Functionalization of 3,5,8-trichlorinated BODIPY dyes.

Catalytic hydrogenation of dibenzyl 5-dipyrroketone-2,9-dicarboxylates followed by decarboxylative iodination affords a 2,9-diiododipyrroketone which gives a 2,5,9-trichlorodipyrromethene hydrochloride after nucleophilic addition/elimination, with adventitious chloride to replace the two iodide groups. Treatment with BF3·Et2O gives a 3,5,8-trichloro-BODIPY that readily undergoes regioselective Stille coupling at the 8-position, or homo/mixed couplings at the 3,8- or 3,5- and 8-positions. Stepwise and controlled replacement of the 3,5- and 8-chlorine atoms using Stille reagents results in formation of a completely unsymmetrical trisubstituted BODIPY. Several examples of unsymmetrical BODIPYs were synthesized and characterized using this methodology. Structure features of new BODIPYs are discussed within the context of 14 new X-ray structures, and photophysical parameters of all new BODIPY compounds are reported and discussed.

Introduction

4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (known as BODIPY) is a class of very versatile fluorophores that has been widely recognized and exploited in the last several decades. These dyes have found various applications as labeling agents, chemical sensors, photosensitizers, and energy-related cassettes and in luminescent devices.[1−4] BODIPY dyes have advantages compared with other fluorophores, including large molar absorption coefficients and high fluorescence quantum yields, redox active, relatively high thermal and photochemical stability, and easy functionalization that enables the tuning of their properties, such as absorption/emission wavelengths, charge-transfer, and amphiphilicity.[5−7] Due in part to their relatively low molecular weight, BODIPYs and their conjugates usually show good permeability across the membranes of living cells, making them suitable for biological and medical applications.[4−10]

Various methods have been developed for the functionalization of BODIPYs to change their photophysical, hydrophobic, and charge-transfer properties. These methods include, but are not limited to, electrophilic and nucleophilic substitutions, palladium-catalyzed cross-couplings, aromatic ring fusion, and Knoevenagel condensations.[5−7] Among these, aromatic ring fusion[7,11,12] and cross-coupling reactions[13−16] are particularly useful for inducing bathochromic shifts of the BODIPY optical transitions via extension of π-conjugation, while substitution reactions[17−21] are often used to modify the molecular amphiphilicity upon introduction of heteroatom-based groups, and for bioconjugations. Halogenated BODIPYs are particularly versatile substrates for functionalization purposes via both cross-coupling and nucleophilic substitution reactions, and all halogens (fluoride, chloride, bromide, and iodide) have been introduced into the pyrrolic positions of BODIPY (or a dipyrromethane or pyrrole precursor), mainly using electrophilic substitution.[5,6,22−26] In particular, functionalization of the BODIPY core at the 3,5-positions significantly affects the spectroscopic and photophysical properties, and this strategy has been exploited for the synthesis of a variety of functionalized BODIPYs, from 3,5-dichloro- or 3,5-diiodo-BODIPY precursors.[13,14,17−21] On the other hand, a very useful method for facile transformation of dipyrroketones into 5-chlorodipyrromethene salts using phosgene was developed by Fischer and Orth[27] and has since been exploited by others[28,29] and ourselves.[30] The resulting 8-chloro-BODIPYs are reactive toward palladium-catalyzed cross-coupling reactions and to nucleophilic aromatic substitutions using N-, O-, and S-based nucleophiles. Palladium-catalyzed Suzuki, Stille, Sonogashira, and Heck cross-coupling reactions have all been performed on 3,5-chloro-BODIPY, while Suzuki, Stille, and Sonogashira reactions have been achieved at the 8-position. Among these, the milder Stille reaction conditions, using Pd(PPh3)4 and a organotin reagent in toluene, in the absence of a base, gave 8-aryl, -alkyl, and -ethynyl-BODIPYs in yields >93%,[30] making it a highly efficient methodology for the functionalization of chloro-BODIPYs. Herein we report the synthesis of a symmetrical 3,5,8-trichloro-BODIPY (5) and describe both its global and regioselective functionalization using Stille coupling reactions to afford both symmetric and unsymmetric BODIPY dyes with extended π-conjugated systems. The spectroscopic properties of the 19 new BODIPY derivatives synthesized and structurally characterized, including 14 X-ray structures, are compared and discussed.

Results and Discussion

Syntheses

3,5,8-Trichloro-BODIPY 5, bearing two methyl propanoate groups that could subsequently be used for bioconjugation, was prepared as shown in Scheme 1. Symmetrical dipyrromethane 1 was obtained by treatment of benzyl 4-(2-methoxycarbonylethyl)-3,5-dimethylpyrrole-2-carboxylate on a 10–20 g scale with 1 equiv of bromine in diethyl ether, followed by heating in methanol. It was then oxidized with Pb(OAc)4/PbO2 in acetic acid[31] to give the corresponding dipyrrylketone 2 in 60% yield. Unlike our previously reported tetra- and hexaalkyldipyrrylketones,[30] the electron-deficient dipyrrylketone 2 could not be converted into the corresponding 5-chlorodipyrromethene hydrochloride by reaction with phosgene. Therefore, dipyrrylketone 2 was subjected instead to palladium-catalyzed debenzylation in a hydrogen atmosphere, followed by decarboxylative iodination to provide the 3,5-diiododipyrrylketone 3 in 69% overall yield.[32] Upon treatment with excess phosgene, the 3,5-diiododipyrrylketone 3 was converted into the fully conjugated meso-chlorodipyrromethene hydrochloride 4 which was not isolated but immediately complexed with BF3·Et2O in situ under basic conditions, to afford BODIPY 5 as the major product in 55% yield from 3. BODIPYs 6 and 7 were also isolated as minor byproducts, obtained in 11% and 5% yields from 3, respectively, after chromatographic separation. The trans-halogenation of 3,5-diiododipyrrylketone 3 to give 4 is probably a result of nucleophilic addition/elimination by chloride during the process, as nucleophilic substitutions at the 3,5- and 8-positions of the BODIPY have been shown to occur in the presence of a variety of nucleophiles.[17,28,30] On the other hand, byproducts 6 and 7 likely resulted from dehalogenation of the 3- and 3,5-positions, respectively, under the reaction conditions. The structures of BODIPYs 5 and 7 were unequivocally identified by their X-ray structures, shown in Figure 1.

Scheme 1

Synthesis of Halogenated BODIPYs by Phosgenation of Dipyrroketone 2

Reaction conditions: (i) Br2, Et2O; (ii) MeOH, Δ (70% yield, two steps); (iii) Pb(OAc)4/PbO2, (60%); (iv) Pd/C, H2, THF, (92%); (v) I2, NaHCO3, MeOH/H2O, (75%); (vi) COCl2 (toluene soln); (vii) BF3·Et2O, DIEA, (5, 55%), (6, 11%), (7, 5%).

Figure 1

X-ray structures of BODIPYs 5 and 7, with 50% ellipsoids.

Both molecules have essentially C2 symmetry, with 7 lying on a crystallographic 2-fold axis, and 5 having nearly the same conformation. The torsion angle about the CH2–CH2 bonds of the methyl propanoate substituents is −66.1° in 7, while in 5, the two torsion angles differ by 21.2°, but their mean value, −66.2°, closely matches that in 7. The central C3N2B ring is slightly more twisted in 5, with N atoms lying ±0.11 Å out of the C3B plane, compared to ±0.05 Å in 7. The N2B and BF2 planes form a dihedral angle of 89.2° in 5 and 89.9° in 7.

Because, as mentioned above, the milder palladium-catalyzed Stille cross-coupling reaction[33,34] gave the highest yields of functionalized BODIPYs,[30] in this study we investigated Stille couplings, using four different stannane reagents, in increasing order of reactivity: tributylphenyltin, trimethyl[(tributylstannyl)ethynyl]silane, tributyl(1-ethoxyvinyl)tin, and 2-(tributylstannyl)thiophene, to produce 8-mono-, 3,8-di-, and 3,5,8-trisubstituted BODIPYs, as shown in Schemes 2–5.

Scheme 2

Global Stille Coupling Reactions of 3,5,8-Trichloro-BODIPY 5 To Give BODIPYs 8–10

Scheme 5

Consecutive Stille Coupling Reactions of BODIPY 5 To Give Differentially Functionalized BODIPYs 20 and 21

Anticipating regioselectivity in the reactions of the 3,5,8-trichloro-BODIPY 5, we first addressed the global Stille coupling to demonstrate that functionalization at the 3,5,8-positions of BODIPY 5 can be performed in one step. A typical procedure involved refluxing a toluene mixture of 3,5,8-trichloro-BODIPY 5 and excess organotin reagent (4.5 equiv), in the presence of Pd(PPh3)4, for 5–24 h. The global Stille reactions proceeded in moderate to good yields, producing the corresponding 3,5,8-trisubstituted BODIPYs 8–10 in 42–83% yields (Scheme 2). The least reactive tin reagent used, the tributylphenyltin, required the longest time refluxing in toluene for 24 h, and gave the lowest yield of product. Products 8–10 showed red-shifted absorptions compared with the starting material 3,5,8-trichloro-BODIPY 5, which absorbs at λmax 538 nm; BODIPY 10 showed the most red-shifted absorption (λmax 648 nm), followed by BODIPY 8 (λmax 594 nm) and 9 (λmax 546 nm) (see Table 1). This is a result of a nearly perpendicular orientation of the phenyl groups on the trisubstituted BODIPYs 9, particularly the 8-phenyl, which prevents orbital interactions, whereas the linear trimethylsilylethynyl group lies in the plane of the BODIPY core, efficiently extending its π-conjugation (see Figure 2). In addition, in the case of the electron-rich thienyl group, the thiophene tends to decrease the HOMO–LUMO gap, therefore increasing the absorbance wavelength relative to the phenyl analogue (vide infra).[35] Figure 2 shows the X-ray structures of BODIPYs 8 and 10.

Table 1

Spectroscopic Properties of BODIPYs in Dichloromethane Solution at Room Temperaturea

BODIPY	abs λmax (nm)	emission λmax (nm)	Stokes shift (cm–1)	Φf	ε
5	538	550	406	0.58	112200
6	534	549	512	0.45	60300
7	528	547	658	0.30	38000
8	594	649	1427	0.10	43700
9	546	576	954	0.43	29500
10	648	660	280	0.01	88000
11	548	559	359	0.24	77600
12	534	544	344	0.86	69200
13	584	597	372	0.03	67600
14	560	591	936	0.27	17800
15	609	616	186	0.22	89100
16	574	629	1524	0.45	38900
17	594	600	168	0.34	47900
18	636	702	1478	0.08	29500
19	601	634	866	0.05	38900
20	616	625	234	0.21	46800
21	645	679	776	0.05	29500
22	555	587	982	0.53	33300
23	559	597	1138	0.67	13000

Fluorescence quantum yields (Φf) were calculated as follows: rhodamine 6G was used as the standard for compounds 5–9 and for compounds 11 and 12; rhodamine B was used as the standard for compounds 13, 14, 16, 17, 22, and 23; methylene blue was used as the standard for compounds 10, 15, 18–21.

Figure 2

X-ray structures of BODIPYs 8 and 10, with 50% ellipsoids.

Unlike the structures of 5 and 7 (Figure 1), both 8 and 10 have their propanoate substituents extended, with torsion angles about their CH2–CH2 bonds 170.4° and 179.7° for 8, 157.7° and 179.7° for 10. All three of the thiophenes in 8 exhibit disorder by 2-fold rotation about the C–C bonds joining them to the rest of the molecule, with only the major conformers shown in Figure 2. The central C3N2B ring in both molecules has a slight boat distortion, with B and the C opposite it lying, respectively, 0.18 and 0.04 Å on the same side of the plane formed by the other four atoms for 8, 0.19 and 0.04 Å for 10. The N2B and BF2 planes form a dihedral angle of 89.8° in both 8 and 10. The 12-atom BODIPY core of 8 makes a dihedral angle of 89.6° with the 8-thiophene plane and 68.1° and 39.9° with the other two.

Regioselective coupling reactions were performed on the 3,5,8-trichloro-BODIPY 5 using the same organotin reagents as described above for the synthesis of 8–10, but in a 1:1 ratio to the BODIPY rather than in excess. We anticipated monosubstitution at the most electrophilic 8-position of the BODIPY.[23] The coupling reaction with 2-(tributylstannyl)thiophene in refluxing toluene for 5 h gave the monothienyl-BODIPY 11 as the sole product, in 72% yield (Scheme 3). Under similar conditions, BODIPY 13 was also obtained in a reasonable yield (65%) along with trace amount of the corresponding 3,8-disubstituted product. Using the least reactive tin reagent, BODIPY 12 was obtained in only 21% yield; however, the yield of 12 was increased to 57% when 2 equiv (rather than 1) of organotin were used, and no disubstitution product was detected. The 1,7-propanoate groups likely lead to an increased dihedral angle between the BODIPY core and the phenyl group, resulting in blue-shifted absorption and emission bands. The X-ray structures of BODIPYS 11–13 are shown in Figure 3.

Scheme 3

Regioselective Stille Coupling Reactions of BODIPY 5 at the 8-Position To Give BODIPYs 11–13

Figure 3

X-ray structures of BODIPYs 11–13, with 50% ellipsoids.

Both 11 and 12 have two independent molecules in the crystal (only one shown in Figure 3), and the thiophene in both molecules of 11 is disordered. The propanoate substituents of all three molecules are extended, with torsion angle magnitudes in the range 175.9–179.8° for 11, 170.0–176.6° for 12, and 178.5° and 179.8° for 13. In the central C3N2B ring of all three molecules, only the B atom is distinctly out of plane, by a mean distance of 0.10 Å for 11, 0.14 Å for 12, and 0.12 Å for 13. In all three molecules, the BN2 and BF2 planes form dihedral angles of 89.7° to 89.8°. The 12-atom BODIPY core of 11 forms dihedral angles of 89.3° and 90.0° with the thiophene planes in the two independent molecules. The BODIPY core of 12 forms dihedral angles with the phenyl rings of 86.5° and 87.8° for the two independent molecules.

For the three new 8-substituted BODIPYs 11–13, different functional groups were introduced at the 3,5-positions by Stille coupling reactions using 2.4 equiv of selected organotin reagents, as shown in Scheme 4. Specifically, the 8-thienyl-BODIPY 11 was functionalized at the 3,5-positions with phenyl and trimethylsilylethynyl groups to provide BODIPYs 14 and 15, the 8-phenyl-BODIPY 12 was functionalized with thienyl and trimethylsilylethynyl groups to give BODIPYs 16 and 17, and BODIPY 13 was functionalized with phenyl and thienyl groups to produce BODIPYs 18 and 19. These double Stille reactions proceeded in good yields (51–78%), the highest obtained using the most reactive 2-(tributylstannyl)thiophene reagent and the lowest using the least nucleophilic tributylphenyltin. Five of these differentially substituted BODIPY compounds (specifically 15–19) were also characterized by single crystal X-ray crystallography, shown in Figure 4.

Scheme 4

Double Stille Coupling Reactions of BODIPYs 11–13 To Give Differentially Functionalized BODIPYs 14–19

Figure 4

X-ray structures of BODIPYs 15–19, with 50% ellipsoids.

Of the thiophene-containing molecules, 15 has its thiophene ordered, 18 has one ordered and the other disordered, and 16 has both disordered. BODIPY 19 has disorder both in the phenyl and COOMe conformations. Only the major conformers are shown in Figure 4. All five molecules have their methyl propanoate substituents extended, with torsion angle magnitudes about the CH2–CH2 bonds in the range 168.9–179.3°. There is some variation in the conformations of the central C3N2B rings. BODIPY 16 has the B atom 0.19 Å out of the best plane of the other five atoms, while in the two independent molecules of 19, the deviations are 0.19 and 0.35 Å. BODIPYs 15 and 17 have the slight boat distortion, with deviations 0.12 (for B) and 0.05 Å (for C) in 15, and 0.22 and 0.04 Å, respectively, for 17. The central C3N2B ring of 18 differs from the others, having a twist conformation with the B atom 0.07 Å and a N atom 0.13 Å on opposite sides of the plane of the other four atoms. The BN2/BF2 dihedral angles in 15, 16, 17, and 19 are all 89.6–90.0°, while that of 18 is slightly smaller, 88.9°. In 15, the BODIPY core forms a dihedral angle of 77.0° with the thiophene plane. In 16 and 17, respectively, the BODIPY core forms a dihedral angle of 87.6° and 80.0° with the phenyl plane. In 18, the BODIPY core forms dihedral angles of 58.1° and 44.9° with the two thiophene planes. In 19, the BODIPY core forms dihedral angles in the range 60.5–74.9° (mean value 70.5°) with the phenyl planes in the two independent molecules.

The synthesis of asymmetric BODIPYs was also accomplished using first 2 equiv of organotin reagent, followed by a second organotin; this strategy produces asymmetrical BODIPYs on account of the higher reactivity at the 8-position and the molecular symmetry about the 3,5-positions. The reaction of BODIPY 5 with 2 equiv of trimethyl[(tributylstannyl)ethynyl]silane produced the 3,8-disubstituted BODIPY 20 as the major product in 53% yield, along with a trace amount of the trisubstituted-BODIPY 10 (Scheme 5). BODIPY 20 was then treated with 2-(tributylstannyl)thiophene to yield BODIPY 21 in 63% yield. The structure of BODIPYs 20 and 21 were confirmed by their X-ray crystallography, shown in Figure 5.

Figure 5

X-ray structures of BODIPYs 20 and 21, with 50% ellipsoids.

As with all previous structures, except for 5 and 7, the methyl propanoate substituents of 20 and 21 are extended, with torsion angle magnitudes about the CH2–CH2 bonds in the range 175.0° to 179.0°. The conformation of the central rings are fairly planar, similar to those of 11–13, with the B atom 0.11 Å out of the C3N2 plane for 20 and 0.15 Å for 21. The BN2/BF2 dihedral angle is typical of these compounds, 89.6° for 20 and 89.5° for 21. In 21, the BODIPY core forms a dihedral angle of 43.1° with the thiophene plane.

Attempts to introduce three different groups at the 3-, 5-, and 8-positions of the BODIPY core were also investigated by consecutive Stille reactions using different organotin reagents, to produce a completely asymmetric BODIPY. The phenyl group was first regioselectively introduced at the most reactive 8-position to give the 8-phenyl BODIPY 12. Next, thiophene was introduced at the 3-position of BODIPY 12 using 1 equiv of 2-(tributylstannyl)thiophene, resulting in the isolation of asymmetric BODIPY 22 in 43% yield along with a trace amount of BODIPY 16 (Scheme 6). Finally, an ethoxyvinyl group was introduced into the 5-position of BODIPY 22 by reaction with tributyl(1-ethoxyvinyl)tin to provide the fully asymmetric BODIPY 23 in 51% yield.

Scheme 6

Stille Coupling Reactions of BODIPY 12 To Give 23 Featuring Three Different Groups on the 3,5,8-Positions

Spectroscopic Properties

The spectroscopic properties of all BODIPYs synthesized, including UV/visible absorption and steady-state fluorescence emission, were studied in dichloromethane solution, and the results are summarized in Table 1. Furthermore, as an example, Figure 6 shows the normalized absorption and fluorescence spectra for BODIPYs 5, 9, 13, and 15 (others are presented in Supporting Information). All BODIPYs show typical absorption and emission spectra for this type of compound, with strong absorption bands corresponding to the S0–S1 transition (log ε = 4.1–5.1), a shoulder at shorter wavelength due to the 0–1 vibrational band of the same transition, and Stokes-shifted emission bands. The Stokes shifts vary considerably for this group of BODIPYs, from 186 to 1524 cm–1; BODIPYs 8, 16, and 18, bearing 3,5-thienyl groups, have the largest Stokes shifts (1427–1524 cm–1) followed by BODIPYs 21–23, bearing only one thienyl group at the 5-position. In agreement with these values, Stokes shifts of ca. 1500 cm–1 have been reported for 3,5-thienyl-substituted BODIPYs, and larger values were achieved upon boron substitution with alkynylaryl groups via intramolecular energy transfer.[11,36] It has also been shown that 8-thienyl-substituted BODIPYs normally show small Stokes shifts (ca. 350 cm–1) typical of BODIPY derivatives,[2] and that 2,6-dithienyl-BODIPYs can show even larger Stokes shifts, presumably due to increased geometry relaxation, i.e., the geometry difference between the S0 and the S1 states, upon photoexcitation.[37,38]

Figure 6

Normalized UV/visible absorption (solid line) and fluorescence emission (dashed line) spectra of selected BODIPYs 5, 9, 13, and 15 (left to right) in dichloromethane solution.

The introduction of chlorines at the 3,5-positions slightly red-shifts the absorption and emission bands and increases the molar extinction coefficients and fluorescence quantum yields, as previously observed, due to the decrease in nonradiative deactivation processes.[24,39,40] As expected, the global Stille coupling on BODIPY 5 caused pronounced red-shifts in the absorption and emission bands, particularly for the 3,5,8-trimethylsilylethynyl-BODIPY 10 which showed a 110 nm bathochromic shift compared with 5 due to larger electronic coupling with the BODIPY chromophore, therefore extending the π-conjugation system and decreasing the HOMO–LUMO gap.[41] On the other hand, the aromatic substituents on 8 and 9, particularly the 8-aryl groups, orient themselves nearly perpendicular to the BODIPY core to minimize steric interactions, inducing smaller red-shifts. In addition, the electron-releasing effect of the thiophene group tends to decrease the HOMO–LUMO gap,[35] inducing larger red-shifts compared with the phenyl-substituted analogues (see below). Similarly, the 3,5,8-trisubstituted BODIPYs 14–19, 21, and 23 obtained by mixed Stille coupling reactions all show bathochromic shifts (21–107 nm) compared with BODIPY 5; the greatest red-shifts were observed for the trimethylsilylethynyl-containing BODIPYs 15, 17–19, and 21, and the smallest for the phenyl-containing BODIPYs 14 and 16.

Regioselective coupling at only the 8-position caused a slight blue-shift in the case of 8-phenyl-BODIPY 12, and a slight red-shift in the case of 8-thienyl-BODIPY 11, as previously observed,[30] indicating that the most pronounced effect on the absorption and emission wavelengths of the BODIPYs arise from 3,5-aryl (rather than 8-) substitution. The large dihedral angle (ca. 87° from crystal structure) between the 8-phenyl group and the BODIPY core in 12 as a result of 1,7-disubstitution induces blue-shifted absorption and emission spectra. On the other hand, an 8-trimethylsilylethynyl group, as found in BODIPY 10, effectively extends the π-conjugation, inducing a 46 nm bathochromic shift. In agreement with these results, it has been previously observed that an 8-(2-phenylethynyl) group induces ca. 40 nm red-shifts although small Stokes shifts.[41,42] Although the 8-thienyl group forms an even larger dihedral angle with the BODIPY core in 11 (ca. 89° from crystal structure), the electron-releasing effect of the thienyl group decreases the HOMO–LUMO gap, therefore increasing the absorbance and emission wavelengths relative to BODIPY 12.[35]

The fluorescence quantum yields determined in dichloromethane were significantly higher for the phenyl-substituted BODIPYs compared with the thienyl- and trimethylsilylethynyl-substituted BODIPY analogues. For example, the 8-phenyl-BODIPY 12 showed the highest quantum yield (Φf = 0.86) of all BODIPYs in this series, whereas the 3,5,8-trimethylsilylethynyl-BODIPYs 10 showed the lowest (Φf = 0.01). These results are in agreement with our previous studies[30,35] and reflect the greater freedom of rotation of the smaller thienyl group in comparison with phenyl, even in the presence of the 1,7-propanoate substituents, increasing the amount of energy lost to nonradiative decay to the ground state. The aryl-ring rotation has been demonstrated to be critical in determining the excited-state dynamics of BODIPYs, and in particular their fluorescence quantum yields.[43,44] On the other hand, the trimethylsilylethynyl groups increase the nonradiative molecular relaxation which decreases the fluorescence quantum yields. We have previously shown that upon deprotection of the trimethylsilyl group, the resulting 8-ethynyl-BODIPY shows increased fluorescence quantum yield.[30]

Conclusions

A very useful method for transformation of dipyrroketones into 5-chlorodipyrromethene hydrochlorides by using phosgene is inhibited by the presence of conjugated 2,9-ester substituents. However, catalytic debenzylation followed by decarboxylative iodination affords a 2,9-diiodopyrroketone which does undergo the phosgene reaction to provide 2,5,9-trichlordipyrromethene hydrochlorides after nucleophilic addition/elimination with chloride to replace the two iodo groups. Treatment of these 3,5,8-trichlorodipyrromethene salts with BF3·Et2O gives a 3,5,8-trichloroBODIPY that readily undergoes regioselective Stille coupling at the 8-position, or a combination of differential 3,8-disubstitution or 3,5- and 8-trisubstitution. X-ray structures of 14 new BODIPYs are reported and analyzed. Global Stille coupling at the 3,5,8-positions of BODIPY 5 caused up to 110 nm bathochromic shifts (in the case of the 3,5,8-trimethylsilylethynyl-BODIPY 10) in the absorption and emission bands of the BODIPYs. Regioselective and consecutive Stille coupling reactions produced a variety of asymmetric BODIPYs; the 3,5-aryl and 3(5)- and/or 8-ethynyl substitution induced the largest bathochromic shifts whereas the presence of a 3(5)-thienyl substituent caused the largest Stokes shifts (up to 1524 cm–1). The 8-phenyl-BODIPYs showed the highest fluorescence quantum yields (Φf = 0.34–0.86), followed by the 8-thienyl-BODIPYs (Φf = 0.10–0.27), whereas the 8-ethynyl-BODIPYs showed the lowest quantum yields (Φf = 0.01–0.21).

Experimental Section

General

1H and 13C NMR spectra were measured on a 400 MHz NMR spectrometer at room temperature. Chemical shifts (δ) are given in ppm relative to TMS. High-resolution mass spectra were obtained using the ESI-TOF mode. UV–visible absorption spectra and fluorescence emission spectra were recorded on a commercial spectrophotometer (190–900 nm scan range). The slit width was set at 3.0 nm. Relative fluorescence quantum yields (Φf) were calculated as follows: rhodamine 6G was used as the standard for compounds 5–9 and for compounds 11 and 12; rhodamine B was used as the standard for compounds 13, 14, 16, 17, 22, and 23; methylene blue was used as the standard for compounds 10, 15, 18–21. All commercial reagents were used without further purification. Water- and air-sensitive reactions were performed under argon protection and in dry solvents.

Dibenzyl 3,7-Bis(2-methoxycarbonylethyl)-2,8-dimethyldipyrromethane-1,9-dicarboxylate 1

Benzyl 4-(2-methoxycarbonylethyl)-3,5-dimethylpyrrole-2-carboxylate (15.7 g, 0.05 mol) was dissolved in anhydrous diethyl ether (500 mL), and bromine (2.56 mL, 0.05 mol) was added dropwise. The solution turned brown during addition, and the mixture was further stirred at room temperature overnight, whereupon a thick precipitate was apparent. Then the diethyl ether was removed under vacuum to give a pink solid that was dissolved in methanol (100 mL) and refluxed overnight. When the solution was cooled to room temperature, a precipitate appeared, which was filtered and washed with cold methanol to give a white solid (10.70 g, 70%) of dipyrromethane 1. Mp 102–104 °C, (lit.[45] mp 102–103 °C). 1H NMR (400 MHz; CDCl3): δ 9.00 (s, 2H), 7.38–7.31 (m, 10H), 5.25 (s, 4H), 3.97 (s, 2H), 3,56 (s, 6H), 2.75 (t, 4H), 2.51 (t, 4H), 2.28 (s, 6H); 13C NMR (100 MHz; CDCl3): 173.9, 161.4, 136.5, 130.9, 128.5, 128.0, 127.9, 127.2, 120.2, 118.0, 65.5, 51.8, 34.5, 22.4, 19.2, 10.4; HRMS (ESI-TOF) calcd for C35H39N2O8 [M + H]+ 615.6928, found 615.6908.

Dibenzyl 3,7-Bis(2-methoxycarbonylethyl)-2,8-dimethyldipyrroketone-1,9-dicarboxylate 2

A solution of dipyrromethane 1 (2.0 g, 3.25 mmol) in acetic acid (80 mL) was treated with Pb(OAc)4 (3.12 g, 7.0 mmol) and stirred at room temperature for 4 d under argon. Then PbO2 (2.4 g, 9.3 mmol) was added, and the solution was stirred for another 2 d. The solution was centrifuged, and the supernatant was poured into ice–water. The precipitate was collected and dissolved in diethyl ether before being washed with water, 5% aqueous NaHCO3, and brine and then dried over anhydrous Na2SO4. Then the solution was concentrated to a minimum volume and crystallized in a refrigerator to give product as a yellowish white solid (1.2 g, 60%), mp 170–171 °C (lit.[46] mp 173–174 °C). 1H NMR (400 MHz; CDCl3) δ 7.38–7.31 (m, 10H), 5.00 (s, 4H), 3,67 (s, 6H), 3.01 (broad, 4H), 2.71 (broad, 4H), 2.27 (s, 6H); 13C NMR (100 MHz; CDCl3) δ 176.7, 173.6, 161.7, 135.0, 132.2, 130.2, 128.7, 128.4, 127.7, 127.0, 121.7, 66.8, 51.6, 35.2, 20.3, 10.4; HRMS (ESI-TOF) calcd for C35H36N2O9 [M + H]+: 629.2499, found 629.2497.

1,9-Diiodo-3,7-bis(2-methoxycarbonylethyl)-2,8-dimethyldipyrroketone 3

Dipyrroketone 2 (6.14 g, 0.01 mol) was dissolved in 300 mL of THF, and then 5% Pd/C (350 mg) catalyst was added. The suspension was stirred under a H2 atmosphere overnight. After TLC showed that reaction was complete, it was stopped and the reaction solution was passed through a Celite cake to remove the catalyst. The sticky solid on the top of the Celite cake was redissolved and neutralized in water with aqueous ammonia, and the solution was passed through the Celite cake once again. The filtrate was acidified with acetic acid which caused a precipitate to appear from the aqueous solution. The solid was collected by filtration. The THF filtrate was evaporated and combined with the solid to give a total of 4.0 g (92%) of the 1,9-dicarboxylic acid product. This dicarboxylic acid was suspended in a solution of H2O (250 mL)/MeOH (100 mL), and NaHCO3 (4.48 g, 51.2 mmol) was added to the solution, which was sonicated to form a slurry and then a clear solution. Then a solution of I2 (3.84 g, 14.72 mmol) in methanol (60 mL) was added to the mixture dropwise at room temperature with vigorous stirring, and some brown solid was formed during the addition. When the addition of iodine was complete, the stirring was continued for another 2 h and the precipitate was filtered and washed with water, saturated aqueous NaHCO3, and water again, followed by hexane to remove any excess I2, to yield a yellowish solid. The product was left to air-dry or dissolved in CH2Cl2 and dried over anhydrous Na2SO4 before removal of the solvent to give diiodopyrroketone 3 (4.2 g, 75%), mp 162 °C. 1H NMR (400 MHz; CDCl3) δ 9.47 (s, 2H), 3.65 (s, 6H), 2.70 (t, J = 7.6 Hz, 4H), 2.61 (t, J = 7.6 Hz, 4H), 2.04 (s, 6H); 13C NMR (100 MHz; CDCl3) δ 173.8, 173.5, 132.7, 128.5, 126.4, 51.8, 33.9, 20.9, 12.2; HRMS (ESI-TOF) calcd for C19H23I2N2O5 [M + H]+: 612.9691, found: 612.9697.

BODIPYs 5–7

Diiodopyrroketone 3 (1.0 g, 1.63 mmol) was dissolved in CHCl3 (150 mL), and excess phosgene in toluene solution was added to the solution, which turned deep red with time; the reaction was monitored by UV/vis spectrophotometry, and the reaction was stopped when a sharp absorption peak appeared at about 480 nm. Then N2 gas was passed through the solution to purge it of excess phosgene into an aqueous NaHCO3 solution trap. Solvent was removed in vacuo to give a reddish solid, which was dissolved in 150 mL of CHCl3, followed by addition of DIEA (2 mL, 7.0 equiv). The solution was stirred for 30 min, BF3·OEt2 (2.1 mL, 10 equiv) was added, and the solution turned bright red with a yellow fluorescence under long wavelength UV light. The reaction was monitored by UV/vis spectroscopy, which showed a sharp peak at 538 nm. The mixture was stirred for 24 h before being washed with water, saturated aqueous NaHCO3, and brine and then dried over anhydrous Na2SO4 to give a red solid. The product was purified by silica gel column chromatography, eluting with ethyl acetate/hexane (1:4) to give the product 5 (430 mg, 55%) as the major fraction and 6 (88.5 mg, 11%) and 7 (40.2 mg, 5%) as minor products. BODIPY 5: mp 156–157 °C; 1H NMR (400 MHz; CDCl3) δ 3.72 (s, 6H), 3.20 (t, J = 8.0 Hz, 4H), 2.57 (t, J = 8.0 Hz, 4H), 2.05 (s, 6H); 13C NMR (100 MHz; CDCl3) δ 172.5, 144.0, 142.3, 134.9, 128.5, 127.3 52.0, 33.8, 22.8, 8.9; HRMS (ESI-TOF) calcd for C19H20 BCl3FN2O4 [M – F]+: 475.0566, found: 475.0562; UV/vis (CH2Cl2): λmax (ε) = 538 nm (112 200). BODIPY 6: mp 116–118 °C; 1H NMR (400 MHz; CDCl3) δ 7.57 (s, 1H), 3.71 (s, 3H), 3.71 (s, 3H), 3.20 (m, 4H), 2.58 (m, 4H), 2.07 (s, 3H), 2.04 (s, 3H); 13C NMR (100 MHz; CDCl3) δ 172.5, 172.5, 143.5, 142.6, 142.4, 136.8, 130.1, 129.1, 128.7, 127.3, 126.8, 52.0, 51.9, 33.9, 33.9, 22.8, 22.2, 9.9, 8.9; HRMS (ESI-TOF) calcd for C19H21BCl2FN2O4 [M – F]+ 441.0955, found 441.0935, UV/vis (CH2Cl2): λmax (ε) = 534 nm (60 300). BODIPY 7: mp 148–149 °C; 1H NMR (400 MHz; CDCl3) δ 7.58 (s, 2H), 3.73 (s, 3H), 3.21 (t, J = 8.1 Hz, 4H), 2.59 (t, J = 8.1 Hz, 4H), 2.08 (s, 3H); 13C NMR (100 MHz; CDCl3) δ 172.8, 143.1, 142.5, 138.7, 130.4, 128.8, 51.9, 34.0, 22.2, 9.8; HRMS (ESI-TOF) calcd for C19H22BClFN2O4 [M – F]+ 407.1345, found 407.1342. UV/vis (CH2Cl2): λmax (ε) = 528 nm (38 000).

General Procedure for Stille Coupling Reactions

Global Coupling Reactions

BODIPY 5 (15 mg, 0.03 mmol) and Pd(PPh3)4 (2.0 mg, 5%) were added to a round-bottomed flask. The flask was flushed with argon, and then anhydrous toluene (15 mL) was injected, followed by injection of the organotin reagent (0.14 mmol, 4.5 equiv). The solution was refluxed for 12 h until the starting material disappeared from TLC and the UV/vis spectrum showed a sharp peak around 600 nm. Then the toluene was removed, and the residue was taken up in CH2Cl2, washed with water and brine, and then dried over anhydrous Na2SO4. The crude product was purified by chromatography to give the fully (tri-) substituted products.

BODIPY 8

(16.0 mg, 83%), mp 198 °C; 1H NMR (400 MHz; CDCl3) δ 7.56–7.49 (m, 5H), 7.20–7.09 (m, 4H), 3.63 (s, 6H), 2.33–2.22 (m, 6H), 2.00 (s, 6H), 1.94–1.86 (m, 2H); 13C NMR (100 MHz; CDCl3) δ 172.5, 149.7, 142.4, 134.4, 133.2, 133.0, 131.7, 129.7, 128.8, 128.0, 127.4, 127.2, 51.6, 35.1, 21.4, 10.6; HRMS (ESI-TOF) calcd for C31H30BF2N2O4S3 [M + H]+ 639.1429, found 639.1429. UV/vis (CH2Cl2): λmax (ε) = 594 nm (43 700).

BODIPY 9

(8.2 mg, 42%), mp 165–166 °C; 1H NMR (400 MHz; CDCl3) δ 7.53–7.38 (m, 15H), 3.60 (s, 6H), 2.12 (m, 4H), 2.00 (m, 4H), 1.80 (s, 6H); 13C NMR (100 MHz; CDCl3) δ 172.4, 156.6, 142.23, 134.6, 132.0, 131.3, 129.7, 129.4, 128.8, 128.7, 128.4, 128.3, 127.8, 51.5, 34.5, 21.7, 9.7; HRMS (ESI-TOF) calcd for C37H35BFN2O4 [MW – F]+ 601.2674, found 601.2656. UV/vis (CH2Cl2): λmax (ε) = 546 nm (29 500).

BODIPY 10

(12.6 mg, 61%), mp 171 °C; 1H NMR (400 MHz; CDCl3) δ 3.69 (s, 6H), 3.25 (t, J = 8.0 Hz, 4H), 2.25 (t, J = 8.0 Hz, 4H), 2.08 (s, 6H). 0.32 (s, 9H), 0.28 (s, 9H); 13C NMR (100 MHz; CDCl3) δ 172.8, 140.5, 136.0, 134.7, 132.8, 118.3, 114.0, 113.3, 99.2, 96.4, 51.7, 34.2, 21.4, 14.1, 9.5; HRMS (ESI-TOF) calcd for C34H48BF2N2O4Si3 [M + H]+ 680.3014, found 680.3001. UV/vis (CH2Cl2): λmax (ε) = 648 nm (88 000).

Regioselective Stille Coupling Reactions

The selective coupling reactions followed the procedure used for the global coupling reactions. The only difference was that 1 equiv of organotin reagent was used instead of excess organotin reagents.

BODIPY 11

Starting with BODIPY 5 (29.2 mg, 0.059 mmol), 23.07 mg (72%) of the monosubstituted BODIPY was obtained, mp 212 °C; 1H NMR (400 MHz; CDCl3) δ 7.56 (dd, J = 5.0, 1.3 Hz, 1H), 7.15 (d, J = 1.8 Hz, 1H), 7.09 (d, J = 1.6, 1H), 3.62 (s, 6H), 2.28–2.02 (m, 6H), 1.96 (s, 6H), 1.89–1.83 (m, 2H); 13C NMR (100 MHz; CDCl3) δ 172.1, 145.0, 143.3, 133.5, 132.8, 131.0, 129.1, 128.5, 127.4, 126.9, 51.7, 34.8, 21.5, 8.8; HRMS (ESI-TOF) calcd for C23H23BCl2FN2O4S [MW – F]+ 523.0833, found 523.0836. UV/vis (CH2Cl2): λmax (ε) = 548 nm (77 600).

BODIPY 12

A 1:1 ratio of BODIPY 5 (30.4 mg, 0.061 mmol) and tributylphenyltin (20.0 μL, 0.061 mmol) was used to give the product 12 (7.0 mg, 21%); a 1:2 ratio of BODIPY 5 (32.6 mg, 0.066 mmol) and tributylphenyltin (40.0 μL, 0.122 mmol) was used to give the product 12 (19.45 mg, 57%), mp 172 °C; 1H NMR (400 MHz; CDCl3) δ 7.56–7.38 (m, 5H), 3.58 (s, 6H), 2.04 (m, 4H), 1.95 (m, 10H); 13C NMR (100 MHz; CDCl3) δ 171.9, 144.4, 143.2, 141.1, 133.3, 130.1, 129.9, 129.0, 128.1, 126.5, 51.6, 34.3, 21.4, 8.7; HRMS (ESI-TOF) calcd for C25H25BCl2FN2O4 [M – F]+: 517.1268, found: 517.1278. UV/vis (CH2Cl2): λmax (ε) = 534 nm (69 200).

BODIPY 13

Starting with BODIPY 5 (20.0 mg, 0.04 mmol), 15.2 mg (65%) of 13 was isolated, mp 121 °C; 1H NMR (400 MHz; CDCl3) δ 3.71 (s, 6H), 3.30 (t, J = 8.8 Hz, 4H), 2.59 (t, J = 8.8 Hz, 4H), 2.04 (s, 6H), 0.30 (s, 9H); 13C NMR (100 MHz; CDCl3) δ 172.6, 143.0, 142.1, 131.7, 126.4, 119.3, 114.8, 98.4, 51.8, 34.2, 21.7, 8.8; HRMS (ESI-TOF) calcd for C24H29BCl2FN2O4Si [M – F]+ 537.1321, found 537.1340. UV/vis (CH2Cl2): λmax (ε) = 584 nm (67 600).

Consecutive Stille Coupling Reactions

BODIPY 11 (16.5 mg, 0.030 mmol) and Pd(PPh3)4 (3.4 mg, 5%) were added to a round-bottomed flask and flushed with argon several times. Anhydrous toluene (10 mL) was added, followed by injection of tributylphenyltin (28.0 μL, 3.0 equiv); the solution was refluxed for 12 h until a sharp peak appeared in the UV/vis spectrum at 562 nm in CH2Cl2. The reaction was stopped, and the toluene was removed; the residue was taken up in CH2Cl2, which was washed with water and brine and then dried over anhydrous Na2SO4. The crude product was purified by silica gel column chromatography, eluting with ethyl acetate/hexane (1:4) to give the product as a purple-red solid. All the other Stille cross-coupling reactions followed this procedure.

BODIPY 14

(10.6 mg, 56%), mp >260 °C. 1H NMR (400 MHz; CDCl3) δ 7.59–7.14 (m, 13H), 3.65 (s, 6H), 2.29–2.27 (m, 6H), 2.07–1.96 (m, 2H), 1.86 (s, 6H); 13C NMR (100 MHz; CDCl3) δ 172.6, 157.2, 142.5, 134.5, 132.3, 131.9, 129.6, 128.9, 128.7, 128.3, 127.9, 127.8, 127.2, 51.6, 35.1, 21.5, 9.8; HRMS (ESI-TOF) calcd for C35H33BFN2O4S [M – F]+ 607.2238, found 607.2234. UV/vis (CH2Cl2): λmax (ε) = 560 nm (17 800).

BODIPY 15

Starting with BODIPY 11 (14.3 mg, 0.026 mmol) afforded the product 15 (11.1 mg, 64%), mp 187 °C. 1H NMR (400 MHz; CDCl3) δ 7.54 (m, 1H), 7.14 (m, 1H), 7.08 (m, 1H), 3.63 (s, 6H), 2.19 (m, 6H), 2.02 (s, 6H), 1.90 (m, 2H), 0.33 (s, 18H); 13C NMR (100 MHz; CDCl3) δ 172.4, 141.7, 137.8, 134.0, 133.6, 133.2, 129.0, 128.1, 127.2, 113.7, 96.2, 51.6, 34.9, 21.2, 9.5, 0.3; HRMS (ESI-TOF) calcd for C33H42BF2N2O4SSi2 667.2465, found 667.2473. UV/vis (CH2Cl2): λmax (ε) = 609 nm (89 100).

BODIPY 16

Starting with BODIPY 12 (15.1 mg, 0.029 mmol) afforded the product 16 (14.4 mg, 78%), mp 166 °C. 1H NMR (400 MHz; CDCl3) δ 7.59–7.47 (m, 9H), 7.14 (dd, J = 5.1, 3.6 Hz, 2H), 3.60 (s, 6H), 2.14–2.09 (m, 4H), 1.99–1.96 (m, 10H); 13C NMR (100 MHz; CDCl3) δ 172.3, 149.3, 142.2, 141.2, 134.5, 132.0, 131.8, 131.5, 129.5, 129.3, 128.9, 128.5, 128.4, 127.3, 51.5, 34.5, 21.3, 10.5; HRMS (ESI-TOF) calcd for C33H31BFN2O4S2 [M – F]+ 613.1802, found 613.1803. UV/vis (CH2Cl2): λmax (ε) = 574 nm (38 900).

BODIPY 17

Starting with BODIPY 12 (17.3 mg, 0.033 mmol) gave 17 (15.7 mg, 71%), mp 182 °C. 1H NMR (400 MHz; CDCl3) δ 7.52–7.45 (m, 3H), 7.37–7.28 (m, 2H), 3,57 (s, 6H), 2.06–2.00 (m, 10H), 1.94–1.89 (m, 4H), 0.33 (s, 18H); 13C NMR (100 MHz; CDCl3) δ 172.2, 149.3, 141.5, 140.5, 137.3, 133.8, 132.9, 129.6, 128.8, 128.3, 112.8, 96.2, 51.5, 34.3, 21.1, 9.5, 1.0; HRMS (ESI-TOF) calcd for C35H43BF2N2NaO4Si2 [M + Na]+ 683.2720, found 683.2723. UV/vis (CH2Cl2): λmax (ε) = 594 nm (47 900).

BODIPY 18

Starting with BODIPY 13 (12.6 mg, 0.023 mmol) gave 18 (11.3 mg, 76%), mp 179 °C. 1H NMR (400 MHz; CDCl3) δ 7.54–7.49 (m, 4H), 7.11 (ddd, J = 5.2, 3.8, 1.6 Hz, 2H), 3.72 (s, 6H), 3.39 (t, J = 8.2 Hz, 4H), 2.64 (t, J = 8.2 Hz, 4H), 2.09 (s, 6H), 0.32 (s, 18H); 13C NMR (100 MHz; CDCl3) δ 173.0, 147.9, 141.2, 133.8, 131.9, 131.7, 129.1, 128.7, 127.3, 119.2, 113.6, 99.4, 51.7, 34.4, 31.6, 21.6, 10.6, 1.1; HRMS (ESI-TOF) calcd for C32H35BFN2O4S2Si [MW – F]+ 633.1885, found 633.1883. UV/vis (CH2Cl2): λmax (ε) = 636 nm (29 500).

BODIPY 19

Starting with BODIPY 13 (11.0 mg, 0.02 mmol) gave product 19 (6.5 mg, 51%), mp 195 °C. 1H NMR (400 MHz; CDCl3) δ 7.45–7.36 (m, 10H), 3.72 (s, 6H), 3.39 (t, J = 7.8 Hz, 4H), 2.67 (t, J = 7.8 Hz, 4H), 1.89 (s, 6H), 0.33 (s, 9H); 13C NMR (100 MHz; CDCl3) δ 173.0, 155.5, 141.3, 133.1, 131.9, 129.7, 128.8, 128.1, 127.7, 113.3, 99.3, 51.6, 34.4, 21.0, 9.7, 1.1; HRMS (ESI-TOF) calcd for C36H39BFN2O4Si [M – F]+ 621.2756, found 621.2757. UV/vis (CH2Cl2): λmax (ε) = 601 nm (38 900).

BODIPY 20

BODIPY 5 (15.0 mg, 0.03 mmol) and Pd(PPh3)4 (3.4 mg, 5%) were added to a round-bottomed flask. The flask was flushed with argon and then anhydrous toluene (15 mL) was injected, followed by injection of the organotin reagent trimethyl[(tributylstannyl)ethynyl]silane (22.3 μL, 0.06 mmol). The mixture was refluxed until the starting material disappeared as observed by TLC and the UV/vis spectrum showed a sharp peak around 615 nm. Then the toluene was removed and the residue was taken up in CH2Cl2 and washed with water, brine and then dried over anhydrous Na2SO4. The crude product was purified by silica gel column chromatography to give the disubstituted product 20 (10.0 mg, 53%), mp 122 °C. 1H NMR (400 MHz; CDCl3) δ 3.68 (s, 3H), 3.68 (s, 3H), 3.25 (m, 4H), 2.56 (m, 4H), 2.07 (s, 3H), 2.02 (s, 3H), 0.30 (s, 9H), 0.27 (s, 9H); 13C NMR (100 MHz; CDCl3) δ 172.8, 172.7, 144.0, 142.1, 140.5, 135.2, 133.3, 132.9, 126.6, 118.9, 114.4, 113.1, 98.7, 96.0, 51.8, 51.7, 34.2, 34.1, 21.7, 21.4, 9.5, 8.2, 0.3, 1.2; HRMS (ESI-TOF) calcd for C29H39BClF2N2O4Si2 [M + H]+ 619.2198, found 619.2185. UV/vis (CH2Cl2): λmax (ε) = 616 nm (46,800).

BODIPY 21

BODIPY 20 (10 mg, 0.016 mmol) and Pd(PPh3)4 (2.0 mg, 5%) were added to a round-bottomed flask. The flask was flushed with argon, and then anhydrous toluene (15 mL) was injected, followed by injection of the organotin reagent 2-(tributylstannyl)thiophene (8.0 μL, 1.5 equiv); the mixture was then refluxed for 5 h. The toluene was removed, and the residue was taken up in CH2Cl2, washed with water and brine, and then dried over anhydrous Na2SO4. The crude product was purified by silica gel column chromatography to give the fully substituted product 21 (6.8 mg, 63%), mp 151 °C. 1H NMR (400 MHz; CDCl3) δ 7.75 (d, J = 3.44 Hz, 1H), 7.58 (d, J = 4.92 Hz, 1H), 7.20 (t, J = 4.24 Hz, 1H), 3.71 (s, 3H), 3.70 (s, 3H), 3.37 (t, J = 7.88 Hz, 2H), 3.28 (t, J = 7.36 Hz, 3H), 2.64 (t, J = 7.88 Hz, 3H), 2.57 (t, J = 7.36 Hz, 3H), 2.15 (s, 3H), 2.09 (s, 3H). 0.30 (s, 9H), 0.28 (s, 9H); 13C NMR (100 MHz; CDCl3) δ 172.9, 151.9, 150.2, 142.5, 139.2, 133.6, 132.9, 132.6, 131.7, 129.7, 129.5, 127.5, 118.5, 113.6, 112.0, 99.3, 96.6, 51.7, 51.6, 34.4, 34.2, 21.6, 21.4, 10.9, 9.6. 1.0; HRMS (ESI-TOF) calcd for C33H42BF2N2O4SSi2 [M + H]+ 667.2465, found 667.2478. UV/vis (CH2Cl2): λmax (ε) = 645 nm (29 500).

BODIPY 22

BODIPY 12 (21.6 mg, 0.042 mmol) and Pd(PPh3)4 (5.3 mg, 5%) were added to a round-bottomed flask. The flask was flushed with argon, and then anhydrous toluene (15 mL) was injected, followed by injection of the organotin reagent 2-(tributylstannyl)thiophene (14.0 μL, 1.0 equiv); the mixture was then refluxed for 5 h. The toluene was removed, and the residue was taken up in CH2Cl2, washed with water and brine, and then dried over anhydrous Na2SO4. The crude product was purified by silica gel column chromatography hexane/ethyl acetate (4:1) to give product 22 (10.5 mg, 43%), mp 164 °C. 1H NMR (400 MHz; CDCl3) δ 7.58–7.18 (m, 8H), 3.58 (s, 6H), 2.11–1.91 (m, 14H); 13C NMR (100 MHz; CDCl3) δ 172.2, 172.1, 150.4, 143.2, 143.1, 142.2, 141.1, 133.9, 132.0, 131.6, 130.4, 130.1, 129.7, 129.0, 129.0, 128.9, 128.2, 127.4, 126.1, 51.6, 34.4, 26.9, 21.9, 10.5, 7.5; HRMS (ESI-TOF) calcd for C29H28BClF2N2NaO4S [M + Na]+ 607.1417, found 607.1391. UV/vis (CH2Cl2): λmax (ε) = 555 nm (33 300).

BODIPY 23

BODIPY 22 (9.4 mg, 0.016 mmol) and Pd(PPh3)4 (2.1 mg, 5%) were added to a round-bottomed flask. The flask was flushed with argon, and then anhydrous toluene (15 mL) was injected, followed by injection of the organotin reagent tributyl(1-ethoxyvinyl) (11.0 μL, 1.5 equiv); the mixture was refluxed for 5 h. The toluene was removed, and the residue was taken up in CH2Cl2, washed with water and brine, and then dried over anhydrous Na2SO4. The crude product was purified by silica gel column chromatography hexane/ethyl acetate (4:1) to give the fully substituted BODIPY 23 (5.6 mg, 51%), mp, >260 °C. 1H NMR (400 MHz; CDCl3) δ 7.59–7.15 (m, 8H), 4.62 (s, 2H), 3.90 (q, J = 7.1, 2H), 3.57 (s, 6H), 2.11–1.91(m, 14H), 1.35(t, J = 7.1, 3H); 13C NMR (100 MHz; CDCl3) δ 172.4, 172.3, 152.3, 151.5, 142.6, 142.30 142.0, 141.9, 135.4, 134.4, 133.4, 131.5, 129.5, 129.3, 129.3, 128.8, 128.6, 128.4, 128.4, 128.2, 127.2,91.1, 63.7, 53.4, 51.5, 34.5, 21.4, 21.1, 14.3, 10.5, 9.3; HRMS (ESI-TOF) calcd for C33H36BF2N2O5S [M + H]+ 621.2406, found 621.2406. UV/vis (CH2Cl2): λmax (ε) = 559 nm (13 000).