“Golden” Cascade Cyclization to Benzo[c]-Phenanthridines

Article abstract of DOI:10.1002/chem.202102134

Herein, we describe a gold-catalyzed cascade cyclization of Boc-protected benzylamines bearing two tethered alkyne moieties in a domino reaction initiated by a 6-endo-dig cyclization. The reaction was screened intensively, and the scope was explored, resulting in nine new Boc-protected dihydrobenzo[c]phenanthridines with yields of up to 98 %; even a π-extension and two bidirectional approaches were successful. Furthermore, thermal cleavage of the Boc group and subsequent oxidation gave substituted benzo[c]phenanthridines in up to quantitative yields. Two bidirectional approaches under the optimized conditions were successful, and the resulting π-extended molecules were tested as organic semiconductors in organic thin-film transistors.

Full text of DOI:10.1002/chem.202102134

Accepted Article
Accepted Article
Title: “Golden” Cascade Cyclization to Benzo[c]-Phenanthridines
Authors: Christoph M. Hendrich, Sebastian Senn, Lea Haas, Marvin
T. Hoffmann, Ute Zschieschang, Frank Rominger, Matthias
Rudolph, Hagen Klauk, Andreas Dreuw, and A. Stephen K.
Hashmi
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To be cited as: Chem. Eur. J. 10.1002/chem.202102134
Link to VoR: https://doi.org/10.1002/chem.202102134
01/2020

10.1002/chem.202102134
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“Golden” Cascade Cyclization to Benzo[c]-Phenanthridines
Christoph M. Hendrich,[a] Sebastian Senn,[a] Lea Haas,[a] Marvin T. Hoffmann,[b] Ute Zschieschang,[c]
Frank Rominger+,[a] Matthias Rudolph,[a] Hagen Klauk,[c] Andreas Dreuw,[b] and A. Stephen K.
Hashmi*[a]
[a]
M. Sc. C. M. Hendrich, B. Sc. S. Senn, B. Sc. L. Haas, Dr. F. Rominger, Dr. M. Rudolph, Prof. Dr. A. S. K. Hashmi
Organisch-Chemisches Institut
Heidelberg University
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
E-mail: hashmi@hashmi.de (homepage: http://www.hashmi.de)
M. Sc. M. T. Hoffmann, Prof. Dr. A. Dreuw
[b]
Interdisciplinary Center for Scientific Computing (IWR)
Heidelberg University
Im Neuenheimer Feld 205A, 69120 Heidelberg (Germany)
Dr. U. Zschieschang, Dr. H. Klauk
Max Planck Institute for Solid State Research
Heisenbergstr. 1, 70569 Stuttgart (Germany)
Crystallographic investigation
[c]
+
Abstract: Herein we describe a gold-catalyzed cascade cyclization of
Boc-protected benzylamines bearing two tethered alkyne moieties via
a domino reaction initiated by a 6-endo-dig cyclization. The reaction
was screened intensively and the scope was explored, resulting in
nine new Boc-protected dihydrobenzo[c]phenanthridines with yields
of up to 98%; even a -extension and two bidirectional approaches
were successful. Furthermore, a thermal cleavage of the Boc-group
and subsequent oxidation was possible to obtain substituted
benzo[c]phenanthridines in up to quantitative yields. Two bidirectional
approaches were successful using the optimized conditions and the
resulting -extended molecules were tested as organic
semiconductors in organic thin-film transistors.
cyclization covering an innovative expansion of Utimoto’s indole
cyclization.[4] In the following years this methodology was even
extended to up to five tethered alkynes, which in some cases even
gave access to helically chiral compounds.[5] Due to their ability to
create complex molecular structures in only a few steps, cascade
reactions became a powerful synthetic strategy in the recent
time.[6] While in literature many examples for the cyclization of
anilines to indole derivatives are reported (Scheme 1),[7]
examples for a corresponding cyclization of benzylamines to six-
membered N-heterocycle derivatives are rare[8] and Ohno-like
cascade cyclizations of tethered alkynes are completely missing.
We envisioned that such
a
process might deliver
benzo[c]phenanthridines, which are useful intermediates in
organic synthesis and important subunits of various
pharmaceutically important alkaloids.[9] In this context, we herein
wanted to present our studies on a gold-catalyzed cascade
Introduction
cyclization
benzo[c]phenanthidine
of
benzylamines
for
the
which
formation
of
Homogeneous gold catalysis went through an impressive
evolution during the last decades.[1] Not only for scientific reasons,
but also for applications - e.g. natural product synthesis[2] or
materials science,[3] gold catalysis became a versatile tool in
organic chemistry. In 2010, Ohno et al. published a cascade
derivatives,
strategically
complements other synthetic approaches like different palladium-
catalyzed variations[10]
variants.[11,12]
,
light
,
or tert-butoxide-promoted
previous work
NH2
R1
[Au]+
H
N
R2
R1
Ohno et al.
Yamamoto et al.
23 examples
10-96%
R2
R3
R3
electron-rich -systems
this work
Boc
[Au]+
Boc
N
N
1) T
2) O2
R1
R1
H
N
R1
R2
9 examples
44-98%
R2
quant.
R2
R3
R3
electron-poor -systems
R3
Scheme 1. Comparable previous cascade cyclizations of anilines and our benzylamine approach.
1
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Next, we focused on the optimization of this gold-catalyzed step
(Scheme 4). With IPrAuNTf2, a 2.5 mol% catalyst loading turned
out to be most suitable (for more details see Supporting
Information). Then, AgSbF6, PtCl2 and Pd(OAc)2 were tested, but
no product formation was observed with these metal salts (Table
1, entries 1-3). For the screening of the counter anion,[16] IPrAuCl
was activated with different silver salts in CDCl3, before the in situ
formed catalyst was added to the reaction mixture (entries 5-7).
SbF6- turned out to be the best counter ion. The same procedure
was carried out for the screening of the ligand (Figure 1). Besides
the sterically more hindered NHC ligand IPr* (9, entry 8), also
some phosphane-based ligands were tested (9-12), of which the
JohnPhos ligand showed the highest yield. Noticeable is the
Results and Discussion
Our first approach started with the cyclization of the primary
benzylamine 1 as model substrate. To the best of our knowledge
only one gold-catalyzed cyclization for a similar substrate was
conducted until now.[13] Interestingly, besides not identified side
products, 10% of the already oxidized isoquinoline 2 could be
obtained when 1 was treated with 5 mol% of commercially
available IPrAuNTf2. But the low yield could not be improved,
even when the reaction was conducted under an oxygen
atmosphere. The first effort to achieve a cascade cyclization with
primary amine 3 only led to an unselective decomposition of the
starting material instead of the desired formation of
benzo[c]phenanthridine 4 (Scheme 2).
slightly
higher
yield
for
the
pre-activated
JohnPhosAu(MeCN)SbF6 complex (entry 13) in comparison to
the in situ activated catalyst. Interestingly, for some cases also
the intermediate 7a could be observed. Especially for the SPhos
ligand (entry 9), the reaction seems to stop at 7a of the sequence,
the observed yield of 7a was almost ten times higher than the
yield of 6a. Next, temperature variations and different solvents
were tested. The reaction in deuterated DCM or DCE at 50 °C
increased the yields to 96% - in just 1 h reaction time. Surprisingly,
the reaction seems to be highly dependent on the solvent. Even
after 5 h at 50 °C in deuterated benzene and acetonitrile the
conversion is rather low and remarkable amounts of intermediate
7a could be observed.
IPrAuNTf2
NH2
N
(5 mol%)
Ph
DCE, rt
10%
Ph
1
2
NH2
IPrAuNTf2
(5 mol%)
N
DCE, rt
decomposition
Ph
IPr
IPr*
Ph
Ph
4
3
Ph
Ph
Ph
N
Scheme 2. First evaluations for the synthesis of isoquinoline
benzo[c]phenanthridine 4.
2 and
N
N
N
Ph
Ph
Ph
JohnPhos
Ph
8
9
Based on these results and preceding work of Takemoto et al.,
who successfully screened the cyclization of Boc protected
benzylamines to isoquinoline derivatives,[14] benzylamine 3 was
protected with a Boc group (= 5a). This addressed first cyclization
step of our sequence (for the mechanism, compare Scheme 6),
Catalan and co-workers had demonstrated that for similar Boc-
protected benzylamine substrates a 6-endo-dig cyclization is
preferred over a 5-exo-dig cyclization, the latter is dominating for
substrates bearing an electron-withdrawing group (e.g. CF3) in the
benzylic position.[15]
XPhos
SPhos
Cy
Cy
Cy
tBu
P
P
Cy
P
tBu
iPr
iPr
MeO
OMe
10
11
12
iPr
Figure 1. Chemical structure of some ligands used for the screening.
Boc
N
Boc
H
IPrAuNTf2
(5 mol%)
N
DCE, EtOH, rt
52%
Ph
Ph
5a
6a
Scheme 3. Gold-catalyzed cascade cyclization of Boc-protected diyne 5a.
Scheme 4. Screened reaction of diyne 5a to 6a via intermediate 7a.
Thus, the Boc-protected diyne 5a was treated with 5 mol% of
IPrAuNTf2, yielding the expected product 6a in 52% (Scheme 3).
2
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Table 1. Overview of the catalyst systems and conditions for the NMR screening.
Entry
1
Catalyst
Solvent
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CD2Cl2
CD3CN
C6D6
Temperature
Time [h]
Conversion
-
Yield 7a[a]
Yield 6a[a]
AgSbF6
rt
5
5
5
2
2
2
2
5
5
5
2
2
2
1
5
1
1
5
5
1
-
-
2
PtCl2
rt
-
-
-
3
Pd(OAc)2
rt
3%
-
-
4
IPrAuNTf2
rt
75%
100%
100%
100%
7%
3%
3%
2%
-
56%
64%
65%
67%
3%
5
IPrAuCl/AgBF4
rt
6
IPrAuCl/AgPF6
rt
7
IPrAuCl/AgSbF6
rt
8
IPr*AuCl/AgSbF6
SPhosAuCl/AgSbF6
PPh3AuCl/AgSbF6
XPhosAuCl/AgSbF6
JohnPhosAuCl/AgSbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
rt
1%
19%
2%
-
9
rt
27%
11%
99%
100%
100%
52%
94%
100%
100%
76%
53%
100%
2%
10
11
12
13
14
15
16
17
18
19
20
rt
1%
rt
86%
87%
92%
39%
51%
94%
96%
40%
3%
rt
-
rt
-
0 °C
0 °C
50 °C
50 °C
50 °C
50 °C
50 °C
4%
29%
-
-
26%
41%
-
d4-DCE
96%
[a] NMR yield.
Our mechanistic proposal is shown in Scheme 6. We assume that
a similar sequence as published for the indole cascade cyclization
from Ohno is operating.[5a] The nucleophilic attack of the Boc-
protected secondary amino group to the gold-activated triple bond
(A) forms the vinyl gold species (B), which first undergoes
protodeauration, followed by a second nucleophilic attack of the
newly formed double bond to the tethered alkyne (C). The
observation of 7a in the catalyst screenings and isolation of 7j
(compare Table 1 and Table 2) further support this mechanism.
Final protodeauration of vinyl gold species D furnishes product 6a.
After optimization of the gold-catalyzed step we focused on the
cleavage of the Boc-protecting group. Besides common ways like
acid-mediated deprotection methods,[17] an approach of Cava
from 1985[18] looked promising, which we already successfully
used for indolocarbazoles.[3a] This solvent-free thermal
deprotection, originally used for pyrrole-based substances, was
also effective for our Boc-protected product 6a. For this step our
substrate was heated to 200 °C under a nitrogen atmosphere for
solvent under reduced pressure without the need of any further
purification (Scheme 5).
Boc
N
N
1) 200°C, N2
2) CHCl3, air
Ph
Ph
6a
13a
Scheme 5. Conditions for the thermal Boc-deprotection and subsequent
oxidation to benzo[c]phenanthridine 13a.
Even though this procedure already was very simple, we tried to
further simplify it by applying a semi-one-pot synthesis of the gold
catalysis and the deprotection. In a test reaction first the gold
catalysis with 5a was conducted as described, but instead of the
work up, the crude product was directly used for the thermal
deprotection after removing the solvent under reduced pressure.
After complete conversion, it was dissolved in chloroform. Then
air was bubbled through the solution for the oxidation, followed by
flash column chromatography. However, this semi-one pot variant
about 3 h. In
a
very efficient way the oxidized
benzo[c]phenanthridine 13a was directly obtained by bubbling air
through a chloroform solution of the residue after the thermal
treatment. The final product was obtained after removing the
3
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resulted only in a 74% yield, compared to a 95% combined yield
for the two step method.
the backbone of the benzyl moiety. For 6b an isolated yield of
90% was obtained, whereas the yield for the electron-rich 6c
dropped to 44%.
Next, the aryl group connecting the two alkynes was varied.
Besides an electron-withdrawing (R2 = F, 5d) and an electron-
donating group (R2 = Me, 5e), also an attempt for a -extended
naphthalene backbone (5f) was conducted. In contrast to the
upper trend a fluoro substituent at this position (6d) led to a drop
in yield to 67% while 6e bearing the slightly electron-donating
methyl group furnished the corresponding product in 96% yield.
An excellent yield was also obtained for the -extended 6f (90%).
For this substrate, the thermal treatment for the cleavage of the
Boc protecting group was not quantitative, but needed a further
purification step. A short column chromatography resulted in 39%
yield of 13f.
Lastly, different substituents on the alkyne moiety were tested
(5g-j). Substrate 5g, bearing an alkyl group instead of an aryl
substituent, with 98% delivered the highest yield among all
substrates investigated here. With sterically hindered substituents
like TMS- (5h) or tert-butyl (5j) groups only intermediates 7h and
7j were formed which can be explained by the steric repulsion for
the second cyclization step. After its isolation, 5j was again
treated with 2.5 mol% gold catalyst in DCE at higher reaction
temperatures. But even at 80 °C and 100 °C no conversion could
be observed. A possible 5-exo-dig cyclization was not observed
as well. Surprisingly the terminal alkyne 5i did not convert at all.
Boc
N
Boc
H
N
Ph
[Au]
6a
Ph
5a
proto-
deauration
Boc
N
Boc
N
H
Ph
[Au]
-activation
6-endo-dig
hydroarylation
[Au]
D
H
A
Ph
carbo-
auration
amino-
auration
6-endo-dig
hydroamination
Boc
N
Boc
N
C
[Au]
H
Ph
Ph
[Au]
proto-
deauration
B
-activation
Scheme 6. Proposed mechanism.
Boc
Boc
N
JohnPhos(MeCN)SbF6
(2.5 mol%)[a]
N
R1
R1
H
R2
Once, the gold-catalyzed step and the cleavage of the Boc group
were optimized, we explored the scope of this new method
(Scheme 7 and Table 2). For synthesizing the corresponding
alkyne systems 5, different synthetic strategies involving
sequences of Sonogashira cross couplings, were used (see SI for
more details). First, we installed an electron-withdrawing (R1 = F,
5b) and an electron-donating group (R1 = two OMe groups, 5c) in
DCE, 50 °C, 1-4.5 h
R2
R3
5
44-98%
6
R3
Scheme 7. Conditions for the scope of the reaction.[a]For 5c additional 2.5 mol%
catalyst were used.
Table 2. Overview of all examined structures including yields of the gold catalysis and deprotection/oxidation.
Starting material
Diyne 5a-l
Cyclization product 6a-l
Yield
Oxidation product 13a-l
Yield
5a
6a 95%
13a quant.
5b
5c
5d
6b 90%
6c 44%[b]
6d 67%[b]
13b quant.
13c quant.
13d quant.
4
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5e
6e 96%
6f 90%
6g 98%
13e quant.
13f 39%[c]
13g quant.
5f
5g
-
-
5h
5i
7h 76%[d]
-
-
-
-
-
5j
7j 87%
-
5k
6k 65%[f]
13k 77%
5l
6l -[g]
13l 33%[h]
[a] Yield for an one-pot approach. [b] Yields were reproduced by a second independent attempt. [c] An additional purification step in form of a short column
chromatography was needed. [d] NMR yield. [e] No conversion was observed. [f] Combined yields for two isomers (see SI). [g] 6l was not isolated properly and
therefore directly used for the next step. [h] Yield over two steps.
To further expand the possibilities of this powerful cascade
reaction, also two bidirectional approaches were established (5k
and 5l). Unfortunately, the non-aromatized intermediates of 6k
and 6l of the bidirectional gold catalysis could not be isolated and
characterized properly. This might be due to the fact that different
stereoisomers can be formed. The strong twisted N-heterocycle,
in combination with the steric demanding Boc protection group
could form diasteromers, which is also manifested in the X-ray
structure of 6c (Figure 2, left).[19] Nevertheless, the structure of 6k
showing a “trans”-conformation of the two Boc groups was
confirmed by X-ray analysis (Figure 3, left and right top).
was similar to the mono directional method, but needed an
additional workup in form of column chromatography and
subsequent recrystallization (see SI for more information). This
resulted in moderate yields over two steps of 36% (for 13k) and
27% (for 13l), respectively. Both structures, 13k and 13l, were
also confirmed by X-ray crystallography.
In order to estimate the rotational barrier of the Boc groups as well
as the phenyl rings attached to the aromatic core, relaxed scans
were performed on the PBE0-D3/aug-pcseg-1 level of theory as
implemented in the TeraChem software package (for more
information see SI). The barrier for the rotation of the Boc group
is 20.7 kcal/mol, whereas a rotational barrier of 12.6 kcal/mol for
the phenyl group turned out to be lower. Interestingly, in NMR
experiments a coalescence temperature of 318 K between the
two structures can be observed.
Figure 2. Solid state molecular structures of 6c (left) and 13a (right).
Due to the mentioned difficulties the products of the gold catalysis
were directly used for the next step. The deprotection procedure
5
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10.1002/chem.202102134
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thermally cleave the Boc-group and to oxidize the cyclization
products
in
a
semi
one-pot
strategy
to
furnish
benzo[c]phenanthridine derivatives. Lastly, two bidirectional
approaches were successfully conducted and tested as organic
semiconductor in thin-film transistors. The presented reaction
enables an elegant way for the synthesis of highly substituted six-
membered N-heterocycles. This synthetic strategy is especially
interesting for materials science, but could also be used for the
synthesis of pharmaceutically important alkaloids.
Acknowledgements
The authors are grateful to funding by the DFG (SFB 1249-N-
Heteropolyzyklen als Funktionsmaterialien).
Keywords: Homogeneous gold catalysis • cascade reactions •
benzylamines • benzo[c]phenanthridines
Figure 3. Solid state molecular structures of compounds generated in a
bidirectional manner. Left, top: 6k; Right, top: side view of 6k (the Ph-
substituents are omitted for clarity); Left, bottom: 13k; Right, bottom: 13l.
[1]
a) G. Dyker, Angew Chem. Int. Ed. 2000, 39, 4237; Angew. Chem. 2000,
112, 4407; b) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180–3211; c) A.
Arcadi, Chem. Rev. 2008, 108, 3266–3325; d) L. Liu, G. B. Hammond,
Chem. Soc. Rev. 2012, 41, 3129–3139; e) A. S. K. Hashmi, Acc. Chem.
Res. 2014, 47, 864–876; f) D. Zhang, X. Tang, M. Shi, Acc. Chem. Res.
2014, 47, 913–924; g) A. M. Asiri, A. S. K. Hashmi, Chem. Soc. Rev.
2016, 45, 4471-4503; h) A. S. K. Hashmi, F. D. Toste, Modern Gold
Catalyzed Synthesis, Wiley-VCH, Weinheim, 2012; i) F. D. Toste, V.
Michelet, Gold Catalysis: An Homogeneous Approach, Imperial College
Press, London, 2014; j) Z. Rappoport, J. F. Liebman, I. Marek, The
Chemistry of Organogold Compounds, John Wiley & Co., Hoboken, 2014.
a) A. S. K. Hashmi, M. Rudolph, Chem. Soc. Rev. 2008, 37, 1766-1775;
b) D. Pflästerer, A. S. K. Hashmi, Chem. Soc. Rev., 2016, 45, 1331-1367.
c) P. Y. Toullec, V. Michelet, Isr. J. Chem. 2018, 58, 578-585.
Due to the large -system of both bidirectionally obtained
phenanthridines, 13k and 13l are potentially interesting as
organic semiconductors for materials science. Thus, their optical
properties (UV/Vis and fluorescence spectra can be found in SI)
and their potential charge-transport properties were evaluated.
Both molecules are fluorescent and show two local maxima, with
13l exhibiting a bathochromic shift of about 14 nm. The same
trend is observed for the absorption spectra, with an onset of
423 nm for 13k and 438 nm for 13l. Using both materials, we
attempted the fabrication of thin-film transistors (TFTs) in the
inverted staggered (bottom-gate, top-contact) device architecture
on heavily doped silicon substrates using different gate dielectrics
and by deposition of the organic semiconductors by thermal
sublimation in vacuum.[20] However, we were unable to measure
any appreciable drain current or field effect with either 13k or 13l.
Atomic force microscopy (AFM) and scanning electron
microscopy (SEM) images (see SI) indicate that 13l did not form
a closed (or even percolated) film on any of the substrates, which
explains the lack of charge transport. Compound 13k appears to
form a closed film, so the reason for the lack of charge transport
remains unclear. The fact that we were not able to fabricate
functional transistors by vacuum deposition of 13k and 13l does
not mean that these materials may not form well-ordered films
with good charge-transport properties when processed from
solution or produced in the form of single-crystals.
[2]
[3]
a) C. M. Hendrich, L. M. Bongartz, M. T. Hoffmann, U. Zschieschang, J.
W. Borchert, D. Sauter, P. Krämer, F. Rominger, F. F. Mulks, M. Rudolph,
A. Dreuw, H. Klauk, A. S. K. Hashmi, Adv. Synth. Catal. 2021, 363, 549–
557; b) K. Sekine, J. Schulmeister, F. Paulus, K. P.Goetz, F. Rominger,
M. Rudolph, J. Zaumseil, A. S. K. Hashmi, Chem. Eur. J. 2019, 25, 216–
220; c) K. P. Goetz, K. Sekine, F. Paulus, Y. Zhong, D. Roth, D. Becker-
Koch, Y. J. Hofstetter, E. Michel, L. Reichert, F. Rominger, M. Rudolph,
S. Huettner, Y. Vaynzof, E. M. Herzig, A. S. K. Hashmi, J. Zaumseil, J.
Mater. Chem. C 2019, 7, 13493-13501; d) For a review of gold in
materials science, see: C. M. Hendrich, K. Sekine, T. Koshikawa, K.
Tanaka, A. S. K. Hashmi, Chem. Rev. 10.1021/acs.chemrev.0c00824.
a) K. Iritani, S. Matsubara, K. Utimoto, Tetrahedron Lett. 1988, 29, 1799–
1802; b) K. Hirano, Y. Inaba, T. Watanabe, S. Oishi, N. Fujii, H. Ohno,
Adv. Synth. Catal. 2010, 352, 368-372.
[4]
[5]
a) K. Hirano, Y. Inaba, N. Takahashi, M. Shimano, S. Oishi, N. Fujii, H.
Ohno, J. Org. Chem. 2011, 76, 1212–1227; b) K. Hirano, Y. Inaba, K.
Takasu, S. Oishi, Y. Takemoto, N. Fujii, H. Ohno, J. Org. Chem. 2011,
76, 9068–9080. [6] For reviews about cascade reactions, see: a) K. C.
Nicolaou, D. J. Edmonds, P. G. Bulger, Angew. Chem. Int. Ed. 2006, 45,
7134; b) S. F. Kirsch, Synthesis 2008, 20, 3183–3204.
Conclusion
[7]
[8]
G. Abbiati, F. Marinelli, E. Rossi, A. Arcadi, Isr. J. Chem. 2013, 53, 856–
868.
We present a highly effective new cascade cyclization using gold
catalysis. It was possible to optimize the gold-catalyzed step from
initially 52% up to 96% NMR yield by screening different catalysts
and reaction conditions. Overall seven differently substituted Boc-
protected dihydrobenzo[c]phenanthridines were synthesized
showing the dependence of electron-drawing and electron
withdrawing substituents on different positions of the molecule as
well as steric effects. This reaction pattern was then transferred
successfully to bidirectional variants enabling the formation of
large N-heterocyclic -systems. It was further possible to
a) T. Enomoto, S. Obika, Y. Yasui, Y. Takemoto, Synlett 2008, 11, 1647–
1650; b) T. Enomoto, A.-L. Girard, Y. Yasui, Y. Takemoto, J. Org. Chem.
2009, 74, 9158–9164, for other similar strategies see: c) M.-J. Wu, C.-F.
Lin, S.-H. Chen, Org. Lett. 1999, 1, 767–768; d) M.-J. Wu, C.-F. Lin, W.-
D. Lu, J. Org. Chem. 2002, 67, 5907–5912; e) D. Kadzimirsz, D.
Hildebrandt, K. Merz, G. Dyker, Chem. Commun. 2006, 661–662; two
very recent examples: f) G. Tian, L. Song, Z. Li, K. Robeyns, L. Van
Meervelt, E. V. Van der Eycken, Org. Lett. 2020, 22, 8441–8445; g) L.
Song, G. Tian, L. Van Meervelt, E. V. Van der Eycken, Org. Lett. 2020,
22, 6537–6542.
6
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[9]
a) Y. L. Janin, A. Croisy, J.-F. Riou, E. Bisagni, J. Med. Chem. 1993, 36,
3686-3692; b) T. Ishikawa, Med. Res. Rev. 2001, 21, 61–72.
[10] a) S. Pramanik, M. Jash, D. Mondal, C. Chowdhury, Adv. Synth. Catal.
2019, 361, 5223–5238; b) G. Saini, P. Kumar, G. S. Kumar, A. R. K.
Mangadan, M. Kapur, Org. Lett. 2018, 20, 441−444; c) S.-Y. Yang, W.-
Y. Han, D.-L. Zhang, X.-J. Zhou, M. Bai, B.-D. Cui, N.-W. Wan, W.-C.
Yuan, Y.-Z. Chen, Eur. J. Org. Chem. 2017, 996–1003; d) M. Blanchot,
D. A. Candito, F. Larnaud, M. Lautens, Org. Lett. 2011, 13, 1486–1489;
e) G. Maestri, M.-H. Larraufie, É. Derat, C. Ollivier, L. Fensterbank, E.
Lacôte, M. Malacria, Org. Lett. 2010, 12, 5692–5695; f) W. C. Fu, Z.
Wang, W. T. K. Chan, Z. Lin, F. Y. Kwong, Angew. Chem. Int. Ed. 2017,
56, 7166–7170; Angew. Chem. 2017, 129, 7272–7276; g) D. A. Candito,
M. Lautens, Angew. Chem. Int. Ed. 2009, 48, 6713–6716; Angew. Chem.
2009, 121, 6841–6844.
[11] a) H. Jiang, X. An, K. Tong, T. Zheng, Y. Zhang, S. Yu, Angew. Chem.
Int. Ed. 2015, 54, 4055–4059; Angew. Chem. 2015, 127, 4127–4131; b)
M. E. Budén, V. B. Dorn, M. Gamba, A. B. Pierini, R. A. Rossi, J. Org.
Chem. 2010, 75, 2206–2218; c) S. De, S. Mishra, B. N. Kakde, D. Dey,
A. Bisai, J. Org. Chem. 2013, 78, 7823–7844.
[12] For an interesting review about phenanthridines, see: V. Talukdar, A.
Vijayan, N. K. Katari, K. V. Radhakrishnan, P. Das, Adv. Synth. Catal.
2021, 363, 1202–1245.
[13] a) K. Li, J. Ou, S. Gao, Angew. Chem. Int. Ed. 2016, 55, 14778–14783;
Angew. Chem. 2016, 128, 14998–15003; for using a copper catalyst,
see: b) B. Zelenay, P. Munton, X. Tian, S. Díez-González, Eur. J. Org.
Chem. 2019, 29, 4725–4730.
[14] a) T. Enomoto, S. Obika, Y. Yasui, Y. Takemoto, Synlett 2008, 11, 1647–
1650; b) T. Enomoto, A.-L. Girard, Y. Yasui, Y. Takemoto, J. Org. Chem.
2009, 74, 9158–9164.
[15] S. Fustero, I. Ibanez, P. Barrio, M. A. Maestro, S. Catalan, Org. Lett.
2013, 15, 832–835.
[16] J. Schießl, J. Schulmeister, A. Doppiu, E. Wörner, M. Rudolph, R. Karch,
A. S. K. Hashmi, Adv. Synth. Catal. 2018, 360, 3949–3959.
[17] P. G. M. Wuts, T. W. Greene in Greene’s Protective Groups in Organic
Synthesis, 4th ed., John Wiley & Sons, Inc., Hoboken, New Jersey, 2006,
pp. 725–735.
[18] V. H. Rawal, M. P. Cava, Tetrahedron Lett. 1985, 26, 6141–6142.
[19] Deposition
Numbers
<url
href="https://www.ccdc.cam.ac.uk/services/structures?id=doi:10.1002/c
hem.202102134"> 2087651 (for 6c), 2087652 (for 6k), 2087653 (for 13a),
2087654 (for 13f), 2087655 (for 13k), and 2087656 (for 13l)</url> contain
the supplementary crystallographic data for this paper. These data are
provided free of charge by the joint Cambridge Crystallographic Data
Centre and Fachinformationszentrum Karlsruhe <url href="
http://www.ccdc.cam.ac.uk/structures
service</url>.”
">Access
Structures
[20] a) M. Aghamohammadi, R. Rödel, U. Zschieschang, C. Ocal, H.
Boschker, R. T. Weitz, E. Barrena, H. Klauk, ACS Appl. Mater. Interfaces
2015, 7, 22775-22785; b) U. Kraft, J. E. Anthony, E. Ripaud, M. A. Loth,
E. Weber, H. Klauk, Chem. Mater. 2015, 27, 998–1004.
7
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Entry for the Table of Contents
Boc
thermal
deprotection
& oxidation
N
Boc
R1
[Au]+
H
N
N
R1
R1
R2 quantitative
R2
R2
up to 98%
R3
R3
 modular & convergent synthesis
 indroduction of different substituents
 catalyst screening
 late stage functionalisation
R3
The synthesis of substituted benzo[c]phenanthridines using gold catalysis is reported. The applied cascade reaction using different
substituted alkyne systems as starting materials, furnished the corresponding benzo[c]phenanthridines in very high overall yields. In
addition, two -extended molecules were studied as organic semiconductors in organic thin-film transistors.
8
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