HETEROCYCLES

Paper | Special issue | Vol. 90, No. 2, 2015, pp. 1158-1167
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,* Mitsunori Nakamura, Kazuki Jodai, Shigeki Mori, and Tetsuo Okujima

Department of Chemistry and Biology, Graduate School or Science and Engineering, Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan

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 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.

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 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.

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

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 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 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), 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); 13C 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) 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 title compounds as a pale yellow solid: mp 80-82 °C; 1H 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), 1.31 (t, J 7.1 Hz, another); 13C 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-dihydropyrrol[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 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 powdery solid: mp 173 °C (decomp); 1H 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: 303.1345, found 303.1348. syn-4: 1H 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- 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-tetraazabenzo[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, dried over Na2SO4, and concentrated in vacuo to leave 1 mg of the title compound as a purple solid: 1H 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.

References

1. L. Luan, L. Ding, W. Zhang, J. Shi, X. Yu, and W. Liu, Bioorg. Med. Chem. Lett., 2013, 23, 3775. CrossRef
2. T. Funayama, M. Sakane, T. Abe, and N. Ochiai, Photomed. Laser Surg., 2012, 30, 47; CrossRef Y. Yang, Q. Guo, H. Chen, Z. Zhou, Z. Guo, and Z. Shen, Chem. Commun., 2013, 49, 3940; CrossRef J. Tian, L. Ding, H.-J. Xu, Z. Shen, H. Ju, L. Jia, L. Bao, and J.-S. Yu, J. Am. Chem. Soc., 2013, 135, 18850. CrossRef
3. P. Sarder, S. Yazdanfar, W. J. Akers, R. Tang, G. P. Sudlow, C. Egbulefu, and S. Achilefu, J. Biomed. Opt., 2013, 18, 106012. CrossRef
4. L. Yao, S. Zhang, R. Wang, W. Li, F. Shen, B. Yang, and Y. Ma, Angew. Chem. Int. Ed., 2014, 53, 2119. CrossRef
5. H. Uno, ‘Methods and Applications of Cycloaddition Reactions in Organic Syntheses,’ ed. by N. Nishiwaki, “Cycloreversion Approach For Preparation of Large π-Conjugated Compounds” John Wiley & Sons Inc., Chap 15, 429–470, 2014.
6. M. Nakamura, M. Kitatsuka, K. Takahashi, T. Nagata, S. Mori, D. Kuzuhara, T. Okujima, H. Yamada, T. Nakae, and H. Uno, Org. Biomol. Chem., 2014, 12, 1309; CrossRef M. Nakamura, H. Tahara, K. Takahashi, T. Nagata, H. Uoyama, D. Kuzuhara, S. Mori, T. Okujima, H. Yamada, and H. Uno, Org. Biomol. Chem., 2012, 10, 6840. CrossRef
7. H. Uno, S. Ito, M. Wada, H. Watanabe, M. Nagai, A. Hayashi, T. Murashima, and N. Ono, J. Chem. Soc., Perkin Trans. 1, 2000, 4347. CrossRef
8. P. S. Clezy, C. J. R. Fookes, and A. H. Mirza, Aust. J. Chem., 1977, 30, 1337. CrossRef
9. M. A. Filatov, A. V. Cheprakov, and I. P. Beletskaya, Eur. J. Org. Chem., 2007, 3468. CrossRef
10. T. Okujima, G. Jin, Y. Hashimoto, H. Yamada, H. Uno, and N. Ono, Heterocycles, 2006, 70, 619. CrossRef
11. H. Uno, M. Nakamura, and K. Takahashi, Jpn. Kokai Tokkyo Koho, JP 2013177551, A 20130909 (2013); V. V. Roznyatovskiy, R. Carmieli, S. M. Dyar, K. E. Brown, and M. R. Wasielewski, Angew. Chem. Int. Ed., 2014, 53, 3457. CrossRef