4,8-dihydropyrrol[3,4-f]isoindole as a useful building block for near-infrared dyes

Article abstract of DOI:10.3987/COM-14-S(K)91

4,8-Dihydropyrrol[3,4-f]isoindole was prepared from 4,7-dihydroisoindole based on the modified Barton-Zard reaction. Addition of phenylsulfenyl chloride followed by oxidation and dehydrochlorination gave phenylsulfonyldihydroisoindole, which underwent the

Full text of DOI:10.3987/COM-14-S(K)91

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HETEROCYCLES, Vol. 90, No. 2, 2015
HETEROCYCLES, Vol. 90, No. 2, 2015, pp. 1158 - 1167. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 24th July, 2014, Accepted, 7th August, 2014, Published online, 19th August, 2014
DOI: 10.3987/COM-14-S(K)91
4,8-DIHYDROPYRROL[3,4-f]ISOINDOLE AS A USEFUL BUILDING
BLOCK FOR NEAR-INFRARED DYES
Hidemitsu Uno,a* Mitsunori Nakamura,a Kazuki Jodai,a Shigeki Mori,b and
Tetsuo Okujimaa
a
Department of Chemistry and Biology, Graduate School of Science and
Engineering, Ehime University, Matsuyama 790-8577, Japan, e-mail:
uno@ehime-u.ac.jp
b Integrated Center for Sciences, Ehime University, Matsuyama 790-8577, Japan
Dedicated to Prof. Dr. Isao Kuwajima on the occasion of his 77th birthday
Abstract
–
4,8-Dihydropyrrol[3,4-f]isoindole
was
prepared
from
4,7-dihydroisoindole based on the modified Barton-Zard reaction. Addition of
phenylsulfenyl chloride followed by oxidation and dehydrochlorination gave
phenylsulfonyldihydroisoindole, which underwent the smooth reaction with an
isocyanoacetate
under
basic
conditions
to
give
4,8-dihydropyrrol[3,4-f]isoindole-1,5- and 1,7-dicarboxylates in good yields. The
pyrrolisoindole was successfully converted to the benzene-fused bisBODIPY,
absorption maximum of which was 758 nm.
INTRODUCTION
Considerable interest has been paid for near-infrared (NIR) dyes due to a broad range of applications.
They have been reported as promising dyes both for clinical use as NIR photosensitizers1 in
photo-dynamic therapy2 and microscopic imaging agents3 in diagnosis due to good transparency in living
cells and for functional material use as NIR light emitting diode.4 We have explored a new class of
NIR-selective dyes based on the retro-Diels-Alder protocol for chromophore fusion:5 bisBODIPYs 2
connected with a bicyclo[2.2.2]octadiene (BCOD) skeleton was thermally converted to benzene-fused
bisBODIPYs 3 in the final step (Scheme 1).6 The NIR dyes were proven to have an advantageous
property for NIR-selective filters. They were almost transparent in the visible region although the dyes
had very strong absorption maxima in the red to NIR region. This property is closely related to the fusion
mode of the BODIPY chromophore.6 4,8-Ethano-4,8-dihydropyrrol[3,4-f]isoindole (1)7 was the key

HETEROCYCLES, Vol. 90, No. 2, 2015
1159
compound for the synthesis of the bisBODIPYs and the preparation of 1 was the bottle neck for the
application of the dyes. The preparation must be started from rather expensive 1,3-cyclohexadiene. One
of the alternative methods for the thermal conversion of BCOD to benzene is oxidation of
1,4-cyclohexadiene to benzene moieties.8 Filatov et al. have explored the synthesis of π-expanded
porphyrins based on the oxidation protocol using 4,7-dihydroisoindole as the key compound.9 In this
paper, we describe the synthesis of 4,8-dihydropyrrol[3,4-f]isoindole (4) and its application for the
synthesis of NIR-selective bisBODIPY dye 3a.
Scheme 1. Preparation of benzene-fused bisBODIPY
RESULTS AND DISCUSSION
In order to prepare 4,8-dihydropyrrol[3,4-f]isoindole (4), we planned to construct a pyrrole ring at the
double bond of dihydroisoindole 7, which was reported to be prepared from the modified Barton-Zard
reaction of 1-tosyl-1,4-cyclohexadiene (5a) with ethyl isocyanoacetate by Filatov et al (Scheme 2).9 The
key 1,4-diene 5a was prepared by the Diels-Alder reaction of 1,3-butadiene with tosylacetylene.10 We
prepared 1,4-diene 5b starting from readily available 1,4-cyclohexadiene due to practically difficult
treatment of 1,3-butadiene with high vapor pressure: addition of phenylsulfenyl chloride followed by
oxidation
with
m-chloroperbenzoic
acid
(mCPBA)
and
then
treatment
with
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).11 In this method, however, a mixture of aimed 5b and 6 were
obtained in a ratio of 2:1 and this mixture was used for the modified Barton-Zard reaction.
Dihydroisoindole 7 was obtained in a total yield of 18% from 1,4-cyclohexadiene. Addition of
phenylsulfenyl chloride to dihydroisoindole 7 gave a diastereomeric mixture (ca. 1:1) of β-chloro sulfides
8a and 8b in 84% yield. Oxidation of the sulfide mixture with mCPBA gave diastereomeric β-chloro
sulfones 9a and 9b (ca. 1:1) in good yield. Dehydrochlorination of β-chloro sulfones 9a and 9b with
potassium tert-butoxide gave regioisomeric α,β-unsaturated sulfones, which was then subjected to the
modified Barton-Zard reaction with ethyl isocyanoacetate to give dipyrrole 4. Chromatographic
purification of the reaction mixture with ether gave an analytically pure sample of regioisomeric dipyrrole

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4, ratio of which was determined to be anti:syn = 10:3 by 1H NMR. Recrystallization of the sample from
acetone/hexane gave pure anti-4 in 11% yield.
Scheme 2. Reagents, conditions, and yields: i) tosylacetylene, rt, 48 h, pressure bottle; 95%; see ref 9; ii)
PhSCl; CH2Cl2, −78 °C; 86%; iii) mCPBA; CH2Cl2, 0 °C; 64%; iv) DBU; CH2Cl2, rt; 62% (5b:6 = 2:1);
v) CNCH2CO2Et; KOtBu, THF, 0 °C; 53%; vi) PhSCl; CH2Cl2, −78 °C; 84%; vii) mCPBA; CH2Cl2,
0 °C; 99%; viii) KOtBu; THF, rt; 76%; ix) CNCH2CO2 Et; KOtBu, THF, 0 °C; 24% (anti-4:syn-4 = 10:3).
R
Me
Et
F
F
Et
Me
Et
B
HN
N
R
iii)
i)
N
Et
Me
NH
Et
anti-4
HN
Et
N
F
R
NH
N
Et
B
F
Et
R
Me
10: R = CO2Et
11: R = Me
12
ii)
F
Me
F
Et
Me
B
N
iv)
N
Et
Me
Et
N
F
N
B
F
Et
Me
3a
Scheme 3. Reagents, conditions, and yields: i) ethyl 5-acetoxymethyl-3,4-diethylpyrrole-2-carboxylate,
AcOH, p-TsOH, rt; 50%; ii) LiAlH4, THF, reflux; iii) chloranil, CH2Cl2, rt; Et(i-Pr)2N, BF3·OEt2; 56%;
iv) chloranil, CH2Cl2, rt; quant.

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1161
As the reactivity of dipyrrole 4 was thought be similar to a simple pyrrole-2-carboxylate ester, the
conversion of anti-4 to a bisdipyrromethane derivative was achieved under the similar conditions as those
of BCOD-fused dipyrroles.6 Dihydropyrrolisoindole anti-4 was alkylated with ethyl
2-acetoxymethyl-3,4-diethylpyrrole-1-carboxylate under acid-catalyzed conditions with p-toluenesulfonic
acid to afford bisdipyrromethane 10 in 50% yield. After the ester groups of 10 were reduced to methyl
groups with LiAlH4 in refluxing THF, double BODIPY formation was performed. The resulting
tetramethyl derivative 11 was oxidized with chloranil and then reacted with BF3·OEt2 in the presence of
ethyldiisopropylamine to give cyclohexadiene-connected bisBODIPY 12 contaminated with further
oxidized bisBODIPY 3a in 56% yield. Dehydrogenation of bisBODIPY 12 with chloranil gave fully
conjugated bisBODIPY 3a, UV-vis spectrum of which was the same as that of reported one (Figure 1).6
Abs.
Wavelength/nm
Figure 1. UV-vis-NIR spectra of 12 (dotted line, contaminated with 3a) and 3a (solid line)
In conclusion, we succeeded in the exploitation of an alternative route for the synthesis of bisBODIPY,
chromophores of which were fully conjugated by the benzene moiety. The route is based on the
dehydrogenation of cyclohexadiene to benzene moieties.
EXPERIMENTAL
General: Melting points were measured on a Yanagimoto micro-melting point apparatus and are
uncorrected. NMR spectra were obtained with a JEOL AL-400 spectrometer at the ambient temperature
by using CDCl3 as a solvent and tetramethylsilane as an internal standard for 1H and 13C. IR spectra were
obtained by a Thermo Scientific Nicolet iS5 FT-IR spectrometer with an iD5 ATR diamond plate. Mass

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spectra (EI, 70 eV; FAB+, p-nitrobenzyl alcohol, MALDI-TOF) were measured with a JEOL JMS-700 or
a Voyager DE Pro instrument. Elemental analyses were performed with a Yanaco MT-5 elemental
analyzer at Integrated Center for Sciences. Dehydrated tetrahydrofuran and dichloromethane were
purchased from Kanto Chemical Co. (Tokyo Japan) and used without further purification. Potassium
tert-butoxide was sublimed at 200 °C under a reduced pressure (ca. 13 Pa) and dissolved in dry THF (1.0
mol·L−1). DBU was distilled from CaH2 under a reduced pressure and stored on molecular sieves 13X.
Other commercially available materials were used without further purification.
Ethyl 4,7-dihydroisoindole-1-carboxylate (7):11 To a stirred solution of 1,4-cyclohexadiene (5.0 mL, 53
mmol) in dry CH2Cl2 (50 mL) was slowly added phenylsulfenyl chloride (6.0 mL, 53 mmol) at −78 °C.
After the addition, the reaction mixture was allowed to warm up to room temperature and stirred for 1 h.
The reaction mixture was sequentially washed with a saturated aqueous solution of NaHCO3, water, and
brine, dried over Na2SO4, and concentrated in vacuo to leave 10.26 g (86%) of (4R*,5R*)-4-chloro-5-
phenylsulfanylcyclohexene as colorless viscous oil, which was proven to be analytically pure: 1H NMR δ
7.45 (m, 2H), 7.31 (m, 3H), 5.67 (m, 1H, H2*), 5.60 (m, 1H, H1*), 4.19 (q, J 4.5 Hz, 1H, H5), 3.59 (q, J
4.5 Hz, 1H, H4), 2.97 (br d, J 18.3 Hz, 1H, H3eq†), 2.84 (m, 1H, H6eq†), 2.25 (br d, J 18.3 Hz, 1H, H3ax‡),
2.38 (br d, J 18.6 Hz, 1H, H6ax‡) (asterisks, daggers, and double daggers denote changeable assignment);
13C NMR δ 133.56, 132.09, 128.95, 127.38, 123.60, 122.27, 56.95, 47.43, 31.14, 27.80; IR νmax 3072,
3032, 1479, 1429, 1219 cm−1; MS (FAB+) m/z 225 {M+(35Cl) + 1}; HRMS calcd for C12H1335ClS + H+:
225.0505, found 225.0485. Anal. Calcd for C12H13ClS: C, 64.13; H, 5.83. Found: C, 63.92; H, 5.93%.
This adduct (10.26 g, 46 mmol) was dissolved in dry CH2Cl2 (500 mL) and cooled to 0 °C. Commercially
available mCPBA (purity: ca. 70%; 24.1 g, 92 mmol) was slowly added and the mixture was stirred at
room temperature overnight. The resulting suspension was filtered through a Celite pad. The filtrate was
washed with a saturated aqueous solution of NaHCO3, water, and brine, dried over Na2SO4, and
concentrated in vacuo. The residue was chromatographed on silica gel to give 7.55 g (64%) of
(4R*,5R*)-4-chloro-5-phenylsulfonylcyclohexene as colorless oil: 1H NMR δ 7.93 (m, 2H), 7.69 (m, 1H),
7.59 (m, 2H), 5.68 (m, 1H, H2*), 5.67 (m, 1H, H1*), 4.64 (q, J 4.7 Hz, 1H, H5), 3.58 (dt, J 6.9, 4.7 Hz, 1H,
H4), 2.94 (dm, J 18.7 Hz, 1H, H3eq†), 2.65 (m, 1H, H6eq†), 2.56 (dm, J 17.6 Hz, H6ax‡), 2.38 (br d, J 18.6
Hz, 1H, H3ax‡) (asterisks, daggers, and double daggers denote changeable assignment); 13C NMR δ 138.22,
133.90, 129.19, 128.57, 122.81, 122.23, 63.69, 51.48, 32.44, 22.08; IR νmax (KBr) 3037, 1431, 1308, 1144,
1084 cm−1; MS (FAB+) m/z 257 {M+(35Cl) + 1}; HRMS calcd for C12H1335ClSO2 + H+: 257.0403, found
257.0408. To a stirred solution of the sulfone (3.87 g, 15.1 mmol) in dry CH2Cl2 (56 mL) was added
DBU (2.24 mL, 15.1 mmol) at 0 °C and the mixture was allowed to warm up to room temperature. After
3 h, the mixture was sequentially washed with a 1-M solution of HCl, a saturated aqueous solution of
NaHCO3, water, and brine, dried over Na2SO4, and concentrated in vacuo. The residue was

HETEROCYCLES, Vol. 90, No. 2, 2015
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chromatographed on silica gel to give 2.06 g (62%) of a diene mixture, which consisted of
1-phenylsulfonyl-1,4-cyclohexadiene {5b, 1H NMR δ 7.87 (m, 2H), 7.62 (m, 1H), 7.54 (m, 2H), 7.05 (m,
1H, H2), 5.68 (m, 1H, H4*), 5.65 (m, 1H, H5*), 2.96 (m, 2H, H3*), 2.81 (m, 2H, H6*), asterisks denote
changeable assignment.} and 5-phenylsulfonyl-1,3-cyclohexadiene {6, 1H NMR δ 7.86 (m, 2H), 7.62 (m,
1H), 7.49 (m, 2H), 6.09 (dd, J 10.2, 4.8 Hz, 1H, H2), 5.80 (dd, J 9.6 Hz, 1H, H3), 5.60-5.48 (m, 2H, H1
and H4), 3.88 (dtd, J 10.7, 5.4, 1.0 Hz, H5), 2.99 (dt, J 19.4, 4.9 Hz, 1H, H6eq), 2.67 (ddt, J 19.4, 10.9, 2.4
Hz, 1H, H6ax)} in a ratio of 2:1. This mixture was used in the next step without further purification. The
diene sulfone mixture (1.08 g, 4.9 mmol) was dissolved in dry THF (40 mL) and ethyl isocyanoacetate
(0.65 mL, 6 mmol) was added. To the cooled mixture at 0 °C was added a 1-M solution of KOtBu in THF
(12 mL, 12 mmol) and the mixture was allowed to warm up to room temperature. After being stirred for
12 h, the reaction mixture was quenched with a 1-M solution of HCl. The mixture was extracted with
EtOAc. The organic extract was washed with a saturated aqueous solution of NaHCO3, water, and brine,
dried over Na2SO4, and concentrated. The residue was chromatographed on silica gel to give 500 mg
(53%) of the title compound as colorless crystals: mp 94 °C; 1H NMR δ 8.88 (br, 1H, NH), 6.71 (m, 1H),
13
5.88 (m, 2H), 4.30 (q, 2H, J 7.0 Hz), 3.44 (m, 2H), 3.22 (m, 2H), 1.35 (t, 3H, J 7.0 Hz); C NMR δ
161.55, 124.79, 124.31, 123.72, 118.83, 118.44, 117.42, 59.88, 24.14, 22.44, 14.63; IR νmax (KBr) 3288,
1685, 1675, 1323, 1250, 1154 cm−1; MS (FAB+) m/z 192 (M+ + 1). HRMS calcd for C11H13NO2 + H+:
192.1025, found 192.1014. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C, 68.92; H,
7.03; N, 7.42%.
Ethyl (5S*,6S*)-5-chloro-6-phenylsulfanyl-4,5,6,7-tetrahydroisoindole-1-carboxylate (8a) and ethyl
(5S*,6S*)-6-chloro-5-phenylsulfanyl-4,5,6,7-tetrahydroisoindole-1-carboxylate (8b): Phenylsulfenyl
chloride (1.99 mL, 17 mmol) was added to a stirred solution of dihydroisoindole 7 (3.35 g, 17.5 mmol) in
dry CH2Cl2 (150 mL) at −78 °C and the mixture was allowed to warm to room temperature. After 1 h,
the mixture was sequentially washed with a saturated aqueous solution of NaHCO3, water, and brine,
dried over Na2SO4, and concentrated. The residue was purified by silica-gel chromatography to give 4.95
g (84%) of a 1:1 diastereomer mixture of the title compounds as a pale yellow powdery solid: mp
110-112 °C; 1H NMR δ 8.94 (br, 1H, both NH), 7.47 (m, 2H, both), 7.36-7.27 (m, 3H, both), 6.74 (m, 1H,
both H3), 4.45 (m, 1H, one of CHS), 4.40 (m, 1H, another CHS), 4.30 (m, 2H, both OCH2), 3.84 (m, 2H,
both CHCl), 3.63 (dd, J 18.9, 5.3 Hz, 1H, one), 3.52 (d, J 17.7 Hz, 1H, another), 3.52 (dt, J 17.7, 5.3 Hz,
1H, one), 3.40 (dd, J 18.9, 5.3 Hz, 1H, another), 3.34 (dd, J 18.9, 5.3 Hz, 1H,one), 3.23 (dd, J 18.9, 5.3
Hz, 1H, another), 2.93 (dd, J 16.9, 5.3 Hz, 1H, one), 2.84 (dd, J 16.9, 5.3 Hz, 1H, another), 1.36 (t, J 7.1
Hz, 3H, one), 1.34 (t, J 7.1 Hz, 3H, another); 13C NMR (typical signals) δ 161.39, 161.33, 133.66, 133.63,
132.27, 132.14, 129.19, 129.18, 127.64, 127.60, 122.66, 121.91, 119.42, 119.25, 118.57, 118.34, 116.85,
116.17, 60.02, 60.00, 57.51, 57.43, 47.94, 47.80, 28.81, 27.31, 25.07, 23.54, 14.49, 14.45; IR νmax (KBr)

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HETEROCYCLES, Vol. 90, No. 2, 2015
3278, 1684, 1429, 1331, 1147 cm−1; MS (FAB+) m/z 336 {M+(35Cl) + 1}; HRMS calcd for
C17H1835ClNO2S: 336.0825, found 336.0824. Anal. Calcd for C17H18ClNO2S: C, 60.80; H, 5.40; N, 4.17.
Found: C, 61.10; H, 5.67; N, 3.84%.
Ethyl (5S*,6S*)-5-chloro-6-phenylsulfonyl-4,5,6,7-tetrahydroisoindole-1-carboxylate (9a) and ethyl
(5S*,6S*)-6-chloro-5-phenylsulfonyl-4,5,6,7-tetrahydroisoindole-1-carboxylate (9b): To a stirred
solution of the mixture of 8a and 8b (4.95 g, 14.7 mmol) in dry CH2Cl2 (150 mL) was added mCPBA
(purity ca. 70%; 7.05 g, 29.4 mmol) at 0 °C. The mixture was allowed to warm up to room temperature
and stirred for 16 h. The resulting suspension was filtered through a Celite pad. The filtrate was washed
with a saturated aqueous solution of NaHCO3, water, and brine, dried over Na2SO4, and concentrated in
vacuo. The residue was purified by silica-gel chromatography to give 5.40 g (99%) of a mixture of the
1
title compounds as a pale yellow solid: mp 80-82 °C; H NMR δ 8.95 (br, 1H, both NH), 7.92 (m, 2H,
both), 7.68 (m, 1H, both), 7.58 (m, 2H, both), 6.73 (m, 1H, both H3), 5.05 (m, 1H, one), 4.94 (m, 1H,
another), 4.30 (m, 2H, both), 3.79-3.70 (m, 1H, both), 3.61 (dd, J 18.7, 4.5 Hz, 1H, one), 3.50 (dd, J 17.1,
4.1 Hz, 1H, one), 3.44 (m, 2H, another), 3.31 (dd, J 18.7, 7.2 Hz, 1H, one), 3.21 (dd, J 17.9, 6.6 Hz, 1H,
another), 3.16 (dd, J 17.9, 2.4 Hz, 1H, another), 3.04 (dd, J 17.1, 1.5 Hz, 1H, one), 1.35 (t, J 7.1 Hz, one),
13
1.31 (t, J 7.1 Hz, another); C NMR (typical signals) δ 161.1, 161.0, 138.1, 137.9, 134.4, 134.0, 132.2,
130.0, 129.6, 129.3, 129.2, 128.7, 128.6, 125.6, 121.7, 121.1, 119.5, 118.8, 118.5, 118.0, 116.2, 115.2,
64.1, 64.0, 60.2, 60.1, 52.6, 52.4, 30.9, 30.2, 28.8, 19.5, 18.2, 14.5; IR νmax (KBr) 3313, 1697, 1419, 1319,
1144, 727 cm−1; MS (FAB+) m/z 368 {M+(35Cl) + 1}; HRMS calcd for C17H18ClNO4S: 368.0723, found
368.0688.
Diethyl 4,8-dihydropyrrol[3,4-f]isoindole-1,5-dicarboxylate (anti-4) and Diethyl 4,8-dihydro-
pyrrol[3,4-f]isoindole-1,7-dicarboxylate (syn-4): To a stirred solution of a mixture of 9a and 9b (1.12 g,
3.05 mmol) in dry THF (30 mL) was added a 1-M solution of KOtBu (3.04 mL, 3.04 mmol) at 0 °C. The
mixture was allowed to warm up to room temperature and stirred for 4 h. The reaction mixture was
quenched with a 1-M solution of HCl and the mixture was extracted with EtOAc. The organic extract was
washed with a saturated aqueous solution of NaHCO3, water, and brine, dried over Na2SO4, and
concentrated in vacuo. The residue was dissolved in CHCl3 and passed through a short silica-gel column.
The filtrate was concentrated to give 770 mg (76%) of a 5:4 mixture of ethyl
6-phenylsulfonyl-4,7-dihydroisoindole-1-carboxylate {1H NMR δ 8.94 (br, 1H, NH), 7.91 (m, 2H), 7.59
(m, 1H), 7.54 (m, 3H), 6.72 (d, J 2.7 Hz, 1H, H5), 4.28 (q, J 7.1 Hz, 2H, OCH2), 3.73 (m, 1H), 3.59 (m,
1H), 3.52 (m, 1H), 3.38 (m, 1H), 1.36 (t, J 7.1 Hz, 3H)} and ethyl 5-phenylsulfonyl-4,7-dihydroisoindole-
1-carboxylate {1H NMR δ 8.93 (br, 1H, NH), 7.93 (m, 2H), 7.59 (m, 1H), 7.54 (m, 3H), 6.70 (d, J 2.6 Hz,
1H, H6), 4.31 (q, J 7.1 Hz, 2H, OCH2), 3.73 (m, 1H), 3.59 (m, 1H), 3.52 (m, 1H), 3.38 (m, 1H), 1.33 (t, J
7.1 Hz, 3H)}; MS (FAB+) m/z 332 (M+ + 1). This material was used in the next step without further

HETEROCYCLES, Vol. 90, No. 2, 2015
1165
purification. The isomeric mixture of vinyl sulfones (680 mg, 2.05 mmol) and ethyl isocyanoacetate (0.27
mL, 2.5 mmol) were dissolved in dry THF (20 mL). After the solution was cooled to 0 °C, a 1-M solution
of KOtBu in THF (5.1 mL, 5.1 mmol) was added. The mixture was allowed to warm up to room
temperature and stirred for 12 h. The mixture was quenched with a 1-M solution of HCl and extracted
with EtOAc. The organic extract was washed with a saturated aqueous solution of NaHCO3, water, and
brine, dried over Na2SO4, and concentrated in vacuo. The solid residue was treated with a small amount
of ether and then the triturated powdery solid was subject to the chromatographic purification on silica gel
(CHCl3). The analytically pure title compounds were obtained in 24% (150 mg) yield in a ratio of 10:3.
Recrystallization of the mixture from acetone/hexane gave 70 mg (11%) of pure anti-4 as a pale brown
1
powdery solid: mp 173 °C (decomp); H NMR δ 8.95 (br, 2H, NH), 6.86 (d, J 2.7 Hz, 2H, H3 and H7),
4.35 (d, J 7.2 Hz, 4H, OCH2), 3.99 (s, 4H, H4 and H8), 1.39 (t, J 7.2 Hz, 6H, CH3); IR νmax (KBr) 3294,
1666, 1311, 1151, 1028, 775, 600 cm−1; MS (FAB+) m/z 303 (M+ + 1); HRMS calcd for C16H18N2O4:
1
303.1345, found 303.1348. syn-4: H NMR δ 8.95 (br, 2H, NH), 6.83 (d, J 2.7 Hz, 2H, H3 and H7), 4.35
(d, J 7.6 Hz, 4H, OCH2), 4.21 (s, 2H, H8), 3.75 (s, 2H, H4), 1.40 (t, J 7.6 Hz, 6H, CH3).
Diethyl 3,7-bis(5’-ethoxycarbonyl-3’,4’-diethylpyrrol-2’-yl)-4,8-dihydropyrrol[3,4-f]isoindole-1,7-
dicarboxylate (10): Pyrrolisoindole anti-4 (68 mg, 0.27 mmol) and ethyl 5-acetoxymethyl-
3,4-diethylpyrrole-2-carboxylate (143 mg, 0.53 mmol) was dissolved in acetic acid (7 mL) and then
p-toluenesulfonic acid monohydrate (23 mg, 0.12 mmol) was added. After the mixture was stirred at
room temperature for 3 h, the reaction was quenched with water. The mixture was extracted with CHCl3.
The organic extract was washed with a saturated aqueous solution of NaHCO3, water, and brine, dried
over Na2SO4, and concentrated. The residual solid was triturated with a mixture of acetone/hexane (1/10)
to give 98 mg (50%) of the title compound as a pale purple solid: 1H NMR δ 8.83 (m, 2H, NH), 8.70 (m,
2H, NH), 4.25-4.33 (m, 12H), 3.96 (m, 4H), 3.83 (m, 4H), 2.75 (q, J 6.8 Hz, 4H), 2.45(q, J 6.8 Hz, 4H),
1.27-1.40 (m, 12H), 1.85 (m, J 6.8 Hz, 6H), 1.09 (m, J 7.6 Hz, 6H); IR νmax (KBr) 3294, 1670, 1419,
1311, 1153 cm−1; MS (FAB) m/z 717 (M+ + 1).
1,2,8,9-Tetraethyl-4,4,11,11-tetrafluoro-3,5,10,12-tetramethyl-4,11-dibora-3a,4a,10a,11a-tetraaza-
6,11-dihydrobenzo[1,2-a:4,5-a']di-s-indacene (12): Bisdipyrromethane tetraester 10 (74 mg, 0.1 mmol)
was dissolved in dry THF (10 mL) and cooled at 0 °C under an inert atmosphere. Lithium aluminum
hydride (76 mg, 2 mmol) was slowly added and then the mixture was heated under reflux conditions for 3
h. After being cooled to room temperature, the reaction mixture was quenched with an aqueous solution
of NaOH. The resulting suspension was filtered through a Celite pad and the filtrate was extracted with
EtOAc. The organic extract was washed with water and brine, dried over Na2SO4, and concentrated. The
residue was passed through a short silica-gel column. The filtrate was concentrated in vacuo to leave 33
mg (68%) of a mixture of 3,7-bis(3’,4’-diethyl-5’-methylpyrrol-2’-yl)-1,7-dimethyl-4,8-dihydro-

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pyrrol[3,4-f]isoindole and its mono-dehydrogenated product {11: MS (MALDI-TOF) m/z 484 (M+), 482
(M+-2)}, which was used in the next step without purification. This material was dissolved in dry CH2Cl2
(5 mL) and chloranil (35 mg, 0.14 mml) was added with stirring at room temperature. After 1 h,
diisopropylethylamine (0.17 mL, 0.97 mmol) and BF3·Et2O (0.13 mL, 1.1 mmol) were added. After 2 h,
the mixture was quenched with water. The resulting suspension was filtered through a Celite pad. The
filtrate was washed with a saturated aqueous solution of NaHCO3, water, and brine, dried over Na2SO4,
and concentrated in vacuo. The residue was chromatographed on silica gel (CH2Cl2) to give 33 mg (56%,
2 steps) of the title compound as a purple solid: 1H NMR δ 6.99 (m, 2H), 3.66 (m, 4H), 2.60 (m, 4H), 2.57
(s, 6H), 2.53 (s, 6H), 2.41 (m, 4H), 1.19-1.26 (m, 12H); IR νmax (KBr) 2972, 1602, 1408, 1180 cm−1;
UV-vis (CHCl3) λ 551 nm; MS (FAB+) m/z 576 (M+); HRMS calcd for C32H38B2F4N4: 576.3219, found:
576.3207.
1,2,8,9-Tetraethyl-4,4,11,11-tetrafluoro-3,5,10,12-tetramethyl-4,11-dibora-3a,4a,10a,11a-tetraaza-
benzo[1,2-a:4,5-a']di-s-indacene (3a):6 Dihydro-bisBODIPY 11 (1 mg, 0.002 mmol) was dissolved in
dry CH2Cl2 (5 mL) and chloranil (0.5 mg, 0.002 mmol) was added and the mixture was stirred for 4 h.
The mixture was quenched with a saturated aqueous solution of NaHCO3, washed with water and brine,
1
dried over Na2SO4, and concentrated in vacuo to leave 1 mg of the title compound as a purple solid: H
NMR δ 8.15 (s, 2H), 7.27 (s, 2H), 3.03 (s, 6H), 2.65 (q, 4H, J 7.6 Hz), 2.52 (s, 6H), 2.43 (q, 4H, J 7.6 Hz),
1.25 (t, 6H, J 7.6 Hz), 1.12 (t, 6H, J 7.6 Hz); UV-vis (CHCl3) λ 758 (ε = 1.90 × 105 M−1·cm−1) nm.
ACKNOWLEDGEMENTS
This work was partially supported by Grant-in-Aid for Scientific Research on Innovative Areas
“Molecular Architectonics: Orchestration of Single Molecules for Novel Functions” (25110003) from the
Japanese Ministry of Education, Culture, Sports, Science and Technology.
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