Synthesis and characterization of pyrrolyldipyrrin F-BODIPYs

Abstract

A series of synthetic analogs of the tripyrrolic natural product prodigiosin were complexed with boron trifluoride to generate the corresponding F-BODIPYs. The maximum wavelengths of absorption and emission of the pyrrolyldipyrrin F-BODIPYs were tuned through variation of the substituents about the pyrrolyldipyrrinato core. The limited variation of substituents on the C-ring did not significantly affect absorption and emission. However, variation of substituents on the B-ring and A-ring resulted in a corresponding red-shift in absorption and emission reaching maximum wavelengths of 600 nm. The presence of electron donating substituents on the B-ring caused a decrease in the Stokes shift, while the presence of electron-withdrawing substituents caused an increase, ranging from 3–25 nm. Stokes shifts were solvent-dependant for some compounds. The inclusion of a dimethylamino group resulted in photo-induced electron transfer and thus quenched fluorescence which was restored upon protonation.

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Introduction

Tripyrrolic compounds that contain a dipyrrin and a pyrrolic unit, connected at the 9-position, constitute what are known as pyrrolyldipyrrins. The presence of this third pyrrolic unit extends the π-conjugation of the dipyrrinato ligand and causes red-shifted absorption maxima that have facilitated applications in the life sciences and materials chemistry.¹ The natural product prodigiosin and its synthetic analogues, termed prodigiosenes (Fig. 1), belong to the pyrrolyldipyrrin family² and exhibit significant biological activity including immunosuppressive,³ anti-malaria,⁴ anti-microbial⁵ and anti-cancer activity.^6,7

Fig. 1 Prodigiosin, F-BODIPY and pyrrolyldipyrrin metal complexes.

Dipyrrins coordinate to a variety of metals^1,8 but the most prominent type of dipyrrinato complex features a –BF₂ unit to yield 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs, Fig. 1). F-BODIPYs are chemically robust, as well as thermally, photochemically and physiologically stable. They exhibit sharp fluorescence, with high molar extinction coefficients and quantum yields, making them useful in applications such as cell imaging, chemosensors and laser dyes.^9–12 Like dipyrrins, several metal complexes of pyrrolyldipyrrins have been reported, including those of cobalt, copper, tin, zinc and boron.^4,13–17 Compared to boron complexes of dipyrrins, pyrrolyldipyrrinato complexes absorb and emit light at much longer wavelengths, due to the extended π-conjugation of the dipyrrinato ligand. As a result, these highly fluorescent complexes are useful as probes in biological applications, e.g., the commercially available fluorescent dyes BODIPY 576/589 and BODIPY 650/665 (absorption/emission, respectively).^16,18–20 Other reported examples of boron difluoro pyrrolyldipyrrinato complexes include the unsubstituted pyrrolyldipyrrin²⁰ and those with substituted aromatics,^{15,17,21–23} heterocycles²² and alkyl groups²¹ at the meso-position, phenyl substitution at the meso-position with different functional groups present on the A-ring^24,25 or the presence of halogens about the pyrrolyldipyrrin core^26,27 and isoindole substitution of the B-ring.^16,28 Boron difluoro complexes of prodigiosenes (pyrrolyldipyrrins bearing a methoxy substituent on the B-ring) have recently been reported. However, the purpose of the synthesis was to afford the desired synthetic natural products in a facile manner by removal of the –BF₂ protecting group.²⁹ Additionally, our group has recently synthesized two pyrrolyldipyrrin BF₂ complexes bearing ester functionality on the C-ring of the pyrrolyldipyrrin core.^4,13,30 To the best of our knowledge these are the only reported examples of pyrrolyldipyrrin F-BODIPYs. Despite these examples, a thorough study investigating how changing the substituents about the three rings of the pyrrolyldipyrrin core affects the photophysical properties is lacking. Herein, a series of pyrrolyldipyrrin F-BODIPYs with varying substituents on each of the pyrrolic rings, and their respective photophysical properties, are described.

Results and discussion

To investigate the photophysical properties of prodigiosene-based F-BODIPYs, the pyrrolyldipyrrin HCl salts 1 bearing modifications to the A, B and C-rings were synthesized.^4,6,31 Modifications included conjugated carbonyl and alkyl substituents on the C-ring, electron-withdrawing and electron-donating groups on the B-ring, and indole substitution at the A-ring. The pyrrolyldipyrrin HCl salts 1 were complexed with boron trifluoride in the presence of base.^11,32 Several additions of Lewis acid and base, plus extended reaction times, were required to afford the eighteen novel pyrrolyldipyrrin F-BODIPYs 2–4 in 38–95% yields after multiple purification attempts via column chromatography (Scheme 1).

Scheme 1 Synthesis of pyrrolyldipyrrin F-BODIPYs 2–4.

A crystal suitable for X-ray analysis of pyrrolyldipyrrin F-BODIPY 2d was obtained from the slow evaporation of a chloroform solution. The thermal ellipsoid diagram of 2d is shown in Fig. 3 and illustrates that the pyrrolyldipyrrin core is perpendicular to the plane of the coordinated F–B–F atoms. The B–N bond distances range from 1.54–1.56 Å indicating that the dipyrrinato unit is significantly resonance stabilized, as expected. The core structure of 2d is essentially planar, with the uncoordinated pyrrolic unit slightly out of plane, which may accommodate a hydrogen bond between the hydrogen atom of the pyrrolic nitrogen and a fluorine. The NH–F hydrogen bond distance ranges from 2.05–2.53 Å.

The pyrrolyldipyrrin F-BODIPYs featured a variety of substituents on the C-ring (2a–2l, Fig. 2) and B-ring (3m–3p, Fig. 4). In addition, two analogues 4q and 4r (Fig. 5) of Obatoclax,³³ bearing an indole moiety in lieu of the A-ring, were prepared. F-BODIPY 2a (Fig. 2), the unsubstituted pyrrolyldipyrrin bearing only the signature methoxy group on the B-ring, was chosen as a parent compound to which the properties of the C-ring substituted pyrrolyldipyrrin F-BODIPYs would be compared. Such substituents included a mimic of the natural product prodigiosin (2b), conjugated esters (2c–2f, 2l), conjugated ketones (2g–2i) and derivatives of ethanoic acid (2j and 2k). These substituents provide a wide scope to demonstrate the influence that C-ring substituents have on the photophysical properties of pyrrolyldipyrrin F-BODIPYs.

Fig. 2 Pyrrolyldipyrrin F-BODIPYs (2a–2l) with C-ring modifications.

Fig. 3 Thermal ellipsoid diagram of 2d (50%). Selected bond distances (Å): B(1)–N(1), 1.539(2); B(1)–N(2), 1.551(2); selected bond angles (°): N(1)–B(1)–N(2), 108.36(11); selected torsional angles (°): N(2)–C(9)–C(17)–N(3), −7.5(2); hydrogen bond distance (Å): N(3)–H(3N)⋯F(1), 2.529(17), N(3)–H(3N)⋯F(2), 2.049(18).

Fig. 4 Pyrrolyldipyrrin F-BODIPYs (3m–3p) with B-ring modifications.

Fig. 5 Pyrrolyldipyrrin F-BODIPYs (4q–4r) A-ring (indole) modifications.

The synthetic analog 2b of prodigiosin was selected as the parent compound by which substrates (3m–3p), bearing benzoxy or phenoxy substituents in lieu of the methoxy group, would be compared. In this regard, the effect that the methoxy substituent has upon the photophysical properties would be evaluated. The nature of this substituent is highly important to some aspects of the biological activity of prodigiosenes, yet substituting the methyl group for benzyl or phenyl groups does not diminish the anticancer properties of the compound.⁶ Lastly, pyrrolyldipyrrin F-BODIPYs 4q and 4r feature an indole moiety which further extends the π-conjugation of the F-BODIPY core and as a result are expected to inherently absorb and emit at longer wavelengths. Compounds 2b and 2f (Fig. 2) represent the parent compounds of the A-ring indole analogs, 4q and 4r.

The photophysical properties of solutions of pyrrolyldipyrrin F-BODIPYS (2–4) in CH₂Cl₂ were evaluated. All absorbance spectra exhibited a similar band structure in the visible region, with a peak and shoulder that are characteristic of BF₂ dipyrrin complexes. Additionally, all compounds emitted at wavelengths in the yellow/orange visible region, displaying high extinction coefficients (11 000–156 000 mol M⁻¹ cm⁻¹) and have Stokes’ shift in the range of 3–25 nm. As representative examples, the absorbance and emission spectra of F-BODIPY 2a and 3o (Fig. 6) illustrate the increase in Stokes’ shift observed for electron-withdrawing groups of the B-ring compared to the unsubstituted pyrrolyldipyrrin. A summary of the results is presented in Table 1.

Fig. 6 Normalized absorbance and emission spectra of 2a (left, black, Stokes shift 13 nm) and 3o (right, pink, Stokes shift 25 nm).

Table 1 Photophysical properties of F-BODIPYs 2–4 in CH₂Cl₂ at 22 °C

F-BODIPY	λ abs (nm)	λ em (nm)	Stokes shift (nm)	log ε	Φ F
a Relative to Rhodamine 6G in EtOH (ΦF = 0.94). b Relative to Rhodamine 101 in EtOH (ΦF = 0.96). c Hexanes used instead of CH2Cl2 for quantum yield data.
2a	530	543	13	4.57	0.95^b
2b	565	578	13	4.69	0.84^b
2c ^34	542	555	13	4.81	0.85^a
2d	543	555	12	4.83	0.90^a
2e	539	555	16	4.80	0.90^a
2f ^4	542	553	11	5.20	1.00^a
2g	544	557	13	4.04	0.78^a
2h	545	557	12	4.85	0.85^a
2i	546	559	13	4.93	0.90^a
2j	561	574	13	4.65	0.81^b
2k	558	571	13	5.10	0.79^b
2l	540	559	19	4.74	0.70^a
3m	573	597	24	4.88	0.89^b
3n	566	572	6	4.74	0.98^a
3o	575	600	25	4.41	0.74^b
3p	567	570	3	4.69	0.55^b^,^c
4q	579	591	12	4.73	1.00^b
4r	562	574	12	4.87	0.95^b

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To evaluate the effects of C-ring substituents on the absorption maxima, each compound was compared to the parent (2a) bearing only the methoxy substituent on the B-ring. F-BODIPY 2a itself has a maximum absorbance wavelength of 530 nm, which is hypsochromically shifted by 44 nm from the unsubstituted pyrrolyldipyrrin F-BODIPY.¹⁶ This indicates that the electron-donating methoxy group causes a blue-shift in absorption. All modifications to the C-ring (2b–2l) bathochromically shifted the absorbance wavelength (9–35 nm) compared to the unsubstituted, methoxy bearing F-BODIPY 2a (see ESI, Fig. S3 and S4†). The greatest shift in absorption wavelength maxima of the C-ring modified pyrrolyldipyrrin F-BODIPYs occurred with the alkyl and ethanoic acid derivative substituents: 2b, 2j and 2k bearing a –CH₂CH₃, –CH₂C(O)NEt₂ and –CH₂CO₂Bn group, respectively. This trend is in agreement with that observed for F-BODIPYs whereby as the core becomes more alkyl substituted, the fluorophore absorbs at a higher wavelength.

The presence of electron-withdrawing groups on the B-ring (–Ph-pCl, 3m or –Ph-pCF₃, 3o) resulted in a slight red-shift in absorption and emission wavelengths when compared to the parent compound 2b (see ESI, Fig. S5 and S6†) A similar trend has been reported for dipyrrin F-BODIPYs that contain electron-withdrawing groups in the meso-position.³⁵ Both F-BODIPYS 4q and 4r bearing the indole moiety in lieu of the A-ring pyrrole, exhibited significantly red-shifted absorbance maxima compared to the unsubstituted F-BODIPY 2a. Furthermore, 4q and 4r, the A-ring indole analogs of 2b and 2f, respectively, exhibited a red shift in absorption of 14–20 nm of their A-ring pyrrole analogues, courtesy of the indole moiety (see ESI, Fig. S7 and S8†).

Unlike their constituent ligands, pyrrolyldipyrrin F-BODIPYs (2–4) exhibited considerable fluorescence with excellent relative quantum yields (Φ_F > 0.70, Table 1) with the exception of F-BODIPY 3p. Pyrrolyldipyrrin F-BODIPY 3p did not display fluorescence when dissolved in CH₂Cl₂ (Fig. 7a). However, when 3p was dissolved in hexanes, an immediate display of fluorescence was evident (Fig. 7b). The emission spectra of 3p in CH₂Cl₂ and hexanes is shown in ESI Fig. S9.† As well as a broader band structure for the emission of 3p in hexanes, compared to that of F-BODIPY 2a (see Fig. 6), 3p exhibited a very narrow Stokes’ shift of 3 nm and much lower quantum yield of 0.55.

Fig. 7 3p in CH₂Cl₂ (a), hexanes (b), CH₂Cl₂ without 1 M HCl (c) and CH₂Cl₂ with 1 M HCl (d) under ambient light and UV light.

The lack of emission of 3p in CH₂Cl₂ can be attributed to the lone pair of the amino substituent transferring an electron to the F-BODIPY fluorophore to quench its fluorescence through photo-induced electron transfer (PET).^36,37 This process can be effectively controlled by variation of the polarity of the solvent or by protonation of the amino substituent. To investigate the PET process observed for 3p, a solution of this compound in hexanes was titrated with CH₂Cl₂ and indeed fluorescence quenching was observed (Fig. 8a). Treatment of a CH₂Cl₂ solution of 3p, using 5 μL of 1 M HCl, restored fluorescence (Fig. 7 and 8b). The maximum wavelength of emission for 3p in CH₂Cl₂ with the addition of 1 M HCl is 597 nm with a Stokes’ shift of 28 nm and a quantum yield of 0.41. The absorbance spectra of 3p in CH₂Cl₂ shows a red-shift in the maximum wavelength of absorption (569 nm–574 nm) upon addition of 1 M HCl (see ESI Fig. S10†).

Fig. 8 (a) Observed fluorescence quenching of 3p in hexanes via titration with CH₂Cl₂; (b) emission spectra of 3p dissolved in CH₂Cl₂ and in CH₂Cl₂ with addition of 1 M HCl.

Additionally, solvatochromatic effects of 2b (ESI Fig. S11 and S12†) and 3n–3p were observed in hexane, toluene, dichloromethane, tetrahydrofuran, acetonitrile and methanol and is summarized in the ESI (Table S1†). Interestingly, when 3p was dissolved in polar solvents such as tetrahydrofuran, acetonitrile and methanol, the Stokes’ shift was significantly increased from 3 nm (in hexanes) to 22–25 nm, yet with a lower quantum yield ranging from 0.22–0.30. Such an effect was not observed for 2b and 3m–3o, where the Stokes’ shift and relative quantum yield did not vary amongst the different solvents. A slight blue-shift in absorption and emission wavelengths was observed for 2b and 3m–3o when dissolved in polar solvents (acetonitrile and methanol) compared to the wavelengths observed for these compounds dissolved in CH₂Cl₂.

The solvatochromatic effect on the emission of 3p is illustrated by the Lippert–Mataga plot (Fig. 9) of solvent orientation polarizability (Δf) versus Stokes’ Shift (in cm⁻¹). There is a linear correlation between the solvent polarity and magnitude of the Stokes’ Shift, with high polarity solvents exerting the greatest effect. It should be noted that Lippert–Mataga plots for compounds 2b and 3m–3o (ESI Fig. 13†) do not illustrate such correlation, alluding that these compounds are not as sensitive to solvent polarity as 3p. The larger Stokes’ shift observed for 3p dissolved in more polar solvents can be rationalized by considering the magnitude of the slope from the Lippert–Mataga plot, which gives an estimation of the change in dipole moment of the excited state and ground state of 3p. In general, polar species can orient around the dipole of the excited state and thereby lower the energy of the excited state and shift emission maxima to longer wavelengths.

Fig. 9 Lippert–Mataga plot of 3p illustrating the Stokes’ shift as a function of orientation polarizability (Δf). Solvents from left-right: hexane, toluene, tetrahydrofuran, acetonitrile and methanol. Dichloromethane is not represented on the plot as there was no measurable emission maximum for the compound in this solvent.

Conclusions

A series of pyrrolyldipyrrin F-BODIPYS with varying substituents on the A, B and C rings has been synthesized. Variation of substituents on the B-ring and A-ring result in the corresponding red-shift in absorption and emission reaching maximum emission wavelengths of 600 nm. Complexes bearing electron withdrawing substituents on the B-ring exhibited the largest Stokes’ shift of 24–25 nm, while complexes bearing electron donating groups on the B-ring displayed the smallest Stokes’ shift of only 3–6 nm. Extending the conjugation of the pyrrolyldipyrrin F-BODIPY core via placement of an indole substituent in lieu of the A-ring (4q and 4r), results in the exhibition of a red-shift in absorption and emission wavelength (562–579 nm) with Stokes’ shift comparable to that of C-ring substituents. Pyrrolyldipyrrin F-BOIPY 3p exhibited interesting photophysical properties where the fluorescence is controlled depending on the polarity of the solvent. In hexanes, 3p displays appreciable fluorescence, while in CH₂Cl₂ the fluorescence is effectively quenched. Additionally, the small Stokes’ shift observed for 3p could be enhanced when dissolved in polar solvents such as tetrahydrofuran, acetonitrile and methanol, or upon protonation with HCl. These data regarding the effects of substitution upon absorption and emission provide insight regarding how pyrrolyldipyrrin F-BODIPYs can be designed to match performance criteria.

Experimental procedures

General experimental

All chemicals, including anhydrous solvents and reagents, were obtained from commercial sources and used as received unless otherwise noted. CH₂Cl₂ and hexanes for chromatography were obtained crude and distilled under air at 1 atm pressure before use. Column chromatography was performed using 150 mesh Brockman III, basic or neutral aluminum oxide. NMR spectra were obtained using a 500 MHz or 300 MHz instrument using CDCl₃ as solvent. Chemical shifts are reported in parts per million using the solvent signals as an internal ¹H and ¹³C references. ¹¹B and ¹⁹F chemical shifts were referenced using BF₃·Et₂O (15% in CDCl₃) and CCl₃F defining the 0 ppm position as per the absolute referencing procedure standard for Bruker digital spectrometers. Coupling constants (J) are reported in hertz. Mass spectra were recorded using ESI TOF ionization. UV-Vis and emission analyses were performed using a UV-visible spectrophotometer and PTI spectrofluorometer, respectively. X-ray crystallography measurements were made on a CCD-equipped diffractometer (30 mA, 50 kV) using monochromated Mo Kα radiation (λ = 0.71073 Å) at 125 K. Compounds 1a–1r were prepared according to literature procedures.^4,6,31

General procedure for absorbance and emission measurements

In all measurements, a 10 mm quartz cuvette was used for solutions. For fluorescence experiments, a slit width of 3 nm was used for both excitation and emission.

Fluorescence quantum yield

Relative fluorescence quantum yields were obtained by comparing the area under the emission spectrum of the compound of interest to that of the standard, rhodamine 6G (ϕ = 0.94 in ethanol) or rhodamine 101 (ϕ = 0.96 in ethanol).³⁸ The excitation wavelength was 520 nm for rhodamine 6G and 546 nm for rhodamine 101. The excitation wavelength was 520 nm for 2c–2i, 2l and 3n and compared to rhodamine 6G excited at 520 nm. The excitation wavelength for 2a–2b, 2j–2k, 3m, 3o–3p and 4q–4r was 546 nm and compared to rhodamine 101 excited at 546 nm. Relative quantum yields were determined using eqn (1),³⁹ where Φ_st is the reported quantum yield of the standard, I is the area of the integrated emission spectra, A is the absorbance at the excitation wavelength and η is the refractive index of the solvent used. The subscripts “X” and “st” denote the unknown and standard, respectively.

Relative quantum yield (Φ_X):

General procedure (GP1) for BF₂ complexation of pyrrolyldipyrrins

The corresponding pyrrolyldipyrrin HCl salt (1 equiv.) was dissolved in dry CH₂Cl₂ under a nitrogen atmosphere. Triethylamine (6 equiv.) was added and the reaction mixture then stirred for 10 minutes. BF₃·OEt₂ (9 equiv.) was then added slowly, over a period of a few minutes. The reaction mixture was stirred until complete loss of starting material according to analysis using thin layer chromatography. Subsequent additions of base (6 equiv.) and BF₃·OEt₂ (9 equiv.) were added after a period of 8 hours. Reaction time and total amount of base and BF₃·OEt₂ varied (5 h–96 h) depending upon the substrate. Upon completion, the reaction mixture was quenched via addition to 1 M HCl (15 mL) and then extracted with CH₂Cl₂ (25 mL). The organic phase was washed with 1 M HCl (1 × 15 mL) and brine (2 × 15 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting crude material was purified via column chromatography on basic or neutral alumina eluting with 5–20% ethyl acetate in hexanes, unless otherwise stated.

Boron, difluoro[[(2H-pyrrol-2-ylidene)methyl]-4-methoxy-1H,1′H-2,2′-bipyrrole] (2a). Following GP1, over a 72 hour period a solution of 1a (20 mg, 0.07 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (233 μL, 1.89 mmol) and NEt₃ (176 μL, 1.26 mmol). The product was purified using column chromatography on basic alumina, eluting with 10–25% CH₂Cl₂ in hexanes, to provide F-BODIPY 2a (9 mg, 45% yield). ¹H NMR (500 MHz, CDCl₃) 10.61 (br s, 1H), 7.51 (s, 1H), 7.20–7.18 (m, 1H), 7.13 (s, 1H), 7.01–6.99 (m, 1H), 6.77–6.76 (m, 1H), 6.42–6.37 (m, 2H), 6.12 (s, 1H), 3.98 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz) 165.3, 152.7, 134.1, 131.3, 130.5, 126.9, 123.5, 121.7, 119.2, 117.8, 114.9, 111.8, 97.1, 58.8; ¹¹B NMR (CDCl₃, 160 MHz) 1.23 (t, J = 35 Hz); ¹⁹F NMR (235 MHz_, CDCl₃) −139 (q, J = 34 Hz); UV/vis (CH₂Cl₂) λ_max (nm) 530, ε 37 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_ex (nm), 543, Φ_F: 0.95; LRMS: 310.1 (M + Na)⁺; HRMS: 310.0925. Found, 310.0934 calculated for C₁₄H₁₂BF₂N₃NaO.

Boron, difluoro[5-[(3,5-dimethyl-4-pentyl-2H-pyrrol-2ylidene)methyl]-4-methoxy-1H,1′H-2,2′-bipyrrole] (2b). Following GP1, over a 4 day period a solution of 1b (18 mg, 0.05 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (278 μL, 2.25 mmol) and NEt₃ (167 μL, 1.20 mmol). The product was purified using column chromatography on neutral alumina, eluting with 1%, 3%, 5% and then 10% ethyl acetate in hexanes, to provide F-BODIPY 2b (10 mg, 53% yield). M.p. 124–126 °C; ¹H NMR (500 MHz, CDCl₃) 10.43 (br s, 1H), 7.08–7.07 (m, 1H), 7.05 (s, 1H), 6.84 (m, 1H), 6.33–6.31 (m, 1H), 6.10 (s, 1H), 3.95 (s, 3H), 2.49 (s, 3H), 2.37 (t, J = 7.7 Hz, 2H), 2.15 (s, 3H), 1.48–1.41 (m, 2H), 1.37–1.30 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) 162.6, 150.2, 147.8, 134.3, 130.7, 129.5, 126.2, 124.2, 124.1, 115.6, 114.8, 110.8, 96.5, 58.4, 31.9, 30.2, 24.3, 22.7, 14.2, 12.6, 9.7; ¹¹B NMR (160 MHz, CDCl₃) 1.41 (t, J = 36 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −139 (q, J = 33 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 565, ε 49 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 578, Φ_F: 0.84; LRMS: 408.2 (M + Na)⁺; HRMS: 408.2031. Found, 408.2029 calculated for C₂₁H₂₆BF₂N₃NaO.

Boron, difluoro[ethyl 2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)-methylene]-3,5-dimethyl-2H-pyrrole-4-carboxylate] (2c)¹³. Following GP1, over a 24 hour period a solution of 1c (50 mg, 0.13 mmol) in CH₂Cl₂ (6 mL) was reacted with BF₃·OEt₂ (610 μL, 4.94 mmol) and NEt₃ (544 μL, 3.90 mmol). The reaction mixture was quenched via addition of 5% citric acid and extracted with diethyl ether (20 mL). The product was purified using column chromatography on neutral alumina, eluting with 75% CH₂Cl₂ in hexanes, to provide F-BODIPY 2c (42 mg, 81% yield). ¹H NMR (500 MHz, CDCl₃) 10.50 (br s, 1H), 7.19–7.18 (m, 1H), 7.17 (s, 1H), 6.97–6.96 (m, 1H), 6.39–6.37 (m, 1H), 6.14 (s, 1H), 4.31 (q, J = 7.1 Hz, 2H), 3.99 (s, 3H), 2.81 (s, 3H), 2.43 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); ¹¹B NMR (160 MHz, CDCl₃) 1.39 (t, J = 36 Hz); ¹HNMR and ¹¹B NMR chemical shifts were in agreement with literature values.¹³ UV/vis (CH₂Cl₂) λ_max (nm): 542, ε 64 000 mol L⁻¹cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 555, Φ_F: 0.85.

Boron, difluoro[isopropyl 2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)-methylene]-3,5-dimethyl-2H-pyrrole-4-carboxylate] (2d). Following GP1, over a 72 hour period a solution of 1d (23 mg, 0.08 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (133 μL, 1.08 mmol) and NEt₃ (100 μL, 0.72 mmol). The product was purified using column chromatography on neutral alumina, eluting with 5%, 10% and then 25% ethyl acetate in hexanes, to provide F-BODIPY 2d (22 mg, 92% yield). M.p. 191–193 °C; ¹H NMR (300 MHz, CDCl₃) 10.50 (br s, 1H), 7.18–7.16 (m, 1H), 7.15 (s, 1H), 6.97–6.94 (m, 1H), 6.38–6.36 (m, 1H), 6.12 (s, 1H), 5.21 (sep, J = 6.2 Hz, 1H), 3.97 (s, 3H), 2.80 (s, 3H), 2.41 (s, 3H), 1.35 (d, J = 6.3 Hz, 6H); ¹³C NMR (CDCl₃, 125 MHz): 165.0, 164.4, 153.0, 151.4, 136.7, 129.5, 129.4, 126.4, 123.7, 118.6, 118.3, 115.1, 111.8, 97.3, 67.1, 58.8, 22.5, 14.5, 12.0; ¹¹B NMR (160 MHz, CDCl₃) 1.38 (t, J = 36 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −138 (q, J = 34 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 543, ε 68 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 555, Φ_F: 0.90; LRMS: 424.2 (M + Na)⁺; HRMS: 424.1607. Found, 424.1614 calculated for C₂₀H₂₂BF₂N₃NaO₃.

Boron, difluoro[phenyl 2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)-methylene]-3,5-dimethyl-2H-pyrrole-4-carboxylate] (2e). Following GP1, over a 24 hour period a solution of 1e (50 mg, 0.12 mmol) in CH₂Cl₂ (6 mL) was reacted with BF₃·OEt₂ (267 μL, 2.16 mmol) and NEt₃ (201 μL, 1.44 mmol). The product was purified using column chromatography on neutral alumina, eluting with 60% CH₂Cl₂ in hexanes, to provide F-BODIPY 2e (37 mg, 70% yield). M.p. 248–250 °C; ¹H NMR (500 MHz, CDCl₃) 10.52 (br s, 1H), 7.41 (t, J = 7.93 Hz, 2H), 7.25–7.23 (m, 1H), 7.21–7.20 (m, 3H), 7.19 (s, 1H), 7.01–7.00 (m, 1H), 6.40–6.39 (m, 1H), 6.17 (s, 1H), 4.01 (s, 3H), 2.88 (s, 3H), 2.52 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) 164.6, 163.6, 153.4, 152.0, 150.9, 136.4, 129.9, 129.6, 126.8, 125.6, 123.5, 122.2, 119.1, 114.8, 111.9, 97.4, 58.8, 14.6, 12.0; ¹¹B NMR (160 Hz, CDCl₃) 1.41 (t, J = 36 Hz); ¹⁹F NMR (235 Hz, CDCl₃) −138 (q, 34 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 539, ε 63 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 555, Φ_F: 0.90; LRMS: 458.1 (M + Na)⁺; HRMS: 458.1459. Found, 458.1458 calculated for C₂₃H₂₀BF₂N₃NaO₃.

Boron, difluoro[benzyl 2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)-methylene]-3,5-dimethyl-2H-pyrrole-4-carboxylate] (2f). Following GP1, over a 24 hour period a solution of 1f (22 mg, 0.05 mmol) in CH₂Cl₂ (8 mL) was reacted with BF₃·OEt₂ (56 μL, 0.45 mmol) and NEt₃ (42 μL, 0.30 mmol). The product was purified using column chromatography on neutral alumina, eluting with 25% CH₂Cl₂ in hexanes, to provide F-BODIPY 2f (6 mg, 26% yield). ¹H NMR (500 MHz, CDCl₃) 10.49 (br s, 1H), 7.45–7.34 (m, 1H), 7.20–7.17 (m, 1H), 7.16 (s, 1H), 6.99–6.96 (m, 1H), 6.40–6.36 (m, 1H), 6.14 (s, 1H), 5.32 (s, 2H), 3.99 (s, 3H), 2.81 (s, 3H), 2.42 (s, 3H); ¹¹B NMR (160 MHz, CDCl₃) 1.35 (t, J = 36 Hz). ¹H and ¹¹B NMR chemical shifts were in agreement with literature values.⁴⁰ UV/vis (CH₂Cl₂) λ_max (nm): 542, ε 156 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 553, Φ_F: 1.00.

Boron, difluoro[1-[2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)methylene]-3,5-dimethyl-2H-pyrrol-4-yl]ethanone] (2g). Following GP1, over a 48 hour period a solution of 1g (13 mg, 0.04 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (99 μL, 0.80 mmol) and NEt₃ (84 μL, 0.60 mmol). The product was purified using column chromatography on basic alumina, eluting with 25% ethyl acetate in hexanes, F-BODIPY 2g (5 mg, 38% yield). ¹H NMR (500 MHz, CDCl₃) 10.50 (br s, 1H), 7.20 (s, 1H), 7.18 (s, 1H), 6.99 (s, 1H), 6.39 (s, 1H), 6.15 (s, 1H), 4.00 (s, 3H), 2.80 (s, 3H), 2.48 (s, 3H), 2.44 (s 3H); ¹³C NMR (125 MHz, CDCl₃) 195.4, 164.4, 152.1, 151.8, 134.3, 129.5, 127.2, 126.7, 123.5, 118.9, 115.0, 114.8, 111.8, 97.3, 58.8, 31.7, 15.2, 12.5; ¹¹B NMR (160 MHz, CDCl₃) 1.41 (t, J = 36 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −138 (q, J = 29 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 544, ε 11 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 557, Φ_F: 0.78; LRMS: 380.1 (M + Na)⁺; HRMS: 380.1363. Found, 380.1352 calculated for C₁₈H₁₈BF₂N₃NaO₂.

Boron, difluoro[N-tert-butyl-6-[2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)methylene]-3,5-dimethyl-2H-pyrrol-4-yl]-6-oxohexanamide] (2h). Following GP1, over a 60 hour period a solution of 1h (21 mg, 0.04 mmol) in CH₂Cl₂ (3 mL) was reacted with BF₃·OEt₂ (74 μL, 0.60 mmol) and NEt₃ (50 μL, 0.36 mmol). The product was purified using column chromatography on neutral alumina, eluting with 40% ethyl acetate in hexanes, to provide F-BODIPY 2h (16 mg, 73% yield). M.p. 214–216 °C; ¹H NMR (500 MHz, CDCl₃) 10.49 (s, 1H), 7.19–718 (m, 1H), 7.16 (s, 1H), 7.00–6.97 (m, 1H), 6.39–6.37 (m, 1H), 6.14 (s, 1H), 5.44 (br s, 1H), 3.99 (s, 3H), 2.79–2.76 (m, 5H, overlapping CH₃ and CH₂), 2.42 (s, 3H), 2.15 (t, J = 7.0 Hz, 2H), 1.73–1.68 (m, 4H), 1.35 (s, 9H); ¹³C NMR (125 MHz, CDCl₃) 197.9, 172.2, 164.4, 151.9, 151.7, 133.8, 129.7, 129.5, 127.3, 126.6, 123.5, 118.9, 114.8, 111.8, 97.3, 58.8, 51.3, 42.9, 37.8, 29.0, 25.6, 23.8, 15.2, 12.6; ¹¹B NMR (160 MHz, CDCl₃) 1.41 (t, J = 32 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −138 (q, J = 34 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 545, ε 71 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 557, Φ_F: 0.85; LRMS: 521.3 (M + Na)⁺; HRMS: 521.2517. Found, 521.2506 calculated for C₂₆H₃₃BF₂N₄NaO₃.

Boron, difluoro[ethyl 10-[2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)methylene]-3,5-dimethyl-2H-pyrrol-4-yl]-10-oxodecanoate] (2i). Following GP1, over a 72 hour period a solution of 1i (24 mg, 0.05 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (111 μL, 0.90 mmol) and NEt₃ (77 μL, 0.55 mmol). The product was purified using column chromatography on basic alumina, flushing first with 100% hexanes and then eluting compound with CH₂Cl₂, to provide F-BODIPY 2i (20 mg, 74% yield) M.p. 138–140 °C; ¹H NMR (300 MHz, CDCl₃): 10.50 (br s, 1H), 7.19 (s, 1H), 7.16 (s, 1H), 6.98 (s, 1H), 6.38 (s, 1H), 6.14 (s, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.98 (s, 3H), 2.78 (s, 3H), 2.74 (t, J = 7.4 Hz, 2H), 2.42 (s, 3H), 2.28 (t, J = 7.6 Hz, 2H), 1.72–1.54 (m, 4H), 1.33 (s, 8H), 1.25 (t, J = 7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) 198.5, 174.1, 164.4, 151.9, 151.6, 134.0, 129.7, 129.6, 127.6, 126.6, 123.6, 118.8, 114.9, 111.8, 97.3, 60.3, 58.8, 43.3, 34.6, 29.6, 29.4, 29.3, 25.2, 24.5, 15.2, 14.5, 12.5; ¹¹B NMR (160 MHz, CDCl₃) 1.41 (t, J = 30 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −138, J = 36 Hz; UV/vis (CH₂Cl₂) λ_max (nm): 546, ε 85 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 559, Φ_F: 0.90; LRMS: 550.3 (M + Na)⁺; HRMS: 550.2661. Found, 550.2659 calculated for C₂₈H₃₆BF₂N₃NaO₄.

Boron, difluoro[N,N-diethyl-2-[2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)methylene]-3,5-dimethyl-2H-pyrrol-4-yl]acetamide] (2j). Following GP1, over a 72 hour period a solution of 1j (17 mg, 0.04 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (89 μL, 0.72 mmol) and NEt₃ (67 μL, 0.48 mmol). The product was purified using column chromatography on basic alumina, eluting with 25% and then 50% ethyl acetate in hexanes, to provide F-BODIPY 2j (11 mg, 61% yield). ¹H NMR (500 MHz, CDCl₃) 10.44 (br s, 1H), 7.09 (s, 1H), 7.07 (s, 1H), 6.86 (s, 1H), 6.33 (s, 1H), 6.10 (s, 1H), 3.95 (s, 3H), 3.44 (s, 2H), 3.37 (dq, 22.4, 7.2 Hz, 4H), 2.49 (s, 3H), 2.17 (s, 3H), 1.14 (dt, J = 10.7, 7.1 Hz, 6H); ¹³C NMR (CDCl₃, 125 MHz) 169.3, 162.9, 149.1, 148.4, 134.4, 130.1, 126.7, 124.4, 123.8, 121.8, 116.1, 114.7, 110.8, 96.4, 58.2, 42.1, 40.4, 30.1, 14.1, 13.0, 12.5, 9.7; ¹¹B NMR (160 MHz, CDCl₃) 1.40 (t, J = 36 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −139 (q, J = 34 Hz) UV/vis (CH₂Cl₂) λ_max (nm): 561, ε 45 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 546 (nm); λ_max (nm), 574, Φ_F: 0.81; LRMS: 451.2 (M + Na)⁺; HRMS: 451.2081. Found, 451.2087 calculated for C₂₂H₂₇BF₂N₄NaO₂.

Boron, difluoro[benzyl 2-[2-[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)methylene]-3,5-dimethyl-2H-pyrrol-4-yl]acetate] (2k). Following GP1, over a 48 hour period a solution of 1k (12 mg, 0.03 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (100 μL, 0.81 mmol) and NEt₃ (75 μL, 0.54 mmol). The product was purified using column chromatography on basic alumina, eluting with CH₂Cl₂, to provide F-BODIPY 2k (9 mg, 75% yield) ¹H NMR (500 MHz, CDCl₃): 10.46 (br s, 1H), 7.35–7.30 (m, 5H), 7.11–7.10 (m, 1H), 7.08 (s, 1H), 6.89–6.88 (m, 1H), 6.35–6.33 (m, 1H), 6.11 (s, 1H), 5.13 (s, 2H), 3.96 (s, 3H), 3.46 (s, 2H), 2.49 (s, 3H), 2.17 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) 171.0, 163.3, 149.1, 136.0, 135.3, 134.5, 131.0, 128.7, 128.2, 127.2, 124.9, 124.0, 120.5, 116.7, 115.0, 111.1, 106.1, 96.7, 66.8, 58.5, 30.6, 12.6, 9.8; ¹¹B NMR (160 MHz, CDCl₃) 1.39 (J = 36 Hz); ¹⁹F (235 MHz, CDCl₃) −139 (J = 35 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 558, ε 127 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 546 (nm); λ_max (nm), 571, Φ_F: 0.79; LRMS: 486.2 (M + Na)⁺; HRMS: 486.1778. Found, 486.1771 calculated for C₂₅H₂₄BF₂N₃NaO₃.

Boron, difluoro[benzyl 2[(4-methoxy-1H,1′H-2,2′-bipyrrol-5-yl)methylene]-3-(3-methoxy-3-oxopropyl)-5-methyl-2H-pyrrole-4-carboxylate] (2l). Following GP1, over a 48 hour period a solution of 1l (19 mg, 0.04 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (89 μL, 0.72 mmol) and NEt₃ (67 μL, 0.48 mmol). The product was purified using column chromatography on basic alumina, eluting with 2%, 4%, 8%, 10% and then 25% ethyl acetate in hexanes, to provide F-BODIPY 2l (18 mg, 95% yield). ¹H NMR (300 MHz, CDCl₃): 10.50 (s, 1H), 7.44–7.32 (m, 5H), 7.23–7.17(m, 2H), 6.99 (s, 1H), 6.38 (s, 1H), 6.12 (s, 1H), 5.30 (s, 2H), 3.98 (s, 3H), 3.61 (s, 3H), 3.12 (t, J = 7.5 Hz, 2H), 2.80 (s, 3H), 2.56 (t, J = 7.4 Hz, 2H); ¹³C NMR (125 MHz, CDCl₃) 173.4, 164.7, 152.7, 152.3, 137.6, 136.5, 130.3, 129.0, 128.7, 128.5, 128.2, 127.0, 123.4, 119.3, 114.9, 111.9, 97.4, 65.9, 58.8, 51.7, 35.4, 21.3, 14.6; ¹¹B NMR (160 MHz, CDCl₃) 1.34 (J = 36 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −138 (J = 35 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 540, ε 55 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 559, Φ_F: 0.70; LRMS: 544.2 (M + Na)⁺; HRMS: 544.1825. Found, 544.1826 calculated for C₂₇H₂₆BF₂N₃NaO₅.

Boron, difluoro[4-(4-chlorophenoxy)-5-[(3,5-dimethyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1′H-2,2′-bipyrrole] (3m). Following GP1, over a 72 hour period a solution of 1m (20 mg, 0.04 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (148 μL, 1.2 mmol) and NEt₃ (109 μL, 0.78 mmol). The product was purified using column chromatography on basic alumina, eluting with 20% CH₂Cl₂ in hexanes, to provide F-BODIPY 3m (18 mg, 90% yield). M.p. °C 135–137 °C; ¹H NMR (500 MHz, CDCl₃) 10.35 (br s, 1H), 7.40–7.38 (m, 2H), 7.19–7.16 (m, 3H), 7.07–7.05 (m, 1H), 6.70–6.68 (m, 1H), 6.29–6.27 (m, 1H), 5.98 (s, 1H), 2.53 (s, 3H), 2.38 (t, J = 7.7 Hz, 2H), 2.18 (s, 3H), 1.46–1.41 (m, 2H), 1.35–1.30 (m, 4H), 0.91 (t, J = 6.9 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) 158.3, 154.7, 153.3, 146.0, 136.2, 131.7, 130.7, 130.2, 130.1, 125.9, 124.1, 124.0, 120.9, 115.5, 115.4, 110.8, 100.4, 31.8, 30.1, 24.2, 22.7, 14.3, 12.9, 9.8; ¹¹B NMR (CDCl₃, 160 MHz) 1.37 (J = 31 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −140 (J = 33 Hz); UV-vis (CH₂Cl₂) λ_max (nm): 573, ε 75 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 546 (nm); λ_max (nm), 597, Φ_F: 0.89; LRMS: 504.2 (M + Na)⁺; HRMS: 504.1793. Found, 504.1796 calculated for C₂₆H₂₇BClF₂N₃NaO.

Boron, difluoro[4-(benzyloxy)-5-[(3,5-dimethyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1′H-2,2′-bipyrrole] (3n). Following GP1, over a 96 hour period a solution of 1n (16 mg, 0.04 mmol) in CH₂Cl₂ (8 mL) was reacted with BF₃·OEt₂ (160 μL, 1.3 mmol) and NEt₃ (120 μL, 0.86 mmol). The product was purified using column chromatography on basic alumina, eluting with 2%, 4%, 6% and then 8% ethyl acetate in hexanes, to provide F-BODIPY 3n (9 mg, 50% yield). ¹H NMR (500 MHz, CDCl₃) 10.42 (br s, 1H), 7.46–7.38 (m, 5H), 7.10 (s, 1H), 7.07 (s, 1H), 6.81 (s, 1H), 6.33–6.31 (m, 1H), 6.14 (s, 1H), 5.16 (s, 2H), 2.49 (s, 3H), 2.36 (t, 2H), 2.14 (s, 3H), 1.48–1.40 (m, 2H), 1.37–1.29 (m, 4H), 0.90 (t, 3H); ¹³C NMR (126 MHz, CDCl₃) 161.4, 156.5, 147.6, 135.7, 134.6, 130.8, 129.6, 128.9, 128.8, 128.0, 126.4, 124.2, 124.1, 115.6, 115.0, 110.8, 97.4, 73.2, 31.9, 30.2, 24.3, 22.7, 14.2, 12.7, 9.7; ¹¹B NMR (160 MHz, CDCl₃) 1.41 (J = 36 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −139 (J = 34 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 566, ε 55 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 520 (nm); λ_max (nm), 572, Φ_F: 0.98. LRMS: 484.2 (M + Na)⁺; HRMS: 484.2339. Found, 484.2342 calculated for C₂₇H₃₀BF₂N₃NaO.

Boron, difluoro[5-[(3,5-dimethyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-4-[4-(trifluoromethyl)phenoxy]-1H,1′H-2,2′-bipyrrole] (3o). Following GP1, over a 48 hour period a solution of 1o (12 mg, 0.02 mmol) in CH₂Cl₂ (8 mL) was reacted with BF₃·OEt₂ (54 μL, 0.44 mmol) and NEt₃ (42 μL, 0.30 mmol). The product was purified using column chromatography on basic alumina, eluting with 5% ethyl acetate in hexanes, to provide F-BODIPY 3o (12 mg, 92% yield). ¹H NMR (500 MHz, CDCl₃) 10.34 (br s, 1H), 7.68 (d, J = 8.7 Hz, 2 H), 7.32 (J = 8.6 Hz, 2H), 7.13 (s, 1H), 7.07–7.05 (m, 1H), 6.72–6.70 (m, 1H), 6.30–6.28 (m, 1H), 6.11 (s, 1H), 2.54 (s, 3H), 2.39 (t, J = 7.7, 2H), 2.18 (s, 1H), 1.49–1.41 (m, 2H), 1.38–1.31 (m, 4H), 0.91 (t, J = 6.8 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃,) 159.2, 154.5, 145.8, 136.8, 131.2, 131.0, 129.0, 127.6, 126.1, 124.2, 124.0, 119.0, 115.7, 115.4, 110.9, 110.1, 101.6, 68.3, 31.9, 30.0, 24.3, 22.7, 14.2, 13.0, 9.8; ¹¹B NMR (160 MHz, CDCl₃) 1.27 (J = 35 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −62 (s, CF₃), −140 (q, J = 35 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 575, ε 26 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 546 (nm); λ_max (nm), 600, Φ_F: 0.74. LRMS: 516.2 (M + Na)⁺; HRMS: 516.2262. Found, 516.2240 calculated for C₂₇H₂₈BF₅N₃NaO.

Boron, difluoro[4-[5-((3,5-dimethyl-4-pentyl-2H-pyrrol-2-ylidene)methyl)-1H,1′H-2,2′-bipyrrol4-yloxy]-N,N-dimethylaniline] (3p). Following GP1, over a 48 hour period a solution of 1p (16 mg, 0.03 mmol) in CH₂Cl₂ (8 mL) was reacted with BF₃·OEt₂ (67 μL, 0.54 mmol) and NEt₃ (50 μL, 0.36 mmol). The product was purified using column chromatography on basic alumina, eluting with 2%, 4%, 6%, and then 8% ethyl acetate in hexanes, to provide F-BODIPY 3p (12 mg, 75% yield). ¹H NMR (500 MHz, CDCl₃) 10.38 (br s, 1H), 7.21 (s, 1H), 7.10 (d, J = 9.0 Hz, 2H), 7.04 (t, J = 1.8 Hz, 1H), 6.75 (d, J = 9.0 Hz, 2H), 6.67 (t, J = 1.8 Hz, 1H), 6.26–6.25 (m, 1H), 5.87 (s, 1H), 2.98 (s, 6H), 2.51 (s, 3H), 2.38 (t, J = 7.7 Hz, 2H), 2.18 (s, 3H), 1.49–1.43 (m, 2H), 1.36–1.31 (m, 4H), 0.91 (t, J = 6.9 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) 161.2, 150.3, 148.4, 146.6, 134.9, 131.1, 130.1, 126.0, 123.6, 120.6, 115.5, 115.2, 114.4, 113.4, 110.7, 99.6, 41.1, 31.9, 30.2, 24.3, 22.7, 14.2, 12.5, 9.7 (one carbon signal missing); ¹¹B NMR (160 MHz, CDCl₃) 1.41 (J = 35 Hz); ¹⁹F NMR (235 MHz, CDCl₃,) −139 (q, J = 35 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 569, ε 55 000 mol L⁻¹ cm⁻¹. LRMS: 491.3 (M + H)⁺; HRMS: 491.2803. Found, 491.2788 calculated for C₂₈H₃₄BF₂N₄O.

Boron, difluoro[2-[5-((3,5-dimethyl-4-pentyl-2H-pyrrol-2-ylidene)methyl)-4-methoxy-1H-pyrrol-2-yl]-1H-indole] (4q). Following GP1, over a 5 day period a solution of 1q (28 mg, 0.07 mmol) in CH₂Cl₂ (15 mL) was reacted with BF₃·OEt₂ (273 μL, 2.21 mmol) and NEt₃ (205 μL, 1.47 mmol). The product was purified using column chromatography on basic alumina, eluting with 0%, 1%, 2% and then 4% ethyl acetate in hexanes, to provide F-BODIPY 4q (22 mg, 76% yield). ¹H NMR (500 MHz, CDCl₃) 10.19 (br s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.2 Hz, 1H), 7.28–7.24 (m, 1H), 7.13–7.09 (m, 3H), 6.30 (s, 1H), 3.95 (s, 3H), 2.56 (s, 3H), 2.39 (t, J = 7.7 Hz, 2H), 2.17 (s, 3H), 1.49–43 (m, 2H), 1.38–1.32 (m, 4H), 0.92 (t, J = 6.8 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) 161.8, 153.5, 146.4, 138.2, 136.3, 131.8, 130.7, 129.5, 128.1, 126.0, 124.4, 121.2, 120.6, 116.0, 112.2, 107.9, 98.0, 58.4, 31.9, 30.0, 24.3, 22.7, 14.2, 13.0, 9.7; ¹¹B NMR (160 MHz, CDCl₃) 1.39 (t, J = 35 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −138 (q, J = 35 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 579, ε 54 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 546 (nm); λ_max (nm), 591, Φ_F: 1.0; LRMS: 458.2 (M + Na)⁺; HRMS: 458.2183. Found, 458.2186 calculated for C₂₅H₂₈BF₂N₃NaO.

Boron, difluoro[benzyl 2-[(5-(1H-indol-2-yl)-3-methoxy-1H-pyrrol-2-yl)methylene]-3,5-dimethyl-4-pentyl-2H-pyrrol-4-carboxylate] (4r). Following GP1, over a 5 hour period a solution of 1r (14 mg, 0.03 mmol) in CH₂Cl₂ (4 mL) was reacted with BF₃·OEt₂ (48 μL, 0.39 mmol) and NEt₃ (38 μL, 0.27 mmol). The product was purified using column chromatography on basic alumina, eluting with CH₂Cl₂, to provide F-BODIPY 4r (10 mg, 71% yield). ¹H NMR (500 MHz, CDCl₃,) 10.24 (br s, 1H), 7.67 (d, J = 8 Hz, 1H), 7.54 (d, J = 8 Hz, 1H), 7.48 (d, J = 7 Hz, 2H), 7.43 (t, J = 7 Hz, 2H), 7.39–7.304 (m, 2H), 7.31 (s, 1H), 7.25 (s, 1H), 7.17 (t, J = 8 Hz, 1H), 6.38 (s, 1H), 5.37 (s, 2H), 4.05 (s, 3H), 2.90 (s, 3H), 2.49 (s, 3H); ¹³C NMR (126 MHz, CDCl₃) 164.8, 164.0, 155.3, 151.1, 139.1, 139.0, 136.6, 130.3, 130.2, 129.3, 128.7, 128.4, 18.2, 127.9, 125.9, 121.7, 121.2, 117.0, 112.5, 111.1, 98.6, 65.9, 58.8, 14.8, 12.1; ¹¹B NMR (160 MHz, CDCl₃) 1.39 (J = 36 Hz); ¹⁹F NMR (235 MHz, CDCl₃) −137 (q, J = 31 Hz); UV/vis (CH₂Cl₂) λ_max (nm): 562, ε 74 000 mol L⁻¹ cm⁻¹; fluorescence (CH₂Cl₂) λ_exci, 546 (nm); λ_max (nm), 574, Φ_F: 0.95; LRMS: 522.2 (M + Na)⁺; HRMS: 522.1762. Found, 522.1771 calculated for C₂₈H₂₄BF₂N₃NaO₃.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We thank Dr Estelle Marchal for preparation of pyrrolyldipyrrin HCl salts, Pankaj Subedi for assistance with obtaining fluorescence spectra and Dr Norman Schepp for spectrofluorometer access.

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Footnote

† Electronic supplementary information (ESI) available: ¹H, ¹³C NMR, absorption/emission spectra for all new compounds and crystal data for 2d. CCDC 1573487. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7pp00341b

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