Dibenzopyrrolo[1,2-a][1,8]naphthyridines: Synthesis and Structural Modification of Fluorescent L-Shaped Heteroarenes

Article abstract of DOI:10.1021/acs.joc.7b02674

The L-shaped, π-extended pentacycle dibenzopyrrolo[1,2-a][1,8]naphthyridine and its derivatives were synthesized using two methods: fully intramolecular [2 + 2 + 2] cycloaddition and oxidative aromatization using substituted carbodiimide and modification of an electron-rich indole ring of an L-shaped skeleton via electrophilic reaction and cross-coupling. These L-shaped compounds emitted fluorescence in high quantum yield. The position of substituents affected the fluorescence color through two different mechanisms, π-conjugation and skeletal distortion, which caused the substituted L-shaped compounds to emit fluorescence in a variety of colors and to exhibit solvato-fluorochromism.

Full text of DOI:10.1021/acs.joc.7b02674

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Article
Dibenzopyrrolo[1,2-a][1,8]naphthyridines: Synthesis and
Structural Modification of Fluorescent L-Shaped Heteroarenes
Kotaro Tateno, Rie Ogawa, Ryota Sakamoto, Mizuho Tsuchiya, Noriki
Kutsumura, Takashi Otani, Kosuke Ono, Hidetoshi Kawai, and Takao Saito
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02674 • Publication Date (Web): 12 Dec 2017
Downloaded from http://pubs.acs.org on December 15, 2017
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Page 1 of 15
The Journal of Organic Chemistry
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Dibenzopyrrolo[1,2-a][1,8]naphthyridines: Synthesis and Structural
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Modification of Fluorescent L-Shaped Heteroarenes
Kotaro Tateno,*,† Rie Ogawa,† Ryota Sakamoto,‡ Mizuho Tsuchiya,‡ Noriki Kutsumura,§ Takashi
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Otani,ǁ Kosuke Ono,† Hidetoshi Kawai,*,† and Takao Saito*,†
† Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjukuꢀku, Tokyo 162ꢀ8601, Japan
‡ Department of Chemistry, Graduate School of Science, University of Tokyo, 7ꢀ3ꢀ1 Hongo, Bunkyoꢀku, Tokyo 113ꢀ0033, Japan.
§ International Institute for Integrative Sleep Medicine (WPIꢀIIIS), University of Tsukuba, 1ꢀ1ꢀ1 Tennodai, Tsukuba, Ibaraki 305ꢀ8575,
Japan.
ǁ Course of Chemical Engineering, National Institute of Technology, Anan Collage, 265 Aoki, Minobayashi, Tokushima 774ꢀ0017, Japan.
Supporting Information
ABSTRACT: A Lꢀshaped πꢀextended pentacycle, dibenzopyrrolo[1,2ꢀ
a][1,8]naphthyridine, and its derivatives were synthesized using two
methods: fully intramolecular [2+2+2] cycloaddition and oxidative
aromatization using substituted carbodiimide, and modification of an
electronꢀrich indole ring of Lꢀshaped skeleton via electrophilic reaction
and crossꢀcoupling. These Lꢀshaped compounds emitted fluorescence in
high quantum yield. The position of substituents affected the fluoresꢀ
cence color through two different mechanisms, πꢀconjugation and
skeletal distortion, which caused the substituted Lꢀshaped compounds to emit fluorescence in a variety of colors and to exhibit
solvatoꢀfluorochromism.
INTRODUCTION
The development of synthetic methods for multiꢀ
functionalized Nꢀheteroarenes1 has attracted attention for
applications such as organic electronic materials, fluorescent
probes, and biologically active compounds.2 Curved Nꢀ
heteroarenes3ꢀ6 have recently emerged as new promising
candidates for lightꢀemitting materials due to their unique
structural and photophysical properties5,6 in addition to wellꢀ
developed linear Nꢀheteroacenes.7 Hetero [2+2+2] cycloaddiꢀ
tion is a synthetically important tools for construction of mulꢀ
tiꢀsubstituted heterocycles.8 However, only a limited number
of examples have been reported for fully intramolecular hetero
[2+2+2] cycloadditions that can yield biꢀ or tricyclic hetꢀ
Scheme
1.
Synthesis
of
dibenzopyrrolo[1,2ꢀ
eroarenes from a single component.9
a][1,8]naphthyridine.3b
Our interest in the synthesis of nitrogenꢀcontaining
heterocycles using functionalized heterocumulenes10 led to
discovery of stoichiometric and catalytic carbodiimide
[2+2+1] cycloadditions (Pauson−Khand reaction) with carbon
monoxide, in which the C=N bond participates as a 2πꢀ
component.10 Furthermore, we have developed a synthetic
method for the Lꢀshaped πꢀextended pentacycle, dibenꢀ
zopyrrolo[1,2ꢀa][1,8]naphthyridine 2, via fully intramolecular
hetero [2+2+2] cycloaddition using carbodiimide 1 with two
alkyne portions (Scheme 1).3b Prominent features of the Lꢀ
shaped pentacycle include:
•
•
•
A curvedꢀplanar 6ꢀ6ꢀ6ꢀ5ꢀ6 ring system3,4 conjugated
between an electronꢀrich indole ring and an electronꢀ
poor quinoline ring.
Spatially separated frontier molecular orbitals
(FMOs) consisting of the HOMO of the indole ring
and the LUMO of the quinoline ring.
Fluorescence that is minimally quenched, even in poꢀ
lar solvents12 (ФF = 0.80 in hexane, ФF = 0.82 in
CH2Cl2, ФF = 0.83 in methanol)
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RESULTS AND DISCUSSION
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1
2
Synthesis of carbodiimides and 6,7-dimethyl pentacycle
The preparation of carbodiimides 1a-f is shown in Scheme 3.
Addition of lithium trimethylsilylacetylide to 2ꢀ
azidobenzaldehyde 10a gave 11a. Silane reduction and
subsequent Staudinger reaction converted phenylazide 12a to
iminophosphorane 13a, followed by deprotection of the TMS
group to give 14a. Dimerization via azaꢀWittig reaction with
CO2 gave the carbodiimide 1a. Similarly, carbodiimides 1b-e
with substituents at the R6/7 positions were prepared from
benzaldehyde 10a or 10e and various alkynes. Azide 17 with a
phenyl group at the benzylic position was prepared from
azidobenzophenone 15 and converted into amine 18 by
successive hydride reductions with triethylsilane and lithium
aluminum hydride. Urea formation from 18 using triphosgene
and subsequent dehydration gave carbodiimide 1f.
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Next, rhodium(I) catalysts (5ꢀ10 mol %) were screened for
the [2+2+2] cycloaddition of carbodiimide 1b to Lꢀshaped
pentacycle 2b (Table 1). Wilkinson catalyst [RhCl(PPh3)3]
showed high catalytic activity for reaction in toluene at 120 °C
for 1 hour to give 2b in 90% yield after aromatization by
MnO2 (entry 1). For aromatization of the intermediate
cycloadduct by dehydrogenation, MnO2 (3.0 equiv) was the
best oxidant when used at room temperature for 6 h. When the
amount of the catalyst was reduced to 5 mol %, the yield of 2a
decreased to 60% (entry 2). Although [RhCl(cod)]2 (5 mol %)
did not give compound 2b (entry 3), the use of [RhCl(cod)]2 (5
mol %) in combination with various bidentate phosphine
ligands (20 mol %) worked. The use of 1,2ꢀ
Scheme 2. Two methods for synthesis of dibenꢀ
zopyrrolo[1,2ꢀa][1,8]naphthyridine with substituents at
various positions.
This report describes the synthesis of highly fluorescent Lꢀ
shaped dibenzopyrrolo[1,2ꢀa][1,8]naphthyridine, structural
modifications at various positions, and fluorescence
properties. The substituted Lꢀshaped pentacycles 2ꢀ9 were
synthesized via fully intramolecular [2+2+2] cycloaddition of
preꢀsubstituted carbodiimides 1aꢀf (Scheme 2, method A) or
via postꢀsubstitution at the electronꢀrich position of the indole
ring on 2c (Scheme 2, method B). Most of these substituted Lꢀ
shaped derivatives emitted fluorescence with a high quantum
yield (ΦF => 0.63) even in polar solvents, except for the amino
derivatives that exhibited solvatoꢀfluorochromism (ΦF = 0.45
～ 0.12). Interestingly, the fluorescence properties of the
phenyl derivatives depended heavily on the introduced
positions of the phenyl and alkyl groups. The 5,6,7,8ꢀ
tetrasubstituted pentacycle, especially, exhibited emission at a
longer wavelength while retaining high fluorescence quantum
yield. The effect of a bend in the corner unit of the curved Nꢀ
heteroarenes on the photophysical properties is discussed.
bis(diphenylphosphino)ethane
and
1,1’ꢀ
bis(diphenylphosphino)ferrocene resulted in low conversion
(entries 4 and 5), whereas 1,3ꢀbis(diphenylphosphino)propane
or 1,4ꢀbis(diphenylphosphino)butane exhibited high catalytic
activity to produce up to 80% yield (entries 6 and 7). The use
of prepared Rh(dppp)2Cl (10 mol %) afforded 2b in 91% yield
(entry 8), whereas the use of 5 mol % catalyst decreased the
yield of 2b to 26% (entry 9). Thus, the optimized conditions
used for entries 1 and 8 were employed for the [2+2+2] cyꢀ
cloaddition reactions.
Scheme 3. Synthesis of substituted carbodiimides 1aꢀf.
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Table 1. Screening of Rh catalysts and reaction conditions.
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2
3
4
5
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9
Entry Catalyst
X
Ligꢀ
and
Time
/ h
Yield
/ %
/ mol %
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1
2
3
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6
7
8
9
Rh(PPh3)3Cl 10
none
none
none
dppf
dppe
dppp
dppb
none
none
1
90
Rh(PPh3)3Cl
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
5
5
5
5
5
5
1
60
6
NR[a]
28
3
6
30
0.3
2
83
80
Rh(dppp)2Cl 10
Rh(dppp)2Cl
0.3
6
91
5
26
[a] N.R. = No Reaction.
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Derivatization using substituted carbodiimides (Method A)
After determining the optimized reaction conditions for the
synthesis of 2b (R6, R7 = Me), carbodiimides 1a, 1c, and 1d
(R6, R7 = H, Pent, Ph) were converted into 2a, 2c, and 2d,
respectively (Scheme 4a). Compounds 2b and 2c with alkyl
chains were obtained in good yield, but the yield of phenyl
derivative 2d was low (13% yield) due to the formation of
dihydrodibenzonaphthyridine 2d’ (70% yield) as a byꢀproduct
from the intramolecular 2ꢀazadieneꢀDiels−Alder reaction.13
The 5,8ꢀdiphenylꢀsubstituted Lꢀshaped compound 3 (R5, R8 =
Ph) was also obtained in 48% yield from carbodiimide 1f via
[2+2+2] reaction along with the Diels−Alder byꢀproduct 3’
(Scheme 4b).14 The formation of the byꢀproducts 2d’ and 3’
suggested the acceleration of the dienophilicity through the
Thorpe−Ingold effect and/or the reactiveꢀrotamer effect15 in
the carbodiimide 1d and 1f.
Scheme 4. Synthesis of a) diꢀ and b) tetrasubstituted
dibenzopyrrolo[1,2ꢀa][1,8]naphthyridines 2a-d and 3.
were obtained from 4a via Suzuki−Miyaura crossꢀcoupling
using Pd(PPh3)4 as a catalyst in aqueous Na2CO3 and tolueneꢀ
ethanol at 100 °C in good yields. Alkynyl groups were also
added to 4a through Sonogashira crossꢀcoupling using
PdCl2(PPh3)2, CuI, and triethylamine in THF at 80 °C to give
5a-c in good yields. In addition, diamine derivatives 6a-c were
obtained by Buchwald−Hartwig crossꢀcoupling of 4a with
secondary amines using Pd2(dba)3 as a catalyst, XPhos as a
ligand, and KOtBu as a base in toluene at 100 °C in good
yields. The structure of 3,10ꢀdiphenyl pentacycle 4b was
confirmed from singleꢀcrystal Xꢀray crystallography of a
single fluorescent yellow crystal, which revealed the planarity
of the Lꢀshaped skeleton (Figure 1).16
The solubilities of 2c and 3 with pentyl side chains were
greater than those of pentacycles 2a, 2b, and 2d in organic
solvent such as dichloromethane. Therefore, nꢀpentyl
substituents (R6, R7 = Pent) were introduced to all of the Lꢀ
shaped compounds, except for the pentacycles 2a, 2b, and 2d,
to guarantee good solubility of the Lꢀshaped pentacycle
derivatives in common organic solvents.
Post-derivatization of L-shaped skeleton (Method B)
Next, the 3,10ꢀdiiodo pentacycle 4a was prepared in 75%
yield from carbodiimide 1e via [2+2+2] cycloaddition and
aromatization (Scheme 5). Arylꢀsubstituted derivatives 4b-d
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is easy for the Lꢀshaped pentacycle 2c because the electronꢀ
1
2
3
4
5
6
7
8
rich pyrrole ring of Lꢀshaped skeleton is the most reactive
position (Scheme 6). Thus, bromination of 2c with 1.0
equivalent of Nꢀbromosuccinimide (NBS) furnished bromide
7a exclusively, whereas bromination of 2c with 3.0 equivalent
of NBS furnished dibromide 8a. An aryl group was added to
bromide 7a and dibromide 8a through Suzuki−Miyaura crossꢀ
coupling. Reaction of 7a and 8a with phenyl, pꢀ
methoxyphenyl, and mꢀnitrophenyl boronic acid delivered the
arylꢀsubstituted compounds 7b-d and 8b-d in good to
excellent yields, while reaction with pꢀnitrophenyl boronic
acid afforded product 7e in moderate yield. Reaction of 2c
with Vilsmeier reagent gave the formyl derivative 9a in 99%
yield. Subsequent Wittig reaction led to acrylic ester 9b in
92% yield.
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Optical properties of L-shaped pentacycle derivatives
To study the effect of substituents of the Lꢀshaped
compounds on optical properties, UVꢀvisible absorption
spectra and fluorescence spectra of Lꢀshaped pentacycles with
substituents at various positions were obtained and compared.
Figure 2 and Table 2 summarize absorption and emission
wavelengths, fluorescence quantum yields, and fluorescence
lifetimes of 6,7ꢀdisubstituted Lꢀshaped pentacycle 2a-d and
phenylꢀsubstituted Lꢀshaped pentacycles 3, 4b, 7b, and 8b in
dichloromethane. The optical properties can be summarized as
follows. Fluorescence quantum yields were high (0.75–0.93),
yet fluorescence wavelengths ranged from 450 to 550 nm,
depending on the type and position of the substituent (i.e.,
these derivatives produced different colored emissions).
Fluorescence lifetimes of the substituted Lꢀshaped derivatives
were on the order of nanoꢀseconds (τs = 4.25–7.07 ns), which
implies that these derivatives emit from a singlet excited state.
Scheme 5. Synthesis of 3,10ꢀdisubstituted dibenꢀ
zopyrrolo[1,2ꢀa][1,8]naphthyridine 4a-d, 5a-c and 6a-c.
Effect of substituent position
First, the effect of substituents at the 6,7ꢀpositions of
dibenzopyrrolo[1,2ꢀa][1,8]naphthyridine 2a-d were compared
(Table 2). The introduction of methyl (2b), pentyl (2c), or
phenyl substituents (2d) at the 6,7ꢀpositions resulted in a small
shift of absorption λmax and emission λem compared to those of
the parent compound 2a.
Figure
1.
Xꢀray
structures
of
3,10ꢀ
Next, the absorption and emission wavelengths of the phenyl
derivatives of 3, 4b, 7b, and 8b were compared to those of 2c
as a reference compound (Table 2). In the UVꢀVis spectra,
diphenyldibenzopyrrolo[1,2ꢀa][1,8]naphthyridine 4b.16 a)
Top view. b) Side view.
λmax of the 3,10ꢀdiphenyl derivative 4b (R3, R10 = Ph, λmax
=
Introducing substituents to the 5ꢀposition of the pentacycles
Scheme 6. Synthesis of 5ꢀ and 2,5ꢀdisubstituted dibenzopyrrolo[1,2ꢀa][1,8]naphthyridines 7aꢀe, 8aꢀd and 9aꢀb.
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In the fluorescence spectra, the effect of substituent position
410, 432, 456 nm) was redꢀshifted 5 nm from that of 2c
1
2
3
4
5
6
7
8
(reference compound, λmax = 404, 425, 451 nm), although the
maximum absorption wavelength (λmax) of the 6,7ꢀdiphenyl
derivative 2d (R6, R7 = Ph, λmax = 403, 426, 449 nm) was
nearly the same as that of 2c. Interestingly, derivatives with a
phenyl group at the 5ꢀposition, 7b (R5 = Ph, λmax = 412, 433,
460 nm), 8b (R2, R5 = Ph, λmax = 420, 444, 471 nm), and 3 (R5,
R8 = Ph, λmax = 420, 441, 466 nm), had the λmax at a more redꢀ
shifted position than those of 2c, 2d, and 4b.
on the maximum emission wavelength (λem) was more
pronounced and depended on the position. While the λem of
6,7ꢀdiphenyl and 3,10ꢀdiphenyl derivatives 2d (R6, R7 = Ph,
λ
em = 479, 513 nm) and 4b (R3, R10 = Ph, λem = 486, 508 nm)
were redꢀshifted less than 10 nm from that of 2c (reference
compound, λem = 479, 512 nm), the λem of 5ꢀphenyl and 2,5ꢀ
diphenyl derivatives 7b (R5 = Ph, λem = 496, 524 nm) and 8b
(R2, R5 = Ph, λem = 509, 535 nm) were redꢀshifted about 20 nm
from that of 2c. Furthermore, the 5,8ꢀdiphenyl derivatives 3
(R5, R8 = Ph, λem = 505, 546 nm) had a λem value that was redꢀ
shifted about 35 nm from that of 2c.17 These results suggest
that a substitution at the 5ꢀ (and 8ꢀ) positions of the Lꢀshaped
compounds produced an effect on the fluorescence properties
that was different compared with substitution at the other
positions.
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a)
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b)
Origin of long wavelength emission: coplanarity or
distortion
To study the origin of the large redꢀshift in the λmax and λem
of 5,8ꢀdiphenyl derivative
3
compared to those of
unsubstituted 2c or 3,10ꢀdiphenylated 4b, the energy level of
6,7ꢀdiethyl pentacycle (model A), 6,7ꢀdiethyl pentacycles with
phenyl groups at the 5,8ꢀpositions (model B) and 3,10ꢀ
positions (model C) (which have ethyl groups instead of
pentyl groups at the 6,7ꢀpositions) were determined using DFT
calculations at the B3LYP 6ꢀ31G(d) level (Figure 3 and Table
3).18
Figure 2. a) UVꢀVis and fluorescence spectra of reference
compound 2c and diphenyl derivatives 3 and 4b in diꢀ
chloromethane. b) Fluorescence emission of pentacycles 3
and 4b in dichloromethane.
Figure 3 shows the energy levels of FMOs of the model
Table 2. Photophysical properties of dibenzopyrrolo[1,2ꢀ
a][1,8]naphthyridine derivatives in dichloromethane.
b
Comp.
λ
max (abs) / nm
λem
ΦF
τs
/ ns
[ε / 104 cm−1M−1]
/ nmb
402a, 420, 447
Figure 3. Calculated FMOs of model pentacycles B and
C. Geometry optimization (and energies) were calculated
at the B3LYP/6ꢀ31G(d) level.
2a
2b
2c
2d
4b
7b
8b
3
469, 501
474, 508
479, 512
479, 513
486, 508
496, 524
509, 535a
505a, 546
0.75 6.24
0.82 6.18
0.89 6.72
0.84 6.62
0.84 4.25
0.90 6.35
0.93 7.07
0.89 6.44
[0.98], [1.3], [0.95]
403a, 421, 442
[1.5], [1.9], [1.4]
Table 3. HOMO and LUMO energy levels of model penꢀ
tacycles A-C optimized at the B3LYP/6ꢀ31G(d) level.
404a, 425, 451
[1.7], [2.2], [1.5]
403a, 426, 449
[1.2], [1.6], [1.2]
410a, 432, 456
[1.3], [1.9], [1.4]
412a, 433, 460a
[1.6], [2.0], [1.5]
Comp. LUMO
/ eV
HOMO
/ eV
ꢀ(LUMO−HOMO) λcalcd
420a, 444, 471a
[1.2], [1.6], [1.2]
/ eV
3.18
3.16
3.08
/ nm
431
438
453
A
B
C
−1.81
−1.89
−1.82
−4.99
−5.05
−4.90
420a, 441, 466a
[1.5], [1.9], [1.4]
aShoulder peak. bExcitation at λmax (abs).
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pentacycles A-C. For both model pentacylcles B and C, the
Page 6 of 15
1
2
3
4
5
6
7
8
LUMO was located at the quinoline moiety of the Lꢀshaped
skeleton, while the HOMO was located at the indole moiety,
regardless of the position of phenyl groups. Table 3 shows
HOMO and LUMO energy levels of model pentacycles A-C.
For the 3,10ꢀdiphenylated model pentacycle B, energy levels
of both the HOMO and the LUMO were more stable than
those of the model pentacycle A, probably due to the πꢀ
conjugation with the phenyl groups at the 3,10ꢀpositions. The
energy gap between the HOMO and the LUMO levels was
slightly smaller than that of model pentacycle A (0.02 eV),
which corresponds to the observed small redꢀshift of the λmax
for 4b with phenyl groups at the 3,10ꢀpositions.
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In contrast, the effect of phenyl groups on the energy level of
LUMO and HOMO for the 5,8ꢀdiphenylated model pentacycle
C was different than that for the 3,10ꢀdiphenylated B (Table
3). The energy level of the LUMO of C was nearly the same
as that of A, while the energy level of the HOMO of the model
pentacycle
C was somewhat destabilized. The former
negligible effect of phenyl groups at the 5,8ꢀpositions on the
energy level of LUMO was due to the inability of the
introduced phenyl groups to adopt a coplanar conformation
with the pyrrolonaphthyridine skeleton because of steric
hindrance with the 6,7ꢀdiethyl moiety. However, the phenyl
groups at the 5,8ꢀpositions contributed to the increase in the
energy level of the HOMO (Table S1). This destabilization of
the HOMO level could be caused by bending of the skeleton
around the olefinic portion at the 6,7ꢀposition due to 1,3ꢀ
allylicꢀtype strain between the ethyl and phenyl groups,
decreasing the coplanarity between indole and quinoline rings
(Figure 4, Table 4).
Figure 4. Calculated ground state structures of the model
pentacycles B and C and excited state structure C∗. Geꢀ
ometry optimization was calculated at the B3LYP/6ꢀ
31G(d) and TDꢀB3LYP/6ꢀ31G(d) levels. Structures are
omitted hydrogen atoms. Figures (a), (c) and (e) show the
side view and Figures (b), (d) and (f) show the top view of
the calculated pentacycles B, C and C∗, along with the
bond lengths (Å) for the corner rings. Figures (g) and (h)
are schematic presentations of the skeleton based on calꢀ
culated bond length.
Due to this distortion of the skeleton, the HOMO level,
where the olefin bond at the 6,7ꢀposition constitutes the
bonding orbital, is destabilized. In contrast, the bending
around the olefinic bond appeared to have no effect on the
LUMO level, where the olefin bond constitutes the
antibonding orbital. Thus, bending around the 6,7ꢀpositions by
the phenyl groups at the 5,8ꢀpositions contributed to the
reduced energy gap between the HOMO and LUMO levels,
corresponding to the observed redꢀshift of the λmax in the UVꢀ
Vis spectra for 3. Overall, these relations of the FMO levels
with the coplanarity of the Lꢀshaped skeleton suggested that
the observed redꢀshift in the UVꢀVis spectra originated from
πꢀconjugation extension to the phenyl groups for the 3,10ꢀ
diphenyl pentacycle 4b, while the bend around the 6,7ꢀ
positions was the main factor for the redꢀshift of the λmax of
the 5,8ꢀdiphenyl pentacycle 3.
Table 4. Bent angle of the center 6ꢀmembered ring in the
calculated model pentacycles A-C in the ground state and
C∗ in the excited state. Geometry optimization was calcuꢀ
lated at the B3LYP/6ꢀ31G(d) level.
In the fluorescence spectra, more drastic redꢀshifts were
observed for the emission wavelength (λem) of the 5,8ꢀ
diphenylated pentacycle
3
compared to that of the
unsubstituted pentacycle 2c and 3,10ꢀdiphenyl pentacycle 4b
(Figure 2b). The maximum emission wavelengths λem of 3,10ꢀ
and 5,8ꢀdiphenyl derivatives 4b (R3, R10 = Ph, λem = 486, 508
nm) and 3 (R5, R8 = Ph, λem = 505, 546 nm) were redꢀshifted
Bent angle of
Comp.
Bond length at
6,7ꢀposition / Å
the central ring / °a
A
B
2.7
5.0
1.369
1.369
1.376
1.453
about 10 nm and 35 nm, respectively, from that of 2c (λem
=
479, 512 nm). The extended πꢀconjugation and inductive
effect of the phenyl groups was expected to contribute to the
redꢀshift of the maximum emission wavelength. Although the
Stokes shift of 1354 cm−1 for 3,10ꢀdiphenylated substituted 4b
was larger than that for the unsubstituted 2c (1296 cm−1). In
contrast, the 5,8ꢀdiphenyl derivative 3 had a large Stokes shift
C
C∗
23.6
18.1
aCalculated from the strain of boat conformation.
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Page 7 of 15
The Journal of Organic Chemistry
the increase in planarity in the excited state leading to
(3144 cm−1) and maintained a high quantum yield (ΦF = 0.89).
1
2
3
4
intramolecular charge transfer from the HOMO localized on
the electronꢀdonating indole to the LUMO localized on the
quinoline moiety, causing redꢀshifted emission from the more
planar excited state. Consequently, the larger Stokes shift of
the 5,8ꢀdisubstituted pentacycle 3 compared to those of the
other pentacycles derived from planarization in the excited
state.
This outstanding fluorescence property was thought to
originate in the dynamic conformational change from the bent
pentacycle in the ground state to a planar structure in the
excited state.19
5
6
7
8
To gain insights into the conformational change in the
excited state, the coplanarity of the 5,8ꢀdiphenylated model
compound C in the ground state and that of C∗ in the excited
state were compared (Figures 4cꢀh and Table 4). The
calculated structure of the model compound C∗ in the excited
state has a charge transfer character between the indole and
quionline rings (Figure 4h). The bent angle of the corner sixꢀ
membered ring indicates that the 5,8ꢀphenylated model C∗ had
a more flattened skeleton compared to the ground state
structure C. The bond alternation manner also changed
significantly from the ground state to the excited state. While
the corner ring in the ground state adopted a pꢀquinoidal
structure (Figure 4g), that ring in the exited structure adopted a
flattened 1,3ꢀcyclohexadieneꢀtype structure (Figure 4h). Thus,
this conformational change in the corner ring contributed to
Substituent effect based on electron donor and acceptor
Next, the effect of other types of substituents, electronꢀ
donating amino derivatives 6a-c and electronꢀwithdrawing
acrylic ester derivative 9b (Figure 5, Table 5), on the optical
properties of Lꢀshaped pentacycles was examined. As shown
in Table 5, the emission peak wavelength λem of
diaminopentacycles 6b (λem = 500, 528 nm) and 6c (λem = 500,
530 nm) were redꢀshifted about 15 nm from that of 2c, and the
λem of 6a (λem = 522, 565 nm) was shifted about 40 nm from
that of 2c, while the quantum yields were decreased (6a: 0.12,
6b: 0.25, 6c: 0.45). This remarkable redꢀshift of λem for 6a
compared to those of 6b and 6c corresponded to the order of
electronꢀdonating properties of amino groups, which also
correlate with the Hammett σ+ constant of amino groups.20
Moreover, the λem of pentacycle 9b with a acrylic ester group
at the 5ꢀposition (λem = 519, 556 nm) was also shifted about 40
nm while maintaining a high quantum yield (0.69) compared
to that of 2c. The larger redꢀshift of acrylic ester 9b compared
to that of 5ꢀphenyl substituted pentacycle 7b (λem = 496, 524
nm) implies that the redꢀshift of 9b was due to the electronꢀ
withdrawing property and coplanar extension of πꢀconjugation
by the acrylic ester moiety linked to the indole rings.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Substituent effect based on solvent polarity
To compare the cause for the redꢀshift and decrease in the
quantum yield of 3,10ꢀdiamino pentacycles 6a-c with those of
the diphenyl derivative 3 that exhibit a similar redꢀshifted
emission with high quantum yield, fluorescence spectra were
obtained in various solvents. Figures 6 and 7 and Table 6 show
the fluorescence spectra and optical properties of 3,10ꢀ
diamino pentacycle 6a and 5,8ꢀdiphenyl pentacycle 3 in
various solvents. As shown in Figure 6 and Table 6, the
emission peak wavelength λem of 3,10ꢀdiamino pentacycle 6a
was affected by solvent polarity. A blue shift of λem was
observed in lowꢀpolarity solvents (ꢁλem = −28 nm, hexane: λem
= 494 nm, dichloromethane: λem = 522 nm), whereas redꢀshifts
of λem were observed in highly polar solvents (ꢁλem = +13 nm,
DMF: λem = 535 nm). In addition, as the solvent polarity was
reduced, the fluorescence quantum yield of pentacycle 6a
increased. This solvatochromic behavior of 6a with amino
groups is typical for donorꢀacceptor type fluorescent dyes.21 In
contrast, the emission peak wavelength λem of 5,8ꢀdiphenyl
pentacycle 3 was minimally affected by solvent polarity
compared to that of λem of pentacycle 6a (Figure 7, Table 6).
The λem of pentacycle 3 redꢀshifted only 16 nm in DMF
compared to that in hexane. In addition, emission peak
strength at shorter wavelengths (ca. 500 nm) decreased as
Figure 5. UVꢀVis and fluorescence spectra of 6,7ꢀdipentyl
pentacycle 2c, 3,10ꢀdiamino pentacycles 6aꢀc and 5ꢀ
acryloyl substituted pentacycle 9b in dichloromethane.
Table 5. Photophysical properties of various substituted
derivatives in dichloromethane.
b
Comp.
λ
max (abs) / nm
λem
ΦF
τs
/ ns
[ε / 104 cm−1M−1]
/ nmb
404a, 425, 451
2c
6a
6b
6c
9b
479, 512
0.89 6.72
[1.7], [2.2], [1.5]
416a, 440, 464
[1.4], [1.7], [1.6]
522, 565[a] 0.12 9.10
500, 528[a] 0.25 10.1
500, 530[a] 0.45 11.0
solvent polarity increased. In addition, pentacycle
3
maintained a high fluorescence quantum yield regardless of
solvent polarity (hexane: ΦF = 0.73, DMF: ΦF = 0.86). These
observations demonstrate that the 5,8ꢀdiphenyl pentacycle 3
produced efficient emission at a longer wavelength region
while maintaining high fluorescence quantum yield compared
to other pentacycle derivatives.
413, 437, 465
[1.5], [1.9], [1.7]
421a, 446, 482
[1.4], [1.8], [1.3]
438a, 458, 487a
[2.0], [2.2], [1.4]
519, 556
0.69 4.60
aShoulder peak. bExcitation at λmax (abs).
ACS Paragon Plus Environment

CONCLUSION
A new series of Lꢀshaped aza aromatic compounds with
pyrrolo[1,2ꢀa][1,8]naphthyridine
corner
units,
which
possessed highly efficient fluorescence properties, was
synthesized. Two effective approaches that introduced
substituents into different positions of the Lꢀshaped
compounds were also developed: direct construction of the Lꢀ
shaped skeleton bearing substituents via fully intramolecular
[2+2+2]
cycloaddition
from
preꢀsubstituted
diyneꢀ
carbodiimides, and postꢀmodification by introducing
substituents through halogenation and subsequent crossꢀ
coupling to the readyꢀmade Lꢀshaped compounds. These Lꢀ
shaped derivatives exhibited different fluorescence properties
that depended on the types and the introduced positions of
their substituents. In particular, 5,8ꢀdiphenyl pentacycle 3
exhibited emission at a longer wavelength while maintaining
high fluorescence quantum yield (546 nm and ΦF = 0.89 in
CH2Cl2) compared to that of 3,10ꢀdiphenyl pentacycle 4b (508
nm and ΦF = 0.84 in CH2Cl2). This fluorescence of pentacycle
3 (ΦF = 0.86 in DMF) was in marked contrast to the 3,10ꢀ
diamino pentacycle 6a, which showed solvatoꢀfluorochromism
with decreasing fluorescence quantum yield in polar solvent
(ΦF = 0.08 in DMF). The ability to adjust the fluorescence and
modify the structural feature, especially to introuce a bend
effect in the corner unit of the curved Nꢀheteroarenes, will be
useful for application to fluorescent probes, lightꢀemitting
devices, and stimuliꢀresponsive materials. Investigation into
the practicality and applicability of these polyꢀazaꢀaromatic
compounds is underway.3a,6a
EXPERIMENTAL SECTION
General: All melting points were determined on a Yanaco
1
melting point apparatus or METTLER TOLEDO MP90. H
and 13C NMR spectral in ppm down field from
tetramethylsilane (TMS) using an internal standard of TMS or
CDCl3. DEPT was used to assign carbon types. IR spectra
were taken on a JASCO FT/IRꢀ4600 (ATR) and a HORIBA
FTꢀ710. HRMS analysis were performed on a JEOL JMSꢀ
S3000 SpiralTOF (MALDIꢀTOF),
a Bruker Daltonics
microTOF or a Hitachi doubleꢀfocusing Mꢀ80B spectrometer.
UVꢀVis absorption, fluorescence, quantum yields, and
Fluorescence lifetime were obtained on the respective
spectrometers. The Xꢀray analysis data were obtained by using
a Rigaku RꢀAXIS RAPID II R chargeꢀcoupled device (CCD)
apparatus (CuKα radiation, λ = 1.54178 Å). A numerical
absorption correction (ꢀ) was applied. The structures were
solved by direct methods and refined by the fullꢀmatrix leastꢀ
squares method on F2 with anisotropic temperature factors for
nonꢀhydrogen atoms. All the hydrogen atoms were located at
the calculated positions and refined with riding. The
compounds 1b,3b 1c,3b 2b,3b 2c,3b 7aꢀe,3a 8a,3a 8d,3a 13a,11b
13d,11b 1522 and (2ꢀazidoꢀ5ꢀiodophenyl)methanol23 were
synthesized according to the reported procedures.
Synthesis of pentacycle 2a via intramolecular [2+2+2]
cycloaddition of carbodiimide 1a: To Rh(dppp)2Cl (38 mg,
0.039 mmol) in heated toluene solution (5 mL), a toluene
solution (1 mL) of 1a (106 mg, 0.39 mmol) was added at 120
°C. The mixture was stirred for 1 h, followed by addition of
MnO2 (1.0 g, 12 mmol) at room temperature and stirring for
12 h. The suspension was filtered through Celite and the

Page 9 of 15
The Journal of Organic Chemistry
(CH×2), 129.1 (CH), 128.3 (CH×2), 128.0 (CH×3), 127.5
filtrate concentrated to remove the solvent in vacuo. The
1
2
3
4
5
6
7
8
residue was purified by silica gel column chromatography
(chloroform/hexane = 1/2) to give 2a (70 mg, 67%) as a
yellow solid: Mp 140.0−140.6 °C; IR (KBr): 3046, 1550,
1488, 1450, 1180, 1049, 856 cm−1; 1H NMR (300 MHz,
(CH), 127.1 (CH), 126.3 (CH), 125.9 (C), 124.4 (CH), 123.7
(CH), 122.7 (CH), 119.2 (CH), 118.3 (CH), 117.4 (C), 115.2
(C), 31.7 (CH2×2), 30.4 (CH2), 29.4 (CH2), 29.0 (CH2), 28.6
(CH2), 22.4 (CH2), 22.3 (CH2), 14.0 (CH3×2); HRMS (ESI)
(m/z): [M+H]+ calcd for C41H41N2: 561.3264, found 561.3269.
CDCl3) δ: 9.67 (d, J = 8.3 Hz, 1H), 8.11 (d, J = 8.3 Hz, 1H),
7.96 (s, 1H) 7.80 (d, J = 7.4 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H),
7.57 (td, J = 7.4, 1.4 Hz, 1H), 7.46 (td, J = 7.4, 1.4 Hz, 1H),
7.41 (td, J = 7.4, 1.1 Hz, 1H), 7.11 (d, J = 9.2 Hz, 1H), 6.87 (d,
Synthesis of pentacycle 4a via intramolecular [2+2+2]
cycloaddition of carbodiimide 1e: The pentacycle 4a (0.66 g,
75%) was obtained from 1e (1.3 g, 2.4 mmol), Rh(PPh3)3Cl
(0.12 g, 0.13 mmol), toluene (15 mL) and MnO2 (0.58 g, 6.7
mmol) using the general procedure for [2+2+2]cycloaddition.
J = 9.2 Hz, 1H), 6.74 (s, 1H); 13C NMR (76 MHz, CDCl3)
δ:
9
147.6 (C), 146.2 (C), 135.8 (C), 134.2 (C), 134.2 (CH), 129.7
(CH), 129.6 (C), 127.9 (CH), 127.3 (CH), 125.3 (C), 124.8
(CH), 123.2 (CH), 122.7 (CH), 122.2 (CH), 120.4 (CH), 120.3
(CH), 119.4 (C), 117.9 (CH), 100.8 (CH); HRMS (ESI) (m/z):
[M+H]+ calcd for C19H13N2: 269.1073, found 269.1073.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Yellow solid: Mp 212.8−213.2 ˚C; IR (KBr): 2924, 2854,
1
1589, 1535, 1450 cm–1; H NMR (500 MHz, CDCl3)
δ: 9.28
(d, J = 8.9 Hz, 1H), 8.20 (d, J = 1.8 Hz, 1H), 8.11 (s, 1H), 8.05
(d, J = 1.8 Hz, 1H), 7.88 (dd, J = 8.9, 1.8 Hz, 1H), 7.79 (d, J =
8.9 Hz, 1H), 7.66 (dd, J = 8.9, 1.8 Hz, 1H), 6.64 (s, 1H), 2.82
(t, J = 8.2 Hz, 2H), 2.76 (t, J = 8.2 Hz, 2H), 1.72−1.60 (m,
4H), 1.55−1.39 (m, 8H), 0.97 (t, J = 7.0 Hz, 3H), 0.96 (t, J =
Synthesis of pentacycle 2d via intramolecular [2+2+2]
cycloaddition of carbodiimide 1d: The pentacycle 2d (22
mg, 16%) and the byꢀproduct 2d’ (116 mg, 71%) were
obtained from 1d (145 mg, 0.34 mmol), Rh(dppp)2Cl (33 mg,
0.034 mmol), toluene (10 mL) and MnO2 (89 mg, 1.0 mmol)
using the general procedure for [2+2+2]cycloaddition.
7.0 Hz, 3H); 13C NMR (76 MHz, CDCl3)
δ: 146.9 (C), 144.1
(C), 138.0 (CH), 137.3 (C), 136.1 (CH), 133.4 (C), 132.1 (C),
131.2 (CH), 130.4 (C), 129.9 (CH), 129.5 (C), 129.1 (CH),
128.9 (CH), 127.1 (C), 120.2 (C), 119.7 (CH), 98.1 (CH), 89.4
(C), 87.2 (C), 32.3 (CH2×2), 29.6 (CH2), 29.5 (CH2), 29.3
(CH2), 27.6 (CH2), 22.5 (CH2×2), 14.1 (CH3×2); HRMS
(ESI) (m/z): [M+H]+ calcd for C29H31I2N2: 661.0571, found
661.0571.
2d8c: Yellow crystal: Mp 226.1−226.3 °C; IR (KBr): 3055,
1
3024, 2924, 2854, 1944, 1589, 1535, 1443 cm−1; H NMR
(400 MHz, CDCl3) δ: 9.80 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 8.4
Hz, 1H), 7.99 (s, 1H), 7.76−7.66 (m, 3H), 7.55 (td, J = 7.5, 1.1
Hz, 1H), 7.42 (td, J = 7.5, 1.1 Hz, 1H), 7.40 (td, J = 7.5, 1.1
Hz, 1H), 7.36−7.19 (m, 10H), 6.52 (s, 1H); 13C NMR (101
Synthesis of diphenylpentacycle 4b via Suzuki−Miyaura
cross-coupling of 4a: A mixture of diiodide 4a (66 mg, 0.10
mmol), Pd(PPh3)4 (4.0 mg, 0.034 mmol), phenylboronic acid
(30 mg, 0.26 mmol) and 2 M aq. Na2CO3 aq (1 mL) in toluene
(2 mL) and ethanol (2 mL) was stirred at 100 °C for 3 h. The
reaction mixture was extracted with chloroform, washed with
brine, dried over anhydrous sodium sulfate, and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (chloroform/hexane = 1/2) to give compound
4b (48 mg, 83%) as a yellow solid: Mp 174.0−174.5 ˚C; IR
MHz, CDCl3) δ: 147.4 (C), 146.3 (C), 137.4 (C), 137.1 (C),
136.6 (C), 135.0 (C), 134.8 (CH), 132.2 (C), 132.0 (C), 131.2
(CH×2), 130.3 (CH×2), 130.2 (CH), 129.9 (C), 128.3 (CH×
2), 128.13 (CH×2), 128.05 (CH), 127.9 (CH), 127.6 (CH),
127.5 (CH), 125.5 (C), 125.0 (CH), 123.7 (CH), 123.0 (CH),
121.3 (C), 120.7 (CH), 118.3 (CH), 102.9 (CH); HRMS (EI)
(m/z): [M]+ calcd for C31H20N2: 420.1626, found 420.1625.
2d’: White crystal: Mp 113.2−115.0 °C; IR (KBr): 3401,
1
2931, 1581, 1488, 1211 cm−1; H NMR (500 MHz, CDCl3) δ:
1
(KBr): 2924, 2360, 1589, 1458, 1381 cm–1; H NMR (500
7.87 (dd, J = 4.8, 3.6 Hz, 1H), 7.57−7.53 (m, 2H), 7.52−7.48
(m, 3H), 7.34 (br, 1H), 7.30–7.25 (m, 5H), 7.14 (d, J = 4.8 Hz,
2H), 7.09 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 7.4 Hz, 1H), 6.83 (t,
J = 7.4 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 4.39 (s, 2H), 3.91 (s,
2H); 13C NMR (126 MHz, CDCl3) δ: 150.7 (C), 147.3 (C),
144.2 (C), 138.5 (C), 136.7 (C), 132.2 (C), 131.7 (CH×2),
129.0 (CH×2), 128.8 (CH×2), 128.5 (CH), 128.2 (CH×2),
128.0 (CH), 128.0 (CH), 127.6 (CH), 127.4 (CH), 125.2 (C),
124.9 (CH), 124.0 (C), 122.6 (CH), 121.2 (CH), 119.5 (C),
115.0 (C), 113.8 (CH), 88.7 (C), 83.0 (C), 30.0 (CH2), 21.5
(CH2); HRMS (ESI) (m/z): [M+H]+ calcd for C31H23N2:
423.1856, found 423.1856.
MHz, CDCl3) δ: 9.74 (d, J = 8.5 Hz, 1H), 8.35 (s, 1H), 8.25 (d,
J = 8.5 Hz, 1H), 8.06 (s, 1H), 8.01−7.97 (m, 2H), 7.78−7.73
(m, 5H), 7.52−7.48 (m, 4H), 7.42−7.34 (m, 2H), 6.83 (s, 1H),
2.91 (t, J = 7.3 Hz, 2H), 2.84 (t, J = 7.3 Hz, 2H), 1.79–1.67
(m, 4H), 1.58–1.41 (m, 8H), 0.97 (m, 6H); 13C NMR (126
MHz, CDCl3) δ: 147.2 (C), 145.0 (C), 142.3 (C), 140.6 (C),
137.7 (C), 137.5 (C), 135.9 (C), 134.0 (C), 131.4 (CH), 130.4
(C), 130.2 (C), 129.3 (CH), 129.1 (C), 128.9 (CH×2), 128.7
(CH×2), 128.1 (CH), 127.5 (CH×2), 127.4 (CH), 127.3 (CH
×2), 126.6 (CH), 125.6 (C), 125.4 (CH), 122.6 (CH), 120.4
(C), 118.5 (CH), 118.2 (CH), 99.2 (CH), 32.4 (CH2), 32.4
(CH2), 29.7 (CH2), 29.6 (CH2), 29.4 (CH2), 27.7 (CH2), 22.6
(CH2×2), 14.1 (CH3×2); HRMS (ESI) (m/z): [M+H]+ calcd
for C41H41N2: 561.3264, found 561.3262.
Synthesis of pentacycle 3 via intramolecular [2+2+2]
cycloaddition of carbodiimide 1f: The pentacycle 3 (0.64 g,
48%) was obtained from 1f (1.3 g, 2.4 mmol), Rh(PPh3)3Cl
(0.22 g, 0.24 mmol), MnO2 (0.10 g, 1.18 mmol) and toluene (2
mL) using the general procedure for [2+2+2]cycloaddition.
Yellow solid: Mp 105.4−105.9 ˚C; IR (ATR): 3062, 2924,
Synthesis of ditolylpentacycle 4c via Suzuki−Miyaura
cross-coupling of 4a: The pentacycle 4c (20 mg, 69%) was
obtained from 4a (33 mg, 0.05 mmol), pꢀmethylphenylboronic
acid (20 mg, 0.15 mmol), Pd(PPh3)4 (2 mg, 0.0017 mmol), 2
M Na2CO3 aq (0.5 mL), ethanol (1.0 mL) and toluene (3 mL)
using the general procedure for Suzuki coupling describing for
4b. Yellow solid; Mp 196.6−198.1 ˚C; IR (KBr): 3052, 3029,
1
2861, 1951, 1450 cm−1; H NMR (400 MHz, CDCl3)
δ: 9.82
(d, J = 8.3 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.68 (t, J = 7.5
Hz, 1H), 7.59−7.28 (m, 15H), 2.45 (t, J = 8.5 Hz, 2H), 2.04 (t,
J = 8.5 Hz, 2H), 1.32−1.18 (m, 2H), 1.16−0.97 (m, 6H),
1
0.85−0.60 (m, 10H); 13C NMR (76 MHz, CDCl3)
δ: 147.7 (C),
2954, 2916, 2854, 1592, 1538, 1519, 1452, 1390 cm–1; H
145.1 (C), 144.1 (C), 139.1 (C), 136.1 (C), 133.5 (C), 133.4
(C), 132.0 (C), 131.7 (C), 131.6 (C), 131.3 (CH×2), 130.1
NMR (300 MHz, CDCl3)
δ: 9.72 (d, J = 8.7 Hz, 1H), 8.31 (s,
1H), 8.21 (d, J = 8.7 Hz, 1H), 8.05−7.93 (m, 3H), 7.73 (dd, J =
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The Journal of Organic Chemistry
Page 10 of 15
8.7, 1.7 Hz, 1H), 7.67 (d, J = 7.8 Hz, 4H), 7.32 (d, J = 7.8 Hz, 32.39 (CH2), 32.36 (CH2), 29.6 (CH2), 29.5 (CH2), 29.3 (CH2),
1
2
3
4
5
6
7
8
4H), 6.81 (s, 1H), 2.97–2.75 (m, 4H), 2.45 (s, 6H), 1.86–1.64
(m, 4H), 1.62–1.36 (m, 8H), 1.06–0.93 (m, 6H); 13C NMR (76
27.6 (CH2), 22.5 (CH2×2), 14.1 (CH3×2); HRMS (ESI) (m/z):
[M+H]+ calcd for C45H41N2: 609.3264, found 609.3263.
MHz, CDCl3) δ: 147.2 (C), 145.0 (C), 139.5 (C), 137.8 (C),
Synthesis of dialkynylpentacycle 5b via Sonogashira cross-
coupling of 4a: The pentacycle 5b (46 mg, 72%) was obtained
from 4a (66 mg, 0.10 mmol), pꢀtolyl acetylene (35 ꢁL, 0.28
mmol), CuI (0.3 mg, 0.002 mmol), PdCl2(PPh3)2 (3.0 mg,
0.004 mmol), triethylamine (1 mL) and THF (2 mL) using the
general procedure for Sonogashira coupling describing for 5a.
137.7 (C), 137.43 (C), 137.35 (C), 136.4 (C), 135.9 (C), 134.0
(C), 131.4 (CH), 130.5 (C), 130.2 (C), 129.8 (C×2), 129.6
(CH×2), 129.3 (CH), 129.2 (C), 128.1 (CH), 127.5 (CH×2),
127.3 (CH×2), 125.7 (C), 125.1 (CH), 122.6 (CH), 120.4 (C),
118.3 (CH×2), 99.2 (CH), 32.6 (CH2), 32.5 (CH2), 29.9
(CH2), 29.7 (CH2), 29.6 (CH2), 27.8 (CH2×2), 22.7 (CH2),
21.31 (CH3), 21.27 (CH3), 14.3 (CH3×2); HRMS (ESI) (m/z):
[M+H]+ calcd for C43H45N2: 589.3577, found 589.3584.
Yellow solid: Mp 178.7−179.0 ˚C; IR (KBr): 3024, 2924,
9
1
2862, 2206, 1543, 1442 cm–1; H NMR (300 MHz, CDCl3)
δ:
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
9.59 (d, J = 8.7 Hz, 1H), 8.24 (s, 1H), 8.11 (d, J = 8.7 Hz, 1H),
8.05 (d, J = 1.6 Hz, 1H), 7.93 (d, J = 1.6 Hz, 1H), 7.81 (dd, J =
8.7, 1.6 Hz, 1H), 7.61 (dd, J = 8.7, 1.6 Hz, 1H), 7.52−7.48 (m,
4H), 7.20 (dd, J = 8.2, 2.1 Hz, 4H), 6.75 (s, 1H), 2.89 (t, J =
7.8 Hz, 2H), 2.82 (t, J = 7.8 Hz, 2H), 2.40 (s, 6H), 1.77−1.63
(m, 4H), 1.60−1.41 (m, 8H), 0.99 (t, J = 7.1 Hz, 3H), 0.98 (t, J
Synthesis of bis(p-nitorophenyl)pentacycle 4d via
Suzuki−Miyaura cross-coupling of 4a: The pentacycle 4d
(46 mg, 93%) was obtained from 4a (64 mg, 0.10 mmol), pꢀ
nitrophenylboronic acid (43 mg, 0.26 mmol), 2 M Na2CO3 aq
(1 mL), Pd(PPh3)4 (4 mg, 0.034 mmol), ethanol (2 mL) and
toluene (2 mL) using the general procedure for Suzuki
coupling describing for 4b. Yellow solid; Mp 258.1−258.4 ˚C;
IR (KBr): 3070, 2924, 2854, 1589, 1512, 1450, 1342 cm–1; 1H
= 7.1 Hz, 3H); 13C NMR (76 MHz, CDCl3)
δ: 147.2 (C), 144.8
(C), 138.5 (C), 137.9 (C), 137.7 (C), 133.9 (C), 132.3 (CH),
131.52 (CH×2), 131.45 (CH×2), 130.9 (CH), 130.8 (CH),
130.3 (C), 129.7 (C), 129.3 (C), 129.2 (CH×2), 129.1 (CH×
2), 127.6 (CH), 126.4 (CH), 125.2 (C), 123.6 (CH), 120.7 (C),
120.4 (C), 120.1 (C), 119.8 (C), 118.0 (CH), 117.4 (C), 99.0
(CH), 90.3 (C), 90.2 (C), 89.8 (C), 88.2 (C), 32.38 (CH2),
32.35 (CH2), 29.6 (CH2), 29.5 (CH2), 29.4 (CH2), 27.7 (CH2),
22.6 (CH2 × 2), 21.6 (CH3), 21.5 (CH3), 14.1 (CH3 × 2);
HRMS (MALDIꢀTOF, DCTB) (m/z): [M+H]+ calcd for
C47H45N2: 637.3577, found 683.3576.
NMR (300 MHz, CDCl3) δ: 9.78 (d, J = 8.7 Hz, 1H), 8.44 (s,
1H), 8.40−8.26 (m, 5H), 8.17 (d, J = 1.8 Hz, 1H), 8.07−7.98
(m, 2H), 7.96−7.84 (m, 4H), 7.76 (t, J = 8.7 Hz, 1H), 6.90 (s,
1H), 2.97 (t, J = 7.6 Hz, 2H), 2.89 (t, J = 8.3 Hz, 2H),
1.86−1.67 (m, 4H), 1.56ꢀ1.45 (m, 8H), 0.99 (t, J = 7.2 Hz,
3H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (151 MHz, CDCl3)
δ:
148.8 (C), 147.9 (C), 147.3 (C), 147.1 (C), 146.8 (C), 145.8
(C), 138.3 (C), 135.3 (C), 134.9 (C), 133.6 (C), 131.9 (CH),
130.8 (C), 130.7 (C), 129.7 (C), 129.0 (CH), 128.8 (CH),
128.1 (CH×2), 128.0 (CH×2), 126.7 (CH), 125.8 (C), 124.4
Synthesis of dialkynylpentacycle 5c via Sonogashira cross-
coupling of 4a: The pentacycle 5c (53 mg, 82%) was obtained
from 4a (66 mg, 0.10 mmol), cyclohexyl acetylene (37 ꢁL,
0.28 mmol), CuI (0.3 mg, 0.002 mmol), PdCl2(PPh3)2 (3.0 mg,
0.004 mmol), triethylamine (1 mL) and THF (2 mL) using the
general procedure for Sonogashira coupling describing for 5a.
Yellow solid: Mp 94.2−94.6 ˚C; IR (ATR): 3055, 2931, 2854,
(CH×2), 124.3 (CH×2), 122.7 (CH), 121.0 (C) 119.4 (CH),
118.8 (CH), 99.8 (CH), 32.6 (CH2 ×2), 29.9 (CH2), 29.8
(CH2), 29.6 (CH2), 27.9 (CH2), 22.78 (CH2), 22.75 (CH2),
14.27 (CH3), 14.25 (CH3); HRMS (EI) (m/z): [M]+ calcd for
C41H38N4O4: 650.2893, found 650.2898.
1
2229, 1589, 1543, 1450, 1389 cm–1; H NMR (400 MHz,
Synthesis of dialkynylpentacycle 5a via Sonogashira cross-
coupling of 4a: A mixture of diiodide 4a (66 mg, 0.10 mmol),
PdCl2(PPh3)2 (3.0 mg, 0.004 mmol), CuI (0.4 mg, 0.002
mmol), triethylamine (1 mL) and phenyl acetylene (30 ꢁL,
0.28 mmol) in THF (3 mL) was stirred at 60 °C for 2 h. The
reaction mixture was quenched by addition of saturated
aqueous ammonium chloride. The mixture was extracted with
ethyl acetate, dried over anhydrous sodium sulfate, and
concentrated in vacuo. The residue was purified by silica gel
column chromatography (chloroform/hexane = 1/4) to give
compound 5a (57 mg, 94%) as a yellow solid: Mp
CDCl3) δ: 9.54 (d, J = 8.6 Hz, 1H), 8.24 (s, 1H), 8.07 (d, J =
8.6 Hz, 1H), 7.95 (d, J = 1.7 Hz, 1H), 7.81 (d, J = 1.7 Hz, 1H),
7.71 (dd, J = 8.6, 1.7 Hz, 1H), 7.49 (dd, J = 8.6, 1.7 Hz, 1H),
6.73 (s, 1H), 2.90 (t, J = 8.0 Hz, 2H), 2.83 (t, J = 8.0 Hz, 2H),
2.73−2.56 (m, 2H), 2.02−1.88 (m, 4H), 1.87−1.57 (m, 13H),
1.52−1.33 (m, 15H), 0.97 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 7.1
Hz, 3H); 13C NMR (76 MHz, CDCl3)
δ: 147.3 (C), 144.8 (C),
137.8 (C), 133.8 (C), 132.8 (CH), 130.83 (CH), 130.80 (CH),
130.4 (C), 129.8 (C), 129.3 (C), 127.6 (CH), 126.7 (CH),
125.3 (C), 123.7 (CH), 120.6 (C), 120.5 (C), 118.3 (C), 117.9
(CH), 99.0 (CH), 95.4 (C), 93.0 (C), 81.7 (C), 80.7 (C), 33.1
(CH2×2), 32.9 (CH2×2), 32.52 (CH2×2), 32.50 (CH2), 30.0
(CH), 29.94 (CH), 29.85 (CH2), 29.8 (CH2), 29.7 (CH2), 29.5
(CH2), 27.8 (CH2), 26.2 (CH2), 26.1 (CH2), 25.2 (CH2), 25.1
(CH2), 22.7 (CH2×2), 14.3 (CH3×2); HRMS (ESI) (m/z):
[M+H]+ calcd for C45H53N2: 621.4203, found 621.4198.
101.4−101.8 ˚C; IR (ATR): 3055, 2924, 2862, 2206, 1597,
1
1443, 1450, 1389 cm–1; H NMR (400 MHz, CDCl3)
δ: 9.57
(d, J = 8.7 Hz, 1H), 8.22 (s, 1H), 8.09 (d, J = 8.7 Hz, 1H), 8.04
(d, J = 2.4 Hz, 1H), 7.92 (d, J = 8.7 Hz, 1H), 7.79 (dd, J = 8.7,
2.4 Hz, 1H), 7.67−7.54 (m, 5H), 7.45−7.32 (m, 6H), 6.73 (s,
1H), 2.87 (t, J = 7.5 Hz, 2H), 2.80 (t, J = 8.2 Hz, 2 H),
1.82−1.64 (m, 4H), 1.61−1.40 (m, 8H), 0.99 (t, J = 6.9 Hz,
Synthesis of diaminopentacycle 6a via Buchwald−Hartwig
cross-coupling of 4a: A toluene solution (2 mL) of Pd2(dba)3
(5.0 mg, 0.005 mmol) and XPhos (10 mg, 0.020 mmol) was
stirred at 100 °C for 10 min, followed by addition of the
mixture of diiodide 4a (66 mg, 0.10 mmol), tBuOK (45 mg,
0.24 mmol) and piperidine (30 ꢂL, 0.30 mmol) and stirring at
100 °C for 5 min. The reaction was quenched by addition of
saturated aqueous ammonium dichloride. The mixture was
extracted with chloroform, dried over anhydrous sodium
3H), 0.98 (t, J = 6.9 Hz, 3H); 13C NMR (126 MHz, CDCl3)
δ:
147.0 (C), 144.8 (C), 137.6 (C), 133.9 (C), 132.1 (CH), 131.63
(CH×2), 131.58 (CH×2), 130.9 (CH), 130.6 (CH), 130.1
(C), 129.7 (C), 129.2 (C), 128.4 (CH×2), 128.3 (CH×3),
127.8 (CH), 127.5 (CH), 126.3 (CH), 125.0 (C), 123.9 (C),
123.7 (CH), 123.3 (C), 120.2 (C), 119.4 (C), 118.0 (CH),
117.1 (C), 99.0 (CH), 91.0 (C), 90.0 (C), 89.6 (C), 88.0 (C),
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The Journal of Organic Chemistry
128.5 (CH), 128.2 (CH), 126.3 (C), 124.4 (CH×4), 123.2
sulfate, and concentrated in vacuo. The residue was purified
1
2
3
4
5
6
7
8
by silica gel column chromatography (ethyl acetate/hexane =
1/20) to give compound 6a (34 mg, 61%) as a yellow solid:
(CH×4), 123.0 (CH), 122.0 (CH), 121.8 (CH), 120.9 (CH),
120.0 (C), 119.6 (CH), 118.8 (CH), 117.7 (CH), 116.9 (CH),
98.2 (CH), 32.35 (CH2), 32.29 (CH2), 29.8 (CH2), 29.5 (CH2),
29.4 (CH2), 27.6 (CH2), 22.6 (CH2), 22.5 (CH2), 14.1 (CH3×2);
HRMS (ESI) (m/z): [M+Na]+ calcd for C53H51N4: 743.4108,
found 743.4103.
Mp 178.7−179.0 ˚C; IR (ATR): 3055, 2931, 2854, 1612, 1535,
1
1458, 1389 cm–1; H NMR (300 MHz, CDCl3)
δ: 9.52 (d, J =
9.2 Hz, 1H), 8.18 (s, 1H), 8.05 (d, J = 9.2 Hz, 1H), 7.53 (dd, J
= 9.2, 2.5 Hz, 1H), 7.28 (d, J = 2.5 Hz, 1H), 7.23 (dd, J = 9.2,
2.5 Hz, 1H), 7.15 (d, J = 2.5 Hz, 1H), 6.69 (s, 1H), 3.30 (t, J =
5.3 Hz, 4H), 3.23 (t, J = 5.3 Hz, 4H), 2.90 (t, J = 7.8 Hz, 2H),
2.82 (t, J = 7.8 Hz, 2H), 1.86−1.59 (m, 16H), 1.57−1.39 (m,
8H), 0.97 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 7.1 Hz, 3H); 13C
Synthesis of 5-phenylpentacycle 7b via Suzuki−Miyaura
cross-coupling of 7a: A toluene solution (0.4 mL) of Pd(dba)2
(1.5 mg, 0.0026 mmol) and 1.0 M tBu3P in toluene (3 ꢁL,
0.003 mmol) was added. The mixture solution was stirred at
room temperature for 10 min, followed by addition of the
mixture of bromide 7a (20.6 mg, 0.042 mmol), K3PO4 (55 mg,
0.26 mmol) and phenylboronic acid (19 mg, 0.16 mmol) and
stirring for 9 hours at 70 °C. The reaction mixture was
quenched by addition of saturated aqueous ammonium
dichloride, extracted with chloroform, dried over anhydrous
sodium sulfate, and concentrated in vacuo. The residue was
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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55
56
57
58
59
60
NMR (76 MHz, CDCl3) δ: 149.1 (C), 148.6 (C), 145.4 (C),
141.1 (C), 137.2 (C), 130.4 (C), 129.74 (CH), 129.68 (C),
129.5 (C), 128.6 (C), 128.1 (CH), 126.2 (C), 123.8 (CH),
119.8 (C), 118.2 (CH), 115.9 (CH), 109.8 (CH), 106.6 (CH),
97.8 (CH), 52.7 (CH2×2), 51.2 (CH2×2), 32.40 (CH2), 32.37
(CH2), 29.8 (CH2), 29.5 (CH2), 29.4 (CH2), 27.6 (CH2), 26.2
(CH2 ×2), 25.9 (CH2 ×2), 24.4 (CH2), 24.3 (CH2), 22.58
purified
by
silica
gel
column
chromatography
(CH2), 22.56 (CH2), 14.1 (CH3 × 2); HRMS (ESI) (m/z):
[M+H]+ calcd for C39H51N4: 575.4108, found 575.4104.
(chloroform/hexane = 1/30) to give compound 7b (19 mg,
94%) as a yellow solid: The spectral data of 7b were identical
to those reported in the literature.3a
Synthesis of diaminopentacycle 6b via Buchwald−Hartwig
cross-coupling of 4a: The title compound 6b (45 mg, 86%)
was obtained from 4a (66 mg, 0.10 mmol), morphorine (26
ꢂL, 0.30 mmol), Xphos (10 mg, 0.020 mmol), Pd2(dba)3 (5.0
mg, 0.005 mmol), KOtBu (45 mg, 0.24 mmol) and toluene (2
mL) using the general procedure for Buchwald−Hartwig
coupling describing for 6a. Yellow solid; Mp 208.3−208.7 ˚C;
IR (ATR): 3062, 2954, 2854, 1612, 1535, 1396 cm–1; 1H NMR
Synthesis
of
2,5-diphenylpentacycle
8b
via
Suzuki−Miyaura cross-coupling of 8a: A mixture of
dibromide 8a (16 mg, 0.028 mmol), Pd(PPh3)4 (2.0 mg, 0.0017
mmol), phenylboronic acid (13 mg, 0.11 mmol) and 2 M
K2CO3 aq (0.1 mL) in 1,4ꢀdioxane (0.3 mL) was stirred at 90
°C for 6 h. The reaction mixture was diluted with H2O (10
mL) and extracted with CHCl3 (3×25 mL). The combined
organic layers were dried over anhydrous sodium sulfate and
concentrated in vacuo. The residue was purified by silica gel
column chromatography (chloroform/hexane = 1/2) to give 8b
(9.5 mg, 61%) as a yellow solid: Mp 134.2−134.5 ˚C; IR
(KBr): 3055, 3024, 2954, 2924, 2854, 1597, 1450, 1389 cm–1;
(500 MHz, CDCl3) δ: 9.53 (d, J = 8.7 Hz, 1H), 8.17 (s, 1H),
8.05 (d, J = 8.7 Hz, 1H), 7.47 (dd, J = 8.7, 2.4 Hz, 1H), 7.24
(d, J = 8.7 Hz, 1H), 7.17 (dd, J = 8.7, 2.4 Hz, 1H), 7.11 (d, J =
2.4 Hz, 1H), 6.69 (s, 1H), 3.93 (t, J = 4.5 Hz, 8H), 3.28 (t, J =
4.5 Hz, 4H), 3.24 (t, J = 4.5 Hz, 4H), 2.87 (t, J = 8.0 Hz, 2H),
2.80 (t, J = 8.0 Hz, 2H), 1.75−1.64 (m, 4H), 1.55−1.38 (m,
8H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (t, J = 6.9 Hz, 3H); 13C
1H NMR (300 MHz, CDCl3)
δ: 10.20 (d, J = 1.4 Hz, 1H), 8.33
(s, 1H), 8.19 (d, J = 8.3 Hz, 1H), 7.95−7.85 (m, 3H), 7.73
(ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.65−7.45 (m, 9H), 7.44−7.32
(m, 2H), 2.88 (t, J = 8.3 Hz, 2H), 2.56 (t, J = 8.3 Hz, 2H),
1.78–1.62 (m, 2H), 1.55–1.41 (m, 4H), 1.39–1.22 (m, 2H),
1.11 (tq, J = 7.3, 7.3 Hz, 2H), 0.98 (t, J = 7.3 Hz, 3H), 0.79 (t,
J = 7.3 Hz, 3H), 0.75 (tq, J = 7.9, 7.9 Hz, 2H); 13C NMR (76
MHz, CDCl3) δ: 147.8(C), 145.8 (C), 142.9 (C), 137.0 (C),
136.3 (C), 133.9 (C), 132.6 (C), 131.7 (C), 131.6 (CH×2),
131.4 (C), 131.0 (CH), 130.0 (C), 129.6 (CH), 129.0 (CH×2),
128.2 (CH×2), 127.82 (CH×2), 127.77 (CH×2), 127.4
(CH), 126.8 (CH), 125.7 (C), 124.9 (CH), 122.4 (CH), 120.1
(C), 119.6 (CH), 116.9 (CH), 115.2 (C), 32.5 (CH2), 31.9
(CH2), 29.9 (CH2×2), 28.8 (CH2), 27.7 (CH2), 22.7 (CH2),
22.5 (CH2), 14.24 (CH3), 14.15 (CH3); HRMS (ESI) (m/z)
[M+H]+ calcd for C41H41N2: 561.3264, found 561.3271.
NMR (126 MHz, CDCl3) δ: 148.1 (C), 147.5 (C), 145.6 (C),
141.3 (C), 137.5 (C), 130.5 (C), 129.9 (CH), 129.9 (C), 129.7
(C), 128.7 (C), 128.4 (CH), 126.1 (C), 122.5 (CH), 120.0 (C),
118.4 (CH), 114.6 (CH), 109.6 (CH), 105.9 (CH), 97.9 (CH),
67.2 (CH2×2), 66.9 (CH2×2), 51.2 (CH2×2), 49.9 (CH2×2),
32.39 (CH2), 32.38 (CH2), 29.7 (CH2), 29.6 (CH2), 29.4 (CH2),
27.7 (CH2), 22.57 (CH2), 22.55 (CH2), 14.09 (CH3), 14.07
(CH3); HRMS (ESI) (m/z): [M+H]+ calcd for C37H47N4O2:
579.3694, found 579.3695.
Synthesis of diaminopentacycle 6c via Buchwald−Hartwig
cross-coupling of 4a: The pentacycle 6c (63 mg, 86%) was
obtained from 4a (66 mg, 0.10 mmol), diphenylamine (51 mg,
0.30 mmol), Xphos (10 mg, 0.020 mmol), Pd2(dba)3 (5.0 mg,
0.005 mmol), KOtBu (45 mg, 0.24 mmol) and toluene (2 mL)
using the general procedure for Buchwald−Hartwig coupling
describing for 6a. Brown solid; Mp 68.8−69.3 ˚C: IR (ATR):
Synthesis of 2,5-diarylpentacycle 8c via Suzuki−Miyaura
cross-coupling of 8a: The pentacycle 8c (9.7 mg, 66%) was
obtained from dibromide 8a (13 mg, 0.024 mmol), pꢀ
methoxyphenylboronic acid (14 mg, 0.091 mmol), 2 M K2CO3
aq (0.1 mL), Pd(PPh3)4 (1.7 mg, 0.0016 mmol) and 1,4ꢀ
dioxane (0.3 mL) using the general procedure for Suzuki
coupling describing for 8b. Yellow solid; Mp 170.1−170.5 ˚C;
1
3448, 3055, 2924, 2862, 1589, 1457, 1389 cm−1; H NMR
(300 MHz, CDCl3) δ: 9.61 (d, J = 9.0 Hz, 1H), 8.15 (s, 1H),
8.03 (d, J = 9.0 Hz, 1H), 7.58−7.51 (m, 3H), 7.40−7.29 (m,
6H), 7.25−7.15 (m, 11H), 7.11 (td, J = 6.8, 1.3 Hz, 2H), 7.00
(td, J = 6.8, 1.3 Hz, 2H), 6.67 (s, 1H), 2.86 (tt, J = 7.5, 7.5 Hz,
4H), 1.80−1.63 (m, 4H), 1.57−1.39 (m, 8H), 0.97 (t, J = 7.1
Hz, 3H), 0.96 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz,
IR (KBr): 3055, 2954, 2924, 2854, 1605, 1520, 1450, 1396
1
CDCl3)
δ: 148.6 (C×2), 147.7 (C×2), 146.2 (C), 144.5 (C),
cm–1; H NMR (300 MHz, CDCl3)
δ: 10.14 (d, J = 1.4 Hz,
142.8 (C), 142.4 (C), 137.7 (C), 131.3 (C), 130.8 (C), 130.1
(CH), 130.0 (C), 129.4 (CH×4), 129.1 (C), 129.0 (CH×4),
1H), 8.30 (s, 1H), 8.18 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 8.0 Hz,
1H), 7.82 (d, J = 8.8 Hz, 2H), 7.72 (td, J = 7.5, 1.4 Hz, 1H),
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7.57 (dd, J = 8.2, 1.4 Hz, 1H), 7.48 (td, J = 7.5, 0.9 Hz, 1H), 51.7 (CH3), 32.5 (CH2), 31.9 (CH2), 30.1 (CH2), 30.0 (CH2),
1
2
3
4
5
6
7
8
7.44 (d, J = 8.6 Hz, 2H), 7.37 (d, J = 8.2 Hz, 1H), 7.10 (d, J =
8.8 Hz, 2H), 7.05 (d, J = 8.6 Hz, 2H), 3.93 (s, 3H), 3.92 (s,
3H), 2.86 (t, J = 8.1 Hz, 2H), 2.58 (t, J = 8.5 Hz, 2H), 1.78–
1.63 (m, 2H), 1.56–1.25 (m, 6H), 1.13 (tq, J = 7.5, 7.5 Hz,
2H), 0.98 (t, J = 7.5 Hz, 3H), 0.88–0.71 (m, 5H); 13C NMR
(76 MHz, CDCl3) δ: 159.1(C), 158.9 (C), 147.9 (C), 145.8 (C),
136.7 (C), 135.6 (C), 133.9 (C), 132.5 (CH×2), 131.9 (C×2),
131.3 (C), 130.8 (CH), 129.7 (C), 129.6 (CH), 128.7 (CH×2),
128.3 (C), 127.83 (CH), 127.80 (CH), 125.7 (C), 124.9 (CH),
122.1 (CH), 120.2 (C), 119.5 (CH), 116.4 (CH), 114.9 (C),
114.5 (CH×2), 113.7 (CH×2), 55.6 (CH3×2), 32.6 (CH2),
32.0 (CH2), 30.0 (CH2), 29.9 (CH2), 28.8 (CH2), 27.7 (CH2),
22.7 (CH2), 22.6 (CH2), 14.24 (CH3), 14.20 (CH3); HRMS
(ESI) (m/z): [M+H]+ calcd for C43H45N2O2: 621.3476, found
621.3472.
29.9 (CH2), 27.9 (CH2), 22.8 (CH2), 22.7 (CH2), 14.2 (CH3×
2); HRMS (EI) (m/z): [M]+ calcd for C33H36N2O2: 492.2771,
found 429.2779.
Synthesis of 2-azido-5-iodobenzaldehyde 10e: To
a
dichloromethane suspension (150 mL) of PCC (4.9 g, 23
mmol) and Celite (10 g), a dichloromethane solution (20 mL)
of (2ꢀazidoꢀ5ꢀiodophenyl)methanol (4.2 g, 15 mmol) was
added at room temperature. After being stirred for 16 h, the
suspension was filtered through a pad of silica (chloroform:
500 mL) and the filtrate concentrated to remove the solvent in
vacuo. The residue was recystalized (chloroform/hexane) to
give azidoaldehyde 10a (2.4 g, 58%) as a brown solid: Mp;
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
81.8−82.8 ˚C; IR (KBr): 3069, 2862, 2123, 1669, 1573, 1458,
1
1389, 1292, 1273, 1254 cm–1; H NMR (400 MHz, CDCl3)
δ:
10.22 (s, 1H), 8.15 (d, J = 2.2 Hz, 1H), 7.88 (dd, J = 8.5, 2.2
Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H); 13C NMR (101 MHz,
Synthesis of formylpentacycle 9a via Vilsmeir reaction of
2c: A DMF solution (1 mL) of phosphoryl chloride (0.11 mL,
1.2 mmol) was stirred for 30 min at 0 °C, followed by addition
of 2c (120 mg, 0.3 mmol) at room temperature and stirring for
2 h. The reaction mixture was quenched by addition of cooled
water, extracted with ethyl acetate, dried over anhydrous
sodium sulfate, and concentrated in vacuo. The residue was
CDCl3) δ: 187.2 (CHO), 143.9 (CH), 142.8 (C), 137.9 (CH),
128.4 (C), 121.1 (CH), 88.5 (C); HRMS (FAB) (m/z): [M+H]+
calcd for C7H5IN3O: 273.9477, found 273.9475.
Synthesis of alkynyl benzylalcohol 11e: To a THF solution
(100 mL) of 1ꢀheptyne (2.9 mL, 22 mmol) was added a 2.54
M hexane solution of nꢀbutyllithium (8.1 mL, 21 mmol) at
−78 °C. After being stirred for 1 h, a THF solution (5 mL) of
2ꢀazidoꢀ5ꢀiodobenzaldehyde 10e (4.7 g, 17 mmol) was added.
The reaction mixture was quenched by addition of saturated
aqueous ammonium chloride, extracted with ethyl acetate,
washed with brine, dried over anhydrous magnesium sulfate,
and concentrated in vacuo. The residue was purified by silica
gel column chromatography (ethyl acetate/hexane = 1/4) to
give alkynyl azide 11e (6.2 g, 98%) as a yellow oil; IR (neat):
3386, 2931, 2862, 2129, 1473, 1296 cm–1; 1H NMR (400 MHz,
purified
by
silica
gel
column
chromatography
(chloroform/hexane = 1/8) to give compound 9a (127 mg,
99.7%) as a yellow solid: Mp 163.2−163.3 ˚C; IR (KBr):
3055, 2954, 2924, 2862, 1635, 1589, 1551, 1504, 1458 cm–1;
1H NMR (300 MHz, CDCl3)
δ: 10.66 (s, 1H), 9.86 (dd, J =
7.9, 1.3 Hz, 1H), 8.81 (dd, J = 7.9, 1.2 Hz, 1H), 8.52 (s, 1H),
8.23 (d, J = 7.9 Hz, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.81 (td, J =
7.9, 1.3 Hz, 1H), 7.62−7.49 (m, 3H), 3.13−2.97 (m, 4H),
1.87−1.66 (m. 4H), 1.59−1.40 (m, 8H), 0.99 (t, J = 7.4 Hz,
3H), 0.97 (t, J = 7.4 Hz, 3H); 13C NMR (126 MHz, CDCl3)
δ:
CDCl3) δ: 7.97 (d, J = 2.0 Hz, 1H), 7.65 (dd, J = 8.3, 2.0 Hz,
1H), 6.91 (d, J = 8.3 Hz, 1H), 5.56 (brs, 1H), 2.52 (d, J = 5.7
Hz, 1H), 2.27 (dt, J = 8.7, 2.0 Hz, 2H), 1.57−1.50 (m, 2H),
1.44−1.27 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H); 13C NMR (76
187.0 (CHO), 146.4 (C), 146.0 (C), 141.5 (C), 136.9 (CH),
134.5 (C), 133.0 (CH), 131.0 (CH), 129.9 (C), 128.4 (C),
128.23 (CH), 128.15 (CH), 126.0 (CH), 125.9 (C), 125.5
(CH), 125.0 (CH), 122.7 (CH), 118.7 (CH), 118.6 (C), 113.4
(C), 32.5 (CH2), 32.2 (CH2), 31.0 (CH2), 30.0 (CH2), 29.1
(CH2), 28.3 (CH2), 22.69 (CH2), 22.65 (CH2), 14.2 (CH3×2);
HRMS (ESI) (m/z): [M+H]+ calcd for C30H33N2O: 437.2587,
found 437.2584.
MHz, CDCl3) δ: 138.0 (CH), 137.0 (CH, C), 134.1 (C), 119.9
(CH), 88.5 (C), 88.0 (C), 78.4 (C), 59.7 (CH), 30.9 (CH2), 28.0
(CH2), 22.1 (CH2), 18.7 (CH2), 13.9 (CH3); HRMS (ESI)
(m/z): [M+Na]+ calcd for C14H16IN3ONa: 392.0230, found
392.0227.
Synthesis of alkynyl benzylalcohol 16: The alkynyl
benzylalcohol 16 (5.7 g, 84%) was obtained from 15 (4.7 g, 21
mmol), 1ꢀheptyne (3.6 mL, 27 mmol), 2.66 M hexane solution
of nꢀbutyllithium (9.5 mL, 25 mmol) and THF (100 mL) using
the general procedure for the introduction of alkyne describing
Synthesis of pentacycle 9b via Wittig reaction of 9a: A
xylene solution (1 mL) of aldehyde 9a (10 mg, 0.023 mmol),
methyl(triphenylphosphoranylidene) acetate (38 mg, 0.12
mmol) was stirred for 12 h at 140 °C, then the mixture was
concentrated in vacuo. The residue was purified by silica gel
column chromatography (chloroform/hexane = 1/1) to give 9b
(11 mg, 92%) as a red solid: Mp 134.9−135.1 ˚C; IR (KBr):
3062, 2947, 2924, 2862, 1697, 1612, 1581, 1550, 1496, 1450
for 11e. Yellow oil; IR (neat): 3394, 3062, 2931, 2861, 2129,
1
1951 cm−1; H NMR (500 MHz, CDCl3)
δ: 7.65 (dt, J = 7.6,
1.2 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.28−7.00 (m, 6H), 4.09
(t, J = 2.1 Hz, 1H), 2.25 (td, J = 7.2, 2.1 Hz, 2H), 1.52
(quintet, J = 7.2 Hz, 2H), 1.38−1.24 (m, 4H), 0.86 (t, J = 7.2
cm–1; 1H NMR (400 MHz, CDCl3)
δ: 9.91 (d, J = 8.1 Hz, 1H),
8.43−8.36 (m, 2H), 8.20 (d, J = 8.1 Hz, 1H), 8.07 (d, J = 8.1
Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.76 (td, J = 7.5, 1.3 Hz,
1H), 7.54 (td, J = 7.5, 0.8 Hz, 1H), 7.51 (td, J = 7.5, 0.8 Hz,
1H), 7.46 (td, J = 8.1, 0.8 Hz, 1H), 6.57 (d, J = 15.8 Hz, 1H),
3.87 (s, 3H), 3.07−2.92 (m, 4H), 1.84−1.58 (m, 8H),
1.51−1.40 (m, 4H), 1.00 (t, J = 7.2 Hz, 3H), 0.98 (t, J = 7.2
Hz, 3H); 13C NMR (126 MHz, CDCl3)
δ: 144.3 (C), 136.8 (C),
135.4 (C), 129.0 (CH), 128.2 (CH), 127.9 (CH), 127.8 (CH),
127.4 (CH), 126.3 (CH), 125.9 (CH), 124.4 (CH), 119.0 (CH),
88.4 (C), 81.8 (C), 73.6 (C), 30.9 (CH2), 28.1 (CH2), 22.0
(CH2), 18.8 (CH2), 13.8 (CH3); HRMS (ESI) (m/z): [M+Na]+
calcd for C20H21N3ONa: 342.1577, found 342.1577.
Hz, 3H); 13C NMR (76 MHz, CDCl3)
δ: 168.2 (C), 146.0 (C),
139.34 (C), 139.30 (CH), 135.7 (C), 134.9 (C), 133.1 (C),
131.83 (C), 131.81 (CH), 130.9 (C), 130.2 (CH), 128.5 (C),
128.0 (CH), 127.9 (CH), 125.8 (C), 125.4 (CH), 124.4 (CH),
123.9 (CH), 119.9 (CH), 119.5 (C), 119.0 (CH), 109.0 (CH),
Synthesis of azidopropargylbenzene 17 by silane reduction:
To a dichloromethane solution (30 mL) of alcohol 16 (2.0 g,
6.2 mmol), ammonium fluoride (0.45 g, 12 mmol) and
triethylsilane (2.0 mL, 12 mmol), a dichloromethane solution
ACS Paragon Plus Environment

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The Journal of Organic Chemistry
(CH), 134.8 (C, d, J = 22.0 Hz), 132.6 (CH×6, d, J = 9.6 Hz),
(10 mL) of trifluoroacetic acid (1.8 mL, 25 mmol) was added
1
2
3
4
5
6
7
8
at −40 °C. After being stirred at −5 °C for 1 h, the reaction was
quenched by addition of saturated aqueous sodium hydrogen
carbonate. The mixture was extracted with chloroform,
washed with brine, dried over anhydrous magnesium sulfate,
and concentrated in vacuo. The residue was purified by silica
gel column chromatography (hexane) to give 17 (1.1 g, 57%)
as a yellow oil; IR (neat): 3062, 2931, 2861, 2121, 1951 cm−1;
131.9 (CH×3, d, J = 2.4 Hz), 131.1 (C×3, d, J = 98.5 Hz),
128.8 (CH×6, d, J = 11.9 Hz), 122.3 (CH, d, J = 9.3 Hz), 83.0
(C), 79.0 (C), 78.7 (C), 31.3 (CH2), 29.0 (CH2), 22.4 (CH2),
22.3 (CH2), 19.1 (CH2), 14.2 (CH3); HRMS (ESI) (m/z):
[M+H]+ calcd for C32H32INP: 588.1312, found 588.1312.
Synthesis of iminophosphorane 14a by deprotection: A
methanol solution (30 mL) of iminophosphorane 13a (2.9 g,
6.3 mmol) and K2CO3 (175 mg, 12.6 mmol) was stirred at
room temperature for 4 h. Then, the reaction mixture was
filtrated through a pad of Celite, and the filtrate was
concentrated under reduced pressure. The residue was purified
by silica gel column chromatography (ethyl acetate/hexane =
1/4) to give iminophosphorane 14a (1.1 g, 46%) as colorless
crystals: Mp; 74.8−76.5 ˚C; IR (KBr): 3294, 3054, 3016, 2113,
1589, 1481, 1180, 1056, 848 cm–1; 1H NMR (400 MHz,
1H NMR (300 MHz, CDCl3)
δ: 7.53 (dd, J = 7.7, 1.6 Hz, 1H),
7.39−7.05 (m, 8H), 5.31 (t, J = 2.3 Hz, 1H), 2.26−2.18 (td, J =
7.0, 2.3 Hz, 2H), 1.58−1.25 (m, 6H), 0.89 (t, J = 7.0 Hz, 3H);
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13C NMR (76 MHz, CDCl3)
δ: 141.7 (C), 136.9 (C), 133.7 (C),
129.6 (CH), 128.3 (CH×2), 128.1 (CH), 127.7 (CH×2), 126.6
(CH), 125.0 (CH), 118.0 (CH), 84.5 (C), 80.3 (C), 37.2 (CH),
31.1 (CH2), 28.6 (CH2), 22.2 (CH2), 18.8 (CH2), 14.0 (CH3);
HRMS (ESI) (m/z): [M+Na]+ calcd for C20H21N3Na: 326.1628,
found 326.1625.
CDCl3) δ: 7.80−7.71 (m, 6H), 7.56−7.41 (m, 10H), 6.80 (td, J
Synthesis of iminophosphorane 13a by Staudinger
= 7.5, 1.7 Hz, 1H), 6.68 (td, J = 7.4, 0.9 Hz, 1H), 6.43 (dd, J =
7.7, 1.0 Hz, 1H), 3.91 (d, J = 2.7 Hz, 2H), 2.14 (t, J = 2.7 Hz,
reaction:
A
dichloromethane solution (5 mL) of
1H); 13C NMR (75 MHz, CDCl3)
δ: 148.6 (C), 132.3 (CH×6,
triphenylphosphine (2.0 g, 7.7 mmol) was added to a
dichloromethane solution (50 mL) of 12a (1.7 g, 7.0 mmol) at
room temperature. After being stirred for 1 h, the reaction
mixture was concentrated in vacuo. The residue was purified
by silica gel column chromatography (ethyl acetate/hexane =
1/10) to give iminophosphorane 13a (2.3 g, 72%) as colorless
crystals: Mp; 105.6−107.3 ˚C; IR (KBr): 3055, 2954, 1589,
d, J = 9.5 Hz), 131.5 (CH×3, d, J = 2.5 Hz), 131.0 (C×3, d, J
= 99.5 Hz), 130.0 (C, d, J = 22.4 Hz), 128.4 (CH×6, d, J =
12.0 Hz), 127.9 (CH, d, J = 1.7 Hz), 126.7 (CH), 120.2 (CH, d,
J = 10.0 Hz), 117.2 (CH), 84.0 (C), 69.8 (CH), 21.9 (CH2);
HRMS (ESI) (m/z): [M+H]+ calcd for C27H23NP: 392.1563,
found 392.1556.
1
1481, 1358, 1103, 841, 748, 694 cm–1; H NMR (400 MHz,
Synthesis of propargylaniline 18: To a THF solution (50
mL) of lithium aluminium hydride (0.66 g, 17 mmol), THF
solution (20 mL) of alkynyl azide 17 (2.1 g, 6.9 mmol) was
added slowly at 0 °C. After being stirred for 30 min, the
reaction mixture was quenched by addition of water. The
mixture was extracted with ethyl acetate, dried over anhydrous
magnesium sulfate, and concentrated in vacuo. The residue
was purified by silica gel column chromatography (ethyl
acetate/hexane = 1/4) to give 18 (1.6 g, 82%) as a yellow oil:
IR (neat): 3448, 3370, 3062, 2931, 2861, 1619 cm−1; 1H NMR
CDCl3) δ: 7.80−7.72 (m, 6H), 7.54−7.48 (m, 3H), 7.48−7.40
(m, 7H), 6.79 (td, J = 7.5, 1.2 Hz, 1H), 6.68 (t, J = 7.4 Hz, 1H),
6.41 (d, J = 7.7 Hz, 1H), 3.95 (s, 2H), 0.15 (s, 9H); 13C NMR
(101 MHz, CDCl3) δ: 148.9 (C), 132.7 (CH×6, d, J = 9.8 Hz),
131.71 (CH×3, d, J = 2.6 Hz), 131.69 (C×3, d, J = 99.3 Hz),
130.6 (C, d, J = 22.5 Hz), 128.7 (CH×6, d, J = 12.4 Hz),
128.2 (CH, d, J = 2.1 Hz), 126.8 (CH), 120.5 (CH, d, J = 9.8
Hz), 117.4 (CH), 107.3 (C), 85.9 (C), 23.8 (CH2), 0.42 (CH3×
3); HRMS (ESI) (m/z): [M+H]+ calcd for C30H31NPSi:
464.1958, found 464.1964.
(500 MHz, CDCl3) δ: 7.54 (d, J = 7.4 Hz, 2H), 7.47−7.42 (m,
Synthesis of iminophosphorane 13e by Staudinger
reaction: To a dichloromethane solution (100 mL) of alcohol
11e (6.2 g, 17 mmol), ammonium fluoride (1.3 g, 34 mmol)
and triethylsilane (5.4 mL, 34 mmol), a dichloromethane
solution of trifluoroacetic acid (5.2 mL, 68 mmol) was added
at −40 °C. After being stirred at −5 °C for 1 h, the reaction
mixture was quenched by addition of saturated aqueous
sodium hydrogen carbonate. The mixture was extracted with
chloroform, washed with brine, dried over anhydrous
magnesium sulfate, and concentrated in vacuo. The residue
was purified by silica gel column chromatography (hexane) to
give 12e (4.2 g, 12 mmol). A dichloromethane solution (10
mL) of triphenylphosphine (3.4 g, 13 mmol) was added to a
dichloromethane solution (50 mL) of 12e (4.2 g, 12 mmol) at
room temperature. After being stirred for 1 h, the mixture was
concentrated in vacuo. The residue was purified by silica gel
column chromatography (ethyl acetate/hexane = 1/8) to give
iminophosphorane 13e (6.7 g, 68% in 2 steps) as a brown
solid: Mp; 98.2−98.8 ˚C; IR (KBr): 3054, 2931, 2862, 1566,
2H), 7.38 (d, J = 7.4 Hz, 1H) , 7.34 (d, J = 7.4 Hz, 1H), 7.23
(t, J = 7.0 Hz, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.76 (d, J = 7.4
Hz, 1H), 5.14 (s, 1H), 3.87 (brs, 2H), 2.42 (dt, J = 7.0, 2.1 Hz,
2H), 1.71 (sx, J = 7.0 Hz, 2H), 1.58−1.45 (m, 4H), 1.07 (t, J =
7.0 Hz, 3H); 13C NMR (126 MHz, CDCl3)
δ: 144.1 (C), 140.1
(C), 129.3 (CH), 128.4 (CH×2), 127.8 (CH), 127.7 (CH×2),
126.7 (CH), 126.1 (C), 118.4 (CH), 116.5 (CH), 85.4 (C), 79.1
(C), 39.6 (CH), 31.0 (CH2), 28.5 (CH2), 22.0 (CH2), 18.8
(CH2), 13.9 (CH3); HRMS (ESI) (m/z): [M+Na]+ calcd for
C20H23NNa: 300.1723, found 300.1720.
Synthesis of urea 19: To a THF solution (10 mL) of
alkynylaniline 18 (2.3 g, 8.4 mmol) and triethylamine (2.6 mL,
18 mmol), triphosgene (0.42 g, 1.4 mmol) was added. After
being stirred for 1 h at 60 °C, the reaction mixture was
concentrated in vacuo and the residue was purified by silica
gel column chromatography (ethyl acetate/hexane = 1/10) to
give 19 (2.2 g, 92%) as a yellowish oil: IR (neat): 3309, 3062,
1
2931, 2861, 1951, 1681 cm−1; H NMR (500 MHz, CDCl3)
δ:
7.42 (t, J = 7.1 Hz, 2H), 7.34 (t, J = 7.1 Hz, 2H), 7.23−7.12
(m, 14H), 6.58 (d, J = 10.0 Hz, 2H), 4.98 (brs, 2H), 2.11−2.02
(m, 4H), 1.48−1.40 (m, 4H), 1.34−1.22 (m, 8H), 0.86 (t, J =
1466 cm–1; 1H NMR (500 MHz, CDCl3)
δ: 7.77−7.69 (m, 7H),
7.47−7.35 (m, 9H), 7.00 (dd, J = 8.4, 2.3 Hz, 1H), 6.17 (d, J =
2.4 Hz, 1H), 3.84 (s, 2H), 2.21 (tt, J = 7.2, 2.3 Hz, 2H),
1.54−1.27 (m, 6H), 0.88 (t, J = 7.2 Hz, 3H); 13C NMR (100
7.0 Hz, 6H); 13C NMR (126 MHz, CDCl3)
δ: 153.8 (C), 139.9
(C×2), 135.4 (C×2), 135.1 (C×2), 129.2 (CH×2), 128.5
(CH×4), 128.0 (CH×2), 127.6 (CH×4), 126.8 (CH×2), 126.2
MHz, CDCl3) δ: 148.7 (C), 136.7 (CH, d, J = 1.9 Hz), 135.3
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The Journal of Organic Chemistry
Page 14 of 15
(CH×2), 125.6 (CH×2), 85.9 (C), 85.8 (C), 79.03 (C), 78.97
1.54 (quintet, J = 7.0 Hz, 4H), 1.41−1.26 (m, 8H), 0.89 (t, J =
7.0 Hz, 6H); 13C NMR (126 MHz, CDCl3)
: 141.9 (C×2),
1
2
3
4
5
6
7
8
(C), 39.4 (CH×2), 31.1 (CH2×2), 28.4 (CH2×2), 22.0 (CH2×2),
18.7 (CH2×2), 13.9 (CH3×2); HRMS (ESI) (m/z): [M+Na]+
calcd for C41H44N2ONa: 603.3346, found 603.3348.
δ
136.4 (C×2), 135.7 (C×2), 134.1 (C), 129.3 (CH×2), 128.3
(CH×4), 127.9 (CH×2), 127.8 (CH×4), 126.5 (CH×2), 125.8
(CH×2), 125.0 (CH×2), 84.6 (C×2), 80.5 (C×2), 38.3 (CH×2),
31.1 (CH2×2), 28.6 (CH2×2), 22.2 (CH2×2), 18.9 (CH2×2),
14.0 (CH3×2); HRMS (ESI) (m/z): [M+H]+ calcd for
C41H43N2: 563.3421, found 563.3421.
Synthesis of carbodiimides 1a by aza-Wittig reaction: A
dichloromethane solution (10 mL) of iminophosphorane 14a
(780 mg, 2.0 mmol) was degassed, and charged with carbon
dioxide using a balloon and stirred for 10 h at room
temperature. The reaction mixture was concentrated in vacuo,
and the residue was purified by silica gel column
ASSOCIATED CONTENT
9
chromatography (hexane/chloroform
=
2/1) to give
Supporting Information
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11
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60
carbodiimide 1a (162 mg, 60%) as a colorless oil: IR (neat):
The Supporting Information is available free of charge on the
ACS Publications website at DOI:
1
3286, 3062, 2159, 2113, 1581, 1488, 1172, 1095 cm−1; H
Xꢀray crystallographic data for compound 4b (CCDC: 1574644)
(CIF).
NMR (500 MHz, CDCl3)
7.26−7.24 (m, 4H), 7.24−7.18 (m, 2H), 3.74 (d, J = 2.7 Hz,
4H), 2.25 (t, J = 2.7 Hz, 2H); 13C NMR (126 MHz, CDCl3)
δ: 7.59 (d, J = 7.9 Hz, 2H),
1
Copies of H NMR and 13C NMR spectra. UVꢀVis and fluoresꢀ
δ:
cence spectra, Xꢀray crystallographic data, and DFT data (PDF).
136.2 (C×2), 133.6 (C), 130.2 (C×2), 129.2 (CH×2), 127.9
(CH×2), 125.7 (CH×2), 124.7 (CH×2), 81.3 (C×2), 70.8
(CH×2), 21.2 (CH2×2); HRMS (ESI) (m/z): [M+Na]+ calcd for
C19H14N2Na: 293.1049, found 293.1049.
AUTHOR INFORMATION
Corresponding Author
Synthesis of carbodiimides 1d by aza-Wittig reaction: The
title compound 1d (211 mg, 69%) was obtained from
iminophsophorane 13d (468 mg, 1.0 mmol) and
dichloromethane (10 mL) using the general procedure for azaꢀ
Wittig reaction describing for 1a. Colorless oil: IR (neat):
*Eꢀmail: b115702@ed.tus.ac.jp
*Eꢀmail: kawaih@rs.tus.ac.jp
*Eꢀmail: tsaito@rs.kagu.tus.ac.jp
Author Contributions
3062, 3024, 2893, 2188, 1581, 1488, 1218, 1172, 1095, 840
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the manuꢀ
script.
1
cm−1; H NMR (400 MHz, CDCl3)
δ: 7.66−7.61 (m, 2H),
7.51−7.44 (m, 4H), 7.36–7.26 (m, 8H), 7.23–7.16 (m, 4H),
3.96 (s, 4H); 13C NMR (101 MHz, CDCl3)
δ: 136.6 (C×2),
Notes
133.8 (C), 131.8 (CH×4), 131.1 (C×2), 129.6 (CH×2), 128.4
(CH×4), 128.1 (CH×2), 128.0 (CH×2), 125.9 (CH×2), 124.9
(CH×2), 123.8 (C×2), 87.1 (C×2), 83.1 (C×2), 22.5 (CH2×2);
HRMS (ESI) (m/z): [M+H]+ calcd for C31H23N2: 423.1856,
found 423.1856.
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by JSPS KAKENHI Grant Number
16J08668.
Synthesis of carbodiimides 1e by aza-Wittig reaction: The
title compound 1e (1.8 g, 79%) was obtained from
iminophsophorane 13e (4.0 g, 6.8 mmol) and dichloromethane
(10 mL) using the general procedure for azaꢀWittig reaction
describing for 1a. A yellow oil: IR (neat): 2931, 2862, 2152,
REFERENCES
(1) For recent reviews on metalꢀcatalyzed cycloadditions in Nꢀfused
heterocycles, see: (a) Guo, X.ꢀX.; Gu, D.ꢀW.; Wu, Z.; Zhang, W.;
Chem. Rev. 2015, 115, 1622. (b) Majumdar, K. C.; De, N.; Ghost, T.;
Roy. B. Tetrahedron, 2014, 70, 4827. (c) Krause, N.; Winter, C.
Chem. Rev., 2011, 111, 1994. (d) Patil, N. T.; Yamamoto, Y. Chem.
Rev., 2008, 108, 3395. (e) Nakamura, I.; Yamamoto, Y. Chem. Rev.,
2004, 104, 2127.
(2) For organic electronic compounds: (a) Li, J.; Zhang, Q. ACS Appl.
Mater. Interfaces, 2015, 7, 28049. (b) Suzuki, Y.; Yokoyama, K.
Biosensors, 2015, 5, 337. (c) MateoꢀAlonso, A. Chem. Soc. Rev.,
2014, 43, 6311. For molecular probes: (d) Carter, K. P.; Young, A.
M.; Palmer, A. E. Chem. Rev., 2014, 114, 4564. (e) Bunz, U. H. F.;
Engelhart, J. U.; Lindner, B. D.; Schaffroth, M. Angew. Chem. Int.
Ed., 2013, 52, 3810. For biological active compounds: (f) Zhang, M.ꢀ
Z.; Chen, Q.; Yang, G.ꢀF. Eur. J. Med. Chem., 2015, 89, 421. (g)
Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J. Med. Chem., 2014,
57, 5845. (h) Solomon, V. R.; Lee, H. Curr. Med. Chem., 2011, 18,
1488. (i) Kaila, N.; Janz, K.; DeBernardo, S.; Bedard, P. W.;
Camphausen, R. T.; Tam, S.; Tsao, D. H. H.; Keith, J. C. Jr.;
NickersonꢀNutter, C.; Shilling, A.; YoungꢀSciame, R.; Wang, Q. J.
Med. Chem., 2007, 50, 21.
1473 cm–1; 1H NMR (500 MHz, CDCl3)
δ: 7.84 (d, J = 1.8 Hz,
2H), 7.46 (dd, J = 8.2, 1.8 Hz, 2H), 6.89 (d, J = 8.2 Hz, 2H),
3.57 (s, 4H), 2.19 (tt, J = 7.0, 2.4 Hz, 4H), 1.51 (quintet, J =
7.0 Hz, 4H), 1.41−1.25 (m, 8H), 0.91 (t, J = 7.0 Hz, 6H); 13C
NMR (126 MHz, CDCl3) δ: 138.1 (CH×2), 136.5 (CH×2),
135.6 (C×2), 134.1 (C×2), 132.4 (C), 126.2 (CH×2), 89.9
(C×2), 84.0 (C×2), 75.8 (C×2), 31.1 (CH2×2), 28.6 (CH2×2),
22.2 (CH2×2), 21.4 (CH2×2), 18.8 (CH2×2), 14.0 (CH3×2);
HRMS (ESI) (m/z): [M+H]+ calcd for C29H33I2N2: 663.0728,
found 663.0725.
Synthesis of a carbodiimide 1f: To a dichloromethane
solution (10 mL) of urea 19 (0.77 g, 1.3 mmol),
triphenylphosphine (0.52 g, 2.0 mmol) and triethylamine (46
mL, 3.3 mmol), a dichloromethane solution (1 mL) of carbon
tetrabromide (0.79 g, 1.4 mmol) was added. After being stirred
for 4 h, the mixture was concentrated in vacuo. The residue
was purified by silica gel column chromatography
(chloroform/hexane = 1/2) to give 1f (0.73 g, 98%) as a yellow
oil: IR (neat): 3062, 3024, 2931, 2861, 2114, 1581, 1481 cm−1;
(3) (a) Tateno, K.; Ogawa, R.; Sakamoto, R.; Tsuchiya, M.; Otani, T.;
Saito, T. Org. Lett., 2014, 16, 3215. (b) Otani, T.; Saito, T.; Sakamoꢀ
to, R.; Osada, H.; Hirahara, A.; Furukawa, N.; Kutsumura, N.; Matꢀ
suo, T.; Tamao, K. Chem. Commun., 2013, 49, 6206.
(4) (a) Li, S.ꢀS.; Liu, C.ꢀF.; Zhang, G.ꢀT.; Xia, Y.ꢀQ.; Li, W.ꢀH.;
Dong, L. Chem. Asian. J., 2017, 12, 415. (b) Kumar, K. S.; Bhaskar,
B.; Ramulu, M. S.; Kumar, N. P.; Ashfaq, M. A.; Pal, M. Org. Bioꢁ
1H NMR (500 MHz, CDCl3)
δ: 7.57−7.54 (m, 2H), 7.42−7.40
(m, 4H), 7.26 (t, J = 7.3 Hz, 4H), 7.19−7.10 (m, 6H),
7.03−7.00 (m, 2H), 5.52 (s, 2H), 2.25 (td, J = 7.0, 2.1 Hz, 4H),
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The Journal of Organic Chemistry
mol. Chem., 2017, 15, 82. (c) Morioka, R.; Nobushige, K.; Satoh, T.;
(9) The examples of fully intramolecular hetero [2+2+2] cycloaddiꢀ
tion were limited to only nitrileꢀdiynes type. For recent reviews on
fully intramolecular hetero [2+2+2] cycloaddition, see: (a) Okamoto,
S.; Sugiyama, Y. Synlett, 2013, 1044. (b) Broere, D. L. J.; Ruijter, E.
Synthesis, 2012, 2639. (c) Tanaka, K. Heterocycles, 2012, 85, 1017.
(d) Weding, N.; Hapke, M. Chem. Soc. Rev., 2011, 40, 4525. (e) Li,
S.; Zhou, L.; Kanno, K.; Takahashi, T. J. Heterocycl. Chem., 2011, 48,
517. (f) Perreault, S.; Rovis, T. Chem. Soc. Rev., 2009, 38, 3149.
(10) (a) Hirota, S.; Kato, R.; Suzuki, M.; Soneta, Y.; Otani, T.; Saito,
T. Eur. J. Org. Chem., 2008, 2075. (b) Saito, T.; Ohkubo, T.; Kuboki,
H.; Maeda, M.; Tsuda, K.; Karakasa, T.; Satsumabayashi, S. J. Chem.
Soc. Perkin Trans. 1, 1998, 3065. (c) Saito, T.; Tsuda, K.; Saito, Y.
Tetrahedron Lett., 1996, 37, 209.
Hirano, K.; Miura, M. Org. Lett., 2015, 17, 3130. (d) Shoker, T. A.;
Ghattass, K. I.; Fettinger, J. C.; Kurth, M. J.; Haddadin, M. J. Org.
Lett., 2012, 14, 3704. (e) Hachiya, S.; Hashizume, D.; Maki, S.; Niwa,
H.; Hirano, T. Tetrahedron Lett., 2010, 51, 1401. (f) Volovnenko, T.
A.; Turov, A.V.; Volovenko, Y. M. Chem. Heterocycl. Compd., 2009,
45, 1489. (g) Ahmed, E.; Briseno, A. L.; Xia, Y.; Jenekhe, S. A. J.
Am. Chem. Soc., 2008, 130, 1118. (h) Litvinenko, S. V.; Volovenko,
Y. M.; Babichev, F. S. Chem. Heterocycl. Compd., 1993, 194. (i)
Litvinenko, S. V.; Volovenko, Y. M.; Babichev, F. S. Chem. Heteroꢁ
cycl. Compd., 1992, 1307.
1
2
3
4
5
6
7
8
9
(5) Hahn, S.; Geyer, F. L.; Koser, S.; Tverskoy, O.; Rominger, F.;
Bunz, U. H. F. J. Org. Chem., 2016, 81, 8485.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6) (a) Otani, T.; Tsuyuki, A.; Iwachi, T.; Someya, S.; Tateno, K.;
Kawai, H.; Saito, T.; Kanyiva, K. S.; Shibata, T. Angew. Chem. Int.
Ed., 2017, 56, 3906. (b) Zhang, X.; Clennan, E. L.; Arulsamy, N.;
Weber, R.; Weber, J. J. Org. Chem., 2016, 81, 5474. (c) Sakamaki,
D.; Kumano, D.; Yashima, E.; Seki, S. Angew. Chem. Int. Ed., 2015,
54, 5404. (d) Nakamura, K.; Furumi, S.; Takeuchi, M.; Shibuya, T.;
Tanaka, K. J. Am. Chem. Soc., 2014, 136, 5555. (e) Suzuki, T.; Saꢀ
kano, Y.; Tokimizu, Y.; Miura, Y.; Katoono, R.; Fujiwara, K.; Yoshiꢀ
oka, N.; Fujii, N.; Ohno, H. Chem. Asian. J., 2014, 9, 1841. (f)
Chocholoušová, J. V.; Vacek, J.; Andronova, A.; Míšek, J.; Songis,
O.; Šámal, M.; Stará, I. G.; Meyer, M.; Bourdillon, M.; Pospíšil, L.;
Starý, I. Chem. Eur. J., 2014, 20, 877. (g) Kaneko, E.; Matsumoto, Y.;
Kamikawa, K. Chem. Eur. J., 2013, 19, 11837.
(7) (a) Biegger, P.; Tverskoy, O.; Rominger, F.; Bunz, U. H. F. Chem.
Eur. J., 2016, 22, 16315. (b) Jahng, Y.; Karim, M. Tetrahedron, 2016,
72, 199. (c) Li, J.; Zhang, Q. ACS Appl. Mater. Interfaces, 2015, 7,
28049. (d) Miao Q. in Polycyclic Arenes and Heteroarenes: Synthesis
Properties, and Applications, (Eds.: Lakshminarayana, A. N.; Chi,
C.), WileyꢀVCH Verlag GmbH & Co. KGaA, 2015, chap. 9. (e)
Wang, C.; Zhang, J.; Long, G.; Aratani, N.; Yamada, H.; Zhao, Y.;
Zhang, Q. Angew. Chem. Int. Ed., 2015, 54, 6292. (f) Bunz, U. H. F.
Acc. Chem. Res., 2015, 48, 1676. (g) Miao, Q. Adv. Mater., 2014, 26,
5541.
(8) Recent review on partially intramolecular hetero [2+2+2] cyꢀ
cloaddition, see: (a) Jungk, P.; Täufer, T.; Thiel, I.; Hapke, M. Synꢁ
thesis, 2016, 48, 2026. (b) Satoh, Y.; Obora, Y. Eur. J. Org. Chem.,
2015, 2015, 5041. (c) Amatore, M.; Aubert, C. Eur. J. Org. Chem.,
2015, 2015, 265. (d) Yamamoto, Y. Heterocycles, 2013, 87, 2459. (e)
Dominguez, G.; PérezꢀCastells, J. Chem. Soc. Rev., 2011, 40, 3430.
Partially intramolecular [2+2+2] cycloadditions of carbodiimides with
two alkynes, see: (f) Ishii, M.; Mori, F.; Tanaka, K. Chem. Eur. J.,
2014, 20, 2169. Microwaveꢀmediated reactions of polymer supported
carbodiimide with diyne. (g) Young, D. D.; Teske, J. A.; Deiters, A.;
Synthesis, 2009, 3785. (h) Young, D. D.; Deiters, A. Angew. Chem.
Int. Ed., 2007, 46, 5187. Asymmetric rhodiumꢀcatalyzed [2+2+2]
cycloaddition of alkynyl carbodiimides with alkyne. (i) Yu, R. T.;
Rovis, T. J. Am. Chem. Soc., 2008, 130, 3262.
(11) For Mo(CO)6ꢀpromoted P−K reactions of carbodiimides: (a)
Saito, T.; Shiotani, T.; Otani, T.; Hasaba, S. Heterocycles, 2003, 60,
1045. For Rh(I)ꢀcatalyzed P−K reactions of carbodiimides with carꢀ
bon monoxide: (b) Saito, T.; Furukawa, N.; Otani, T. Org. Biomol.
Chem., 2010, 8, 1126. (c) Saito, T.; Sugizaki, K.; Otani, T.; Suyama,
T. Org. Lett., 2007, 9, 1239.
(12) (a) Shaya, J.; FontainꢀVine, F.; Michel, B. Y.; Burger, A. Chem.
Eur. J., 2016, 22, 10627. (b) Niko, Y.; Kawauchi, S.; Konishi, G.
Chem.Eur. J., 2013, 19, 9760.
(13) (a) Kutsumura, N.; Koyama, Y.; Tateno, K.; Yamamoto, N.;
Nagase, H.; Saito, T. Chem. Pharm. Bull., 2016, 64, 1364. (b) Kiꢀ
mura, H.; Torikai, K.; Ueda, I. Chem. Pharm. Bull., 2009, 57, 393.
(14) The [2+2+2] cycloaddition from carbodiimide 1f gave a mixture
of 3 and 3’ without the starting material or other byproducts.
(15) Jung, M. E.; Piizzi, G. Chem. Rev., 2005, 105, 1735.
(16) Crystal data of 4b: MF C41H40N2, FW 560.78, monoclinic P21/c,
a = 12.3768(2), b = 8.25551(15), c = 30.2129(6) Å, α = 90, β =
98.416(7), γ = 90°, V = 3053.81(11) Å3, ρ(Z = 4) = 1.220 g cm−3, T =
123 K, R = 6.5%. CCDC1574644. See supporting information for
crystallographic data in CIF.
(17) Stokes shift values: 2a: 1049, 2b: 1527, 2c: 1296, 2d: 1395, 4b:
1353, 7b: 1578, 8b: 1585 and 3: 3144 cm−1, respectively.
(18) (a) Spartan’16, Wavefunction, Inc. Irvine, CA 2016. (b) Sparꢀ
tan’14, Wavefunction, Inc. Irvine, CA 2014.
(19) (a) Zhang, Z.; Wu, Y.ꢀS.; Tang, K.ꢀC.; Chen, C.ꢀL.; Ho, J.ꢀW.;
Su, J.; Tian, H.; Chou, P.ꢀT. J. Am. Chem. Soc., 2015, 137, 8509. (b)
Yuan, C.; Saito, S.; Camacho, C.; Irle, S.; Hisaki, I.; Yamaguchi, S. J.
Am. Chem. Soc., 2013, 135, 8842.
(20) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker,
B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H.
J. Am. Chem. Soc., 2001, 123, 9500.
(21) Grisanti, L.; D’Avino, G.; Paonelli, A.; Guasch, J.; Ratera, I.;
Veciana, J. J. Phys. Chem. B, 2009, 113, 4718.
(22) Stokes, B. J.; Vogel, C. V.; Urnezis, L. K.; Pan, M.; Driver, T. G.
Org. Lett., 2010, 12, 2884.
(23) Sabbatini, P.; Wellendorph, P.; Høg, S.; Pedersen, M. H. F.;
BräunerꢀOsborne, H.; Martiny, L.; Frølund, B.; Clausen, R. P. J. Med.
Chem., 2010, 53, 6506.
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