Diversity-oriented approach to spirocycles with indole moiety via Fischer indole cyclization, olefin metathesis and Suzuki-Miyaura cross-coupling reactions

Article abstract of DOI:10.1016/j.tet.2014.11.024

A range of aryl substituted spirocycles containing the indole moiety have been assembled through Claisen rearrangement, Fischer indole cyclization, ring-closing metathesis and the Suzuki-Miyaura cross-coupling reactions. Some of these molecules contain ei

Full text of DOI:10.1016/j.tet.2014.11.024

Accepted Manuscript
Diversity-oriented approach to spirocycles with indole moiety via Fischer indole
cyclization, olefin metathesis and Suzuki–Miyaura cross-coupling reactions
Sambasivarao Kotha , Rashid Ali , Venu Srinivas , Nimita G. Krishna
PII:
S0040-4020(14)01596-8
10.1016/j.tet.2014.11.024
TET 26173
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 August 2014
Revised Date: 5 November 2014
Accepted Date: 7 November 2014
Please cite this article as: Kotha S, Ali R, Srinivas V, Krishna NG, Diversity-oriented approach to
spirocycles with indole moiety via Fischer indole cyclization, olefin metathesis and Suzuki–Miyaura
cross-coupling reactions, Tetrahedron (2014), doi: 10.1016/j.tet.2014.11.024.
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ACCEPTED MANUSCRIPT
Diversity-oriented approach to spirocycles with indole moiety via Fischer indole
cyclization, olefin metathesis and Suzuki–Miyaura cross-coupling reactions
Sambasivarao Kotha,* Rashid Ali, Venu Srinivas and Nimita G. Krishna
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai-400076
India, Phone: +91-22-2576 7160, Fax: +91(22)-2572 7152; E-mail: srk@chem.iitb.ac.in
ABSTRACT
A range of aryl substituted spirocycles containing the indole moiety have been assembled
through Claisen rearrangement, Fischer indole cyclization, ring-closing metathesis and the
Suzuki–Miyaura cross-coupling reactions. Some of these molecules contain either a
spirocyclic system or an indeno[1,2-b]indole framework which is present in diverse bioactive
targets. Here, we have used simple and readily available starting materials to generate a
library of spirocycles with an indole unit in their structures.
Graphical abstract
Keywords
Spirocycles, Claisen rearrangement, Fischer indole cyclization, Ring-closing metathesis,
Suzuki–Miyaura cross-coupling
1
. Introduction
Indole is a unique heterocycle and functionalized indoles have been referred as privileged
1
structures because they are a feature in a large number of bioactive molecules. The
construction and derivatization of compounds containing an indole moiety has drawn a
considerable amount of attention of synthetic organic chemists. Over the last decade, several
2
efforts have been directed to develop simple and efficient methodologies for the synthesis of
indole-based compounds. More specifically, the indeno[1,2-b]indole framework 1 (Fig. 1)
has gained importance in the realm of biological as well as pharmacologically active
3
substances. The structures of some important bioactive molecules containing the indole
4
moiety are shown in Fig. 1.
1

ACCEPTED MANUSCRIPT
Spirocycles have drawn a considerable amount of attention of the synthetic as well as
5
material chemists due to the challenges involved in the creation of a quaternary centre. A
variety of complex molecules such as fredericamycin, fenestrindane alicyclic
6
[
5.5.5.5]fenestrane contain a spiro linkage as a structural unit. Even though numerous
7
methods are available in the literature to construct spirocycles, most of them have limitations
5
k
due to functional-group tolerence and group diversity.
In view of the importance of spirocycles as well as indoles, we envisioned a novel
synthetic approach to spirocycles with an indole moiety through Claisen rearrangement (CR),
8
-9
Fischer indole cyclization (FIC), ring-closing metathesis (RCM) and Suzuki–Miyaura (SM)
cross-coupling reactions. Furthermore, incorporation of the SM cross-coupling reaction
1
0
during the construction of spirocyclic systems is rather scarce.
Fig 1. Some biologically important compounds
Fig. 2. Ru-catalysts [G-(I-II)] used in our study
2

ACCEPTED MANUSCRIPT
Our interest in spirocycles containing an indole moiety encompasses to prepare a range of
intricate spirocycles with an indole unit and further enhance the indole library via the SM
1
1
cross-coupling reaction.
2
. Results and discussion
To begin with, we generated the di-allyl derivative 8 by treating 6-bromo-2-naphthol 7 with
allyl bromide followed by a microwave irradiated (MWI) CR. The di-allylated compound 8
was then subjected to the RCM sequence in the presence of Grubbs’ second generation
1
2
catalyst (Fig. 2) to deliver the known spiro compound 9 (Scheme 1).
Scheme 1. Design and synthesis of building block 9
Next, the tricyclic spiro derivative 9 was subjected to SM cross-coupling with phenylboronic
acid to furnish the desired cross-coupling product 10a in 96% yield (Scheme 2, Fig. 3). The
scope of the cross-coupling reaction was further extended by using other arylboronic acids to
deliver the desired products 10b-f in good to excellent yields (Fig. 3). The new compounds
1
13
were fully characterized by H, C NMR spectroscopy and further supported by high-
resolution mass spectrometric (HRMS) data.
Scheme 2. The SM cross-coupling of compound 9
3

ACCEPTED MANUSCRIPT
Fig. 3. List of the SM cross-coupling products of 9
To further expand the substrate scope to spirocycles, we have also selected 5-bromo-1-
indanone 11 as a starting material. The allylation of the indanone 11 under NaH/allyl bromide
conditions furnished the di-allyl ketone 12 in 70% yield. This compound was then subjected
to the RCM sequence with the aid of Grubbs’ first generation catalyst (Fig. 2) to generate the
1
2
required spirocyclic framework 13 in excellent yield (Scheme 3).
Scheme 3. Synthesis of 1-indanone-based spirocyclic analogue 13
Having the bromo derivative 13 in hand, the SM cross-coupling reaction with phenylboronic
acid using Pd(PPh ) , Na CO in a THF/toluene/water solvent mixture gave the coupling
3
4
2
3
product 14a in 92% yield (Scheme 4, Fig. 4). Additionally, other SM coupling products 14b-
d were also generated by treating the compound 13 with other functionalized arylboronic
acids (Scheme 4, Fig. 4).
Scheme 4. Synthesis of 1-indanone-based spirocycles 14a-d
4

ACCEPTED MANUSCRIPT
Fig. 4. List of SM cross-coupling products obtained from 13
Spirocycles as well as indole motif containing compounds are useful candidates from a
1
3
biological point of view. Therefore, the molecular skeleton which integrates spirocyclic as
well as indole moieties might possess properties of both and provide new chemical probes in
drug design and development. For this, we are interested in applying the RCM sequence to
assemble a library of hybrid molecules containing both of these units in their structures. To
achieve this goal, the known compounds 17a-c, 24 and 27 were prepared from the readily
available starting materials 15a-c (Scheme 5) and 22 (Scheme 8), respectively. Compound
1
7a was then subjected to FIC with phenylhydrazine hydrochloride using a low melting
mixture of L-(+)-tartaric acid:N,N-dimethylurea [L-(+)-TA:DMU] (30:70) to afford the
desired di-indole derivative 19 along with mono-indole derivative 18 (Scheme 6). The di-
indole derivative 19 on treatment with NaH/MeI in THF afforded the N,N-dimethylated di-
indole derivative 20a in 87% yield.
Scheme 5. Preparation of 17a-c (TBAHS = Tetrabutylammonium hydrogen sulphate)
5

ACCEPTED MANUSCRIPT
Scheme 6. Synthesis of spirocycles containing the indole moiety
We found that the non-N-methylated indole derivatives were unstable and difficult to
handle, therefore, we synthesized the N-methylated indole derivatives 20a-c (Scheme 7), 25
and 28, (Scheme 8) directly by treating their corresponding keto precursors 17a-c (Scheme
7
), 24 and 27 (Scheme 8) with 1-methyl-1-phenylhydrazine by using a low melting mixture
1
4
of L-(+)-TA:DMU (30:70). Several natural products contain the quinone subunit in their
structure. In this context, we have also synthesized quinone-based spiroindole derivatives 21
15
and 26, starting with the corresponding indoles 20c and 25 under selenium dioxide (SeO )
2
conditions in 89% and 85% yields, respectively (Schemes 7 and 8).
Scheme 7. Synthesis of quinone-based spiroindole derivative 21
6

ACCEPTED MANUSCRIPT
Scheme 8. Synthesis of spirocycles containing an indole unit
To further expand the utility of spiroindole derivatives, we used a different sequence
i.e. Fischer indole cyclization, allylation followed by the RCM reaction. Here, the indeno[1,2-
b]indole frameworks are used as the active methylene moiety which were obtained from the
FIC of 1-indanone derivatives. To this end, we performed the FIC of 2-indanone 29 using a
low melting mixture of L-(+)-TA:DMU (30:70) to furnish the indeno[1,2-b]indole derivative
3
0 in 91% yield (Scheme 9). Compound 30 was then subjected to di-allylation by using
NaH/allyl bromide in THF to afford the compound 31 in 71% yield. Next, compound 31 was
exposed to the RCM sequence with the aid of the G-I catalyst to deliver compound 32 in 80%
yield (Scheme 9).
Scheme 9. Synthesis of spirocycles containing an indole moiety starting with 2-indanone 29
To explore the scope of this methodology in terms of substituent effect at the 5-
position of the 1-indanone derivatives, the compounds 33a-c were subjected to FIC using a
low melting mixture of L-(+)-TA:DMU (30:70) to deliver the spiroindole derivatives 34a-c
in good to excellent yields (Scheme 10). The indeno[1,2-b]indole derivatives 34a-c were then
treated with NaH/allyl bromide to furnish the di-allylated systems 35a-c in good yields,
which on a subsequent RCM sequence with the aid of G-I catalyst afforded the spirocyclic
systems with an indole unit in their structures (Scheme 10). Here, we observed that electron
7

ACCEPTED MANUSCRIPT
withdrawing group at 5-position of 1-indanone is useful to provide better yields during the
course of allylation sequence (Scheme 10).
Scheme 10. Synthesis of spirocycles containing the indeno[1,2-b]indole framework
Compounds 36a-c contain the indeno[1,2-b]indole framework which is present in many
biologically relevant molecules (e.g. 2, Fig. 1). Therefore, it was worthy to derivatize
compound 36c through the SM cross-coupling reaction by varying the boronic acid to
generate a library of spirocycles containing the indeno[1,2-b]indole framework. These
reactions proceeded in good to excelent yields (Scheme 11, Fig. 5).
Scheme 11. The SM cross-coupling reaction of 36c
8

ACCEPTED MANUSCRIPT
N
N
N
N
OHC
N
MeO
Me
3
7a (97%)
37b (84%)
37c (85%)
37d (92%)
N
N
N
S
NC
N
F
O
3
7e (89%)
37f (93%)
37g (81%)
37h (90%)
N
N
S
N
H
3
7i (86%)
37j (73%)
37k (96%)
Fig. 5. Substrate scope of spirocycles containing the indeno[1,2-b]indole framework
3
. Conclusions
We have demonstrated a simple strategy to assemble densely functionalized spirocycles
containing the indole moiety in their structure. Here, we have used CR, FIC, RCM and SM
cross-coupling reactions. There are several diversity points embedded in our strategy for
example, by utilizing commercially available boronic acids, one can generate a library of
compounds in a diversity oriented manner. We have demonstrated this idea with substrates 9,
1
3 and 36c by using a variety of boronic acids to assemble a range of spirocycles. In addition,
our theme has diversity points in terms of strategies as well as starting ketone components
used. Here, we have prepared around 46 new compounds with several option for
1
6
divercification.
4
. Experimental section
All commercially accessible reagents were used without further purification and reactions
involving air sensitive catalysts or reagents were performed in degassed solvents. Moisture
sensitive materials were transferred using syringe-septum techniques and the reactions were
maintained under nitrogen atmosphere. Analytical thin layer chromatography (TLC) was
performed on (7.5×2.5 cm) glass plates coated with Acme’s silica gel GF 254 (containing
1
3% calcium sulfate as a binder) by using a suitable mixture of EtOAc and petroleum ether
for development. Column chromatography was performed by using Acme’s silica gel (100-
9

ACCEPTED MANUSCRIPT
2
00 mesh) with an appropriate mixture of EtOAc and petroleum ether. The coupling
constants (J) are given in hertz (Hz) and chemical shifts are denoted in parts per million
ppm) downfield from internal standard, tetramethylsilane (TMS). The abbreviations, s, d, t,
(
q, m, dd and td, refer to singlet, doublet, triplet, quartet, multiplet, doublet of doublets, and
triplet of doublets respectively. Grubbsʼ catalysts were purchased from Sigma Aldrich.
Infrared (IR) spectra were recorded on Nicolet Impact-400 FT IR spectrometer in CHCl3.
1
Proton nuclear magnetic resonance ( H NMR, 300 MHz, 400 MHz and 500 MHz) spectra
1
3
and carbon nuclear magnetic resonance ( C NMR, 75 MHz, 100 MHz and 125 MHz) spectra
were recorded on a Bruker spectrometer. The high-resolution mass measurements were
carried out by using electrospray ionization (ESI, Q-ToF) spectrometer. Melting points were
recorded on a Veego melting point apparatus.
Preparation of the known compounds 9 and 13, 17a and 17c, 17b, 24 and 27, 30, 34a:
1
13
All these compounds were prepared using literature reported procedures, the H and
C
NMR spectra of these compounds matched with the literature reported spectroscopic data,
1
2, 17-21
respectively.
General procedure for the Fischer indole cyclization: To a clear melted mixture (1.5 g) of
o
L-(+)-TA-DMU (30:70) at 70 C, was added 1-methyl-phenyl hydrazine (1.5-3 equiv) and
o
the ketone components (1 equiv). The reaction mixture was stirred at at 70 C for 2-10 h. At
the conclusion of the reaction (TLC monitoring), the warm reaction mixture was diluted with
water. The reaction mixture was cooled to room temperature, filtered through sintered glass
funnel and the solid material was washed with water (4 x 20 mL). The crude products were
purified by silica gel column chromatography using appropriate mixture of ethyl acetate
/
petroleum ether to afford the desired products.
General procedure for the allylation of 30 and 34a-c: To a suspension of sodium hydride
3 equiv) in dry THF (20 mL), was added the compound 30 or 34a-c and the reaction mixture
(
was stirred for 15 min at room temperature. Allyl bromide (3 equiv) was then added and
stirring was continued for 10-30 h at the same temperature. At the conclusion of the reaction
(TLC monitoring), the reaction mixture was diluted with EtOAc and the solvent was removed
under reduced pressure. Compounds were then extracted with CH Cl and the crude products
2
2
were purified by silica gel column chromatography using appropriate mixtures of EtOAc-
petroleum ether to afford the desired di-allylated compound 31 or 35a-c.
General procedure for RCM sequence of 31 and 35a-c: The solution of compound 31 or
3
5a-c in CH Cl (20 mL) was degassed with nitrogen for 15-20 min. Then, G-I (5 mol%)
2 2
catalyst was added and the reaction mixture was stirred at room temperature for 10-12 h. At
1
0

ACCEPTED MANUSCRIPT
the conclusion of the reaction (TLC monitoring), the solvent was removed under reduced
pressure and the crude products were purified by silica gel column chromatography using
appropriate mixtures of EtOAc-petroleum ether to afford the RCM product 32 or 36a-c.
General procedure for the Suzuki–Miyaura cross-coupling reaction: To a solution of
bromo derivatives 9, 13 or 36c in THF/toluene/water (1:1:1, each 10 mL) were added
Na CO (3.0 equiv) and arylboronic acid (2.0 equiv). The reaction mixture was degassed with
2
3
nitrogen for 20 min. Pd(PPh ) (5 mol%) was then added and the reaction mixture was heated
3
4
o
at 100 C. At the conclusion of the reaction (8-30 h, TLC monitoring), the reaction mixture
was diluted with water and the organic layer was extracted with CH Cl . The organic layer
2
2
was washed with water as well as brine and dried (Na SO ). The solvent was removed on
2
4
rotavapour and the crude products were purified by silica gel column chromatography using
appropriate mixtures of EtOAc-petroleum ether to afford the desired Suzuki coupling
products.
Synthesis of compound 10a: This compound was prepared according to the general
procedure by using bromo derivative 9 (40 mg, 0.15 mmol) and phenylboronic acid (35.5 mg,
0
.30 mmol), Na CO (62 mg, 0.58 mmol) and the catalyst Pd(PPh ) (16.8 mg, 0.014 mmol)
2 3 3 4
for 12 h. The crude material was purified by silica gel column chromatography (2% EtOAc-
petroleum ether) to yield the desired product 10a (38 mg, 96%) as a colorless solid; R = 0.45
f
(
silica gel, 5% EtOAc-petroleum ether); mp 122-126 °C; R = 0.45 (silica gel, 5% EtOAc-
f
1
petroleum ether); H NMR (400 MHz, CDCl ):
δ 7.35-7.60 (m, 9H), 6.26 (d, J = 9.8 Hz, 1H),
3
1
3
5
.82 (s, 2H), 3.20 (d, J = 13.8 Hz, 2H), 2.66 (d, J = 13.8 Hz, 2H); C NMR (100 MHz,
CDCl3):
δ 204.7, 148.5, 145.5, 140.2, 140.0, 129.3, 129.1, 128.8, 128.5, 127.8, 127.7, 127.1,
-1
1
26.4, 125.5, 55.9, 49.5; IR (KBr): υmax 3054, 2986, 2305, 1429, 1265 cm ; HRMS (Q-Tof):
+
m/z calcd. for C H O [M+H] 273.1279; found: 273.1288.
2
0
17
Synthesis of compound 10b: Colourless solid; yield = 81% (42 mg, starting from 50 mg of
9
); reaction time = 18 h; mp 146-148 °C; R = 0.17 (silica gel, 2% EtOAc-petroleum ether);
f
1
H NMR (300 MHz, CDCl3):
δ 7.35-7.59 (m, 7H), 7.19 (d, J = 6.7 Hz, 1H), 6.26 (d, J = 9.7
1
3
Hz, 1H), 5.82 (s, 2H), 3.21 (d, J = 13.9 Hz, 2H), 2.68 (d, J = 13.9 Hz, 2H), 2.43 (s, 3H); C
NMR (75 MHz, CDCl3): 204.6, 148.3, 145.4, 140.1, 138.6, 129.2, 128.9, 128.7, 128.5,
28.4, 127.8, 127.7, 126.2, 125.4, 124.2, 55.9, 49.4, 21.6; IR (KBr): υmax 3055, 2922, 2849,
δ
1
2
2
-1
+
304, 1661 cm ; HRMS (Q-Tof): m/z calcd. for C H O [M+H] 287.1436; found:
2
1
19
87.1436.
1
1

ACCEPTED MANUSCRIPT
Synthesis of compound 10c: Colourless solid; yield = 79% (43 mg, starting from 50 mg of
9
); reaction time = 30 h; mp 134-136 °C; R = 0.40 (silica gel, 10% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl3):
δ 10.12 (s, 1H), 7.76-7.82 (m, 4H), 7.64 ( dd, J = 8.1 Hz, J =
1 2
2
2
1
1
.0 Hz, 1H ), 7.51-7.59 (m, 3H), 6.29 (d, J = 9.9 Hz, 1H), 5.83 (s, 2H), 3.21 (d, J = 13.8 Hz,
13
H), 2.66 (d, J = 13.8 Hz, 2H); C NMR (100 MHz, CDCl ):
δ
204.3, 191.9, 149.6, 146.0,
3
45.7, 144.9, 138.4, 136.1, 135.6, 130.54, 130.52, 129.4, 128.8, 128.2, 127.9, 127.6, 126.6,
-1
25.8, 55.9, 49.4; IR (KBr): υmax 3053, 2985, 2304, 1700, 1604 cm ; HRMS (Q-Tof): m/z
+
calcd. for C H O [M+H] 301.1229; found: 301.1218.
2
1
17
2
Synthesis of compound 10d: Colourless solid; yield = 70% (45 mg, starting from 50 mg of
9
); reaction time = 16 h; mp 118-122 °C; R = 0.18 (silica gel, 2% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl3):
δ 7.44-7.60 (m, 8H), 6.27 (d, J = 9.9 Hz, 1H), 5.82 (s, 2H), 3.21
1
3
(
d, J = 13.8 Hz, 2H), 2.67 (d, J = 13.8 Hz, 2H); C NMR (75 MHz, CDCl ):
δ
204.5, 148.9,
3
1
1
45.2, 139.1, 138.8, 132.2, 132.1, 129.0, 128.8, 128.7, 128.6, 127.6, 127.5, 126.5, 125.7,
-1
22.1, 55.9, 53.6, 49.4; IR (KBr): υmax 3054, 2987, 2305, 1655 cm ; HRMS (Q-Tof): m/z
7
9
+
calcd. for C H O Br [M+H] 351.0385; found: 351.0375.
2
0
16
Synthesis of compound 10e: Colourless solid; yield = 92% (46 mg, starting from 50 mg of
9
); reaction time = 20 h; mp 156-158 °C; R = 0.17 (silica gel, 2% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl3):
δ
7.58-7.59 (dd, J = 8.1 Hz, J = 1.9 Hz, 1H), 7.46-7.51 (m,
1
2
3
H), 7.38-7.42 (m, 3H), 6.26 (d, J = 9.8 Hz, 1H), 5.81 (s, 2H), 3.19 (d, J = 13.7 Hz, 2H), 2.66
13
(
d, J = 13.7 Hz, 2H); C NMR (100 MHz, CDCl ):
δ
204.6, 148.3, 145.3, 141.3, 134.7,
3
1
3
2
28.8, 128.6, 128.5, 126.9, 126.7, 126.4, 126.3, 125.5, 120.7, 55.9, 49.4; IR (KBr): υmax 3101,
-1
+
055, 2920, 2849, 1660, 1562 cm ; HRMS (Q-Tof): m/z calcd. for C H OS [M+H]
18
15
79.0844; found: 279.0835.
Synthesis of compound 10f: Colourless solid; yield = 78% (37 mg, starting from 40 mg of
9
); reaction time = 21 h; mp 161-163 °C; R = 0.52 (silica gel, 10% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl3):
δ 7.79-7.86 (m, 2H), 7.71 (dd, J = 8.2 Hz, J = 2.1 Hz, 1H),
1 2
7
7
1
1
.63 (d, J = 2.1 Hz, 1H), 7.57 (s, 1H), 7.53 (d, J = 6.9 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.32-
.39 (m, 2H), 6.29 (d, J = 9.8 Hz, 1H), 5.83 (s, 2H), 3.20 (d, J = 13.8 Hz, 2H), 2.66 (d, J =
1
3
3.8 Hz, 2H); C NMR (100 MHz, CDCl ):
δ
204.2, 149.2, 144.8, 142.9. 140.6, 139.5,
3
33.1, 128.7, 128.4, 126.8, 126.4, 125.8, 124.8, 124.7, 123.7, 122.4, 119.8, 55.9, 49.3; IR
-1
+
(
KBr): υmax 3052, 2986, 1224, 1268 cm ; HRMS (Q-Tof): m/z calcd. for C H OS [M+H]
22 17
3
29.1000; found: 329.0995.
1
2

ACCEPTED MANUSCRIPT
Synthesis of compound 14a: This compound was prepared according to the general
procedure by using bromo derivative 13 (50 mg, 0.19 mmol), phenylboronic acid (35 mg, 2.9
mmol), Pd(PPh ) (11.0 mg, 5 mol%) and Na CO (81 mg, 0.76 mmol) in THF/toluene/water
3
4
2
3
(10 mL) for 18 h. Analytically pure product 14a was isolated by silica gel column
chromatography (1% EtOAc-petroleum ether). (50 mg, 92%) as a thick colorless liquid; R =
f
1
0
.60 (silica gel, 1% EtOAc-petroleum ether); H NMR (400 MHz, CDCl ):
δ
7.85 (d, J = 7.8
3
Hz, 1H), 7.61-7.64 (m, 4H), 7.41-7.50 (m, 3H), 5.75 (s, 2H), 3.23 (s, 2H), 2.93 (d, J = 14.7
13
Hz, 2H), 2.38 (d, J = 14.7 Hz, 2H), C NMR (100 MHz, CDCl ):
δ
210.3, 153.7, 148.0,
3
1
3
2
40.4, 135.3, 129.1, 128.9, 128.5, 127.6, 127.1, 125.1, 124.7, 55.9, 45.7, 45.6; IR (neat): υmax
-1
+
058, 2919, 2841, 1706, 1607, 1283 cm ; HRMS (Q-Tof): calcd. for C H O [M+H]
19
17
61.1279; found 261.1263.
Synthesis of compound 14b: Colourless liquid; yield = 86% (53 mg, starting from 50 mg of
1
1
3); reaction time = 24 h; R = 0.50 (silica gel, 2% EtOAc-petroleum ether); H NMR (400
f
MHz, CDCl3):
δ
7.83 (d, J = 7.8 Hz, 1H), 7.59-7.62 (m, 2H), 7.43 (d, J = 9.2 Hz, 2H), 7.34-
7
3
1
.38 (m, 1H), 7.21-7.25 (m, 1H), 5.74 (s, 2H), 3.22 (s, 2H), 2.92 (d, J = 14.7 Hz, 2H), 2.44 (s,
13
H), 2.38 (d, J = 14.7 Hz, 2H); C NMR (100 MHz, CDCl ):
δ
210.3, 153.7, 148.2, 140.4,
3
38.8, 135.2, 129.3, 129.0, 128.9, 128.4, 127.1, 125.1, 124.8, 124.7, 55.9, 45.8, 45.7; IR
-1
(
neat): υmax 3056, 2923, 2844, 1707, 1607, 1265 cm ; HRMS (Q-Tof): calcd. for C H O
20 19
+
[
M+H] 275.1436; found 275.1425.
Synthesis of compound 14c: Colourless solid; yield = 89% (49 mg, starting from 50 mg of
1
3); reaction time = 18 h; mp 160-162 °C; R = 0.30 (silica gel, 2% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl3):
δ 7.81-7.83 (m, 1H), 7.57-7.60 (m, 4H), 7.00-7.02 (m, 2H),
5
.74 (s, 2H), 3.87 (s, 3H), 3.21 (s, 2H), 2.92 (d, J = 14.7 Hz, 2H), 2.38 (d, J = 14.7 Hz, 2H);
1
3
C NMR (100 MHz, CDCl3):
δ 210.2, 160.2, 153.8, 147.6, 134.8, 132.8, 128.9, 128.8, 126.6,
1
1
24.8, 124.4, 114.6, 55.9, 55.6, 45.8, 45.7; IR (neat): υmax 3055, 2909, 2838, 1707, 1604,
-1
+
251 cm ; HRMS (Q-Tof): calcd. for C H O [M+H] 291.1385; found 291.1396.
2
0
19
2
Synthesis of compound 14d: Colourless solid; yield = 86% (51 mg, starting from 50 mg of
1
3); reaction time = 23 h; mp 126-128 °C; R = 0.40 (silica gel, 2% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl3):
δ
7.72-7.75 (m, 1H), 7.59-7.60 (m, 2H), 7.40-7.41 (m, 1H),
7
2
1
.33-7.35 (m, 1H), 7.07-7.09 (m, 1H), 5.69 (s, 2H), 3.14 (s, 2H), 2.86 (d, J = 14.7 Hz, 2H),
1
3
.32 (d, J = 14.7 Hz, 2H); C NMR (100 MHz, CDCl ):
δ
209.9, 153.9, 143.4, 140.7, 135.3,
3
28.9, 128.6, 126.9, 125.6, 125.1, 125.0, 123.3, 55.9, 45.8, 45.6; IR (neat): υmax 3048, 2986,
1
3

ACCEPTED MANUSCRIPT
-1
+
1
724, 1684, 1254 cm ; HRMS (Q-Tof): calcd. for C H OS [M+H] 267.0844; found
17 15
2
67.0836.
Synthesis of compound 19: To a clear melted mixture (1.5 g) of L-(+)-TA-DMU (30:70) at
o
7
0 C, was added phenyl hydrazine hydrochloride (900 mg, 6.25 mmol) and ketone 17a (400
o
mg, 2.08 mmol). The reaction mixture was stirred at at 70 C for 6 h. At the conclusion of the
reaction (TLC monitoring), the warm reaction mixture was diluted with water. The reaction
mixture was cooled to room temperature, filtered through sintered glass funnel and the solid
material was washed with water (4 x 20 mL). The crude product was purified by silica gel
column chromatography using (5% EtOAc-petroleum ether) to deliver the compound 19 (335
mg, 47%) along with compound 18 (84 mg, 15%) as white solids.
1
Compound 18: mp 98-99 °C; R = 0.53 (silica gel, 10% EtOAc-petroleum ether); H NMR
f
(
400 MHz, CDCl ): δ 7.81 (brs, 1H), 7.62 (d, J = 7.9 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H), 7.05-
3
7
.09 (m, 1H), 6.99-7.03 (m, 1H), 5.73 (s, 2H), 3.07 (d, J = 14.7 Hz, 2H), 2.63 (s, 2H), 2.57
1
3
(
d, J = 14.7 Hz, 2H), 1.42 (s, 6H); C NMR (100 MHz, CDCl ):
δ
210.8, 138.3, 136.9,
3
1
3
3
28.9, 125.0, 121.9, 120.3, 119.6, 116.8, 111.3, 54.5, 53.9, 44.6, 35.4, 30.1; IR (neat): υmax
-1
+
049, 2927, 2851, 1711, 1596, 1470 cm ; HRMS (Q-Tof) calcd. for C H NKO [M+K]
1
8
19
04.1098, found: 304.1098.
1
Compound 19: mp 260-262 °C; R = 0.38 (silica gel, 10% EtOAc-petroleum ether); H NMR
f
(
400 MHz, CDCl ): δ 7.92 (brs, 2H), 7.86 (d, J = 7.3 Hz, 2H), 7.34 (dd, J = 1.1 Hz, J = 6.8
3
1
2
1
3
Hz, 2H), 6.13-6.24 (m, 4H), 6.06 (s, 2H), 3.04 (s, 4H), 1.97 (s, 6H); C NMR (100 MHz,
CDCl3): 136.9, 130.5, 125.3, 121.5, 120.6, 119.3, 118.8, 111.2, 48.3, 42.0, 34.3, 29.4; IR
δ
-1
(
neat): υmax 3417, 3010, 2923, 2840, 1443 cm ; HRMS (Q-Tof) calcd. for C H N K
24 22 2
+
[
M+K] 377.1415, found: 377.1412.
Synthesis of compound 20a:To a suspension of NaH (57 mg, 2.37 mmol) in THF (20 mL),
was added compound 19 ( 200 mg, 0.59 mmol) followed by MeI (0.12 mL, 1.78) and the
reaction mixture was stirred at rt for 16 h. At the conclusion of the reaction (TLC
monitoring), the reaction mixture was diluted with EtOAc and the solvent was removed on
rotavapour. The compound was extracted with CH Cl and the crude product was purified by
2
2
silica gel column chromatography using (4% EtOAc-petroleum ether) to deliver compound
0a (189 mg, 87%) as a white solid.
2
Direct synthesis of compound 20a, 20b, 20c: These compounds were prepared according to
the procedure given for compound 19 using 1-methyl-phenyl hydrazine instead of phenyl
hydrazine hydrochloride.
1
4

ACCEPTED MANUSCRIPT
Compound 20a White solid; yield = 62% (118 mg, starting from 100 mg of 17a) reaction
1
time = 5 h; mp 280-283 °C; R = 0.58 (silica gel, 10% EtOAc-petroleum ether); H NMR
f
(
400 MHz, CDCl ): δ 7.90 (d, J = 7.9 Hz, 2H); 7.33 (d, J = 8.1 Hz, 2H), 7.22-7.25 (m, 2H),
3
1
3
7
.13-7.20 (m, 2H), 6.14 (s, 2H), 3.74 (s, 6H), 3.14 (s, 4H), 1.97 (s, 6H); C NMR (100 MHz,
CDCl3):
δ
139.1, 138.9, 132.1, 124.3, 121.3, 120.9, 118.9, 118.2, 109.3, 48.9, 40.9, 33.9,
-1;
3
0.9, 29.8; IR (neat): υmax 2950, 2925, 2851, 1654, 1583, 1520, 1456, 1262, 740 cm HRMS
+
(
Q-Tof) calcd. for C H N [M+H] 367.2169, found: 367.2166.
26 27 2
Compound 20b: White solid; yield = 69% (59 mg, starting from 50 mg of 17b); reaction
1
time = 5 h; mp 265-267 °C; R = 0.60 (silica gel, 10% EtOAc-petroleum ether); H NMR
f
(
400 MHz, CDCl ): δ 7.29 (t, J = 7.3 Hz, 3H), 7.17 (t, J = 8.2 Hz, 3H), 7.11 (t, J = 7.5 Hz,
3
2
H), 7.06 (t, J = 7.1 Hz, 2H), 6.98-7.04 (m, 1H), 6.87 (t, J = 7.3 Hz, 2H), 6.12 (s, 2H), 5.46
1
3
(
s, 1H), 3.70 (s, 6H), 3.25 (s, 2H), 3.11 (s, 2H); C NMR (100 MHz, CDCl ):
δ
145.9, 140.5,
3
1
4
38.9, 132.3, 131.9, 128.8, 128.4, 126.1, 125.7, 121.5, 119.7, 119.3, 112.0, 108.9, 48.9, 48.3,
-
1
1.1, 39.5, 31.1; IR (neat): υmax 3049, 2927, 2851, 1596, 1470, 1448 cm ; HRMS (Q-Tof)
+
calcd. for C H N [M‒H] 413.2012, found: 413.2012.
3
0
25
2
Compound 20c: White solid; yield = 74% (123 mg, starting from 80 mg of 17c); reaction
1
time = 6 h; mp 290-292 °C; R = 0.53 (silica gel, 10% EtOAc-petroleum ether); H NMR
f
(
400 MHz, CDCl ): δ 7.68 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 7.22-7.25 (m, 2H),
3
1
3
7
.15-7.20 (m, 2H), 6.12 (s, 2H), 4.09 (s, 2H), 3.73 (s, 6H), 3.11 (s, 4H); C NMR (100 MHz,
CDCl3):
9.3; IR (neat): υmax 3043, 2923, 2846, 1475 cm ; HRMS (Q-Tof) calcd. for C H KN
2
δ
140.8, 138.7, 131.9, 126.2, 121.7, 119.3, 118.6, 109.0, 107.3, 48.3, 41.2, 31.0,
-1
1
24
22
+
[
M+K] 377.1415, found: 377.1417.
Synthesis of compound 21: The solution of compound 20c (100 mg, 0.30 mmol) and SeO2
66 mg, 0.60 mmol) in 1,4-dioxane (20 mL) was heated at reflux temperature for 12 h. At the
(
conclusion of the reaction (TLC monitoring), the reaction mixture was filtered through a
sintered glass funnel and the solvent was removed under reduced pressure. The crude product
was purified by silica gel column chromatography using (5% EtOAc-petroleum ether) to
deliver the compound 21 (93 mg, 89%) as a white solid.
1
mp 185-186 °C; R = 0.54 (silica gel, 10% EtOAc-petroleum ether); H NMR (400 MHz,
f
CDCl ): δ 8.57 (d, J = 6.7 Hz, 2H), 7.25-7.34 (m, 6H), 6.19 (s, 2H), 3.75 (s, 6H), 3.15 (s,
3
1
3
4
H); C NMR (100 MHz, CDCl ): δ 180.6, 152.0, 138.7, 131.9, 124.1, 123.1, 122.3, 111.9,
3
-1
1
09.3, 45.8, 42.1, 31.2; IR (neat): υmax 3043, 2923, 2846, 1475 cm ; HRMS (Q-Tof) calcd.
+
for C H N O [M+H] 353.1648, found: 353.1637.
2
4
21
2
1
5

ACCEPTED MANUSCRIPT
Synthesis of compound 25: White solid; yield = 67% (96 mg, starting from 100 mg of 24);
1
reaction time = 6 h; mp 130-133 °C; R = 0.59 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (400 MHz, CDCl ): δ 7.57 (d, J = 7.7 Hz, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.19-7.33 (m,
3
5
H), 7.12-7.16 (m, 1H), 6.06 (s, 2H), 4.16 (s, 2H), 3.69 (s, 3H), 3.06, 3.13 (ABq, J = 1.9 Hz,
1
3
4
H); C NMR (100 MHz, CDCl ):
δ
147.8, 139.5, 138.3, 131.3, 131.1, 128.6, 127.6, 126.2,
3
1
26.0, 125.5, 121.6, 119.2, 118.4, 108.9, 105.8, 53.1, 42.7, 30.5, 26.8; IR (neat): υmax 3049,
-1
+
2
928, 2895, 1522, 1492, 1462 cm ; HRMS (Q-Tof) calcd. for C H N [M+H] 286.1596,
21 20
found: 286.1596.
Synthesis of compound 26: Following the same procedure as for the compound 21.
White solid; yield = 75% (39 mg, starting from 50 mg of 25); reaction time = 15 h; mp 125-
1
1
8
7
27 °C; R = 0.56 (silica gel, 10% EtOAc-petroleum ether); H NMR (400 MHz, CDCl ): δ
f
3
.52-8.54 (m, 1H), 8.34 (d, J = 7.8 Hz, 1H), 7.55 (d, J = 3.8 Hz, 2H), 7.42-7.48 (m, 1H),
13
.35-7.39 (m, 3H), 6.17 (s, 2H), 3.79 (s, 3H), 3.14, 3.26 (ABq, J = 17.8 Hz, 4H); C NMR
180.7, 154.9, 151.9, 138.7, 133.1, 131.3, 130.4, 127.1, 125.6, 124.7,
24.4, 123.8, 122.5, 111.3, 109.4, 50.8, 43.2, 31.0; IR (neat): υmax 3007, 2924, 2859, 1631,
(100 MHz, CDCl3): δ
1
1
-1
+
524, 1468 cm ; HRMS (Q-Tof) calcd. for C H NNa [M+Na] 322.1202, found: 322.1199.
2
1
17
Synthesis of compound 28: White solid; yield = 82% (59 mg, starting from 50 mg of 27);
1
reaction time = 10 h; mp 150-152 °C; R = 0.61 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.61 (dd, J = 2.9 Hz, J = 7.1 Hz, 1H), 7.49 (dd, J = 2.3 Hz, J
2
3
1
2
1
=
8.0 Hz, 1H), 7.27-7.38 (m, 5H), 7.18-7.20 (m, 1H), 4.22 (s, 2H), 3.89 (s, 3H), 2.49-2.52 (m,
1
3
2
H), 2.27-2.33 (m, 6H); C NMR (125 MHz, CDCl ):
δ
148.1, 139.9, 138.4, 132.3, 128.9,
3
1
27.0, 126.6, 126.2, 125.6, 121.5, 119.1, 118.2, 108.8, 106.8, 47.7, 43.6, 31.8, 27.7, 27.2; IR
-1
+
(
neat): υmax 3010, 2945, 2855, 1540 cm ; HRMS (Q-Tof) calcd. for C H N [M+H]
21 22
2
88.1752, found: 288.1752.
Synthesis of compound 31: Brown solid; yield = 71% (145 mg, starting from 150 mg of 30);
1
reaction time = 12 h; mp 105-107 °C; R = 0.73 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (400 MHz, CDCl ): δ 7.83 (dd, J = 0.6 Hz, J = 1.5 Hz, 1H), 7.53 (d, J = 7.2 Hz, 1H),
3
1
2
7
2
1
3
.19-7.35 (m, 5H), 7.06-7.09 (m, 1H), 5.15-5.24 (m, 2H), 4.86-4.92 (m, 2H), 4.70-4.73 (m,
1
3
H), 3.89 (s, 3H), 2.86-2.92 (m, 4H); C NMR (125 MHz, CDCl ):
δ
152.1, 149.3, 141.9,
3
39.6, 133.6, 127.5, 122.7, 122.5, 121.9, 121.0, 120.2, 119.6, 118.3, 117.5, 109.9, 52.1, 41.9,
-1
1.4; IR (neat): υmax 3049, 2929, 2840, 1596, 1525, 1495, 1432 cm ; HRMS (Q-Tof) calcd.
+
for C H NK [M+K] 338.1306, found: 338.1309.
2
2
21
1
6

ACCEPTED MANUSCRIPT
Synthesis of compound 32: Brown solid; yield = 80% (73 mg, starting from 100 mg of 31);
1
reaction time = 6 h; mp 160-161 °C; R = 0.71 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (400 MHz, CDCl ): δ 7.80-7.82 (m, 1H), 7.53 (d, J = 7.2 Hz, 1H), 7.20-7.35 (m 5H),
3
1
3
7
.06 (dt, J = 1.1 Hz, J = 7.5 Hz, 1H), 6.05 (s, 2H), 3.79 (s, 3H), 2.98-3.07 (m, 4H); C
1 2
NMR (125 MHz, CDCl3):
δ
156.0, 155.9, 141.8, 138.2, 130.6, 127.2, 123.3, 121.9, 121.6,
1
1
2
21.1, 120.3, 119.5, 118.1, 110.0, 50.3, 43.2, 31.1; IR (neat): υmax 3016, 2928, 2846, 1602,
-1
+
522, 1491, 1467 cm ; HRMS (Q-Tof) calcd. for C H N [M+H] 272.1434, found:
2
0
18
72.1432.
Synthesis of compound 35a: Brown solid; yield = 65% (89 mg, starting from 100 mg of
3
4a); reaction time = 12 h; mp 99-103 °C; R = 0.67 (silica gel, 10% EtOAc-petroleum ether);
f
1
H NMR (500 MHz, CDCl ): δ 7.55 (d, J = 7.9 Hz, 1H), 7.48 (d, J = 7.5 Hz, 1H), 7.32 (d, J =
3
7
.5 Hz, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.20 (dt, J = 1.1 Hz, J = 7.5 Hz, 1H), 7.10-7.14 (m,
1 2
2
H), 7.05 (t, J = 7.0 Hz, 1H), 5.34-5.40 (m, 2H), 4.78-4.82 (m, 4H), 3.92 (s, 3H), 2.79 (dd, J1
1
3
=
7.5 Hz, J = 13.7 Hz, 2H), 2.56 (dd, J = 7.1 Hz, J = 13.7 Hz, 2H); C NMR (125 MHz,
2 1 2
CDCl3):
δ 155.3, 143.2, 142.2, 135.0, 134.9, 126.9, 126.3, 125.1, 124.1, 123.9, 121.2, 119.7,
1
1
19.6, 117.9, 117.4, 109.9, 51.2, 42.6, 31.3; IR (neat): υmax 3069, 2925, 2851, 1637, 1604,
-1
+
522, 1492 cm ; HRMS (Q-Tof) calcd. for C H NNa [M+Na] 322.1566, found: 322.1566.
2
2
21
Synthesis of compound 36a: Brown solid; yield = 83% (38 mg, starting from 50 mg of 35a);
1
reaction time= 6 h; mp 190-191 °C; R = 0.66 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (400 MHz, CDCl ): δ 7.43-7.48 (m, 3H), 7.27 (d, J = 8.2 Hz, 1H), 7.19 (t, J = 7.5 Hz,
3
1
H), 7.09-7.13 (m, 2H), 7.02 (t, J = 7.2 Hz, 1H), 6.02 (s, 2H), 3.93 (s, 3H), 2.80 (t, J = 3.6
1
3
Hz, 4H); C NMR (100 MHz, CDCl ):
δ
159.3, 142.3, 134.3, 130.9, 130.4, 126.8, 125.7,
3
1
2
2
23.0, 122.7, 121.3, 119.6, 119.4, 117.7, 109.9, 51.6, 43.6, 32.2; IR (neat): υmax 3054, 2924,
-1
+
847, 1604, 1523, 1467 cm ; HRMS (Q-Tof) calcd. for C H N [M+H] 272.1434, found:
20
18
72.1433.
Synthesis of compound 34b: Brown solid; yield = 88% (135 mg, starting from 100 mg of
3
3b); reaction time = 4 h; mp 166-168 °C; R = 0.69 (silica gel, 10% EtOAc-petroleum ether);
f
1
H NMR (500 MHz, CDCl ): δ 7.59 (d, J = 8.2 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.36 (d, J =
3
8
.1 Hz, 1H), 7.13-7.21 (m, 3H), 6.89 (dd, J = 2.4 Hz, J = 8.3 Hz, 1H), 4.02 (s, 3H), 3.88 (s,
1
2
1
3
3
1
2
2
H), 3.69 (s, 2H); C NMR (125 MHz, CDCl ):
δ
157.9, 150.6, 144.9, 141.7, 128.9, 124.5,
3
20.7, 119.7, 118.7, 118.6, 118.0, 112.8, 111.7, 109.8, 55.8, 31.2, 30.5; IR (neat): υmax 3032,
-1
+
974, 1603, 1519, 1463 cm ; HRMS (Q-Tof) calcd. for C H NO [M+H] 250.1226, found:
1
7
16
50.1229.
1
7

ACCEPTED MANUSCRIPT
Synthesis of compound 35b: Brown solid; yield = 60% (79 mg, starting from 100 mg of
3
4b); reaction time = 20 h; mp 115-116 °C; R = 0.72 (silica gel, 10% EtOAc-petroleum
f
1
ether); H NMR (400 MHz, CDCl ): δ 7.60 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.3 Hz, 1H), 7.33
3
(
d, J = 8.1 Hz, 1H), 7.10-7.19 (m, 2H), 7.00 (d, J = 2.4 Hz, 1H), 6.82 (dd, J = 2.4 Hz, J =
1 2
8
.3 Hz, 1H), 5.43-5.51 (m, 2H), 4.88 (dd, J = 1.2 Hz, J = 7.9 Hz, 2H), 4.80 (dd, J = 1.1 Hz,
1 2 1
J = 8.1 Hz, 2H), 4.01 (s, 3H), 3.87 (s, 3H), 2.83 (dd, J = 6.2 Hz, J = 13.7 Hz, 2H), 2.64 (dd,
2
1
2
13
J = 6.9 Hz, J = 13.7 Hz, 2H); C NMR (100 MHz, CDCl ):
δ
158.0, 157.6, 143.2, 141.7,
1
2
3
1
4
34.9, 128.1, 124.6, 124.3, 120.5, 119.6, 119.1, 118.2, 117.4, 111.4, 111.2, 109.8, 55.7, 51.2,
-1
2.8, 31.2; IR (neat): υmax 3043, 2923, 2840, 1599, 1451 cm ; HRMS (Q-Tof) calcd. for
+
C H NO [M+H] 330.1852, found: 330.1859.
23
24
Synthesis of compound 36b: Brown solid; yield = 94% (43 mg, starting from 50 mg of
3
5b); reaction time = 8 h; mp 147-150 °C; R = 0.68 (silica gel, 10% EtOAc-petroleum ether);
f
1
H NMR (500 MHz, CDCl ): δ 7.54 (d, J = 7.7 Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.37 (d, J =
3
8
.2 Hz, 1H), 7.12-7.22 (m, 3H), 6.83-6.86 (m, 1H), 6.14 (s, 2H), 4.01 (s, 3H), 3.88 (s, 3H),
1
3
2
1
3
.91 (s, 4H); C NMR (125 MHz, CDCl ):
δ
161.6, 158.6, 142.1, 141.8, 130.8, 128.7, 127.3,
3
22.9, 120.6, 119.5, 118.9, 118.1, 111.2, 110.3, 109.9, 55.7, 51.6, 43.9, 31.1; IR (neat): υmax
-1
049, 3010, 2929, 2840, 1596, 1525, 1495, 1432 cm ; HRMS (Q-Tof) calcd. for C H NO
21
20
+
[
M+H] 302.1539, found: 302.1539.
Synthesis of compound 34c: Brown solid; yield = 96% (270 mg, starting from 200 mg of
3
3c); reaction time = 2 h; mp 147-148 °C; R = 0.75 (silica gel, 10% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl ): δ 7.57 (d, J = 8.1 Hz, 2H), 7.39-7.43 (m, 2H), 7.32 (d, J = 8.3
3
1
3
Hz, 1H), 7.20-7.23 (m, 1H), 7.14 (t, J = 7.1 Hz, 1H), 3.92 (s, 3H), 3.58 (s, 2H); C NMR
100 MHz, CDCl3): 150.3, 143.8, 142.1, 134.5, 129.6, 128.9, 123.9, 121.8, 120.6, 119.9,
19.3, 118.6, 118.4, 109.9, 31.2, 30.2; IR (neat): υmax 3051, 2922, 1596, 1522, 1492, 1462
(
δ
1
-1
79
+
cm ; HRMS (Q-Tof) calcd. for C H BrNK [M+K] 335.9785, found: 335.9786.
1
6
12
Synthesis of compound 35c: Brown solid; yield = 75% (142 mg, starting from 150 mg of
3
4c); reaction time = 12 h; mp 142-143 °C; R = 0.76 (silica gel, 10% EtOAc-petroleum
f
1
ether); H NMR (500 MHz, CDCl ): δ 7.62 (d, J = 7.9 Hz, 1H), 7.53 (t, J = 1.0 Hz, 1H), 7.41
3
(d, J = 0.9 Hz, 2H), 7.34 (d, J = 8.3 Hz, 1H), 7.20-7.24 (m, 1H), 7.13 (t, J = 7.1 Hz, 1H),
5
2
1
.38-5.46 (m, 2H), 4.79-4.92 (m, 4H), 3.99 (s, 3H), 2.85 (dd, J = 7.5 Hz, J = 13.7 Hz, 2H),
1
2
13
.65 (dd, J = 7.0 Hz, J = 13.6 Hz, 2H); C NMR (125 MHz, CDCl ):
δ
157.4, 142.3, 142.1,
1
2
3
34.3, 133.9, 129.9, 127.3, 126.5, 123.9, 121.7, 119.9, 119.7, 118.9, 117.9, 110.1, 51.5, 42.4,
1
8

ACCEPTED MANUSCRIPT
-1
3
1.3; IR (neat): υmax 3071, 3005, 2920, 2857, 1597, 1496, 1434 cm ; HRMS (Q-Tof)
79
+
calculated for C H BrN [M+H] 378.0852, found: 378.0832.
2
2
21
Synthesis of compound 36c: Brown solid; yield = 86% (79 mg, starting from 100 mg of
3
5c); reaction time = 6 h; mp 170-172 °C; R = 0.73 (silica gel, 10% EtOAc-petroleum ether);
f
1
H NMR (400 MHz, CDCl ): δ 7.65 (dd, J = 0.8 Hz, J = 1.4 Hz, 1H), 7.52 (d, J = 7.8 Hz,
3
1
2
1
1
1
1
1
H), 7.40 (d, J = 1.6 Hz, 2H), 7.35 (d, J = 8.3 Hz, 1H), 7.20-7.25 (m, 1H), 7.12 (t, J = 7.0 Hz,
1
3
H), 6.09 (s, 2H), 4.00 (s, 3H), 2.86 (t, J = 1.9 Hz, 4H); C NMR (100 MHz, CDCl ):
δ
3
61.5, 142.4, 141.1, 133.1, 130.9, 130.3, 129.8, 126.4, 122.5, 121.7, 119.8, 119.5, 119.3,
18.7, 110.1, 51.7, 43.3, 31.2; IR (neat): υmax 3054, 2928, 2839, 1610, 1596, 1528, 1495,
-1
79
+
432 cm ; HRMS (Q-Tof) calcd. for C H BrN [M+H] 350.0539, found: 350.0532.
2
0
17
Synthesis of compound 37a: Brown solid; yield = 97% (29 mg, starting from 30 mg of 36c);
1
reaction time = 8 h; mp 165-167 °C; R = 0.66 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.77 (s, 1H), 7.61-7.65 (m, 3H), 7.54 (t, J = 6.6 Hz, 2H), 7.45 (t,
3
J = 7.8 Hz, 2H), 7.24-7.38 (m, 2H), 7.22 (t, J = 7.1 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 6.13 (s,
1
3
2
1
1
1
H), 4.05 (s, 3H), 2.90, 2.97 (ABq, J = 15.7 Hz, 4H); C NMR (125 MHz, CDCl ): δ 160.1,
3
42.4, 141.8, 141.6, 138.7, 133.4, 130.9, 128.9, 127.2, 125.9, 122.7, 121.9, 121.4, 119.6,
19.5, 117.9, 110.0, 51.7, 43.7, 31.3; IR (neat): υmax 3053, 2929, 2840, 1598, 1525, 1492,
-1
+
444 cm ; HRMS (Q-Tof) calcd. for C H N [M+H] 348.1747, found: 348.1744.
2
6
22
Synthesis of compound 37b: Brown solid; yield = 84% (27 mg, starting from 30 mg of 36c);
1
reaction time = 8 h; mp 188-189 °C; R = 0.65 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.72 (d, J = 1.4 Hz, 1H), 7.53-7.60 (m, 4H), 7.47 (dd, J = 1.6
3
1
Hz, J = 7.8 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.20 (t, J = 7.2 Hz, 1H), 7.11 (t, J = 7.6 Hz,
2
1
1
1
1
H), 6.99 (d, J = 8.7 Hz, 2H), 6.12 (s, 2H), 4.04 (s, 3H), 3.85 (s, 3H), 2.89, 2.96 (ABq, J =
1
3
5.1 Hz, 4H); C NMR (125 MHz, CDCl ):
δ
160.1, 159.2, 142.3, 141.9, 138.4, 134.2,
3
32.8, 130.9, 130.7, 128.3, 128.2, 125.4, 122.8, 121.5, 121.3, 119.6, 119.4, 117.9, 114.4,
-1
09.9, 55.6, 51.7, 43.8, 31.3; IR (neat): υmax 3057, 2928, 2835, 1610, 1528, 1497, 1432 cm ;
+
HRMS (Q-Tof) calcd. for C H NO [M+H] 378.1852, found: 378.1853.
2
7
24
Synthesis of compound 37c: Brown solid; yield = 85% (44 mg, starting from 50 mg of 36c);
1
reaction time = 10 h; mp 180-183 °C; R = 0.66 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.75 (s, 1H), 7.49-7.58 (m, 3H), 7.42 (d, J = 7.2 Hz, 2H), 7.33 (t,
3
J = 7.6 Hz, 2H), 7.08-7.21 (m, 3H), 6.12 (s, 2H), 4.00 (s, 3H), 2.87, 2.96 (ABq, J = 15.3 Hz,
1
3
4
H), 2.42 (s, 3H); C NMR (125 MHz, CDCl ):
δ
159.9, 142.4, 141.8, 141.6, 138.9, 138.5,
3
1
33.3, 130.9, 128.9, 127.9, 125.9, 124.4, 122.8, 121.9, 121.3, 119.6, 119.4, 117.8, 109.9,
1
9

ACCEPTED MANUSCRIPT
-1
5
1.8, 43.7, 31.2, 21.8; IR (neat): υmax 3049, 3016, 2923, 2840, 1606, 1525, 1499, 1448 cm ;
+
HRMS (Q-Tof) calcd. for C H N [M+H] 362.1903, found: 362.1903.
2
7
24
Synthesis of compound 37d: Brown solid; yield = 92% (35 mg, starting from 50 mg of 36c);
1
reaction time = 16 h; mp 193-194 °C; R = 0.60 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 10.02 (s, 1H), 7.92 (d, J = 8.3 Hz, 2H), 7.78 (t, J = 8.2 Hz, 3H),
3
7
.55, 7.57 (ABq, J = 15.2 Hz, 3H), 7.36 (d, J = 8.3 Hz, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.13 (t,
1
3
J = 7.2 Hz, 1H), 6.14 (s, 2H), 4.02 (s, 3H), 2.90, 2.97 (ABq, J = 15.3 Hz, 4H); C NMR (125
MHz, CDCl3): 192.1, 160.3, 147.5, 142.5, 141.4, 136.9, 135.0, 134.6, 131.6, 130.9, 130.5,
27.6, 126.4, 122.6, 121.8, 119.8, 119.6, 118.0, 110.1, 51.7, 43.6, 31.3; IR (neat): υmax 3019,
δ
1
2
3
-1
+
923, 2846, 1695, 1600, 1216 cm ; HRMS (Q-Tof) calcd. for C H NONa [M+Na]
2
7
21
98.1515, found: 398.1514.
Synthesis of compound 37e: Brown solid; yield = 89% (60 mg, starting from 60 mg of 36c);
1
reaction time = 20 h; mp 155-158 °C; R = 0.63 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 8.02 (d, J = 8.3 Hz, 2H), 7.79 (s, 1H), 7.70 (d, J = 8.3 Hz, 2H),
3
7
.55, 7.60 (ABq, J = 15.8 Hz, 3H), 7.36 (d, J = 8.2 Hz, 1H), 7.22 (t, J = 8.1 Hz, 1H), 7.12 (t,
J = 7.6 Hz, 1H), 6.14 (s, 2H), 4.02 (s, 3H), 2.88, 2.97 (ABq, J = 15.6 Hz, 4H), 2.62 (s, 3H);
1
3
C NMR (125 MHz, CDCl3):
δ 197.9, 160.2, 146.1, 142.5, 141.5, 137.1, 135.7, 134.3, 131.4,
1
3
30.9, 129.1, 127.1, 126.2, 122.7, 121.73, 121.71, 119.8, 119.6, 117.9, 110.1, 51.8, 43.6,
-1
1.3, 26.8; IR (neat): υmax 3019, 2928, 1676, 1599, 1216 cm ; HRMS (Q-Tof) calcd. for
+
C H NO [M+H] 390.1852, found: 390.1854.
28
24
Synthesis of compound 37f: Brown solid; yield = 93% (39 mg, starting from 40 mg of 36c);
1
reaction time = 12 h; mp 184-185 °C; R = 0.65 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.70 (d, J = 1.5 Hz, 1H), 7.53-7.59 (m, 4H), 7.46 (dd, J = 1.7
3
1
Hz, J = 7.8 Hz, 1H), 7.36 (d, J = 8.3 Hz, 1H), 7.19-7.23 (m, 1H), 7.10-7.14 (m, 3H), 6.12 (s,
2
1
3
2
H), 4.03 (s, 3H), 2.89, 2.92 (ABq, J = 15.1 Hz, 4H); C NMR (125 MHz, CDCl ):
δ
163.49
and 161.53 (J = 245.0, C- F coupling), 160.2, 142.4, 141.7, 137.7, 133.4, 130.9, 128.8,
28.7, 125.8, 122.7, 121.7, 121.5, 119.7, 119.5, 117.9, 115.9, 115.7, 110.0, 51.7, 43.7, 31.3;
3
1
3
19
1
-1
IR (neat): υmax 3019, 2928, 2851, 1590, 1215 cm ; HRMS (Q-Tof) calcd. for C H NF
26
21
+
[
M+H] 366.1653, found: 366.1653.
Synthesis of compound 37g: Brown solid; yield = 81% (43 mg, starting from 50 mg of 36c);
1
reaction time = 8 h; mp 243-244 °C; R = 0.65 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.75 (s, 1H), 7.71 (d, J = 1.3 Hz, 4H), 7.62 (d, J = 7.9 Hz, 1H),
3
7
.51-7.56 (m, 2H), 7.37 (d, J = 8.3 Hz, 1H), 7.22 (t, J = 6.9 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H),
2
0

ACCEPTED MANUSCRIPT
1
3
6
1
1
1
.13 (s, 2H), 4.04 (s, 3H), 2.89-2.97 (m, 4H); C NMR (125 MHz, CDCl ): δ 160.4, 145.9,
3
42.6, 141.3, 136.3, 134.74, 132.72, 131.6, 130.9, 127.6, 126.2, 122.6, 121.9, 121.6, 119.8,
19.6, 119.3, 118.0, 110.1, 51.7, 43.6, 31.3; IR (neat): υmax 3049, 2927, 2840, 2223, 1598,
-1
+
495, 1444 cm ; HRMS (Q-Tof) calcd. for C H N [M+H] 373.1699, found: 373.1703.
2
7
21
2
Synthesis of compound 37h: Brown solid; yield = 90% (46 mg, starting from 50 mg of 36c);
1
reaction time = 15 h; mp 180-181 °C; R = 0.53 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.76 (d, J = 1.1 Hz, 1H), 7.52-7.58 (m, 3H), 7.36-7.47 (m, 4H),
3
7
.21 (t, J = 7.1 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 6.13 (s, 2H), 4.04 (s, 3H), 2.88, 2.96 (ABq,
13
J = 15.2 Hz, 4H); C NMR (125 MHz, CDCl ):
δ
160.1, 142.8, 142.3, 141.8, 133.4, 133.2,
3
1
5
30.9, 130.8, 126.6, 126.4, 125.2, 122.7, 121.4, 121.2, 119.9, 119.6, 119.4, 117.9, 110.0,
-1
1.7, 43.7, 31.3; IR (neat): υmax 3098, 3038, 2928, 2840, 1607, 1519, 1489 cm ; HRMS (Q-
+
Tof) calcd. for C H NS [M+H] 354.1311, found: 354.1314.
2
4
20
Synthesis of compound 37i: Brown solid; yield = 86% (25 mg, starting from 25 mg of 36c);
1
reaction time = 10 h; mp 178-199 °C; R = 0.55 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.87 (s, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H),
3
7
.63 (dd, J = 1.6 Hz, J = 7.9 Hz, 1H), 7.55 (t, J = 5.3 Hz, 3H), 7.29-7.49 (m, 3H), 7.22 (t, J
1 2
=
6.9 Hz, 1H), 7.15 (t, J = 7.9 Hz, 1H), 6.15 (s, 2H), 4.01 (s, 3H), 2.89, 2.98 (ABq, J = 15.2
1
3
Hz, 4H); C NMR (125 MHz, CDCl ):
δ
160.1, 144.9, 142.5, 141.6, 141.0, 139.5, 134.3,
31.6, 131.4, 130.9, 125.5, 124.9, 124.7, 124.3, 123.6, 122.7, 122.4, 121.7, 120.9, 119.7,
19.6, 119.0, 117.9, 110.1, 51.7, 43.6, 31.3; IR (neat): υmax 3021, 2928, 2851, 1618, 1563,
3
1
1
1
-
1
+
472 cm ; HRMS (Q-Tof) calcd. for C H NS [M+H] 404.1467, found: 404.1468.
2
8
22
Synthesis of compound 37j: Brown solid; yield = 73% (24 mg, starting from 30 mg of 36c);
1
reaction time = 12 h; mp 188-190 °C; R = 0.36 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 8.17 (brs, 1H), 7.90 (s, 1H), 7.82 (s, 1H), 7.45-7.63 (m, 4H), 7.37
3
(d, J = 7.9 Hz, 1H), 7.19-7.24 (m, 3H), 7.10 (t, J = 7.3 Hz, 1H), 6.62 (s, 1H), 6.14 (s, 2H),
1
3
4
1
1
3
3
.06 (s, 3H), 2.90, 3.01 (ABq, J = 15.8 Hz, 4H); C NMR (125 MHz, CDCl ): δ 159.9,
3
42.3, 142.1, 140.2, 135.4, 133.8, 132.5, 130.9, 130.6, 128.6, 126.0, 125.0, 122.8, 122.2,
22.1, 121.1, 119.6, 119.4, 119.3, 117.8, 111.4, 109.9, 103.2, 51.8, 43.8, 31.3; IR (neat): υmax
-1
+
412, 3049, 2923, 2840, 1607, 1443 cm ; HRMS (Q-Tof) calcd. for C H N [M+H]
28
23
2
87.1856, found: 387.1851.
Synthesis of compound 37k: Brown solid; yield = 96% (46 mg, starting from 40 mg of 36c);
1
reaction time = 16 h; mp 205-206 °C; R = 0.68 (silica gel, 10% EtOAc-petroleum ether); H
f
NMR (500 MHz, CDCl ): δ 7.81 (d, J = 1.5 Hz, 1H), 7.64-7.73 (m, 7H), 7.59 (dd, J = 1.6
3
1
2
1

ACCEPTED MANUSCRIPT
Hz, J = 7.8 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.44-7.48 (m, 2H), 7.24-7.39 (m, 2H), 7.21 (t,
2
J = 7.2 Hz, 1H), 7.11 (t, J = 7.2 Hz, 1H), 6.14 (s, 2H), 4.07 (s, 3H), 2.91, 2.99 (ABq, J = 15.1
1
3
Hz, 4H); C NMR (125 MHz, CDCl ):
δ
160.1, 142.4, 140.9, 140.5, 140.1, 138.2, 133.5,
3
1
1
31.0, 130.9, 129.0, 127.7, 127.6, 127.5, 127.2, 125.8, 122.8, 121.7, 121.4, 119.7, 119.5,
-1
17.9, 110.0, 51.8, 43.7, 31.3; IR (neat): υmax 3016, 2934, 1643, 1481 cm ; HRMS (Q-Tof)
+
calcd. for C H NK [M+K] 462.1619, found: 462.1622.
3
2
25
Acknowledgements
We thank Department of Science and Technology (DST), New Delhi, for the financial
support. We also thank Sophisticated Analytical Instrument Facility (SAIF), IIT-Bombay for
recording spectral data. S. K. thanks Department of Science and Technology for the award of
a J. C. Bose fellowship. R. A. thanks University Grants Commission; New Delhi for the
award of a research fellowship and N. G. K thanks Department of Chemistry, IIT-Bombay
for awarding the research fellowship.
References and Notes
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24, 843.
2
2

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4
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7
8
. (a) Kita, Y.; Higuchi, K.; Yoshida, Y.; Lio, K.; Kitagaki, S.; Shuji, A.; Fujioka, H.
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C. N.; Kleiner, G. J. Am. Chem. Soc. 1994, 116, 11275.
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3
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3
2
3

ACCEPTED MANUSCRIPT
Chem. 2007, 5909; (p) Kotha, S.; Shah, V. R.; Mandal, M. Adv. Synth. Catal. 2007,
349, 1159; (q) Kotha, S.; Dipak, M. K. Chem. Eur. J. 2006, 12, 4446; (r) Kotha, S.;
Mandal, K. Eur. J. Org. Chem. 2006, 5387.
9
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Org. Chem. 2008, 6, 1054; (b) Kotha, S.; Bansal, D.; Vinod Kumar, R. Indian J.
Chem. 2009, 225; (c) Kotha, S.; Meshram, M.; Tiwari, A. Chem. Soc. Rev. 2009,
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Singh, K.; Banerjee, S. J. Organomet. Chem. 2011, 696, 1856; (f) Kotha, S.;
Chavan, A. S.; Dipak, M. K. Tetrahedron 2011, 67, 501; (g) Kotha, S.; Goyal, D.;
Thota, N.; Srinivas, V. Eur. J. Org. Chem. 2012, 1843; (h) Kotha, S.; Chavan, A.
S.; Mobin, S. J. Org. Chem. 2012, 77, 482; (i) Kotha, S.; Waghule G. T. J. Org.
Chem. 2012, 77, 6314. (j) Kotha, S.; Ali R.; Tiwari, A. Synlett 2013, 1921; (k)
Kotha, S.; Ali R.; Tiwari, A. Synhesis 2014, 2471.
1
0. Cacatian, S.; Claremon, D. A.; Dillard, L. W.; Fuchs, K.; Heine, N.; Jia, L.; Leftheris,
K.; McKeever, B.; Morales-Ramos, A.; Singh, S.; Venkatraman, S.; Wu, G.; Wu, Z.;
Xu, Z.; Yuan, J.; Zheng, Y. WO 105179, 2010 (Chem. Abstr. 2010, 153, 431370).
1. Selected papers on Suzuki–Miyaura coupling reactions: (a) Kotha, S.; Lahiri, K.;
Kashinath, D. Tetrahedron 2002, 58, 9633; (b) Suzuki, A. J. Organomet. Chem.
1
1997, 36, 2163; (c) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
4020; (d) Kotha, S.; Lahiri, K. Eur. J. Org. Chem. 2007, 1221. (e) Kasai, Y.; Ito, T.;
Sasaki, M.; Org. Lett. 2012, 14, 3186; (f) Kerins, F.; O’Shea, D. F. J. Org. Chem.
002, 67, 4968; (g) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651; (h) Liu,
L.; Zhang, Y.; Xin, B. J. Org. Chem. 2006, 71, 3994; (i) Felpin, F.-X. J. Org. Chem.
005, 70, 8575; (j) Sinclair, D. J.; Sherburn, M. S. J. Org. Chem. 2005, 70, 3730.
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2. (a) Kotha, S.; Mandal, K. Tetrahedron Lett. 2004, 45, 1391; (b) Kotha, S.; Mandal,
K.; Tiwari, A.; Mobin, S. M. Chem. Eur. J. 2006, 12, 8024.
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1
3. (a) Trost, B. M.; Brennan, M. K. Synthesis 2009, 18, 3003; (b) Galliford, C. V.;
Scheidt, K. A. Angew. Chem. Int. Ed. 2007, 46, 8748; (c) Raj, A. A.; Raghunathan,
R.; Sridevikumari, M. R.; Raman, N. Bioorg. Med. Chem. 2003, 11, 407.
4. (a) Sengoku, T.; Xu, S.; Ogura, K.; Emori, Y.; Kitada, K.; Uemura, D. Arimoto, H.
Angew. Chem. Int. Ed. 2014, 53, 4213; (b) Blair, L. M.; Sperry, J. J. Nat. Prod.
2013, 76, 794.
5. Kotha, S.; Hollinshead, S.; Grubisha, D.; Laib, F.; Bennett, D.; Cook, J. M. J. Org.
Chem. 1990, 55, 3858.
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6. (a) Kotha, S.; Waghule, G. T. Tetrahedron Lett. 2014, 55, 4264; (b) Kotha, S.;
Khedkar, P. Eur. J. Org. Chem. 2009, 730; (c)) Zhou, A.; Rayabarapu, D.; Hanson,
P. R. Org. Lett. 2009, 11, 531; (d) Kotha, S.; Goyal, D.; Chavan, A. S. J. Org.
Chem. 2013, 78, 12288; (e) Schreiber. S. L. Science 2000, 287, 1964; (f) Burke, M.
D.; Schreiber, S. L. Angew Chem. Int. Ed. 2004, 43, 46: (g) Taylor, S. J.; Taylor, A.
M.; Schreiber, S. L. Angew. Chem. Int. Ed. 2004, 43, 1681; (h) Kotha, S.; Ali, R.;
Chinnam, A. K. Tetrahedron Lett. 2014, 55, 4492; (i) Kumar, A.; Sharma, S.;
Maurya, R. A.; Sarkar, J. J. Comb. Chem. 2010, 12, 20; (j) Hammill, J. T.;
Contreras-García, J.; Virshup, A. M.; Beratan, D. N.; Yang, W.; Wipf, P.
Tetrahedron, 2010, 66, 5852; (k) Dhara, K.; Midya, G. C.; Dash, J. J. Org. Chem.
2012, 77, 8071.
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7. Kotha, S.; Manivannan, E. Arkivoc 2003, (iii), 67.
8. Deb, A. C, Ph. D Thesis, 2004, IIT Bombay, India.
9. Soni, R.; Collinson, J.-M.; Clarkson, G. C.; Wills, M. Org. Lett. 2011, 13, 4304.
0. Nifantev, I. E.; Kashulin, I. A.; Bagrov, V. V.; Abilev, S. K.; Lyubimova, I. K. Russ.
Chem. Bull. Int. Ed. 2001, 50, 1439.
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1. Gore, S.; Baskaran, S.; König, B. Org. Lett. 2012, 14, 4568.
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Supporting Information
Diversity-oriented approach to spirocycles with indole moiety via Fischer indole
cyclization, olefin metathesis and Suzuki–Miyaura cross-coupling reactions
Sambasivarao Kotha,* Rashid Ali, Venu Srinivas and Nimita G. Krishna
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai-400076
India, Phone: +91-22-2576 7160, Fax: +91(22)-2572 7152; E-mail: srk@chem.iitb.ac.in
Table of components
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1
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H and C NMR spectrum of compound 10a
S3
S4
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H and C NMR spectrum of compound 10b
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H and C NMR spectrum of compound 10c
S5
1
1
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H and C NMR spectrum of compound 10d
S6
13
H and C NMR spectrum of compound 10e
S7
1
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H and C NMR spectrum of compound 10f
S8
1
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H and C NMR spectrum of compound 14a
S9
1
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H and C NMR spectrum of compound 14b
S10
S11
S12
S13
S14
S15
S16
S17
S18
S19
S20
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H and C NMR spectrum of compound 14c
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H and C NMR spectrum of compound 14d
1
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H and C NMR spectrum of compound 18
1
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H and C NMR spectrum of compound 19
1
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H and C NMR spectrum of compound 20a
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H and C NMR spectrum of compound 20b
1
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H and C NMR spectrum of compound 20c
1
13
H and C NMR spectrum of compound 21
1
13
H and C NMR spectrum of compound 25
1
13
H and C NMR spectrum of compound 26
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1
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H and C NMR spectrum of compound 28
S21
S22
S23
S24
S25
S26
S27
S28
S29
S30
S31
S32
S33
S34
S35
S36
S37
S38
S39
S40
S41
S42
S43
S44
13
H and C NMR spectrum of compound 30
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H and C NMR spectrum of compound 31
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H and C NMR spectrum of compound 32
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1
1
1
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H and C NMR spectrum of compound 34a
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H and C NMR spectrum of compound 35a
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H and C NMR spectrum of compound 36a
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H and C NMR spectrum of compound 34b
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1
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H and C NMR spectrum of compound 35b
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H and C NMR spectrum of compound 36b
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H and C NMR spectrum of compound 34c
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1
1
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H and C NMR spectrum of compound 35c
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H and C NMR spectrum of compound 36c
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H and C NMR spectrum of compound 37a
1
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H and C NMR spectrum of compound 37b
1
1
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H and C NMR spectrum of compound 37c
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H and C NMR spectrum of compound 37d
1
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H and C NMR spectrum of compound 37e
1
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H and C NMR spectrum of compound 37f
1
1
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H and C NMR spectrum of compound 37g
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H and C NMR spectrum of compound 37h
1
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H and C NMR spectrum of compound 37i
1
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H and C NMR spectrum of compound 37j
1
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H and C NMR spectrum of compound 37k
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