad functional group tolerance. Applications of this method in a gram scale reaction and a formal synthesis of
Pitavastatin are illustrated.
. © 2017 Elsevier Science. All rights reserved
1. Introduction
An approach reported by Flynn et. al. was via the
electrophilic iodocyclization of 1-(2-N,N-dimethylamino-
aryl)-2-yn-ols (Scheme 1a).7a Liang’s group demonstrated
the preparation of the desired compound through a 6-endo-
dig iodocyclization of 2-tosylaminophenylprop-1-yn-3-ols
with molecular iodine (Scheme 1b).7b Recently, Wang and
co-workers described a synthesis of 3-iodoquinolines via a
Cu(OTf)2 catalyzed tandem reaction of diaryliodonium
salts, halogenated arylacetylenes and nitriles at elevated
temperature (Scheme 1c).7c Another method by
Tummatorn’s group involved a cycloaddition strategy
between benzyl azides and 1-bromoalkynes in presence of
triflic acid followed by the aromatization (Scheme 1d).7d
Despite the significance of these methods, there is still a
need of the development of a general, mild and transition
metal free method from easily accessible precursors leading
to 3-haloquinolines.
Quinolines represent one of the most ubiquitous skeletons
found in diverse natural products and pharmaceuticals.1
Classical reactions such as Friedlander,2 Conrad-Limpach-
Knorr3 and Combes4 approaches are the most prevalent
strategies for construction of the quinoline cores. Recent
works in this regard, various transition metal catalyzed
approaches5 and metal-free protocols6 were developed.
Furthermore, syntheses of halo substituted quinolines are of
special interest, because these molecules can serve as
versatile precursors for further transformation via transition
metal catalyzed coupling reactions including C-O, C-S and
C-N bonds. Though several appealing approaches available
for the synthesis of quinoline unit, established methods for
the synthesis of halo-substituted quinolines are less
reported and few are shown in Scheme 1.
Inspired by Wang’s7c (Scheme 1c) and Yu’s works,8
herein we report an intermolecular cascade annulation
protocol for the construction of 3-haloquinolines by the
reaction of aryldiazonium salt (1) with a nitrile molecule to
yield the N-arylnitrilium ion (2),9 which could further react
with halo-alkyne followed by a cyclization leading to the
desired product (Scheme 2).
Scheme 1. Selected works for Synthesis of haloquinolines
* Corresponding author. E-mail: stliu@ntu.edu.tw
Tel: (8862) 3366-1661
Scheme 2. Proposed synthetic approach

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2
Tetrahedron
Results and Discussion
An investigation of the optimization was conducted with
phenyldiazonium tetrafluoroborate (1a) and 1-iodo-
phenylacetylene (3a) in anhydrous MeCN under heating
conditions. Gratifying, the desired product 4a was isolated
entry
1
2
3
4
5
6
7
8
product (position-substitutent)
4a (R1 = H, X = I)
Yieldb
76%
64%
19%
78%
72%
63%
66%
55%
63%
36%
74%
41%
38%
33%
o
in 62% isolated yield at 110 C (Table 1, entry 1). By
4a’ (R1 = H, X = Br)
o
lowering the reaction temperature to 80 C and with a
4a” (R1 = H, X = Cl)
slightly excess amount of nitrile, the yield can be improved
up to 76% (Table 1, entry 3), but not at room temperature
(entry 4).
4b (R1 = 6-OMe, X = I)
4c (R1 = 6-COOEt, X = I)
4d (R1 = 6-CN, X = I)
4e (R1 = 6-CF3, X = I)
4f (R1 = 6-COPh, X = I)
4g (R1 = 6-C≡CH, X = I)
4h (R1 = 8-CN, X = I)
4i (R1 = 5-Me, 7-Me, X = I)
4j (R1 = 6-Me, 8-Br, X = I)
4k (R1 = 7-Br, X = I)
Table 1. Reaction optimizationa
9
10
11
12
13
4k’ (R1 = 5-Br, X = I)
a Conditions: 1a (0.52 mmol), 3 (0.62 mmol) and anhydrous MeCN (2 mL)
in a sealed reaction tube, 80 oC, 2 h.
entry alkyne
Nitrile
Temp (oC) Time (h) Yield(%) b
b Isolated yields.
1
2
3
4
3a (1.3 eq)
1 mL
1 mL
2 mL
2 mL
110
100
80
3
12
2
62
51
76
< 5%
N(2)
3a (1.3 eq)
3a (1.2 eq)
3a (1.2 eq)
C(17)
rt
12
N(1)
C(7)
a Conditions: Reaction conditions: 1a (0.52 mmol) and 3a in anhydrous
acetonitrile in a sealed reaction tube.
C(10)
C(6)
C(5)
C(9)
b Isolated yields.
C(1)
C(3)
C(11)
C(4)
C(2)
Intrigued by the expected outcome, a comprehensive
investigation on the scope of the aryldiazonium salts was
examined under the optimized reaction conditions. A
diverse set of aryldiazonium salts with functional groups
including esters, ethers, cyano and benzoyl were found to
be compatible with the reaction conditions and provided the
corresponding 2,4-disubstituted-3-iodoquinolines in good
yields (Table 2, entries 4-9). In general, electron-donating
groups on the arenediazonium salts led to slightly better
yields than electron-withdrawing groups. Notably, the
ortho-substituted substrates deliver the desired product in
low yields such as 4h (36%) and 4j (41%), presumably due
to the steric hindrance posed by the substituents (Table 2,
entries 10 and 12). The reaction worked well with the
aryldiazonium salt containing terminal alkyne to afford 4g
in 63% yield, leading to a useful handle for further cross-
coupling reactions. The structure of 4h was unambiguously
confirmed by x-ray crystallography and ORTEP plot of 4h
is shown in Figure 1. Thus, the region-selectivity of this
reaction is established. As expected, meta-substituted
aryldiazonium salt afforded a mixture of separable regio-
isomeric 3-iodoquinolines (4k and 4k’) in good yields
(Table 2, entry 13). The bromo and chloro analogs were
also investigated. Reactions of 1a with 3b gave 2-methyl-3-
bromo-4-phenylquinoline (4a’) in 64% isolated yield, but
the chloro-substituted 4a” was obtained in poor yield
(Table 2, entries 2 and 3). In fact, reaction of 1a with 3c
gave a mixture of various products.
I(1)
Figure 1. ORTEP plot of 4h. I(1)-C(1) 2.093(5)Å; C(17)-N(2) 1.145(8) Å.
(Drawn with 30 % probability ellipsoids)
When aryldiazonium salt with an adjacent benzoyl (5) or
phenyl (6) moiety involved in this reaction, the
intermediate rapidly underwent the intramolecular aromatic
electrophilic substitution to deliver 9H-fluoren-9-one (7)
and 6-methylphenanthridine (10), respectively (Scheme 3).
The expected compound 8 was not formed when using 5 as
the substrate. As for 6, the rate of the intra-molecular
cyclization is apparently faster than that of the electrophilic
addition of N-arylnitrilium ion 9 toward the alkyne
molecule.
Table 2. Substrate scope of aryldiazonium salts with 3 in MeCNa
Scheme 3. Intramolecular cyclization

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Tetrahedron
3
We then contemplated the scope of the reaction with
varieties of readily available aromatic and aliphatic nitriles
(Table 3). Anhydrous benzonitrile was smoothly reacted
with various aryldiazonium salts to furnish the desired
products in good yields (Table 3, entries 1-3). In addition,
aryl nitriles with ortho and meta substitutions gave the
corresponding 3-iodoquinolines in preparatively useful
yields (Table 3, entries 4-5). The synthetic versatility was
further expanded by employing various other nitriles. Thus,
aliphatic nitriles even with a bromo-substituent participated
well in this reaction to furnish 11f ~ 11h in 71%, 66% and
63% yields, respectively (Table 3, entries 6-8). This facile
introduction of variety of substituents illustrates the great
generality and flexibility of this approach. Unfortunately,
the use of benzyl nitrile as the reaction component yielded
a complicated mixture of unidentified products under the
optimized conditions.
79% yield, but diphenylacetylene gave the desired product
2-methyl-3,4-diphenylquinoline in 28 %, which is similar
to the related report.8
The practical application of this three-component
annulation strategy was further demonstrated by a gram
scale synthesis. Phenyldiazonium tetrafluoroborate on a 1g
scale was treated with 3a in acetonitrile under the
optimized conditions yielding the iodo-quinoline 5a in 68%.
To further extend the synthetic utility, we attempted the
synthesis of key intermediate for Pitavastatin, an inhibitor
of HMG-CoA reductase.10 To our delight, treatment of 1a
with 1-fluoro-4-(iodoethynyl)benzene and anhydrous
cyclopropanecarbonitrile under the optimized conditions
furnished 12 in 35 % isolated yield (Scheme 4).
Table 3. Substrate scope with various nitriles and iodoalkynesa
Scheme 4. Formal synthesis of Pitavastatin
entry
1
product (position-substitutent)
11a, R : C6H5-; R1 : H; R2 : C6H5-
Yieldb
72%
68%
63%
67%
58%
71%
66%
63%
70%
26%
38%
66%
63%
3. Summary
2
11b, R : C6H5-; R1 : 6-COOEt; R2 : C6H5-
11c, R : C6H5-; R1 : 6-CN; R2 : C6H5-
11d, R : o-MeC6H4-; R1 : H; R2 : C6H5-
11e, R : m-BrC6H4-; R1 : H; R2 : C6H5-
11f, R : CH3CH2CH2-; R1 : H; R2 : C6H5-
11g, R : BrCH2-; R1 : H; R2 : C6H5-
11h, R : (CH3)2CH-; R1 : H; R2 : C6H5-
11i, R : CH3-; R1 : H; R2 : p-MeC6H4-
11j, R : CH3-; R1 : H; R2 : p-CF3C6H4-
11k, R : CH3-; R1 : H; R2 : p-FC6H4-
11l, R : CH3-; R1 : H; R2 : CH3CH2CH2CH2-
11m, R : CH3-; R1 : H; R2 : ClCH2CH2CH2-
In summary,
a
region-specific, metal-free and
3
environmentally benign method has been developed for the
facile access of functionalized 3-haloquinolines from
readily available aryldiazonium salts, nitriles and halo-
alkynes. This method displays a broad substrate scope and
excellent functional group tolerance under mild conditions.
In addition, the synthetic utilities were further displayed in
a gram scale preparation and application to the formal
synthesis of Pitavastatin, illustrating the possibility for
industrial applications.
4
5
6
7
8
9
10
11
12
13
a Conditions: ArN2BF4 (0.52 mmol), nitrile (0.62 mmol) and anhydrous
RCN (2 mL) in a reaction tube, 80 oC, 2 h.
b Isolated yields.
4. Experimental
4.1. General
To further demonstrate the scope of the reaction, various
1-iodoalkynes including 1-iodo- alkylalkynes were
subjected to this investigation (Table 3, entries 9-13).
Reaction of 1-iodo-toluenylacetylene with 1a in acetonitrile
proceeded smoothly to afford 11i in good yield, whereas
inferior results observed with the strong electron
withdrawing groups such as CF3- and F- substituents (Table
3, entries 10-11). 1-Iodoacetylene bearing alkyl
counterparts were tested under the optimized conditions.
These molecules exerted good reactivity and furnished 3-
iodo-4-alkylquinolines, 11l and 11m, in good yields (Table
3, entries 12 -13). Notably, the alkyl chain with a chloro-
substituent on the side chain does not affect the reaction to
yield compound 11m. Furthermore, we carried out the
study of this reaction with terminal and internal alkynes.
Thus, reaction of 1a with phenylacetylene in acetonitrile
gave the expected product 2-methyl-4-phenylquinoline in
General information. 1H and 13C NMR were recorded in a
400 MHZ spectrometer in CDCl3 and CD3CN referenced to
TMS. All the nitriles were dried over activated 4Ao
molecular sieves and solid nitriles were purchased and used
without any further drying. All the anilines were
commercially purchased and used for diazotization without
further purification. Other chemicals were used as
purchased. Flash chromatography was performed using
silica gel 230-400 mesh. Unless otherwise noted, all the
reactions were performed without any special precautions.
Bromo-11c and chloro-phenylacetylene11d were prepared
according to the literature procedures. FT-IR were recorded
on a Thermo-Scientific Nicolet iS5 spectrometer.
4.2. General procedure for preparing aryldiazonium
tetrafluroborate. All the substituted aryldiazonium salts

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4
Tetrahedron
were synthesized by following the reported methods.
Spectral data of the compounds are in agreement with those
reported in the literature. A typical procedure for preparing
benzenediazonium tetrafluroborate is shown below.11a The
corresponding aniline (10 mmol) was dissolved in a
mixture of water (4 mL) and 50% aqueous hydrofluroboric
acid (19.3 mmol, 1.92 eq.). The mixture was cooled to 0 oC
and a solution of NaNO2 (10 mmol in 1.5 mL of water) was
added slowly. The resulting reaction mixture was stirred at
0 oC for 30 minutes and the precipitate was collected by
filtration. The solid product was dissolved in minimum
acetone and re-precipitated using diethyl ether to yield
aryldiazonium tetrafluroborate which was dried under
vacuum without further purification.
4.3.4.
3-Iodo-6-methoxy-2-methyl-4-phenylquinoline
(4b). (Eluent: 5% EA/hexane), 131 mg, 78%, pale yellow
o
1
solid: mp 146-148 C; H NMR (400 MHz, CDCl3) δ 7.90
(d, J = 8.8 Hz, 1H), 7.54-7.46 (m, 3H), 7.30 (dd, J = 8.8,
2.4 Hz, 1H), 7.21-7.19 (m, 2H), 6.54 (d, J = 2.4 Hz, 1H),
3.63 (s, 3H), 2.97 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
157.6, 157.1, 152.2, 143.0, 142.1, 130.0, 128.9, 128.6,
128.3, 127.6, 121.9, 105.0, 100.9, 55.2, 31.1; HRMS (ESI)
calcd. for C17H15INO (M+H)+ m/z = 376.0198 found
376.0233.
4.3.5.
Ethyl
3-iodo-2-methyl-4-phenylquinoline-6-
carboxylate (4c). (Eluent: 2% EA/hexane), 113 mg, 72%,
o
1
pale yellow solid: mp 121-123 C; H NMR (400 MHz,
CDCl3) δ 8.24 (dd, J = 8.8, 1.6 Hz, 1H), 8.05 (dd, J = 8.8,
1.6 Hz, 2H), 7.56-7.51 (m, 3H), 7.20 (dd, J = 8.0, 2.4 Hz,
2H), 4.30 (q, J = 7.2 Hz, 2H), 3.03 (s, 3H), 1.31 (t, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.9, 162.3,
154.9, 148.6, 141.1, 129.7, 129.2, 128.9, 128.8, 128.77,
128.71, 128.3, 126.0, 101.3, 61.2, 31.8, 14.2; IR (KBr, cm-1)
1718 (υC=O); HRMS (ESI) calcd. for C19H17INO2 (M+H)+
m/z = 418.0304 found 418.0310.
4.3. General procedure for the preparation of 3-
haloquinolines. In a dry 10 mL glass sealed tube,
aryldiazonium tetrafluoroborate (0.52 mmol) and
haloalkyne (0.62 mmol) were dissolved in anhydrous nitrile
(2 mL). The tube was sealed with a Teflon screw cap and
o
heated in an oil bath (80 C) for 2 h. After cooling to room
temperature, reaction mixture was diluted with CH2Cl2 (20
mL) and washed with saturated aqueous NaHCO3 solution
(5 mL). Aqueous layer was extracted with CH2Cl2 (10 mL).
Combined organic layers were dried over anhydrous
Na2SO4. Solvents were removed under reduced pressure
and the residue was chromatographed (SiO2, EA-Hexane,
5% ~ 20%) to yield 3-halo-disubstituted quinolines.
4.3.6. 3-Iodo-2-methyl-4-phenylquinoline-6-carbonitrile
(4d). (Eluent: 2% EA/hexane), 107 mg, 63%, pale yellow
solid: mp 167-169 oC; H NMR (400 MHz, CDCl3) δ 8.07
1
(d, J = 8.8 Hz, 1H), 7.79 (dd, J = 8.4, 1.6 Hz, 1H), 7.70 (d,
J = 1.2 Hz, 1H), 7.59-7.55 (m, 3H), 7.18-7.16 (m, 2H), 3.04
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.5, 154.0, 147.7,
140.4, 133.1, 130.3, 130.0, 129.1, 128.9, 128.7, 126.0,
118.4, 110.0, 102.3, 31.8; IR (KBr, cm-1) 2223 (υC≡N);
HRMS (ESI) calcd. for C17H12IN2 (M+H)+ m/z = 371.0045
found 371.0055.
4.3.1. 3-Iodo-2-methyl-4-phenylquinoline (4a).7c (Eluent:
2% EA/hexane), 136 mg, 76%, pale yellow solid: mp 144-
146 oC; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz,
1H), 7.57 (ddd, J = 12.4, 8.0, 4.4 Hz, 1H), 7.46-7.38 (m,
3H), 7.22 (d, J = 3.6 Hz, 2H), 7.12-7.10 (m, 2H), 2.94 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 159.7, 153.6, 146.7,
141.8, 129.7, 28.9, 128.5, 128.4, 128.3, 126.7, 126.3, 100.2,
31.5; HRMS (ESI) calcd. for C16H13IN (M+H)+ m/z =
346.0093, found 346.0085.
4.3.7.
3-Iodo-2-methyl-4-phenyl-6-(trifluoromethyl)-
quinoline (4e). (Eluent: 2% EA/hexane), 104 mg, 66%,
o
1
pale yellow solid: mp 135-137 C; H NMR (400 MHz,
CDCl3) δ 8.05 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H),
7.54 (s, 1H), 7.50-7.47 (m, 3H), 7.13 (dd, J = 4.4, 2.0 Hz,
2H), 2.98 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.5,
154.5, 147.7, 140.8, 129.8, 128.9, 128.8, 128.2 (q, J = 33
Hz), 125.7, 125.4 (q, J = 4.0 Hz), 125.1, 124.5 (q, J = 4.0
Hz), 122.4, 101.9, 31.8; HRMS (ESI) calcd. for C17H12F3IN
(M+H)+ m/z = 413.9967 found 413.9975.
4.3.2.
3-Bromo-2-methyl-4-phenylquinoline
(4a’).
(Eluent: 2% EA/hexane), 99 mg, 64%, pale yellow solid:
o
mp 108-110 C; 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J
= 8.4 Hz, 1H), 7.67-7.63 (m, 1H), 7.54-7.46 (m, 3H), 7.37-
7.32 (m, 2H), 7.26 (dd, J = 8.0, 1.2 Hz, 2H), 2.92 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 157.7, 148.3, 146.1, 137.8,
129.4, 129.1, 128.6, 128.4, 128.3, 127.4, 126.4, 126.2,
120.2, 27.1; HRMS (ESI) calcd. for C16H1379BrN (M+H)+
m/z = 298.0231, found 298.0244; HRMS (ESI) calcd. for
C16H1381BrN (M+H)+ m/z = 300.0211, found 300.0230.
4.3.8.
(3-Iodo-2-methyl-4-phenylquinolin-6-yl)phenyl
ketone (4f). (Eluent: 2% EA/hexane), 83 mg, 55%, pale
yellow solid: mp 168-170 oC; H NMR (400 MHz, CDCl3)
1
δ 8.10-8.05 (m, 2H), 7.78 (s, 1H), 7.69 (d, J = 8.0 Hz, 2H),
7.54-7.43 (m, 4H), 7.39 (t, J = 7.6 Hz, 2H), 7.20 (d, J = 7.6
Hz, 2H), 3.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 195.2,
162.4, 154.9, 148.3, 141.0, 137.0, 135.2, 132.6, 130.2,
130.0, 129.8, 128.9, 128.8, 128.7, 128.6, 128.2, 125.9,
101.3, 31.8; IR (KBr, cm-1) 1652 (υC=O); HRMS (ESI)
calcd. for C23H17INO (M+H)+ m/z = 450.0355 found
450.0359.
4.3.3. 3-Chloro-2-methyl-4-phenylquinoline (4a”).11e
(Eluent: 2% EA/hexane), 25 mg, 19%, off-white solid: mp
o
115-117 C; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J =
8.4 Hz, 1H), 7.66-7.62 (m, 1H), 7.55-7.47 (m, 3H), 7.37-
7.36 (m, 2H), 7.31-7.29 (m, 2H), 2.86 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 156.8, 145.8, 145.5, 135.6, 129.4,
129.2, 128.7, 128.5, 128.4, 127.8, 127.4, 126.4, 126.0, 24.6;
HRMS (ESI) calcd. for C16H1335ClN (M+H)+ m/z =
254.0737, found 254.0759; HRMS (ESI) calcd. for
C16H1337ClN (M+H)+ m/z = 256.0729, found 256.0754.
4.3.9. 6-Ethynyl-3-iodo-2-methyl-4-phenylquinoline (4g).
(Eluent: 2% EA/hexane), 107 mg, 63%, pale yellow solid:
mp 191-193 oC; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J =
8.8 Hz, 1H), 7.70 (dd, J = 8.8, 1.6 Hz, 1H), 7.56-7.51 (m,

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Tetrahedron
5
3H), 7.47 (s, 1H), 7.19 (dd, J = 8.0, 2.0 Hz, 2H), 3.03 (d, J
= 18.4 Hz, 1H), 3.01 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 160.9, 153.4, 146.4, 141.3, 132.6, 130.9, 128.9, 128.8,
128.7, 128.6, 126.3, 120.2, 101.3, 83.2, 78.4, 31.6; IR (KBr,
cm-1) 3287 (υC≡C-H), 2370 (υC≡C); HRMS (ESI) calcd. for
C18H13IN (M+H)+ m/z = 370.0093 found 370.0094.
4.3.15. 3-iodo-2,4-diphenylquinoline (11a).7c (Eluent: 2%
EA/hexane), 152 mg, 72%, pale yellow solid: mp 117-119
oC; 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 1H),
7.74-7.70 (m, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.58-7.54 (m,
3H), 7.51-7.45 (m, 3H), 7.40 (d, J = 4.0 Hz, 2H), 7.29 (d, J
= 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 161.8, 154.7,
146.8, 143.6, 142.0, 130.1, 129.3, 129.2, 129.0, 128.6,
128.5, 128.4, 127.9, 127.3, 127.2, 126.8, 98.4; HRMS (ESI)
calcd. for C21H15IN (M+H)+ m/z = 408.0249 found
408.0262.
4.3.10.
3-Iodo-2-methyl-4-phenylquinoline-8-carbo-
nitrile (4h). (Eluent: 2% EA/hexane), 61 mg, 36%, off-
white solid: 1H NMR (400 MHz, CDCl3) δ 8.05 (dd, J = 6.8,
0.8 Hz, 1H), 7.56-7.52 (m, 4H), 7.39-7.35 (m, 1H), 7.19-
7.17 (m, 2H), 3.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
162.9, 154.0, 146.2, 140.8, 135.5, 131.7, 128.9 (2C), 128.8,
126.6, 125.6, 117.2, 112.4, 102.5, 31.8; IR (KBr, cm-1)
2222 (υC≡N); HRMS (ESI) calcd. for C17H12IN2 (M+H)+
m/z = 371.0045 found 371.0068.
4.3.16. Ethyl 3-iodo-2,4-diphenylquinoline-6-carboxyl-
ate (11b). (Eluent: 2% EA/hexane), 123 mg, 68%, pale
1
yellow solid: mp 125-127 oC; H NMR (400 MHz, CDCl3)
δ 8.29 (d, J = 8.8 Hz, 1H), 8.19-8.16 (m, 2H), 7.65 (d, J =
6.8 Hz, 2H), 7.58-7.53 (m, 3H), 7.50-7.43 (m, 3H), 7.28 (d,
J = 6.4 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.33 (t, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.8, 163.8,
156.1, 148.5, 143.2, 141.3, 129.8, 129.6, 129.1, 129.0 (2C),
128.9, 128.8, 128.7, 128.0 (2C), 126.5, 99.4, 61.3, 14.2; IR
(KBr, cm-1) 1718 (υC=O); HRMS (ESI) calcd. for
C24H19INO2 (M+H)+ m/z = 480.0460 found 480.0474.
4.3.11. 3-Iodo-2,5,7-trimethyl-4-phenylquinoline (4i).
(Eluent: 2% EA/hexane), 125 mg, 74%, off-white solid: mp
o
1
150-152 C; H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H),
7.46-7.43 (m, 3H), 7.16-7.14 (m, 2H), 7.03 (s, 1H), 2.97 (s,
3H), 2.43 (s, 3H), 1.78 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.9, 152.8, 148.5, 146.4, 139.4, 134.6, 132.1,
129.3, 128.2, 128.1, 127.0, 123.7, 102.7, 31.7, 24.4, 21.4;
HRMS (ESI) calcd. for C18H17IN (M+H)+ m/z = 374.0406
found 374.0411.
4.3.17. 3-Iodo-2,4-diphenylquinoline-6-carbonitrile (11c).
(Eluent: 2 ~ 5% EA/hexane), 125 mg, 63%, pale yellow
o
1
solid: mp 202-204 C; H NMR (400 MHz, CDCl3) δ 8.22
(d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.80 (s, 1H),
7.65-7.63 (m, 2H), 7.60-7.58 (m, 3H), 7.51-7.45 (m, 3H),
7.27-7.25 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 164.8,
155.3, 147.7, 142.8, 140.6, 133.2, 130.8, 130.6, 129.2,
129.1, 129.08, 129.0, 128.8, 128.0, 126.6, 118.3, 110.8,
100.5; IR (KBr, cm-1) 2227 (υC≡N); HRMS (ESI) calcd. for
C22H14IN2 (M+H)+ m/z = 433.0202 found 433.0177.
4.3.12. 8-Bromo-3-iodo-2,6-dimethyl-4-phenylquinoline
(4j). (Eluent: 2% EA/hexane), 62 mg, 41%, orange solid:
mp 149-150 oC; 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J =
1.2 Hz, 1H), 7.55-7.48 (m, 3H), 7.17 (dd, J = 8.0, 2.0 Hz,
2H), 7.00 (s, 1H), 3.05 (s, 3H), 2.32 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 160.1, 153.3, 142.5, 141.8, 136.9, 135.3,
128.9, 128.6, 128.5, 127.8, 125.6, 123.8, 101.8, 31.7, 21.3;
HRMS (ESI) calcd. for C17H1479BrIN (M+H)+ m/z =
437.9354 found 437.9364; HRMS (ESI) calcd. for
C17H1481BrIN (M+H)+ m/z = 439.9334 found 439.9366.
4.3.18. 3-Iodo-4-phenyl-2-(o-tolyl)quinoline (11d).7c
(Eluent: 2% EA/hexane), 146 mg, 67%, pale yellow solid:
o
mp 147-149 C;1H NMR (400 MHz, CDCl3) δ 8.18 (d, J =
8.4 Hz, 1H), 7.76-7.71 (m, 1H), 7.58-7.52 (m, 3H), 7.47-
7.40 (m, 2H), 7.38-7.35 (m, 1H), 7.34-7.32 (m, 5H), 2.19 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 162.8, 154.2, 146.9,
143.6, 141.6, 135.3, 130.1, 130.0, 129.3, 129.1, 129.0,
128.6, 128.5, 128.4, 127.2, 127.1, 126.7, 125.7, 99.9, 19.7;
HRMS (ESI) calcd. for C22H17IN (M+H)+ m/z = 422.0406
found 422.0429.
4.3.13. 7-Bromo-3-iodo-2-methyl-4-phenylquinoline (4k).
(Eluent: 0 ~ 2% EA/hexane), 59 mg, 38%, pale yellow
o
1
solid: mp 149-151 C; H NMR (400 MHz, CDCl3) δ 8.19
(d, J = 2.0 Hz, 1H), 7.55-7.48 (m, 3H), 7.39 (dd, J = 8.8,
1.6 Hz, 1H), 7.18-7.15 (m, 3H), 3.00 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 161.2, 153.7, 147.4, 141.3, 130.8,
129.9, 128.9, 128.7, 128.6, 128.1, 125.4, 123.8, 100.6, 31.6;
HRMS (ESI) calcd. for C16H1279BrIN (M+H)+ m/z =
423.9198 found 423.9186; HRMS (ESI) calcd. for
C16H1281BrIN (M+H)+ m/z = 425.9178 found 425.9178.
4.3.19.
2-(3-Bromophenyl)-3-iodo-4-phenylquinoline
(11e). (Eluent: 2% EA/hexane), 146 mg, 58%, orange solid:
mp 155-156 oC; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J =
8.4 Hz, 1H), 7.80 (t, J = 1.2 Hz, 1H), 7.75-7.71 (m, 1H),
7.59-7.57 (m, 3H), 7.56-7.51 (m, 2H), 7.42-7.41 (m, 2H),
7.34 (t, J = 8.0 Hz, 1H), 7.27 (dd, J = 8.0 Hz, 1.6 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 160.1, 154.9, 146.7, 145.4,
141.8, 132.3, 131.6, 130.2, 129.4, 129.3, 129.0, 128.6,
128.5, 128.0, 127.5, 127.4, 126.8, 121.9, 97.7; HRMS (ESI)
calcd. for C21H1479BrIN (M+H)+ m/z = 485.9354 found
485.9372; HRMS (ESI) calcd. for C21H1481BrIN (M+H)+
m/z = 487.9334 found 487.9362.
4.3.14.
7-Bromo-3-iodo-2-methyl-4-phenylquinoline
(4k’). (Eluent: 0 ~ 2% EA/hexane), 51 mg, 33%, pale
o
1
yellow solid: mp 144-146 C; H NMR (400 MHz, CDCl3)
δ 8.02 (dd, J = 8.4, 1.2 Hz, 1H), 7.75 (dd, J = 7.2, 0.8 Hz,
1H), 7.47-7.43 (m, 4H), 7.16-7.13 (m, 2H), 3.01 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.3, 152.5, 148.8, 144.0,
133.9, 130.1, 129.7, 129.6, 128.5, 128.0, 124.7, 118.5,
105.8, 32.0; HRMS (ESI) calcd. for C16H1279BrIN (M+H)+
m/z = 423.9198 found 423.9213; HRMS (ESI) calcd. for
C16H1281BrIN (M+H)+ m/z = 425.9178 found 425.9181.
4.3.20.
3-Iodo-4-phenyl-2-propylquinoline
(11f).7b
(Eluent: 2% EA/hexane), 137 mg, 71%, pale yellow solid:
o
1
mp 78-80 C; H NMR (400 MHz, CDCl3) δ 8.05 (d, J =

ACCEPTED MANUSCRIPT
6
Tetrahedron
8.4 Hz, 1H), 7.68-7.64 (m, 1H), 7.55-7.49 (m, 3H), 7.31-
7.30 (m, 2H), 7.21-7.19 (m, 2H), 3.26-3.23 (m, 2H), 1.95-
1.85 (m, 2H), 1.10 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.5, 153.8, 146.8, 142.1, 129.6, 129.0, 128.6,
128.5, 128.3, 126.9, 126.7, 126.3, 100.2, 45.0, 22.5, 14.1;
HRMS (ESI) calcd. for C18H17IN (M+H)+ m/z = 374.0406
found 374.0427.
4.3.27. 4-Butyl-3-iodo-2-methylquinoline (11l). (Eluent:
2% EA/hexane), 111 mg, 66%, viscous oil: H NMR (400
1
MHz, CDCl3) δ 7.97-7.94 (m, 2H), 7.65 (ddd, J = 15.2, 8.4,
1.2 Hz, 1H), 7.46 (ddd, J = 15.2, 8.4, 0.8 Hz, 1H), 3.25 (t, J
= 7.2 Hz, 2H), 2.95 (s, 3H), 1.64-1.49 (m, 4H), 1.00 (t, J =
7. 2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8, 151.9,
146.8, 129.4, 129.2, 126.3, 125.7, 123.9, 101.5, 37.8, 31.9,
31.2, 23.1, 13.8; HRMS (ESI) calcd. for C14H17IN (M+H)+
m/z = 326.0406 found 326.0434.
4.3.21. 2-(Bromomethyl)-3-iodo-4-phenylquinoline (11g).
(Eluent: 2% EA/hexane), 145 mg, 66%, orange solid: mp
o
1
125-127 C; H NMR (400 MHz, CDCl3) δ 8.08 (d, J =8.4
Hz, 1H), 7.71 (ddd, J = 16.0, 7.6, 1.6 Hz, 1H), 7.56-7.51 (m,
3H), 7.41-7.33 (m, 2H), 7.22-7.19 (m, 2H), 5.03 (s, 2H);
13C NMR (100 MHz, CDCl3) δ 156.7, 155.2, 146.8, 141.4,
130.2, 129.1, 128.9, 128.6 (2C), 127.8, 127.5, 126.8, 97.7,
39.5; HRMS (ESI) calcd. for C16H12BrIN (M+H)+ m/z =
423.9198 found 423.9206; HRMS (ESI) calcd. for
C16H1281BrIN (M+H)+ m/z = 425.9178 found 425.9196.
4.3.28.
4-(3-Chloropropyl)-3-iodo-2-methylquinoline
(11m). (Eluent: 2% EA/hexane), 112 mg, 63%, off-white
solid: mp 88-89 C; 1H NMR (400 MHz, CDCl3) δ 8.02-
o
7.96 (m, 2H), 7.69-7.66 (m, 1H), 7.50 (t, J = 7.6 Hz, 1H),
3.71 (t, J = 6.0 Hz, 2H), 3.45 (t, J = 8.0 Hz, 2H), 2.96 (s,
3H), 2.13-2.06 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
159.9, 150.0, 146.8, 129.7, 129.3, 126.7, 125.7, 123.6,
101.8, 44.8, 35.4, 31.8, 31.5; HRMS (ESI) calcd. for
C13H1435ClIN (M+H)+ m/z = 345.9859 found 345.9871;
HRMS (ESI) calcd. for C13H1437ClIN (M+H)+ m/z =
347.9829 found 347.9859.
4.3.22. 3-Iodo-2-isopropyl-4-phenylquinoline (11h).
(Eluent: 2% EA/hexane), 122 mg, 63%, pale yellow sticky
solid: H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.4 Hz,
1H), 7.59-7.55 (m, 1H), 7.46-7.39 (m, 3H), 7.24-7.19 (m,
2H), 7.14-7.12 (m, 2H), 3.81-3.71 (sept, J = 6.4 Hz, 1H),
1.34 (d, J = 6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ
166.1, 153.7, 146.9, 142.6, 129.5, 129.0, 128.9, 128.5,
128.2, 127.2, 126.7, 126.3, 101.1, 38.8, 22.0; HRMS (ESI)
calcd. for C18H17IN (M+H)+ m/z = 374.0406 found
374.0419.
1
4.3.29.
2-Methyl-4-phenylquinoline.8 (Eluent:
2%
EA/hexane), 90 mg, 79%, pale yellow solid; 1H NMR (400
MHz, CDCl3) δ 8.07 (d, J = 8.8 Hz, 1H), 7.82 (d, J = 8.4
Hz, 1H), 7.66-7.63 (m, 1H), 7.49-7.43 (m 5H), 7.38 (t, J =
7.2 Hz, 1H), 7.19 (s, 1H), 2.75 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 158.4, 148.4, 148.3, 138.0, 129.4, 129.2,
128.9, 128.4, 128.2, 125.6, 125.5, 125.0, 122.1, 25.2;
HRMS (ESI) calcd. for C16H14N (M+H)+ m/z = 220.1126
found 220.1127.
4.3.24.
3-Iodo-2-methyl-4-(p-tolyl)quinoline
(11i).
(Eluent: 2% EA/hexane), 130 mg, 70%, off-white solid: mp
o
144-146 C;1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.4
4.3.30. 2-methyl-3,4-diphenylquinoline.8 (Eluent: 2 ~ 5%
EA/hexane), 42 mg, 28%, off-white solid; H NMR (400
1
Hz, 1H), 7.63 (ddd, J = 15.2, 7.6, 1.6 Hz, 1H), 7.35-7.27 (m,
4H), 7.08 (d, J = 8.0 Hz, 2H), 3.01 (s, 3H), 2.45 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 159.6, 153.6, 146.7, 138.8,
138.0, 129.6, 129.1, 128.8, 128.4, 126.8, 126.7, 126.2,
100.6, 31.5, 21.4; HRMS (ESI) calcd. for C17H15IN
(M+H)+ m/z = 360.0249 found 360.0279.
MHz, CDCl3) δ 8.04 (d, J = 8.4 Hz, 1H), 7.61 (dt, J = 7.4,
1.2 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.31 (t, J = 7.2 Hz,
1H), 7.19-7.14 (m, 4H), 7.12-7.07 (m, 2H), 7.02-6.97 (m,
4H) ; 13C NMR (100 MHz, CDCl3) δ 157.8, 147.0, 146.6,
138.6, 136.7, 134.0, 130.1, 130.0, 129.1, 128.5, 127.8,
127.6, 127.2, 126.8, 126.6, 126.3, 125.8, 25.3 ; HRMS (ESI)
calcd. for C22H18N (M+H)+ m/z = 296.1439 found
296.1430.
4.3.25. 3-Iodo-2-methyl-4-(4-(trifluoromethyl)phenyl)-
quinoline (11j). (Eluent: 2% EA/hexane), 55 mg, 26%,
o
pale yellow solid: mp 194-196 C; 1H NMR (400 MHz,
CDCl3) δ 8.03 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 2H),
7.69 (ddd, J = 15.6, 7.6, 1.6 Hz, 1 H), 7.36-7.32 (m, 3H),
7.21 (dd, J = 8.4, 0.8 Hz, 1H), 3.02 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 159.9, 152.1, 146.8, 145.3, 130.6 (q, J = 32
Hz), 130.0, 129.6, 128.7, 126.8, 126.3, 126.1, 125.7 (q, J =
4.0 Hz), 125.3, 122.6, 99.6, 31.4; HRMS (ESI) calcd. for
C17H12F3IN (M+H)+ m/z = 413.9967 found 413.9987.
4.3.31. 2-Cyclopropyl-4-(4-fluorophenyl)-3-iodoquino-
line (12). (Eluent: 2 ~ 5% EA/hexane), 68 mg, 35%, pale
1
yellow solid: mp 112-113 oC; H NMR (400 MHz, CDCl3)
δ 7.86(d, J = 8.4 Hz, 1H), 7.56-7.52 (m, 1H), 7.22-7.17 (m,
2H), 7.16-7.15 (m, 1H), 7.13-7.09 (m, 3H), 2.73-2.68 (m,
1H), 1.12-1.00 (m, 2H), 1.06-0.91 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 163.8, 162.2, 161.3, 152.1, 146.8, 138.1 (d,
J = 4 Hz), 130.9 (d, J = 8 Hz), 129.6, 128.7, 127.2, 126.4,
126.0, 102.1, 22.0, 11.0; HRMS (ESI) calcd. for C18H14FIN
(M+H)+ m/z = 390.0155 found 390.0178.
4.3.26.
4-(4-Fluorophenyl)-3-iodo-2-methylquinoline
(11k). (Eluent: 2 ~ 5% EA/hexane), 71 mg, 38%, off-white
o
solid: mp 140-141 C; 1H NMR (400 MHz, CDCl3) δ 7.91
(d, J = 8.4 Hz, 1H), 7.58-7.54 (m, 1H), 7.25-7.18 (m, 2H),
7.14-7.05 (m, 4H), 2.90 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 163.8, 161.3, 159.7, 152.5, 146.7, 137.6 (d, J = 4
Hz), 130.8 (d, J = 8 Hz), 129.8, 128.5, 126.7, 126.4 (d, J =
14 Hz), 115.6 (d, J = 21 Hz), 100.6, 31.5; HRMS (ESI)
calcd. for C16H12FIN (M+H)+ m/z = 363.9998 found
363.9981.
Crystallography. Crystal suitable for X-ray determination
was obtained for 4h by recrystallization. Cell parameters
were determined either by a Siemens SMART CCD
diffractometer. The structure was solved using the
SHELXS-97 program[12a] and refined using the SHELXL-
97 program[12b] by full-matrix least-squares on F2 values.
Crystal data of 4h: C17H11IN2, Mw = 370.18, monoclinic,

ACCEPTED MANUSCRIPT
Tetrahedron
7
RSC. Adv. 2014, 4, 24463. (g) Yan, R.; Liu, X.; Pan, C.; Zhou,
X.; Li, X.; Kang, X.; Huang, G. Org. Lett. 2013, 15, 4876. (h)
Zhang, Y.; Wang, M.; Li, P.; Wang, L. Org. Lett. 2012, 14,
2206. (i) Tang, J.; Wang, L.; Mao, D.; Wang, W.; Zhang, L.;
Wu, S.; Xie, Y. Tetrahedron, 2011, 67, 8465. (j) Majumder,
S.; Gipson, K. R.; Odom, A. L. Org. Lett. 2009, 11, 4720. (j)
Horn, J.; Marsden, S. P.; Nelson, A.; House, D.; Weingarten,
G. G. Org. Lett. 2008, 10, 4117. (k) Zhang, Z.; Tan, J.; Wang,
Z. Org. Lett. 2008, 10, 173. (l) Martinez, R.; Ramon, D. J.;
Yus, M. Eur. J. Org. Chem. 2007, 1599.
space group P2(1)/n; a = 9.3851(2) Å, b = 8.7746(2) Å, c =
17.3359(6) Å, α = 90o, β = 102.340(3)°, γ = 90°; V =
1394.64(6) Å3; Z = 4; ρcalcd. = 1.763 Mgm-3; F(000) = 720;
Crystal size: 0.25 x 0.20 x 0.15 mm3; reflections collected:
6398; independent reflections: 2512 [R(int) = 0.0483]; θ
range 4.97 to 68.00°; goodness-of-fit on F2 1.0432; Final R
indices [I>2sigma(I)] R1 = 0.0400, wR2 = 0.0951; R
indices (all data) R1 = 0.0517, wR2 = 0.1044. CCDC
numbers for 4h is 1543431.
6. (a) Batista, V. F.; Pinto, D. C. G. A.; Silva, A. M. S. ACS
Sustainable Chem. Eng. 2016, 4, 4064. (b) Ramann, G. A.;
Cowen, B. J. Molecules 2016, 21, 986. (c) Saunthwal, R. K.;
Patel, M.; Verma, A. K. Org. Lett. 2016, 18, 2200. (d) Chen,
Z. S.; Yang, F.; Ling, H.; Li, M.; Gao, J. M.; Ji, K. Org. Lett.
2016, 18, 5828. (e) Rehan, M.; Hazra, G.; Ghorai, P. Org.
Lett. 2015, 17, 1668. (f) Bharate, J. B.; Vishwakarma, R. A.;
Bharate, S. B. RSC Adv. 2015, 5, 42020. (g) Liu, J.; Liu, F.;
Zhu, Y.; Ma, X.; Jia, X. Org. Lett. 2015, 17, 1409. (h)
Deshidi, R.; Devari, S.; Shah, B. A. Org. Chem. Front. 2015,
2, 515. (i) Li, Y.; Zhou, X.; Wu, Z.; Cao, J.; Ma, C.; He, Y.;
Huang, G. RSC Adv. 2015, 5, 88214. (j) Zhao, P.; Yan, X.;
Yin, H.; Xi, C. Org. Lett. 2014, 16, 1120 (k) Khong, S.;
Kwon, O. J. Org. Chem. 2012, 77, 8257.
7. (a) Hessian, K. O.; Flynn, B. L. Org. Lett. 2006, 8, 243. (b)
Ali. S.; Zhu, H. T.; Xia, X. F.; Ji, K. G.; Yang, Y. F.; Song, X.
R.; Liang, Y. M. Org. Lett. 2011, 13, 2598. (c) Wang, X.;
Wang, X.; Huang, D.; Liu, C.; Wang, X.; Hu, Y. Adv. Synth.
Catal. 2016, 358, 2332. (d) Tummatorn, J.; Poonsilp, P.;
Nimnual, P.; Janprasit, J.; Thongsornkleeb, C.; Ruchirawat, S.
J. Org. Chem. 2015, 18, 4516.
Acknowledgments
We thank the Ministry of Science and Technology, Taiwan
for the financial support (MOST103-2113-M-002-002-
MY3). We also thank “National Taiwan University Mass
Spectrometry-based Proteomics Core Facility” for the
measurement of ESI mass data.
Appendix A. Supplementary data
Supplementary data related to this article including
spectra of compounds and bond distances & bond angles of
4h
can
be
found
at
http://
dx.doi.org/10.1016/j.tet.2017.xxxxxxxx.
References
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