One-pot synthesis of carbazoles via tandem C-C cross-coupling and reductive amination

Article abstract of DOI:10.1039/c5ob01952d

We have developed a highly efficient synthetic route to carbazoles that employs sequential C-C/C-N bond formation via Suzuki cross-coupling and Cadogan cyclization using commercially available or easily preparable starting materials. The developed method is compatible with electron neutral, rich or deficient substrates. The synthetic utility of this method was demonstrated by the concise syntheses of four natural products (glycozoline, glycozolicine, glycozolidine and clausenalene).

Full text of DOI:10.1039/c5ob01952d

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DOI: 10.1039/C5OB01952D
Organic & Biomolecular Chemistry
ARTICLE
One‐Pot Synthesis of Carbazoles via Tandem C‐C Cross‐Coupling
and Reductive Amination
Received 00th January 20xx,
Accepted 00th January 20xx
Deuk‐young Goo and Sang Kook Woo*
DOI: 10.1039/x0xx00000x
We have developed a highly efficient synthetic route to carbazoles that employs sequential C‐C/C‐N bond formation via
Suzuki cross‐coupling and Cadogan cyclization using commercially available or easily preparable starting materials. The
developed method is compatible with electron neutral, rich or deficient substrates. The synthetic utility of this method
was demonstrated by the concise syntheses of four natural products (glycozoline, glycozolicine, glycozolidine and
clausenalene).
www.rsc.org/
easily preparable starting materials.
Introduction
The Carbazole is an ubiquitous structural motif in a large
number of biologically active natural products and
1
pharmaceuticals. In addition, carbazole derivatives have been
2
widely used as functional organic materials. Thus,
development of efficient synthetic routes to structurally
diverse carbazoles represents an important objective in
organic synthesis. Many methods have been developed for the
3
preparation of carbazole. The most widely used approaches
for synthesis of the carbazole framework are C‐N or C‐C bond
forming cyclizations from substituted biaryls or N,N‐biaryl
amines. Representative C‐N bond forming reactions for
synthesis of carbazoles are summarized in Scheme 1 (a): (A)
4
transition metal free or palladium catalyzed Buchwald‐
5
Hartwig amination from 2‐amino‐2’‐halo‐biphenyls; (B)
6
dehydrogenative C‐H/N‐H coupling of 2‐amino‐biphenyls ; (C)
7
iron‐mediated oxidative amination of iron complex ; (D)
transition metal mediated double amination of 2,2’‐
8
dihalobiphenyls or cyclic diphenyleneiodoniums ; (E) transition
9
10
metal free or rhodium catalyzed nitrene insertion of 2‐azido‐
11
biphenyls; (F) reductive amination of 2‐nitro‐biphenyls .
Similarly, dehydrogenative C‐C bond formation of N,N‐biaryl
1
2
amines leads to carbazoles (Scheme (b)). Although these
methods proceed in good yields and are tolerant of most
organic functional groups. They require the preparation of
complex starting materials, such as substituted biaryls or N,N‐
biaryl amines for the synthesis of diverse carbazoles. Therefore,
we investigated the development of a one‐pot C‐C and C‐N
bond coupling reaction that utilizes commercially available or
Department of Chemistry, University of Ulsan, 93 Daehak‐Ro, Nam‐Gu, Ulsan
4
2
†
4610, Korea. E‐mail: woosk@ulsan.ac.kr; Fax: +82‐52‐259‐2348; Tel: +82‐52‐259‐
338
Electronic Supplementary Information (ESI) available: Details of experimental
1
13
procedures and spectroscopic data for all new com‐pounds ( H NMR, C NMR, IR,
MS), including images of NMR spectra. See DOI: 10.1039/x0xx00000x
Scheme 1. Various synthetic approaches to carbazoles.
This journal is © The Royal Society of Chemistry 2015
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Org aP nl ei ca s &e dB oi on mo to al ed cj uu sl at rm Ca hr ge imn si stry
Page 2 of 9
ARTICLE
Organic & Biomolecular Chemistry
a
a
Table 1. Optimization of the reaction conditions
Table 2. Substrate scope of various aryl boronic acids
View Article Online
DOI: 10.1039/C5OB01952D
B(OH)2
H
N
X
Pd(OAc)2, PPh3
+
K2CO3, o-DCB
NO2
1
2a
3a
(100 mol%)
(120 mol%)
o
time (h) Y (%)b
Entry 1, X
Catalyst (mol%)
Reductant
T ( C)
1
2
3
4
5
6
7
8
9
1a, I
Pd(OAc) (2)
Pd(OAc) (2)
Pd(OAc) (2)
Pd(OAc) (2)
Pd(OAc) (2)
Pd2(dba)3 (2)
Pd(PPh3)4 (2)
Pd(OAc) (1)
Pd(OAc) (4)
Pd(OAc) (2)
Pd(OAc) (2)
Pd(OAc) (2)
Pd(OAc) (2)
PPh3
PPh3
PPh3
PEt3
150
150
150
150
150
150
150
150
150
180
180
Reflux
180
16
16
16
16
16
16
16
16
16
16
24
24
24
24
56
31
12
21
41
29
17
13
72
78
66
86
1b, Br
1c, Cl
1b, Br
1b, Br
1b, Br
1b, Br
1b, Br
1b, Br
1b, Br
1b, Br
P(OEt)3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
10
11
1
2c 1b, Br
3d 1b, Br
1
a
Reaction conditions:
1
(0.5 mmol), 2a (0.6 mmol), catalyst (quantity
CO (200 mol%), o‐DCB (1.0 mL)
under air in pressure tubes. Isolated yield by flash column
noted), reductant (250 mol%), K
2
b
3
c
d
chromatography. Using reflux condenser. 2a (130 mol%).
More recently, one‐pot syntheses of carbazoles have been
1
3
13a
13b, 13d
developed (Scheme 1 (c)). Bedford and Ackermann
reported a palladium catalyzed domino Buchwald‐Hartwig
amination and C‐H activation of 2‐chloroanilines with aryl
13c
bromides or anilines with dichloroarenes. Jean, Jr reported
the Pd‐catalyzed tandem Suzuki cross‐coupling and S Ar
N
reaction of aniline‐derived boronic esters with 2‐fluoro‐3‐
1
3f
halobenzenes. Studer
reported a transition metal‐free
cascade reaction of nitrosoarenes with in situ generated
arynes.
We envision a one‐pot reaction sequence of C‐C cross‐
a
b
c
As given in Table 1, entry 13. 48h. Pd(OAc) (5 mol%), 48h.; yields of
†
coupling and C‐N bond forming cyclization to develop a step‐ isolated material. See ESI for details.
economic method to prepare carbazoles. We considered the
1
4
15
Suzuki reaction and Cadogan cyclization for the one‐pot
Thus chosen for further studies. When other reductants such
1
5e
reaction. Both reactions are widely used methods for C‐C as PEt and P(OEt)
were used, the yield of the reaction did
3
3
cross‐coupling or reductive amination and use similar not improve (Table 1, entries 4 and 5). Moreover, other
1
5d
phosphine reagents for ligand or reductant . Herein, we catalysts such as Pd (dba) and Pd(PPh ) were not effective in
2
3
3 4
present a highly efficient synthetic method to carbazoles that this transformation (Table 1, entries 6 and 7). Reductant and
consists of palladium‐catalyzed tandem C‐C/C‐N bond catalyst screening indicated that Pd(OAc) and PPh were the
2
3
formation via Suzuki reaction and reductive Cadogan best choices. To improve the yield, the catalyst loading, as well
cyclization (Scheme 1).
as reaction temperature and time were surveyed. Increasing
and decreasing the catalyst loading were not efficient (Table 1,
entries 8 and 9). However, the yield did increase with a higher
temperature and longer reaction time (Table 1, entries 10 and
Results and discussion
1
1). Coupling reaction was not efficient in atmospheric
Initially, we explored the domino reaction of 2‐
iodonitrobenzene 1a with phenylboronic acid 2a in the
pressure (Table 1, entry 12). Using 130 mol% phenylboronic
acid 2a, gave the best result (Table 1, entry 13).
We next examined the substrate scope with respect to the
substituted arylboronic acid (Table 2). Under the optimized
conditions, o‐bromonitrobenzene 1b was coupled to a diverse
presence of Pd(OAc) and triphenylphosphine in o‐DCB at 150
2
o
C, which delivered the carbazole 3a and 2‐nitrobiphenyl in 24%
and 20% yield (Table 1, entry 1). Based on this result, other 2‐
halonitrobenzenes were assayed, and it was found that 2‐
bromonitrobenzene 1b was the most efficient (Table 1, entry
range of arylboronic acids
moderate to excellent yields.
2 to form carbazoles 3a‐3o in
2
).
2
| Org. Biomol. Chem., 2015, 00, 1‐9
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Organic & Biomolecular Chemistry
ARTICLE
In particular, 4‐fluoro and 4‐chloroboronic acids were
View Article Online
DOI: 10.1039/C5OB01952D
tolerated under these coupling conditions. Halogen containing
carbazoles are useful for the introduction of additional
functionalization. Thus, we examined the further
functionalization of 3‐chlorocarbazole 3i (Scheme 2). Under
18
modified Suzuki cross‐coupling conditions for unprotected N‐
heterocycles, 3‐chlorocarbazole 3i was coupled to a diverse
range of arylboronic acids to form functionalized carbazoles
(
3e, 3ia‐3id) in good to excellent yields.
To demonstrate the efficiency of this method, we conducted
the gram scale synthesis of carbazole 3a. Coupling reaction of
Scheme 2. Further functionalization of 3‐chlorocarbazole (3i). 2‐bromonitrobenzene 1b (1 g, 5 mmol) with phenylboronic
a
†
See ESI for details.
acid 2a (750 mg, 6.5 mmol) afforded the carbazole 3a in 75%
yields.
Notably, electron neutral and electron rich arylboronic acids
Next, we turned our attention to the domino reaction of
possessing alkyl, aryl, and alkoxy substituents were tolerated phenylboronic acid with a broad range of substituted o‐
in the one‐pot reaction (3a−3h, 3m‐o), as o‐, m‐ and p‐ bromonitrobenzenes (Table 3). Under the optimized
substituted arylboronic acids and 3,4‐disubstitued arylboronic conditions, the one‐pot reaction of substituted o‐
acids afforded the corresponding products (3a−3h, 3m‐o) in bromonitrobenzenes
1 with phenylboronic acid 2a were
good to high yields. Aryl boronic acids possessing bulky groups converted to the corresponding carbazoles in good yields, and
at the para position such as t‐butyl and phenyl were also similar results with respect to substrate scope of various aryl
converted to carbazoles in excellent yields. As expected, boronic acids were observed (Table 3, 3g, 3i, 3j, 3m and 3n).
coupling of m‐substituted arylboronic acids with o‐ These approaches constitute an alternative route that avoids
bromonitrobenzene 1b gave a mixture of corresponding 1‐ and the regioselectivity issue in the synthesis of 1‐ or 3‐substituted
3
3
‐substituted carbazoles as regioisomers. In these experiments, carbazoles (3m – 3q).
‐substituted carbazoles were obtained as major regioisomer
except with 3‐tolylboronic acid. In particular, 3,4‐ Table
methylenedioxy)phenylboronic acid gave a 5.9:1 mixture of bromonitrobenzenes with aryl boronic acids
and 3n’, demonstrating moderate regioselectivity, while 3‐
tolylboronic acid and 4‐methoxy‐3‐methylphenylboronic acid
gave mixtures with low regioselectivity (3m /m’, 3o /o’).
In addition, we explored the scope of electron deficient
arylboronic acids possessing fluorine, chlorine, ketone, and
ester moieties and found they also gave the desired products
4.
Substrate
scope
of
saubstituted
o
‐
(
3
n
1
6
17
(
3i−3l). Slightly lower yields were observed for electron
deficient arylboronic acids except for 4‐fluorophenylboronic
acid.
a
Table 3. Substrate scope of various o‐bromonitrobenzenes
a
b
†
As given in Table 1, entry 13. 48h.; yields of isolated material. See ESI
for details.
a
b
c
As given in Table 1, entry 13. 48h. Pd(OAc) (5 mol%), 48h.; yields of
†
isolated material. See ESI for details.
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Page 4 of 9
ARTICLE
Organic & Biomolecular Chemistry
The scope and limitations of the domino reaction with Hertz. The following abbreviations are used: m V(miewuAlrttiicpleleOtn)l,ines
respect to various substituted o‐bromonitrobenzenes and (singlet), d (doublet), t (triplet), q (quaDrOteI:t1)0,.1d0d39/(Cd5oOuBb0l1e9t52oDf
arylboronic acids were next investigated under the optimized doublets), etc.
conditions(Table 4). Coupling reactions of 1‐bromo‐4‐methoxy‐
2
‐nitrobenzene
fluorophenylboronic acid afforded the corresponding pressure tube (13 x 100 mm) equipped with magnetic stir bar
carbazoles 3s and 3t in 71% and 66% yields. Likewise, o‐ were added o‐bromonitrobenzene (0.5 mmol, 100 mol%),
bromonitrobenzenes possessing methyl and fluoro aryl boronic acid (0.65 mmol, 130 mol%), Pd(OAc) (0.01
substituents were coupled to arylboronic acids to form mmol, 2 mol%), PPh (1.25 mmol, 250 mol %), K CO (1 mmol,
with
3‐tolylboronic
acid
and
4‐
General Procedure for Carbazole Synthesis. To a re‐sealable
1
2
3
2
3
carbazoles 3u and 3v in 70% and 53% yield. This tandem 200 mol%) and o‐DCB (1 mL, 0.5 M concentration with respect
o
reaction was applied to the syntheses of three bioactive to o‐bromonitrobenzene
1
. The mixture was heated at 180 C
(oil bath temperature) for 24‐48 hr, at which point the reaction
and clausenalene 3y , in good yields and mixture was allowed to cool to ambient temperature. The
1
9
20
carbazole alkaloids, glycozoline 3w , glycozolicine 3w’
,
1
3a, 21
22
glycozolidine 3x
moderate regioselectivity.
reaction mixture was filtered through a pad of celite and the
resulting liquor was concentrated in vacuo and purified by
flash column chromatography (SiO ) under the conditions
2
Conclusions
noted to furnish the corresponding product.
6
e
9
H‐carbazole
(3a) .
Purified
by
flash
column
In conclusion, we have developed highly efficient synthetic
methods for carbazoles that are palladium‐catalyzed
sequential C‐C/C‐N bond formations via Suzuki cross‐coupling
and reductive Cadogan cyclization. Electron neutral, rich and
deficient substrates were tolerated in this method. The
synthetic utility of this method was demonstrated by the
concise syntheses of four naturally occurring bioactive
chromatography (SiO ) using 5% acetone in hexanes as eluant
2
1
to give 3a as a white solid (72 mg, 86% yield); H NMR (300
MHz, DMSO) δ 11.33 (s, 1H), 8.12 (d, J = 7.8 Hz, 3H), 7.56 (d, J =
1
3
8
.1 Hz, 2H), 7.45 – 7.39 (m, 3H), 7.21 – 7.16 (m, 3H); C NMR
(
1
(
75 MHz, DMSO) δ 139.79, 125.54, 122.48, 120.18, 118.53,
‐
1
10.98; FTIR (neat): υ 3379, 2946, 1450, 1033 cm ; LRMS m/z
+
EI) 166.8 (M ‐1), 139.0, 83.4, 62.8.
carbazole alkaloids, glycozoline 3w
,
glycozolicine 3w’,
2
3a
2
‐Methyl‐9H‐carbazole (3b)
. Purified by flash column
glycozolidine 3x and clausenalene 3y from commercially
available simple starting materials. Future studies will focus on
further applications of this one‐pot strategy to the syntheses
of complex natural products.
chromatography (SiO ) using 5% acetone in hexanes as eluant
2
1
to give 3b as a white solid (76 mg 84% yield); H NMR (300
MHz, CDCl ) δ 8.03 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 7.9 Hz, 2H),
3
7
2
.42 – 7.35 (m, 2H), 7.24 – 7.18 (m, 2H), 7.07 (d, J = 8.0 Hz, 1H),
1
3
.53 (s, 3H); C NMR (75 MHz, CDCl ) δ 140.09, 139.59, 136.15,
3
Experimental
General Information
125.41, 123.58, 121.19, 121.12, 120.14, 120.13, 119.46, 110.86,
‐
1
1
10.60, 22.21; FTIR (neat) υ 3394, 2920, 1652, 1530, 1365 cm ;
+
LRMS m/z (EI) 179.8 (M ‐1), 151.8, 76.8, 62.8.
4
All reactions were run under an atmosphere of air under
1
0
‐Methyl‐9H‐carbazole (3c) . Purified by flash column
anhydrous
conditions
unless
otherwise
tetrahydrofuran
indicated.
(THF),
chromatography (SiO ) using 5% acetone in hexanes as eluant
2
Dichloromethane
(CH Cl ),
2
2
1
to give 3c as a white solid (79 mg 87% yield); H NMR (300
dimethylformamide (DMF) and toluene (PhMe) were obtained
from Pure‐Solv MD‐5 Solvent Purification System (Innovative
Technology). Pressure tubes (13 x 100 mm, PYREXPLUS) were
dried in oven for overnight and cooled under a stream of
nitrogen prior to use. All commercial reagents were used
directly without further purification. The progress of reaction
was checked on TLC plates (Merck 5554 Kiesel gel 60 F254).
Column chromatography was performed on silica gel (Merck
MHz, CDCl ): δ 8.19 (d, J = 7.9 Hz, 1H), 8.09 (br s, 1H), 7.50 –
3
7
.39 (m, 2H), 7.37 – 7.31 (m, 1H), 7.32 – 7.26 (m, 2H), 7.02 (dd,
1
3
J = 7.3, 0.8 Hz, 1H), 2.89 (s, 3H); C NMR (75 MHz, CDCl ): δ
3
1
1
3
39.54, 139.51, 133.49, 125.77, 125.29, 123.93, 122.68, 121.90,
20.99, 119.44, 110.49, 108.26, 20.92; FTIR (neat) υ 3396,
‐
1
200, 2924, 1653, 1521, 1267, 1048 cm ; LRMS m/z (EI) 181.3
+
(
M ), 182.3, 180.4, 177.5, 155.3, 125.8, 93.7.
1
1d
2
‐(Tert‐butyl)‐9H‐carbazole (3d)
. Purified by flash column
9
385 Kiesel gel 60) using hexanes‐EtOAc (v/v) or hexanes‐
acetone (v/v). Infrared spectra were recorded on a Varian
000 FT‐IR. High‐resolution mass spectra (EI) were obtained on
chromatography (SiO ) using 5% acetone in hexanes as eluant
2
1
to give 3d as a white solid (94 mg 84% yield); H NMR (300
2
MHz, CDCl ) δ 8.05 (d, J = 7.0 Hz, 1H), 8.00 (d, J = 7.5 Hz, 1H),
3
a Jeol JMS700 HRMS at the Korea Basic Science Center(KBSI),
Daegu, Korea and Low‐resolution mass spectra (EI) Varian 450‐
GC/Varian 220‐MS and are reported as m/z (relative intensity).
7
.94 (s, 1H), 7.44 (d, J = 1.6 Hz, 1H), 7.41 – 7.35 (m, 2H), 7.32
13
(
dd, J = 8.3, 1.4 Hz, 1H), 7.25 – 7.20 (m, 1H), 1.44 (s, 9H);
C
+
NMR (75 MHz, CDCl ) δ 149.72, 139.89, 139.82, 125.40, 123.49,
3
Accurate masses are reported for the molecular ion ([M+H] or
+
1
121.03, 120.21, 119.90, 119.41, 117.65, 110.57, 107.25, 35.25,
[
M+Na] ). Nuclear magnetic resonance spectra ( H NMR and
C
‐
1
1
3
31.90; FTIR (neat) υ 3194, 2916, 1650, 1525, 1267 cm ; LRMS
NMR) were recorded with a Bruker (300 MHz)
+
m/z (EI) 222.7 (M ‐1), 207.8, 180.0, 167.0, 89.9.
spectrometer. Chemical shift values were recorded as parts
per million relative to tetramethylsilane as an internal
standard unless otherwise indicated, and coupling constants in
6
d
2
‐Phenyl‐9H‐carbazole (3e) . Purified by flash column
chromatography (SiO ) using 5% acetone in hexanes as eluant
2
1
to give 3e as a white solid (110 mg 90% yield); H NMR (300
4
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Org aP nl ei ca s &e dB oi on mo to al ed cj uu sl at rm Ca hr ge imn si stry
Organic & Biomolecular Chemistry
MHz, Acetone‐d ) δ 10.50 (s, 1H), 8.19 (d, J = 8.1 Hz, 1H), 8.14
ARTICLE
1
1d
6
1‐(9H‐Carbazole‐2‐yl)ethan‐1‐one (3k)
.
Purified by flash
View Article Online
DOI: 10.1039/C5OB01952D
(
(
d, J = 7.7 Hz, 1H), 7.80 – 7.71 (m, 3H), 7.57 – 7.32 (m, 6H), 7.21 column chromatography (SiO ) using 7% acetone in hexanes as
2
td, J = 8.2, 4.3 Hz, 1H); C NMR (75 MHz, DMSO): δ 141.26, eluant to give 3k as a white solid (41 mg, 43% yield); H NMR
1
3
1
1
1
40.43, 140.35, 137.88, 128.99, 127.12, 127.06, 125.70, 122.23, (300 MHz, DMSO) δ 11.56 (s, 1H), 8.22 (t, J = 8.3 Hz, 2H), 8.08
21.88, 120.68, 120.32, 118.76, 117.89, 111.06, 108.93; FTIR (s, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.47 (t, J
‐
1
13
(
(
neat) υ 3377, 3268, 1692, 1528, 1367, 1227 cm ; LRMS m/z = 7.5 Hz, 1H), 7.21 (t, J = 7.4 Hz, 1H), 2.68 (s, 3H); C NMR (75
EI): 242.8 (M ‐1), 120.3, 76.7, 50.9.
+
MHz, DMSO) δ 197.86, 141.29, 139.15, 134.10, 127.03, 126.13,
2
3b
7
H‐Benzo[c]carbazole (3f)
.
Purified by flash column 121.59, 121.15, 120.06, 119.12, 118.66, 111.39, 111.35, 26.98;
‐
1
chromatography (SiO ) using 5% acetone in hexanes as eluant FTIR (neat) υ 3332, 1738, 1366, 1216, 889, 779 cm ; LRMS m/z
to give 3f as a white solid (91 mg 84% yield); H NMR (300 MHz, (EI) : 210.2 (M +1), 209.3, 194.3, 166.3, 139.3.
CDCl ) δ 8.79 (d, J = 8.3 Hz, 1H), 8.58 (d, J = 7.8 Hz, 1H), 8.44 (s,
2
1
+
6
e
3
Methyl‐9H‐carbazole‐2‐carboxylate (3l) . Purified by flash
1
H), 8.01 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.75 – 7.68 column chromatography (SiO ) using 7% acetone in hexanes as
2
1
(
m, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.52 – eluant to give 3l as a white solid (69 mg, 61% yield); H NMR
1
3
7
1
1
.43 (m, 2H), 7.43 – 7.36 (m, 1H); C NMR (75 MHz, CDCl ) δ (300 MHz, DMSO) δ 11.58 (s, 1H), 8.21 (t, J = 8.8 Hz, 2H), 8.12
3
38.52, 137.16, 130.03, 129.32, 127.55, 127.01, 124.46, 124.09, (s, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.47 (t, J
1
3
23.38, 123.13, 122.16, 120.36, 115.54, 112.71, 111.25; FTIR = 7.5 Hz, 1H), 7.21 (t, J = 7.4 Hz, 1H), 3.89 (s, 3H); C NMR (75
‐
1
(
(
neat) υ 3396, 2920, 1876, 1465, 1267, 1120 cm ; LRMS m/z MHz, DMSO) δ 166.95, 141.10, 139.05, 127.06, 126.30, 126.20,
EI): 217.7 (M +1), 216.8, 188.8, 108.2, 95.3.
+
121.60, 121.10, 120.14, 119.25, 119.16, 112.35, 111.42, 52.05;
1
6c
‐1
2
‐Methoxy‐9H‐carbazole (3g)
.
Purified by flash column FTIR (neat) υ 3337, 2937, 1738, 1365, 1216, 888 cm ; LRMS
+
chromatography (SiO ) using 5% acetone in hexanes as eluant m/z (EI): 226.2 (M +1), 225.2, 194.2, 166.2, 139.2, 97.2, 83.2,
to give 3g as a white solid (76 mg, 77% yield); H NMR (300 69.7.
2
1
MHz, CDCl ) δ 7.99 (s, 1H), 7.96 (d, J = 3.4 Hz, 1H), 7.94 (d, J =
3‐Methyl‐9H‐carbazole (3m) and 1‐Methyl‐9H‐carbazole
3
8
2
.6 Hz, 1H), 7.41 – 7.31 (m, 1H), 7.24 – 7.18 (m, 1H), 6.92 (d, J = (3m’). Purified by flash column chromatography (SiO ) using 5%
2
1
3
.1 Hz, 1H), 6.86 (dd, J = 8.5, 2.2 Hz, 1H), 3.91 (s, 1H); C NMR acetone in hexanes as eluant to give 3m
/
3m’ as a white solid
1
(
75 MHz, CDCl ) δ 159.21, 140.93, 139.63, 124.69, 123.67, (80 mg, 88% yield, 3m:3m'=1:1.2 (determined by H NMR and
3
TM
1
21.19, 119.70, 119.63, 117.39, 110.44, 108.29, 94.83, 55.77; GC‐Mass spectrometer)). GC (Varian 450‐GC, SPB ‐680 (30 m
‐
1
o
o
FTIR (neat) υ 3395, 1336, 1200, 1030 cm ; LRMS m/z (EI): x 0.25 mm x 0.25 μm), T : 60 C (hold 4 min), T : Ramp, 250 C
1
4
chromatography (SiO ) using 5% acetone in hexanes as eluant
to give 3h as a white solid (66 mg, 67% yield); H NMR (300 11.10 (s, 1H), 8.05 (d, J = 7.7 Hz, 1H), 7.89 (s, 1H), 7.45 (d, J =
0
1
+
o
97.7 (M +1), 196.7, 181.8, 153.8, 127.8.
at 10 C/min, Carrier: He (1.0 mL/min), Total time 60 min), t
3
m’
1
3f
‐Methoxy‐9H‐carbazole (3h)
.
Purified by flash column = 21.95 min, t3m = 22.32 min, Ratio (3m:3m' = 1:1.2).
6
e 1
2
3‐Methyl‐9H‐carbazole (3m) . H NMR (300 MHz, DMSO) δ
1
MHz, CDCl ) δ 8.34 (d, J = 7.8 Hz, 1H), 8.02 (s, 1H), 7.43 – 7.38 8.1 Hz, 1H), 7.39 – 7.32 (m, 2H), 7.20 (d, J = 8.0 Hz, 1H), 7.12 (t,
3
1
3
(
8
m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.30 – 7.21 (m, 1H), 7.04 (d, J = J = 7.4 Hz, 1H), 2.46 (s, 3H): C NMR (75 MHz, DMSO) δ
.1 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 4.09 (s, 3H); C NMR (75 139.98, 137.96, 127.08, 126.82, 125.29, 122.54, 122.22, 120.02,
1
3
MHz, CDCl ) δ 156.32, 140.92, 138.72, 126.77, 125.01, 123.12, 119.90, 118.23, 110.85, 110.63, 21.10; FTIR (neat) υ 3442,
3
‐
1
+
1
(
(
22.67, 119.70, 112.60, 110.07, 103.62, 100.42, 55.51; FTIR 1701, 1371, 1207 cm ; LRMS m/z (EI): 182.2 (M +1), 181.2,
neat) υ 3386, 2938, 1405, 1248, 1184, 1045 cm ; LRMS m/z 180.3, 152.3, 90.2, 77.2, 63.2, 51.1.
‐
1
+
13f 1
EI): 197.8 (M +1), 196.7, 181.9, 153.9, 128.0.
1‐Methyl‐9H‐carbazole (3m’)
‐Chloro‐9H‐carbazole (3i) . Purified by flash column δ 11.16 (s, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.93 (d, J = 7.7 Hz, 1H),
chromatography (SiO ) using 5% acetone in hexanes as eluant 7.50 (d, J = 8.1 Hz, 1H), 7.38 – 7.34 (m, 1H), 7.20 – 7.10 (m, 2H),
. H NMR (300 MHz, DMSO)
6
e
2
2
1
13
to give 3i as a white solid (71 mg, 70% yield); H NMR (300 7.10 – 7.02 (m, 1H), 2.55 (s, 3H); C NMR (75 MHz, DMSO) δ
MHz, DMSO) δ 11.43 (s, 1H), 8.12 (d, J = 8.2 Hz, 2H), 7.54 – 139.79, 139.04, 125.94, 125.29, 122.79, 121.95, 120.17, 120.05,
.49 (m, 2H), 7.40 (t, J = 7.5 Hz, 1H), 7.20 – 7.14 (m, 2H);
NMR (75 MHz, DMSO) δ 140.30, 140.08, 129.88, 125.98, 1701, 1371, 1207 cm ; LRMS m/z (EI): 181.2 (M ), 180.2, 152.3,
21.81, 121.57, 121.31, 120.35, 119.09, 118.68, 111.23, 110.61; 135.2, 77.2, 63.2, 51.1.
FTIR (neat) υ 3393, 3128, 1636, 1406, 1321, 1178, 754 cm ;
LRMS m/z (EI): 200.7 (M ‐1), 165.7, 138.8, 100.3.
‐Fluoro‐9H‐carbazole (3j)
chromatography (SiO ) using 5% acetone in hexanes as eluant to give 3n
1
3
7
C
118.62, 118.46, 117.60, 111.03, 17.00; FTIR (neat) υ 3442,
‐
1
+
1
‐
1
5H‐[1,3]dioxolo[4,5‐b]carbazole
[1,3]dioxolo[4,5‐a]carbazole (3n’). Purified by flash column
) using 5% acetone in hexanes as eluant
3n’ as a white solid (90 mg, 87% yield, 3n:3n'=5.9:1
(3n)
and
5H‐
+
1
1d
2
. Purified by flash column chromatography (SiO
2
2
/
1
1
to give 3j as a white solid (75 mg, 81% yield)
; H NMR (300 (determined by H NMR and GC‐Mass spectrometer)). GC:
TM
MHz, CDCl ) δ 8.07 (s, 1H), 8.03 – 7.97 (m, 2H), 7.44 – 7.39 (m, (Varian 450‐GC, SPB ‐680 (30 m x 0.25 mm x 0.25 μm), T : 60
3
0
o
o
o
2
6
H), 7.26 – 7.21 (m, 1H), 7.11 (dd, J = 9.6, 2.2 Hz, 1H), 7.02 –
.93 (m, 1H); C NMR (75 MHz, DMSO) δ 161.18 (d, J = 238.6 mL/min), Total time 60 min), t3n’ = 25.38 min, t3n = 26.90 min,
1
C (hold 4 min), T : Ramp, 250 C at 10 C/min, Carrier: He (1.0
1
3
Hz), 140.41, 140.28, 125.25, 122.07, 121.46 (d, J = 10.6 Hz), Ratio (3n:3n' = 5.9:1).
19.97, 119.20, 119.00, 111.02, 106.49 (d, J = 24.1 Hz), 97.34 5H‐[1,3]dioxolo[4,5‐b]carbazole (3n)
d, J = 26.1 Hz); FTIR (neat) υ 3411, 2919, 1362, 1263 cm ; DMSO) δ 11.08 (s, 1H), 7.96 (d, J = 7.7 Hz, 1H), 7.62 (s, 1H),
2
3c
1
1
(
. H NMR (300 MHz,
‐
1
+
LRMS m/z (EI): 186.2 (M +1), 185.2, 184.3, 157.3, 92.8.
7.40 (d, J = 8.0 Hz, 1H), 7.24 (t, J = 7.5 Hz, 1H), 7.09 – 7.02 (m,
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem., 2015, 00, 1‐9 | 5
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Org aP nl ei ca s &e dB oi on mo to al ed cj uu sl at rm Ca hr ge imn si stry
Page 6 of 9
ARTICLE
Organic & Biomolecular Chemistry
1
3
2
1
1
9
H), 6.03 (s, 2H); C NMR (75 MHz, DMSO) δ 146.72, 141.52, DMSO) δ 158.14, 141.07, 140.22, 133.50, 120.54, 120.44,
View Article Online
DOI: 10.1039/C5OB01952D
39.56, 135.14, 123.76, 122.83, 119.26, 118.20, 115.40, 110.79, 120.03, 119.02, 116.32, 110.73, 107.42, 94.53, 55.25, 21.65.;
00.69, 99.36, 92.16; FTIR (neat) υ 3397, 1710, 1266, 1043, FTIR (neat) υ 3394, 1726, 1366, 1219, 1091 cm ; LRMS m/z (EI):
36, 748 cm ; LRMS m/z (EI): 212.0 (M +1), 211.2.
H‐[1,3]dioxolo[4,5‐a]carbazole (3n’). H NMR (300 MHz,
‐
1
‐
1
+
+
212.5 (M +1), 211.6, 196.6, 195.7, 168.5.
1
5
2‐Fluoro‐7‐methoxy‐9H‐carbazole (3t). Purified by flash
DMSO) δ 11.35 (s, 1H), 8.01 (d, J = 7.7 Hz, 1H), 7.67 (d, J = 15.0 column chromatography (SiO ) using 5% acetone in hexanes as
2
1
Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.38 – 7.30 (m, 1H), 7.16 – 7.06 eluant to give 3t as a white solid (71 mg, 66% yield); H NMR
(
m, 1H), 6.86 (d, J = 8.2 Hz, 1H), 6.13 (s, 2H); FTIR (neat) υ 3397, (300 MHz, CDCl ) δ 7.97 (br s, 1H), 7.87 (d, J = 8.5 Hz, 1H),, 7.85
3
‐
1
+
1
2
710, 1266, 1043, 936, 748 cm ; LRMS m/z (EI): 211.9 (M +1), (d, J = 8.3 Hz, 1H), 7.06 (dd, J = 9.5, 2.3 Hz, 1H), 6.98 – 6.93 (m,
11.1, 154.2. 1H), 6.90 (d, J = 2.2 Hz, 1H), 6.86 (dd, J = 8.5, 2.2 Hz, 1H), 3.90
‐Methoxy‐2‐methyl‐9Hcarbazole (3o)
column chromatography (SiO ) using 7% acetone in hexanes as 120.38, 120.25, 116.91, 108.55, 107.82, 107.50, 97.63, 97.27,
1
2k
13
3
. Purified by flash (s, 1H); C NMR (75 MHz, CDCl ) δ 158.87, 141.31, 120.78,
3
2
1
‐1
eluant to give 3o as a yellow solid (54mg, 51% yield); H NMR 95.02, 55.78; FTIR (neat) υ 3192, 2843, 1539, 1406, 1155 cm ;
(
7
7
(
+
300 MHz, Acetone‐d ) δ 10.10 (s, 1H), 7.96 (d, J = 7.7 Hz, 1H), LRMS m/z (EI): 216.5 (M +1), 215.5, 200.6, 199.7, 172.5, 171.5;
6
+
.81 (s, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.28 – 7.23 (m, 1H), 7.13 – HRMS m/z (EI): calcd. For C H FNO (M ) 215.0747, found
13 10
1
3
.08 (m, 1H), 7.02 (s, 1H), 3.90 (s, 3H), 2.31 (s, 3H); C NMR 215.0746.
75 MHz, Acetone‐d ) δ 158.18, 140.73, 140.68, 124.60, 124.12, 10‐Methyl‐7H‐benzo[c]carbazole (3u) . Purified by flash
6
2
3f
1
1
21.94, 119.79, 119.42, 118.89, 116.68, 111.28, 93.30, 55.67, column chromatography (SiO ) using 5% acetone in hexanes as
2
1
6.92; FTIR (neat) υ 3313, 3069, 1783, 1689, 1404, 1270, 1169 eluant to give 3u as a white solid (81 mg , 70% yield); H NMR
‐
1
+
cm ; LRMS m/z (EI): 212.2(M +1), 211.3, 196.6, 195.7, 167.5.
1
(300 MHz, CDCl ) δ 8.79 (d, J = 8.3 Hz, 1H), 8.37 (s, 1H), 8.31 (s,
Purified by flash 1H), 8.01 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.72 (t, J =
3
2
3e
‐Methoxy‐2‐methyl‐9Hcarbazole (3o’)
.
column chromatography (SiO ) using 5% acetone in hexanes as 7.6 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.52 – 7.44 (m, 2H), 7.29 (d,
2
1
13
eluant to give 3o’ as a yellow solid (29mg, 27% yield); H NMR J = 8.4 Hz, 1H), 2.64 (s, 3H); C NMR (75 MHz, CDCl ) δ 137.41,
3
(
300 MHz, Acetone‐d ) δ 10.16 (s, 1H), 7.99 (d, J = 7.7 Hz, 1H), 136.78, 130.09, 129.60, 129.27, 127.27, 126.90, 125.87, 124.27,
6
7
1
2
1
1
1
2
.89 (d, J = 8.5 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.32 – 7.25 (m, 123.39, 122.98, 122.06, 115.22, 112.79, 110.88, 21.96; FTIR
‐
1
H), 7.19 – 7.10 (m, 1H), 6.90 (d, J = 8.5 Hz, 1H), 3.91 (s, 3H), (neat) υ 3470, 2897, 1696, 1542, 1267, 1152 cm ; LRMS m/z
1
3
+
.40 (s, 3H); C NMR (75 MHz, Acetone‐d ) δ 156.86, 141.66, (EI): 232.7 (M +1 ), 231.2, 230.2, 228.8, 197.2, 118.8.
6
41.42, 125.16, 124.60, 120.13, 119.56, 118.53, 118.01, 111.33, 2‐(Tert‐butyl)‐7‐fluoro‐9H‐carbazole (3v). Purified by flash
07.65, 104.63, 56.46, 10.15; FTIR (neat) υ 3313, 3069, 1783, column chromatography (SiO ) using 5% acetone in hexanes as
2
‐
1
+
1
689, 1404, 1270, 1169 cm ; LRMS m/z (EI): 212.3 (M +1), eluant to give 3v as a yellow solid (64 mg, 53% yield); H NMR
11.4, 196.6, 195.7, 167.7. (300 MHz, DMSO) δ 11.24 (s, 1H), 8.04 (dd, J = 8.5, 5.7 Hz, 1H),
‐Methoxy‐9H‐carbazole (3p) . Purified by flash column 7.97 (d, J = 8.3 Hz, 1H), 7.43 (s, 1H), 7.23 (dd, J = 10.3, 2.1 Hz,
6
e
3
1
3
chromatography (SiO ) using 5% acetone in hexanes as eluant 2H), 6.99 – 6.91 (m, 1H), 1.36 (s, 9H); C NMR (75 MHz, DMSO)
to give 3p as a brown solid (59 mg, 60% yield); H NMR (300 δ 160.94 (d, J = 237.8 Hz), 148.29, 140.61, 140.44, 121.08 (d, J
2
1
MHz, CDCl ) δ 8.02 (d, J = 7.8 Hz, 1H), 7.85 (s, 1H), 7.54 (d, J = = 10.5 Hz), 119.71, 119.50, 119.20, 117.01, 107.26, 106.27 (d, J
3
2
=
1
1
1
.4 Hz, 1H), 7.44 – 7.30 (m, 2H), 7.28 – 7.12 (m, 2H), 7.05 (dd, J = 24.1 Hz), 97.30 (d, J = 26.0 Hz), 34.76, 31.60; FTIR (neat) υ
13
‐1
8.7, 2.4 Hz, 1H), 3.91 (s, 3H); C NMR (75 MHz, CDCl ) δ 3475, 3187, 1741, 1598, 1266 cm ; LRMS m/z (EI): 242.1
3
+
53.88, 140.32, 134.42, 125.89, 123.76, 123.34, 120.34, 119.10, (M +1), 241.1, 227.4, 226.5, 198.2; HRMS m/z (EI): calcd. For
+
15.16, 111.46, 110.88, 103.13, 56.14; FTIR (neat) υ 3405, C H FN (M ) 241.1268, found 241.1267.
1
6 16
‐
1
19d
788, 1685, 1400, 1260, 1031 cm ; LRMS m/z (EI): 198.3
Glycozoline (3w)
(SiO ) using 5% acetone in hexanes as eluant to give 3w as a
. Purified by flash column yellow solid (37 mg, 35% yield); H NMR (300 MHz, CDCl ) δ
3
. Purified by flash column chromatography
+
(
M +1), 197.4, 182.7, 181.7, 154.3, 101.5.
2
2
3d
1
2
,3‐Dimethoxy‐9H‐carbazole (3q)
chromatography (SiO ) using 7% acetone in hexanes as eluant 7.85 (s, 1H), 7.77 (s, 1H), 7.54 (d, J = 2.4 Hz, 1H), 7.31 – 7.21 (m,
2
1
13
to give 3q as a white solid (70 mg, 62% yield); H NMR (300 3H), 7.06 (dd, J = 8.7, 2.5 Hz, 1H), 3.94 (s, 3H), 2.54 (s, 3H);
C
MHz, DMSO) δ 10.98 (s, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.66 (s, NMR (75 MHz, CDCl ) δ 153.87, 138.69, 134.89, 128.45, 127.32,
3
1
7
H), 7.43 (d, J = 8.0 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.08 (t, J = 123.76, 123.64, 120.25, 115.01, 111.41, 110.56, 103.23, 56.19,
13
‐1
.4 Hz, 1H), 7.04 (s, 1H), 3.86 (s, 3H), 3.85 (s, 3H); C NMR (75 21.54.; FTIR (neat) υ 3410, 2894, 1706, 1492, 1266, 1131 cm ;
+
MHz, DMSO ) δ 149.18, 143.71, 139.56, 134.63, 123.67, 123.00, LRMS m/z (EI): 212.1 (M +1), 211.2, 197.2, 196.3, 168.2, 167.2.
1
FTIR (neat) υ 3337, 2917, 1402, 1186, 1090 cm ; LRMS m/z (EI): chromatography (SiO ) using 5% acetone in hexanes as eluant
2
3
2
0d
19.26, 118.12, 114.30, 110.72, 103.33, 94.62, 56.21, 55.63;
Glycozolicine (3w’)
.
Purified by flash column
‐
1
2
+
1
28.2 (M +1), 227.5, 212.7, 211.7, 184.5.
‐Methoxy‐7‐methyl‐9H‐carbazole (3s)
to give 3w’ as a yellow solid (41 mg, 39% yield); H NMR (300
Purified by flash MHz, CDCl ) δ 8.17 (s, 1H), 7.87 (s, 1H), 7.67 (d, J = 7.8 Hz, 1H),
2
0d
2
.
3
column chromatography (SiO ) using 5% acetone in hexanes as 7.34 (d, J = 8.2 Hz, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.16 (t, J = 7.8
2
1
13
eluant to give 3s as a white solid (75 mg, 71% yield); H NMR Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 4.00 (s, 3H), 2.54 (s, 3H);
C
(
300 MHz, DMSO) δ 10.98 (s, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.84 NMR (75 MHz, CDCl ) δ 145.79, 137.57, 130.24, 128.76, 127.19,
3
(
8
d, J = 7.9 Hz, 1H), 7.21 (s, 1H), 6.96 – 6.88 (m, 2H), 6.73 (dd, J = 124.32, 123.96, 120.54, 119.61, 112.94, 110.71, 105.87, 55.59,
.5, 2.2 Hz, 1H), 3.82 (s, 3H), 2.44 (s, 3H); C NMR (75 MHz 21.56; FTIR (neat) υ 3410, 2894, 1706, 1492, 1266, 1131 cm ;
1
3
‐1
6
| Org. Biomol. Chem., 2015, 00, 1‐9
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Page 7 of 9
Org aP nl ei ca s &e dB oi on mo to al ed cj uu sl at rm Ca hr ge imn si stry
Organic & Biomolecular Chemistry
ARTICLE
+
LRMS m/z (EI): 212.2 (M +1), 211.3, 197.2, 196.3, 169.1, 168.2, hr, at which point the reaction mixture was allowed to cool to
View Article Online
DOI: 10.1039/C5OB01952D
1
42.1.
ambient temperature. The reaction mixture, treated with
2
0d
Glycozolidine
(3x)
.
Purified
by
flash
column saturated sodium bicarbonate solution, and extracted with
chromatography (SiO ) using 7% acetone in hexanes as eluant dichloromethane (3x). The combined organic layers were dried
2
1
to give 3x as a white solid (56mg, 46% yield); H NMR (300 with magnesium sulfate, filtered, and concentrated in vacuo
MHz, CDCl ) δ 7.76 (s, 1H), 7.56 (s, 1H), 7.46 (d, J = 2.2 Hz, 1H), and purified by flash column chromatography (SiO ) and
3
2
7
1
.15 (d, J = 8.7 Hz, 1H), 6.96 (dd, J = 8.6, 2.3 Hz, 1H), 6.63 (s, recrystallization from dichloromethane and hexanes under the
1
3
H), 3.92 (s, 3H), 3.83 (s, 3H), 2.37 (s, 3H); C NMR (75 MHz, conditions noted to furnish the corresponding product.
2‐([1,1'‐Biphenyl]‐4‐yl)‐9H‐carbazole (3ia). Purified by
18.98, 116.17, 113.10, 111.10, 102.53, 92.53, 56.14, 55.52, recrystallization from dichloromethane and hexanes to give 3ia
CDCl ) δ 157.50, 153.90, 140.10, 134.23, 123.96, 121.47,
1
1
3
1
6.87; FTIR (neat) υ 3389, 3066, 1787, 1637, 1509, 1365, 1270 as a white solid (23 mg, 72% yield); H NMR (300 MHz, DMSO)
‐
1
+
cm ; LRMS m/z (EI): 242.3 (M +1), 241.3, 227.2, 226.3, 198.2, δ 11.35 (s, 1H), 8.20 (d, J = 8.1 Hz, 1H), 8.14 (d, J = 7.8 Hz, 1H),
83.2, 154.1. 7.86 (d, J = 8.1 Hz, 1H), 7.85 (s, 1H), 7.82 – 7.71 (m, 5H), 7.55 –
,6‐Dimethoxy‐1‐methyl‐9H‐carbazole (3x’). Purified by flash 7.46 (m, 4H), 7.44 – 7.36 (m, 2H), 7.18 (t, J = 7.4 Hz, 1H);
1
2
13
C
column chromatography (SiO ) using 5% acetone in hexanes as NMR (75 MHz, DMSO) δ 140.41, 140.33, 140.20, 139.70,
2
1
eluant to give 3x’ as a white solid (27mg, 22% yield). H NMR 138.77, 137.20, 129.03, 127.50, 127.21, 126.56, 125.70, 122.19,
(
(
300 MHz, DMSO) δ 10.76 (s, 1H), 7.85 (d, J = 8.5 Hz, 1H), 7.56 121.94, 120.70, 120.30, 118.74, 117.72, 111.03, 108.74; FTIR
‐
1
d, J = 2.4 Hz, 1H), 7.31 (d, J = 8.7 Hz, 1H), 6.91 (dd, J = 8.7, 2.5 (neat) υ 3403, 3101, 1753, 1691, 1530, 1368, 1206, 763 cm ;
+
Hz, 1H), 6.84 (d, J = 8.6 Hz, 1H), 3.85 (s, 3H), 3.82 (s, 3H), 2.33 HRMS m/z (EI): calcd. For C H N (M ) 319.1361, found
(
2
4 17
1
3
s, 3H); C NMR (75 MHz, DMSO). δ 155.44, 153.04, 141.29, 319.1360.
1
1
1
2
35.08, 123.59, 117.97, 116.79, 113.20, 111.23, 106.54, 103.49, 2‐(4‐Fluorophenyl)‐9H‐carbazole (3ib). Purified by flash
02.67, 56.08, 55.56, 10.24; FTIR (neat) υ 3389, 3066, 1787, column chromatography (SiO ) using 5% acetone in hexanes as
2
‐
1
+
1
637, 1509, 1365, 1270 cm ; LRMS m/z (EI): 242.3 (M +1), eluant to give 3ib as a yellow solid (23 mg, 88% yield); H NMR
41.3, 227.2, 226.3, 198.2, 197.2, 183.2, 154.1. (300 MHz, CDCl ) δ 8.12 (d, J = 7.8 Hz, 1H), 8.10 (s, 1H) 8.09 (d,
Clausenalene (3y) and 7‐Methyl‐10H‐[1,3]dioxolo[4,5‐ J = 7.4 Hz, 1H), 7.68 – 7.61 (m, 2H), 7.58 (s, 1H), 7.46 – 7.40 (m,
3
13
a]carbazole (3y’). Purified by flash column chromatography 3H), 7.30 – 7.22 (m, 1H), 7.19 – 7.11 (m, 2H); C NMR (75 MHz,
SiO ) using 5% acetone in hexanes as eluant to give 3y 3y’ as Acetone‐d ) δ 163.17 (d, J = 243.9 Hz), 141.61, 141.56, 139.27
(
/
2
6
a white solid (61 mg, 80% yield, 3y:3y'=5.3:1 (determined by (d, J = 3.2 Hz), 138.56, 129.87 (d, J = 8.0 Hz), 126.59, 123.71,
1
H NMR and GC‐Mass spectrometer)). GC: (Varian 450‐GC, 123.33, 121.34, 121.00, 119.91, 119.11, 116.33 (d, J = 21.5 Hz),
TM
o
‐1
SPB ‐680 (30 m x 0.25 mm x 0.25 μm), T : 60 C (hold 4 min), 111.80, 109.96; FTIR (neat) υ 3400, 1650, 1367, 1223, 724 cm ;
T : Ramp, 250 C at 10 C/min, Carrier: He (1.0 mL/min), Total LRMS m/z (EI): 262.2 (M +1), 262.2; HRMS m/z (EI): calcd. For
time 60 min), t3y’ = 26.98 min, t3y = 28.69 min, Ratio (3y:3y'
0
o
o
+
1
+
=
C H FN (M ) 261.0954, found 261.0953.
18 12
5
.3:1).
Methyl 4‐(9H‐carbazol‐2‐yl)benzoate (3ic). Purified by
. Purified by recrystallization from recrystallization from dichloromethane and hexanes to give 3ic
2
2c
Clausenalene (3y)
1
1
dichloromethane and hexanes to give 3y as a white solid. H as a white solid (21 mg, 70% yield); H NMR (300 MHz, DMSO)
NMR (300 MHz, Acetone‐d ) δ 10.09 (s, 1H), 7.76 (s, 1H), 7.50 δ 11.39 (s, 1H), 8.22 (d, J = 8.2 Hz, 1H), 8.15 (d, J = 7.7 Hz, 1H),
6
(
6
s, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.09 (dd, J = 8.2, 1.2 Hz, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 1.3
.98 (s, 1H), 6.00 (s, 2H), 2.45 (s, 3H); C NMR (75 MHz, Hz, 1H), 7.54 (dd, J = 8.2, 1.5 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H),
1
3
Acetone‐d ) δ 147.94, 142.82, 139.11, 136.64, 128.26, 126.07, 7.41 (td, J = 8.1, 0.9 Hz, 1H), 7.18 (td, J = 7.7, 0.5 Hz, 1H), 3.89
6
1
3
1
24.45, 119.77, 116.76, 111.26, 101.66, 99.82, 92.85, 21.48; (s, 3H); C NMR (75 MHz, DMSO) δ 166.18, 145.77, 140.47,
FTIR (neat) : υ 3400, 3009, 1728, 1366, 1219, 1093, 533 cm ; 140.28, 136.26, 129.86, 128.01, 127.21, 125.98, 122.59, 122.03,
LRMS m/z (EI): 225.9 (M +1), 225.2.
‐Methyl‐10H‐[1,3]dioxolo[4,5‐a]carbazole (3y’). H NMR (neat) υ 3388, 2139, 1719, 1363, 1218, 1095, 702 cm ; HRMS
300 MHz, Acetone‐d ) δ 10.17 (s, 1H), 7.81 (s, J = 0.6 Hz, 2H), m/z (EI): calcd. For C H NO (M ) 301.1103, found 301.1103.
‐
1
+
120.83, 120.47, 118.85, 117.91, 111.11, 109.26, 52.16; FTIR
1
‐1
7
+
(
6
20 15
2
7
1
.61 – 7.57 (m, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.17 (dd, J = 8.2,
2‐(2‐Methoxyphenyl)‐9H‐carbazole (3id). Purified by
.2 Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 6.07 (s, 2H), 2.46 (s, 3H); recrystallization from dichloromethane and hexanes to give
‐
1
1
FTIR (neat) υ 3400, 3009, 1728, 1366, 1219, 1093, 533 cm ; 3id as a white solid (26 mg, 95% yield); H NMR (300 MHz,
LRMS m/z (EI): 225.9 (M +1), 225.2.
+
Acetone‐d ) δ 10.34 (s, 1H), 8.12 (d, J = 8.2 Hz, 2H), 7.67 (d, J =
6
General Procedure for Suzuki coupling of 3‐chlorocarbazole 0.6 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.43 – 7.39 (m, 2H), 7.37 –
3i). To a re‐sealable pressure tube (13 x 100 mm) equipped 7.30 (m, 2H), 7.22 – 7.16 (m, 1H), 7.11 (d, J = 8.0 Hz, 1H), 7.05
(
13
with magnetic stir bar were 2‐chloro‐9H‐carbazole 3i (0.1 (td, J = 7.4, 0.9 Hz, 1H), 3.81 (s, 3H); C NMR (75 MHz, DMSO)
mmol, 100 mol%), aryl boronic acid (0.15 mmol, 150 mol%), δ 156.58, 140.45, 140.02, 136.01, 131.16, 131.07, 129.05,
Pd (dba) (0.01 mmol, 10 mol%), PCy (0.25 mmol, 25 mol %), 125.98, 122.63, 121.60, 121.27, 120.82, 120.53, 119.99, 119.10,
2
2
3
3
K PO (1.27 M in water, 0.34 mmol) and dioxane (2 mL, 0.05 M 112.23, 112.02, 111.32, 55.90; FTIR (neat) υ 3409, 3012, 1733,
3
4
‐
1
+
concentration with respect to 2‐chloro‐9H‐carbazole 3i). The 1599, 1247, 1032, 866, 748 cm ; LRMS m/z (EI): 273.2 (M ),
slurry was sealed and purged with Argon gas for 5 minutes. 273.9, 258.3; HRMS m/z (EI): calcd. C H NO (M ) 273.1155,
The mixture was heated at 100 C (oil bath temperature) for 2 found 273.1154.
+
1
9 15
o
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Organic & Biomolecular Chemistry
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2. (a) B. Akermark, L. Eberson, E. Jonsson and E. PetterssonV,ieJw. OArrtgic.leCOhenmlin.e,
Acknowledgements
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975, 40, 1365‐1367; (b) H.‐J. Knölker and N. O'Sullivan, Tetrahedron,
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