Synthesis and Photophysical Properties of β-Alkenyl-Substituted BODIPY Dyes by Indium(III)-Catalyzed Intermolecular Alkyne Hydroarylation

Abstract

A new atom-economical synthesis of β-alkenyl-substituted BODIPYs via indium(III)-catalyzed intermolecular alkyne hydroarylation with meso-substituted BODIPYs is described. While catalysis with InI₃ allows the double β-functionalization of BODIPY, resulting in regioselectively branched β,β′-disubstituted alkenyl BODIPYs, catalytic InCl₃ enables the formation of linear β-substituted alkenyl BODIPYs. Subsequent In(III)-catalyzed intermolecular alkyne hydroarylation allows the synthesis of unsymmetrical push–pull BODIPY derivatives. Therefore, indium catalysis offers complementary regioselectivity in good chemical yields and functional group tolerance. The resulting BODIPY dyes displayed bathochromically shifted absorption and emission according to the electron-nature of the substituents in the alkenyl moiety with high molar extinction coefficients (ε up to 88,200 M^–1 cm^–1) and quantum yields (0.14–0.96).

Introduction

4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) and derivatives are a class of valuable small-molecule fluorophores of interest in diverse research areas like bioimaging,¹ fluorescent probes,² photodynamic therapy,³ photocatalysis,⁴ optoelectronic devices,⁵ and so forth.⁶ The growing success of these rigid π-conjugated complexes lies to their excellent features such as narrow absorption and emission bands, high fluorescent quantum yield, good photostability, and solubility.⁷ Hitherto, a plethora of efforts have been made to fine-tuning their properties by introduction of suitable substituents at the different positions of the BODIPY scaffold and in particular, conjugated substituents at C2 and C6 (β) positions through alkenyl extension usually led to red-shifted emission bands with application as fluorescence probes to biothiols,⁸ DNA,⁹ or as photosensitizer.¹⁰

Among the different synthetic approaches so far employed to obtain β-alkenyl BODIPYs, the metal-catalyzed cross-coupling reactions from halogenated or borylated derivatives represent a straightforward methodology (Scheme 1a).^11,12 Late-stage functionalization of the BODIPY core has also been exploited via C–H functionalization using palladium-mediated oxidative olefination (Scheme 1b)¹³ To the best of our knowledge, the synthesis of branched and linear β-alkenyl BODIPYs through intermolecular metal-catalyzed alkyne hydroarylation with BODIPY is unknown, despites its great potential in terms of economy. By taking advantage of the reactivity of C2(6) positions of the BODIPY framework,⁷ we envisioned the synthesis of alkenyl-substituted BODIPYs through intermolecular In(III)-catalyzed alkyne hydroarylation (Scheme 1c).

Scheme 1. Synthetic Approaches to Obtain β-Alkenyl BODIPYs.

Since Shirakawa and Kawakami reported the first examples of Friedel–Crafts alkenylation of arenes using alkynes with indium(III) triflate as the catalyst,¹⁴ this transformation has received much attention, because this approach offers an attractive alternative to Heck and cross-coupling reactions, as can be catalyzed by different transition metals such as palladium, platinum, gold, and iron,¹⁵ that was later expanded to aromatic heterocycles.¹⁶ Indium(III) has also proven to be an efficient π-Lewis acid in inter- and intramolecular hydroarylation transformations which offers advantages in terms of cost and low toxicity.¹⁷ In this research area, we have developed In(III)-catalyzed intramolecular hydroarylation reaction of arenes and hydroalkoxylation and hydroamination reactions,^17a including tandem cycloisomerization reactions.¹⁸ Herein, we report the indium(III)-catalyzed intermolecular alkyne hydroarylation with BODIPY dyes to access to β-alkenyl BODIPYs and the study of their photophysical properties (Scheme 1c).

Results and Discussion

At the outset of this investigation, a variety of meso-substituted BODIPYs 1a–d were synthesized through our recently reported efficient microwave-assisted one-pot pathway.¹⁹ Initially, based on our previous experience, commercially available InI₃ was chosen as the catalyst. Treatment of BODIPY 1a with phenylacetylene (molar ratio of 1:5) in the presence of InI₃ (10 mol %) in DCE (∼0.1 M) at 80 °C afforded branched β-alkenyl BODIPY 2 in 11% yield, as a result of intermolecular hydroarylation with Markovnikov regioselectivity, along with a large amount of remaining unreacted 1a (entry 1, Table 1). No other regioisomer was detected in the reaction mixture. Likewise, when the molar ratio was increased from 1:5 to 1:10 and to 1:14, compound 2 was obtained in 21% and 38% yields, respectively, accompanied by the formation of 2,6-dialkenyl BODIPY 2a (entries 2–3, respectively). Other solvents such as toluene and CH₃CN were less effective (entries 4–5). Moreover, the use of 10 mol % of Au(III), Au(I), or Pt(II) salts was ineffective catalysts recovering in all cases the starting compound 1a (entries 6–8). However, using 20 mol % of InI₃, 2a was isolated in 90% yield after 8 h (entry 9). It was found that both InBr₃ and InCl₃ catalysts allowed a mixture of 2 and 2a in moderate yields (entries 10–11, respectively). On the other hand, the use of In(OTf)₃ (20 mol %) in DCE at 80 °C or toluene at 100 °C did not afford the target product 2a (entries 12–13).

Table 1. Intermolecular In(III)-Catalyzed Double Hydroarylation with Phenylacetylene with BODIPY 1a.

entry	catalyst (mol %)	solventa	time (h)	yield (%)b
				2	2a
1c	InI3 (10)	DCE	48	11	-
2d	InI3 (10)	DCE	24	21	4
3	InI3 (10)	DCE	24	38	14
4	InI3 (10)	toluene	24	25	1
5	InI3 (10)	CH3CN	24	nr	nr
6	AuCl3 (10)	DCE	48	nr	nr
7	PtCl2 (10)	DCE	48	nr	nr
8e	Au(PPh3)Cl (10)	DCE	48	nr	nr
9	InI3 (20)	DCE	8 h	-	90f
10	InBr3 (20)	DCE	48	36	29
11	InCl3 (20)	DCE	48	39	10
12	In(OTf)3 (20)	DCE	72	12	-
13g	In(OTf)3 (20)	toluene	48	nr	nr

^aReactions were carried out using 1a (1 mmol, ∼ 0.1 M) and 14 equiv of phenylacetylene.

^bYields estimated by ¹H NMR using CH₂Br₂ as an internal standard.

^cReaction using 5 equiv of phenylacetylene.

^dReaction using 10 equiv of phenylacetylene.

^eAgSbF₆ (10 mol %) was also used.

^fIsolated yield.

^gReaction carried out at 100 °C.

After the optimal reaction conditions were determined, we examined the scope of the reaction by using meso-substituted BODIPYs 1b–d (Scheme 2). The reaction of 1b, with a thien-2-yl group at the meso position, using 20 mol % of InI₃ in DCE at 80 °C gave the double hydroarylation product 2b in 93% yield. In a similar way, meso-methyl BODIPY 1c also produced the double hydroarylated product 2c in 73% yield. The role of electronic effects was also explored using BODIPY 1d bearing a 4-cyanophenyl substituent at the meso position. Under the previous reaction conditions, the reaction of 1d with phenylacetylene provided only 2,6-dialkenyl BODIPY 2d in 11% along with the monosubstituted BODIPY 11 in 45% yield. This result could be attributed to the basic nitrogen of cyano group or to the low reactivity of BODIPY, resulting in the electron-withdrawing effect of the cyano group.

Scheme 2. Synthesis of Branched 2,6-Dialkenyl BODIPY Dyes through π-acid Catalysis.

Reactions were carried out using 1a–1d (1 mmol, ∼ 0.1 M) and 14 equiv of arylacetylene.

Monohydroarylated product was also obtained in 32% yield.

To further extend the scope of this transformation, the electronic effect of the substituents with respect to the alkyne component was explored. In this endeavor, the reaction of 1a with 4-methoxyphenylacetylene provided 3a in moderate yield (40%) accompanied by monosubstituted BODIPY (32% yield). In addition, treatment of 1a with 3-ethynylthiophene afforded 4a in 63% yield. The indium(III)-catalyzed procedure with BODIPY 1a also proved efficient using 1-ethenyl-3,5-bis(trifluoromethyl)benzene as the alkyne partner, arising selectively the dihydroarylated product 5a in 92% yield. Interestingly, the polyfluorinated fluorophores based on the BODIPY framework are of particular interest for the preparation of fluorescent fluorocarbon nanoemulsions, which can be used for simultaneous fluorescent and ¹⁹F MRI imaging.²⁰

During our research, we also examined (bromoethynyl)benzene²¹ as an alkyne partner in the InI₃-catalyzed reaction with BODIPY 1a. The participation of haloalkynes in the metal-catalyzed nucleophilic addition²² to generate alkenyl-halides constitutes a transformation with significant synthetic value.²³ Alkenyl halides are also a pivotal class of compounds for chemical transformations in natural product total synthesis²⁴ and also have found applications in photodynamic therapy when are linked to a BODIPY scaffold.²⁵ In the event, the reaction of 1a with (bromoethynyl)benzene under the stablished reaction conditions (20 mol % of InI₃, DCE, 80 °C) gave selectively (Z)-2,6-dialkenyl BODIPY 6a in 74% yield (Scheme 2). The Markovnikov regioselectivity was determined in 6a by the NOE experiment (see the Supporting Information).

Remarkably, indium(III) demonstrated a good ability to promote intermolecular alkyne hydroarylation with meso-substituted BODIPY dyes, yielding branched 2,6-alkenyl BODIPYs with Markovnikov regioselectivity independent of the electronic nature of the alkyne and BODIPY moieties.

As the next step, we studied the hydroarylation reaction of BODIPY with electron deficient alkynes under indium(III) catalysis. In this endeavor, we found that 1a reacts regioselectively with ethyl propiolate under the optimal reaction conditions (20 mol % of InI₃, DCE, 80 °C), affording the linear β-addition product 7a in 20% yield (Scheme 3). The stereochemistry of (E)-2-alkenyl BODIPY 7a was assigned by ¹H NMR spectroscopy on the basis of the coupling constants of alkenyl hydrogens (J = 16.2 Hz, see the Supporting Information). Interestingly, we found that using InCl₃ (20 mol %) as the catalyst in DCE at 80 °C, the yield increased up to 40%. This result could be attributed to the oxophilic σ-Lewis acid character of the InCl₃,²⁶ and therefore, we hypothesized that the coordination mode of ethyl propiolate to InCl₃ implies a σ-catalysis instead of π-catalysis. Furthermore, the reaction of 1b with ethyl propiolate afforded the expected β-addition, yielding (E)-2-alkenyl BODIPY 7b (56% yield). In addition, the reactions of 1a with 3-substituted propiolates, under the same reaction conditions, provided the trisubstituted alkenyl BODIPYs 8a and 9a in 42% and 36% yields, respectively, with (Z)-stereochemistry (Scheme 3). The assignment of stereochemistry of both compounds was confirmed by NOESY spectra (see the Supporting Information). Interestingly, the products obtained containing ester moieties are synthetically useful and might provide opportunities to development of BODIPY conjugates.²⁷

Scheme 3. Synthesis of Linear 2-Alkenyl BODIPY Dyes through σ-Catalysis.

Reactions were carried out using 1a–1b (1 mmol, ∼ 0.1 M) and 14 equiv of alkyne.

InI₃ (20 mol %) was used.

In parentheses, yield of the 2,6-dialkenyl products.

These experimental findings revealed that the branched 2,6-dialkenyl BODIPY dyes can be obtained regioselectively as a result of an initial activation of alkyne by π-coordination to InI₃, followed by the anti-addition of the BODIPY through the β-position, further aromatization and protodemetalation, although a mechanism involving an alkenyl cation intermediate could not be discarded.^17b,17d On the other hand, linear (E)-β-alkenyl BODIPYs could be formed through an initial σ-coordination of InCl₃ with the carbonyl moiety followed by the β-conjugated addition of the BODIPY to form a zwitterionic allenyl enolate. The formation of (Z)-trisubstituted alkenes in the reaction of substituted propiolates can be attributed to the high Lewis acidity of InCl₃, which would induce an alkene isomerization equilibrium.^17d

At this point, we explored the synthesis of unsymmetrical 2,6-dialkenyl BODIPYs by sequential hydroarylation reactions. In the event, the reaction of β-alkenyl BODIPY 7b with phenylacetylene in the presence of InI₃ (20 mol %) in DCE at 80 °C allowed the synthesis of unsymmetrical 2,6-dialkenyl BODIPY 8b in 80% yield (Scheme 4). Analogously, we carried out the InI₃-catalyzed intermolecular hydroarylation with BODIPY 9a with 3-ethynylthiophene to give compound 10a in 73% yield. It is remarkably to note that the electron-withdrawing effect of the alkenyl group at C2 does not affect the reactivity in the hydroarylation reaction at C6 in contrast with substitution at the meso position.

Scheme 4. Synthesis of push–pull 2,6-Dialkenyl BODIPY Dyes.

The optical properties of synthesized fluorophores containing substituted alkenyl moieties at C2(6) positions of the BODIPYs 1a–d were measured in CHCl₃ (Table 2). In general, BODIPY dyes are characterized by a narrow absorption band assigned to the strong S₁ ← S₀ transition. Indeed, the absorption maxima of the linear β-alkenyl and branched β,β′-dialkenyl BODIPY dyes 2a–10a, 2b–d, and 7b–8b induced a bathochromic shift (12–31 nm) by the electron-donating or electron-withdrawing substituents (Figure 1a,c). Besides, most compounds present high extinction coefficients (ε) such as the meso-phenyl-BODIPYs 3a and 4a (up to 88,200 M^–1 cm^–1) as the electron-donating ability at C2 and C6 positions increases, a required property in practical applications such as photodynamic therapy and photocatalysis.^6b,28

Table 2. UV–Vis and PL Data of Compounds 2a–10a, 2b–d, and 7b–8b in CHCl₃.

comp.a	λAbsmax (nm) [ε × 103(M–1 cm–1)]	λPLmax (nm)	Stokes shift (nm)	ΦFb
1a	503 (74.4)	512	9	nd
1b	515 (66.5)	522	7	nd
1c	499 (54.4)	508	9	nd
1d	507 (47.4)	519	12	nd
2a	526 (64.9)	552	26	0.72
2b	540 (77.7)	565	25	0.14
2c	520 (38.4)	554	34	0.96
2d	532 (64.8)	562	30	0.49
3a	528 (83.3)	558	30	0.82
4a	521 (88.2)	547	26	0.72
5a	523 (79.2)	543	20	0.79
6a	523 (55.0)	538	15	0.38
7a	528 (56.1)	549	21	0.79
7b	541(43.2)	566	25	0.18
8a	515 (40.3)	528	13	0.69
8b	546 (48.5)	575	29	0.16
9a	514 (75.3)	526	12	0.61
10a	524 (51.6)	544	20	0.77

^aAll spectra were recorded in CHCl₃ solutions at room temperature at 7.5 × 10^–7 M for UV–vis and PL spectra, excited at the respective under λ_max.

^bFluorescence quantum yields determined relative to rhodamine 6G in as standard (Φ_F = 0.94 in EtOH).³²

Figure 1.

Normalized (a) absorbance and (b) emission spectra of BODIPY dyes 1a–8a, 8b, and 10a in CHCl₃ (7.5 × 10^–7 M, excited at the respective under λ_max). (c) Absorbance and (d) emission spectra of BODIPY dyes 2a–d in CHCl₃ (7.5 × 10^–7 M, excited at the respective under λ_max). (e) Photograph of the BODIPYs 2a–10a and 7b–8b under UV irradiation (λ = 365 nm).

2-Alkenyl and 2,6-dialkenyl BODIPYs also show narrow emission bandwidths covering the spectral range from 526 to 575 nm, exhibiting a more pronounced bathochromic effect (14–53 nm), related to the electron richness of the substituent on the alkenyl moiety (Figure 1b,d and Table 2). Interestingly, branched alkenyl BODIPY 2d equipped with a 4-cyanophenyl group at the meso position also showed a bathochromic shift, that could be attributed to a stabilization of the LUMO level due to the electron-withdrawing effect of the cyano group.²⁹

Besides, 2-alkenyl BODIPY 7b, with extending conjugation containing an acrylate moiety, is bathochromically shifted (44 nm) related to 1b due to its D-π-A character. Moreover, when a second alkenyl substituent is placed at the C6 position, the Stokes shift was increased to 53 nm, which confirmed the results from a strong internal charge transfer (ICT) effect in unsymmetrical BODIPY 8b induced by greater push–pull electron movement.

Remarkably, the BODIPY dyes showed in general good-to-excellent quantum yields (up to Φ_F = 0.96), suggesting a very rigid structures (Table 2). The quenched fluorescence observed for 2b, 7b, and 8b is basically due to the greater freedom of rotation of thien-2-yl group at the meso position, increasing the energy lost to nonradiative decay.³⁰ In the case of 2d, the electron-withdrawing effect of the cyano group could lead to a deactivation process through photoinduced electron-transfer (PET) from the electron-rich BODIPY core to the electron poor cyano moiety, reducing the quantum yield.^7,31 Meanwhile, the low Φ_F of BODIPY 6a possessing heavy atoms (bromine) could be attributed that might arise an intersystem crossing from an excited singlet state to an excited triplet state, induced by the halogens linked to the BODIPY core through the alkenyl moiety.⁶

In general, the BODIPYs equipped with substituted alkenyl groups showed a remarkable effect on the absorption and fluorescence properties. Indeed, these compounds exhibit greater photophysical properties compared to the reported BODIPY dyes containing a p-dimethylamino substituent at the α-position of the alkene moiety.^11d The molar absorption coefficients and quantum yield values tend to be excellent in some dyes. Therefore, compounds exhibit brightness when irradiated, as shown in Figure 1e, and show properties of great interest in fluorescence bioimaging.

Conclusions

A new method for the synthesis of β-alkenyl-substituted BODIPYs by the indium(III)-catalyzed intermolecular alkyne hydroarylation reaction of meso-substituted BODIPYs has been developed. Depending on the different nature of the interaction of the alkyne to the indium(III) salt resulted in two different types of products. The double intermolecular hydroarylation reaction of phenylacetylene and analogues with meso-substituted-BODIPYs takes place through the electrophilic π-activation mode using indium triiodide as the catalyst, to provide branched 2,6-dialkenyl BODIPYs with Markovnikov regioselectivity. Conversely, when ethyl propiolate was used, the hydroarylation occurs through the σ-activation mode in the presence of indium trichloride as the catalyst, to give rise linear (E)-2-alkenyl BODIPYs coming from a β-addition. This atom-economical dual catalysis allowed the synthesis of push–pull dialkenyl BODIPY dyes with tuneable spectral properties. The majority of compounds synthesized have brilliant fluorescence with emissions that span from 526 to 575 nm with high quantum yields (0.14–0.96). Further research will be focused on exploring further functionalization, photophysical properties, and applications in bioimaging.

Experimental Section

General Methods

All reactions were carried out in dried glassware, under the argon atmosphere, using standard gastight syringes and septa. Dry toluene, DCE, CH₃CN, and other commercially available reagents were used as received. Reaction temperatures refer to external bath temperatures. All indium(III) salts were used as received under argon in a glovebox system. The BODIPY substrates (1a–d) were prepared according to the literature.¹⁹ Reactions were monitored by thin-layer chromatography, in precoated silica gel foils, using UV light as the visualizing agent and ethanolic phosphomolybdic acid as the developing agent. Flash column chromatography was performed using 230–400 mesh silica gel. ¹H NMR, ¹⁹F{H} NMR, and ¹³C{H} NMR spectra were recorded at room temperature in CDCl₃ using a 300 or 500 MHz spectrometer and calibrated to the solvent peak. DEPT data were used to assign carbon types. Chemical shifts are reported in ppm (δ) relative to the solvent CDCl₃ (δ_H 7.26 ppm and δ_C 77.1 ppm). ¹⁹F NMR are internally referenced with respect to CFCl₃ (δ_F 0.0 ppm). Structural assignments were made with additional information from NOESY, COSY, HSQC, and HMBC experiments. Mass spectra were recorded on a Magnetic Sector EI spectrometer or a QSTAR ESI mass spectrometer, operating in the positive ionization mode. The IR spectra were recorded with attenuated total reflectance (ATR). Ultraviolet/visible (UV/vis) absorption and fluorescence spectra were recorded with standard 1 cm quartz cells. Emission spectra were recorded using a spectrofluorometer equipped with a pulsed xenon flash-lamp as a light source. Compounds were excited at their excitation maxima (band of lowest energy) to record the emission spectra. The concentration of the compound solutions (in CHCl₃) was adjusted to 7.5 × 10^–7 M. Fluorescence quantum yield (Φ_F) values were determined by comparison with rhodamine 6G in ethanol as a reference (Φ_F = 0.94)³² using the equation below, where Φ_ST is the quantum yield of the reference, m is the slope of the line obtained from the best linear fit of the integrated fluorescence intensity versus absorbance data, and η is the refractive index of the solvent.

General Procedure for the Indium(III)-Catalyzed Intermolecular Alkyne Hydroarylation Reaction with BODIPYs

A Schlenk tube equipped with a magnetic stir bar was charged with the indium salt (0.04 mmol, 0.2 equiv) inside a glovebox. Then, the corresponding BODIPY (0.2 mmol, 1 equiv), DCE (2 mL), and the corresponding alkyne (2.8 mmol, 14 equiv) were added. The reaction mixture was heated in an oil bath at 80 °C and monitored by TLC until the starting material was consumed. The reaction mixture was cooled to rt, and the solvent was removed under reduced pressure. The resulting crude was purified by flash chromatography on silica gel (EtOAc/hexanes) to afford after concentration, and high vacuum drying, the corresponding 2-alkenyl or 2,6-dialkyne BODIPYs.

5,5-Difluoro-1,3,7,9-tetramethyl-10-phenyl-2,8-bis(1-phenylvinyl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine (2a)

Following the general procedure, the reaction of 1a (49.9 mg, 0.154 mmol) with InI₃ (15.3 mg, 0.081 mmol) and phenylacetylene (0.24 mL, 2.16 mmol) in DCE (1.5 mL) was heated at 80 °C for 8 h. After purification by chromatography (2–4% EtOAc/hexanes), compound 2a (73.2 mg, 90%) was obtained as a pink solid: mp = 106–107 °C; λ^abs_max (CHCl₃) = 526 nm (ε = 64,944 M^–1 cm^–1); λ^em_max (CHCl₃) = 552 nm; Φ_F (CHCl₃) = 0.72; IR (ATR) ν_max = 2957, 2924, 2853, 1529, 1176 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.43–7.49 (m, 3H), 7.34–7.36 (m, 2H), 7.26–7.31 (m, 10H), 5.85 (d, J = 1.5 Hz, 2H), 5.11 (d, J = 1.5 Hz, 2H), 2.40 (s, 6H), 1.23 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 154.9 (2 × C), 141.9 (2 × C), 141.0 (C), 140.5 (2 × C), 140.2 (2 × C), 135.3 (2 × C), 133.2 (2 × C), 131.3 (C), 129.2 (2 × CH), 129.0 (CH), 128.5 (4 × CH), 128.1 (2 × CH), 127.8 (2 × CH), 126.3 (4 × CH), 117.3 (2 × CH₂), 13.3 (2 × CH₃), 12.8 (2 × CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.80 (q, J_B–F = 32.5 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₅H₃₁BF₂N₂Na, 551.2446, found, 551.2441.

5,5-Difluoro-1,3,7,9-tetramethyl-2,8-bis(1-phenylvinyl)-10-(thiophen-2-yl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine (2b)

Following the general procedure, the reaction of 1b (40.1 mg, 0.121 mmol) with InI₃ (12.0 mg, 0.024 mmol) and phenylacetylene (0.19 mL, 1.69 mmol) in DCE (1.5 mL) was heated at 80 °C for 8 h. After purification by chromatography (2% EtOAc/hexanes), compound 2b (59.8 mg, 93%) was obtained as a pink solid: mp = 112–113 °C. λ^abs_max (CHCl₃) = 540 nm (ε = 77,698 M^–1 cm^–1); λ^em_max (CHCl₃) = 565 nm; Φ_F (CHCl₃) = 0.14; IR (ATR) ν_max = 2962, 2918, 2851, 1259, 1023 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.47 (dd, J = 1.3, 5.1 Hz, 1H), 7.26–7.32 (m, 10H), 7.10 (dd, J = 3.4, 5.1 Hz, 1H), 7.04 (dd, J = 1.2, 3.4 Hz, 1H), 5.87 (d, J = 1.5 Hz, 2H), 5.14 (d, J = 1.5 Hz, 2H), 2.40 (s, 6H), 1.44 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 155.6 (2 × C), 140.8 (2 × C), 140.7 (2 × C), 140.1 (2 × C), 135.0 (2 × C), 134.1 (C), 133.5 (2 × C), 132.3 (C), 128.5 (4 × CH), 128.0 (CH), 127.9 (2 × CH), 127.6 (CH), 127.5 (CH), 126.3 (4 × CH), 117,4 (2 × CH₂), 13.4 (2 × CH₃), 12.0 (2 × CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.74 (q, J_B–F = 32.6 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₃H₂₉BF₂N₂SNa, 557.2010, found, 557.2001.

Scale-Up Experiment for 2b

A Schlenk tube equipped with a magnetic stir bar was charged with InI₃ (120 mg, 0.242 mmol) inside a glovebox. Then, a solution of 1b (400 mg, 1.21 mmol) in DCE (5.6 mL) and phenylacetylene (1.86 mL, 16.9 mmol) were added. The resulting mixture was heated in an oil bath at 80 °C for 8 h. The reaction mixture was cooled to rt, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel (2 to 8% EtOAc/hexanes) to afford after concentration, and high vacuum drying, 2b (517.4 mg, 80%) as a pink solid.

5,5-Difluoro-1,3,7,9,10-pentamethyl-2,8-bis(1-phenylvinyl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine (2c)

Following the general procedure, the reaction of 1c (40.1 mg, 0.153 mmol) with InI₃ (15.1 mg, 0.031 mmol) and phenylacetylene (0.24 mL, 2.14 mmol) in DCE (1.5 mL) was heated at 80 °C for 24 h. After purification by chromatography (2% EtOAc/hexanes), compound 2c (51.6 mg, 73%) was obtained as a pink solid: mp = 168–169 °C. λ^abs_max (CHCl₃) = 520 nm (ε = 38,421 M^–1 cm^–1); λ^em_max (CHCl₃) = 554 nm; Φ_F (CHCl₃) = 0.96; IR (ATR) ν_max = 2956, 2920, 2851, 1544, 1193 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.29–7.36 (m, 10H), 5.95 (d, J = 1.5 Hz, 2H), 5.18 (d, J = 1.5 Hz, 2H), 2.67 (s, 3H), 2.37 (s, 6H), 2.27 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 153.1 (2 × C), 141.5 (C), 141.0 (2 × C), 140.3 (2 × C), 138.3 (2 × C), 133.0 (2 × C), 132.2 (2 × C), 128.5 (4 × CH), 127.9 (2 × CH), 126.3 (4 × CH), 117.4 (2 × CH₂), 17.1 (2 × CH₃), 15.5 (2 × CH₃), 13.2 (CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −146.21 (q, J_B–F = 32.8 Hz, 2F); HRMS (IE) m/z: [M]⁺ calculated for C₃₀H₂₉BF₂N₂, 466.2392, found, 466.2376.

4-(5,5-Difluoro-1,3,7,9-tetramethyl-2,8-bis(1-phenylvinyl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-10-yl)benzonitrile (2d)

Following the general procedure, the reaction of 1d (80.4 mg, 0.229 mmol) with InI₃ (22.7 mg, 0.046 mmol) and phenylacetylene (0.35 mL, 3.21 mmol) in DCE (2 mL) was heated at 80 °C for 48 h. After purification by chromatography (4% EtOAc/hexanes), compound 2d (13.7 mg, 11%) and 2-alkenyl BODIPY 11 (46.4 mg, 45%) were obtained as pink and orange solids, respectively.

Data for 2d

mp = 92–93 °C; λ^abs_max (CHCl₃) = 532 nm (ε = 64,780 M^–1 cm^–1); λ^em_max (CHCl₃) = 562 nm; Φ_F (CHCl₃) = 0.49; IR (ATR) ν_max = 2957, 2922, 2851, 2325, 1587, 1180 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.79 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.28 (s, 10H), 5.86 (s, 2H), 5.11 (s, 2H), 2.40 (s, 6H), 1.20 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 156.2 (C), 140.7 (2 × C), 140.4 (2 × C), 140.0 (2 × C), 139.8 (2 × C), 138.8 (C), 133.8 (C), 133.0 (2 × CH), 130.6 (C), 129.6 (2 × CH), 128.6 (4 × CH), 128.1 (2 × CH), 126.3 (4 × CH), 118.0 (2 × C), 117.6 (2 × CH₂), 113.4 (2 × C), 13.5 (2 × CH₃), 13.1 (2 × CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.78 (q, J_B–F = 33.2 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₆H₃₀BF₂N₃Na, 576.2399, found, 576.2390.

Data for 11

mp = 77–78 °C; IR (ATR) ν_max = 2954, 2921, 2851,2338, 1462, 1377 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.80 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.28 (s, 5H), 6.03 (s, 1H) 5.85 (s, 1H), 5.09 (s, 1H), 2.57 (s, 3H), 2.38 (s, 3H), 1.37 (s, 3H), 1.19 (s, 3H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 156.7 (C), 156.0 (C), 142.6 (C), 140.7 (C), 140.2 (2 × C), 139.9 (2 × C), 139.7 (C), 138.7 (C), 132.9 (2 × CH), 129.5 (2 × CH), 129.4 (C), 128.5 (2 × CH), 128.0 (CH), 126.3 (2 × CH), 121.9 (CH), 118.1 (C), 117.6 (CH₂), 113.3 (C), 14.7 (2 × CH₃), 13.4 (CH₃), 13.0 (CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.96 (q, J_B–F = 32.3 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₂₈H₂₄BF₂N₃Na, 474.1929, found, 474.1918.

5,5-Difluoro-2,8-bis(1-(4-methoxyphenyl)vinyl)-1,3,7,9-tetramethyl-10-phenyl-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine (3a)

Following the general procedure, the reaction of 1a (79.9 mg, 0.247 mmol) with InI₃ (24.5 mg, 0.05 mmol) and 1-ethynyl-4-methoxybenzene (0.45 mL, 3.46 mmol) in DCE (2 mL) was heated at 80 °C for 24 h. After purification by chromatography (1–3% EtOAc/hexanes), compound 3a (57.9 mg, 40%) was obtained as a pink solid: mp = 107–108 °C; λ^abs_max (CHCl₃) = 528 nm (ε = 83,256 M^–1 cm^–1); λ^em_max (CHCl₃) = 558 nm; Φ_F (CHCl₃) = 0.82; IR (ATR) ν_max = 2956, 2925, 2837, 1533, 1172 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.36–7.39 (m, 3H), 7.26–7.28 (m, H), 7.14–7.18 (m, 4H), 6.73 (d, J = 8.6 Hz, 4H), 5.67 (s, 2H), 4.92 (s, 2H), 3.72 (s, 6H), 2.32 (s, 6H), 1.15 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 160.0 (2 × C), 155.4 (C), 142.3 (C), 140.9 (C), 140.8 (4 × C), 135.9 (C), 134.0 (C), 133.3 (4 × C), 131.8 (C), 129.7 (2 × CH), 129.5 (CH), 128.6 (2 × CH), 128.0 (4 × CH), 115.8 (2 × CH₂), 114.3 (4 × CH), 55.8 (2 × CH₃), 13.9 (2 × CH₃), 13.3 (2 × CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.83 (q, J_B–F = 32.9 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₇H₃₅BF₂N₂O₂Na, 611.2657, found, 611.2650.

5,5-Difluoro-1,3,7,9-tetramethyl-10-phenyl-2,8-bis(1-(thiophen-3-yl)vinyl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine (4a)

Following the general procedure, the reaction of 1a (79.8 mg, 0.247 mmol) with InI₃ (24.5 mg, 0.05 mmol) and 3-ethynylthiophene (0.34 mL, 3.46 mmol) in DCE (2 mL) was heated at 80 °C for 23 h. After purification by chromatography (1–3% EtOAc/hexanes), compound 4a (83.8 mg, 63%) was obtained as a pink solid: mp = 98–100 °C; λ^abs_max (CHCl₃) = 521 nm (ε = 88,163 M^–1 cm^–1); λ^em_max (CHCl₃) = 547 nm; Φ_F (CHCl₃) = 0.72; IR (ATR) ν_max = 2956, 2929, 2853, 1536, 1178 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.35–7.42 (m, 3H), 7.23–7.27 (m, 2H), 7.16–7.19 (m, 2H), 7.11–7.13 (m, 2H), 6.83–6.85 (m, 2H), 5.71 (s, 2H), 4.95 (s, 2H), 2.37 (s, 6H), 1.17 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 155.2 (2 × C), 142.7 (C), 142.5 (C), 140.7 (2 × C), 136.3 (2 × C), 135.7 (2 × C), 133.9 (C), 131.7 (C), 129.7 (2 × CH), 129.7 (C), 129.6 (CH), 128.6 (2 × CH), 128.5 (C), 126.6 (2 × CH), 125.9 (2 × CH), 123.2 (2 × CH), 116.5 (2 × CH₂), 13.8 (2 × CH₃), 13.3 (2 × CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.88 (q, J_B–F = 32.7 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₁H₂₇BF₂N₂S₂Na, 563.1574, found, 563.1568.

2,8-Bis(1-(3,5-bis(trifluoromethyl)phenyl)vinyl)-5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine (5a)

Following the general procedure, the reaction of 1a (44.8 mg, 0.139 mmol) with InI₃ (13.8 mg, 0.028 mmol) and 1-ethynyl-3,5-bis(trifluoromethyl)benzene (0.34 mL, 1.94 mmol) in DCE (2 mL) was heated at 80 °C for 6 h. After purification by chromatography (2% EtOAc/hexanes), compound 5a (102.1 mg, 92%) was obtained as a pink solid: mp = 106–107 °C; λ^abs_max (CHCl₃) = 523 nm (ε = 79,174 M^–1 cm^–1); λ^em_max (CHCl₃) = 543 nm; Φ_F (CHCl₃) = 0.79; IR (ATR) ν_max = 2926,2854, 1535, 1279, 1131, 1136 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.78 (s, 2H), 7.72 (s, 4H), 7.46–7.54 (m, 3H), 7.35–7.38 (m, 2H), 6.00 (s, 2H), 5.35 (s, 2H), 2.44 (s, 6H), 1.21 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 154.8 (2 × C), 143.0 (C), 142.4 (2 × C), 141.0 (2 × C), 138.7 (2 × C), 134.8 (2 × C), 132.0 (q, ²J_CF = 33.4 Hz, 4 × C), 131.6 (C), 131.4 (C), 129.4 (2 × CH), 129.3 (CH), 128.0 (C), 127.8 (2 × CH), 126.2 (4 × CH), 123.2 (q, ¹J_CF = 272.3 Hz, 4 × CF₃), 121.6 (2 × CH), 120.9 (2 × CH₂), 13.4 (CH₃), 13.0 (3 × CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −62.86 (s, 4CF₃), −145.73 (q, J_B–F = 33.1 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₉H₂₇BF₁₄N₂Na, 823.1941, found, 823.1941.

2,8-Bis((Z)-2-bromo-1-phenylvinyl)-5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine (6a)

Following the general procedure, the reaction of 1a (20.1 mg, 0.062 mmol) with InI₃ (6.1 mg, 0.012 mmol) and (bromoethynyl)benzene (156.4 mg, 0.86 mmol) in DCE (0.7 mL) was heated at 80 °C for 3 h. After purification by chromatography (3% EtOAc/hexanes), compound 6a (31.3 mg, 74%) was obtained as a pink solid: mp = 105–106 °C; λ^abs_max (CHCl₃) = 523 nm (ε = 54,973 M^–1 cm^–1); λ^em_max (CHCl₃) = 538 nm; Φ_F (CHCl₃) = 0.38; IR (ATR) ν_max = 2955, 2923, 2851, 1461, 1377 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.38–7.49 (m, 5H), 7.27–7.31 (m, 6H), 7.20–7.24 (m, 4H), 6.95 (s, 2H), 2.41 (s, 6H), 1.23 (s, 6H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 154.6 (2 × C), 142.2 (C), 141.0 (C), 139.6 (C), 139.6 (C), 139.0 (2 × C), 138.9 (2 × C), 135.0 (2 × C), 131.5 (C), 130.8 (C), 129.4 (CH), 129.2 (CH), 129.1 (CH), 128.8 (CH), 128.37 (CH), 128.19 (CH), 128.1 (CH), 128.0 (4 × CH), 126.4 (4 × CH), 109.4 (CH), 109.4 (CH), 13.4 (2 × CH₃), 12.9 (2 × CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.67 (q, J_B–F = 33.1 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₅H₂₉BF₂N₂Br₂Na, 707.0656, found, 707.0653.

Ethyl (E)-3-(5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-2-yl)acrylate (7a)

Following the general procedure, the reaction of 1a (44.8 mg, 0.138 mmol) with InCl₃ (6.1 mg, 0.028 mmol) and ethyl propiolate (0.20 mL, 1.93 mmol) in DCE (2 mL) was heated at 80 °C for 48 h. After purification by chromatography (5–20% EtOAc/hexanes), compound 7a (23.4 mg, 40%) was obtained as a pink solid: mp = 155–156 °C; λ^abs_max (CHCl₃) = 528 nm (ε = 56,128 M^–1 cm^–1); λ^em_max (CHCl₃) = 549 nm; Φ_F (CHCl₃) = 0.79; IR (ATR) ν_max = 2955, 2919, 2851, 1711, 1540, 1166 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.55 (d, J = 16.5 Hz, 1H), 7.45–7.47 (m, 3H), 7.21–7.26 (m, 2H), 6.01 (s, 1H), 5.98 (d, J = 16.5 Hz, 1H), 4.17 (q, J = 7.1 Hz, 2H), 2.65 (s, 3H), 2.53 (s, 3H), 1.40 (s, 3H), 1.34 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 167.6 (C), 158.5 (C), 154.45 (C), 145.4 (C), 142.4 (C), 140.5 (C), 135.8 (CH), 134.7 (C), 132.7 (C), 130.6 (C), 129.3 (2 × CH), 129.3 (CH), 128.0 (2 × CH), 125.0 (C), 122.7 (CH), 117.5 (CH), 60.4 (CH₂), 14.8 (CH₃), 14.7 (CH₃), 14.4 (CH₃), 14.0 (CH₃), 12.7 (CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −144.94 (q, J_B–F = 32.9 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₂₄H₂₅BF₂N₂O₂Na, 445.1875, found, 445.1869.

Ethyl (E)-3-(5,5-difluoro-1,3,7,9-tetramethyl-10-(thiophen-2-yl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-2-yl)acrylate (7b)

Following the general procedure, the reaction of 1b (40.1 mg, 0.121 mmol) with InCl₃ (5.4 mg, 0.024 mmol) and ethyl propiolate (0.17 mL, 1.69 mmol) in DCE (2 mL) was heated at 80 °C for 48 h. After purification by chromatography (3–15% EtOAc/hexanes), compound 7b (29.2 mg, 56%) was obtained as a pink solid: mp = 155–156 °C; λ^abs_max (CHCl₃) = 541 nm (ε = 43,246 M^–1 cm^–1); λ^em_max (CHCl₃) = 566 nm; Φ_F (CHCl₃) = 0.18; IR (ATR) ν_max = 2956, 2924, 2852, 1708, 1539, 1284, 1164 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.61 (d, J = 16.3 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 7.16 (t, J = 4.1 Hz, 1H), 7.01 (d, J = 3.2 Hz, 1H), 6.08 (s, 1H), 6.03 (d, J = 16.3 Hz, 1H), 4.23 (q, J = 7.1 Hz, 2H), 2.69 (s, 3H), 2.58 (s, 3H), 1.65 (s, 3H), 1.61 (s, 3H), 1.31 (t, J = 7.2 Hz, 3H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 167.5 (C), 159.2 (C), 155.0 (C), 145.7 (C), 140.7 (C), 135.7 (CH), 134.8 (C), 134.3 (2 × C), 131.4 (C), 128.2 (CH), 127.9 (CH), 127.8 (CH), 125.3 (C), 123.0 (CH), 117.8 (CH), 60.4 (CH₂), 14.9 (CH₃), 14.4 (CH₃), 14.1 (CH₃), 13.9 (CH₃), 12.0 (CH₃); ¹⁹F{1H} NMR (319 MHz, CDCl₃) δ −144.85 (q, J_B–F = 32.4 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₂₂H₂₃BF₂N₂O₂SNa, 451.1439, found, 451.1431.

Methyl (Z)-3-(5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-2-yl)-3-phenylacrylate (8a)

Following the general procedure, the reaction of 1a (60.1 mg, 0.185 mmol) with InCl₃ (8.2 mg, 0.037 mmol) and ethyl 3-phenylpropiolate (0.38 mL, 2.59 mmol) in DCE (2 mL) was heated at 80 °C for 24 h. Then, the temperature was raised to 100 °C, and the reaction was left for 2 more days. After purification by chromatography (5–20% EtOAc/hexanes), compound 8a (37.2 mg, 42%) was obtained as a pink solid: mp = 101–102 °C; λ^abs_max (CHCl₃) = 515 nm (ε = 40,299 M^–1 cm^–1); λ^em_max (CHCl₃) = 528 nm; Φ_F (CHCl₃) = 0.69; IR (ATR) ν_max = 3059, 2951, 1722, 1615, 1157 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.43–7.47 (m, 3H), 7.29–7.37 (m, 7H), 6.49 (s, 1H), 6.01 (s, 1H), 3.68 (s, 3H), 2.58 (s, 3H), 2.34 (s, 3H), 1.39 (s, 3H), 1.11 (s, 3H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 165.7 (C), 155.9 (C), 154.4 (C), 148.7 (2 × C), 143.5 (C), 141.9 (C), 140.4 (C), 139.6 (2 × C), 135.0 (2 × C), 129.7 (CH), 129.2 (CH), 129.1 (CH), 129.0 (CH), 128.8 (2 × CH), 128.2 (CH), 128.1 (CH), 128.0 (CH), 127.4 (2 × CH), 119.7 (CH), 49.9 (CH₃), 14.7 (CH₃), 14.5 (CH₃), 13.3 (CH₃), 12.8 (CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −146.00 (dq, J_F–F = 253.9 Hz, J_B–F = 33.0 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₂₉H₂₇BF₂N₂O₂Na, 507.2031, found, 507.2028.

Methyl (Z)-3-(5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-2-yl)but-2-enoate (9a)

Following the general procedure, the reaction of 1a (80.1 mg, 0.247 mmol) with InCl₃ (10.9 mg, 0.049 mmol) and methyl but-2-ynoate (0.35 mL, 3.46 mmol) in DCE (2.5 mL) was heated at 80 °C for 24 h. Then, the temperature was raised to 100 °C, and the reaction was left for 2 more days. After purification by chromatography (3–10% EtOAc/hexanes), compound 9a (37.5 mg, 36%) was obtained as a pink solid: mp = 134–135 °C; λ^abs_max (CHCl₃) = 514 nm (ε = 75,310 M^–1 cm^–1); λ^em_max (CHCl₃) = 526 nm; Φ_F (CHCl₃) = 0.61; IR (ATR) ν_max = 2954, 2921, 2851, 1783, 1542, 1462 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.37–7.42 (m, 3H), 7.25–7.29 (m, 1H), 7.18–7.22 (m, 1H), 5.96 (q, J = 1.4 Hz, 1H), 5.89 (s, 1H), 3.50 (s, 3H), 2.47 (s, 3H), 2.36 (s, 3H), 1.90 (t, J = 1.3 Hz, 3H), 1.29 (s, 3H), 1.15 (s, 3H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 165.3 (C), 155.3 (C), 152.8 (C), 148.5 (2 × C), 143.0 (C), 141.6 (C), 138.2 (C), 135.1 (2 × C), 145.1 (C), 129.1 (2 × CH), 129.1 (CH), 128.9 (CH), 128.2 (CH), 128.0 (CH), 121.2 (CH), 51.2 (CH₃), 26.3 (CH₃), 14.6 (CH₃), 14.3 (CH₃), 13.1 (CH₃), 12.5 (CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −146.12 (dq, J_F–F = 308.9, J_B–F = 33.2 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₂₄H₂₅BF₂N₂O₂Na, 445.1875, found, 445.1876.

Ethyl (E)-3-(5,5-difluoro-1,3,7,9-tetramethyl-8-(1-phenylvinyl)-10-(thiophen-2-yl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-2-yl)acrylate (8b)

Following the general procedure, the reaction of 7b (24.2 mg, 0.058 mmol) with InI₃ (5.6 mg, 0.012 mmol) and phenylacetylene (0.090 mL, 0.82 mmol) in DCE (1 mL) was heated at 80 °C for 48 h. After purification by chromatography (2–5% EtOAc/hexanes), compound 8b (23.9 mg, 80%) was obtained as a pink solid: mp = 96–97 °C; λ^abs_max (CHCl₃) = 546 nm (ε = 48,515 M^–1 cm^–1); λ^em_max (CHCl₃) = 575 nm; Φ_F (CHCl₃) = 0.16; IR (ATR) ν_max = 2955, 2923, 2852, 1733, 1532, 1461 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.63 (d, J = 16.3 Hz, 1H), 7.53 (dd, J = 1.1, 5.1 Hz, 1H), 7.27–7.33 (m, 5H), 7.13–7.16 (m, 1H), 7.04 (dd, J = 1.2, 3.5 Hz, 1H), 6.08 (d, J = 16.3 Hz, 1H), 5.89 (d, J = 1.3 Hz, 1H), 5.14 (d, J = 1.25 Hz, 1H), 4.25 (q, J = 7.1 Hz, 2H), 2.71 (s, 3H), 2.40 (s, 3H), 1.67 (s, 3H), 1.46 (s, 3H), 1.32 (t, J = Hz, 3H);¹³C{1H} NMR (75 MHz, CDCl₃) δ 167.5 (C), 158.8 (C), 155.0 (C), 142.5 (C), 140.7 (C), 140.3 (2 × C), 139.6 (2 × C), 135.7 (CH), 134.8 (C), 134.5 (C), 128.6 (2 × CH), 128.5 (C), 128.2 (CH), 128.1 (CH), 127.9 (CH), 127.8 (CH), 126.9 (C), 126.3 (CH), 126.2 (2 × CH), 117.8 (CH₂), 60.4 (CH₂), 14.4 (CH₃), 14.1 (CH₃), 13.7 (CH₃), 12.2 (CH₃), 12.1 (CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −144.59 (q, J_B–F = 31.7 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₀H₂₉BF₂N₂O₂SNa, 553.1909, found, 553.1890.

Methyl (Z)-3-(5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-8-(1-(thiophen-3-yl)vinyl)-5H-4λ⁴,5λ⁴-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-2-yl)but-2-enoate (10a)

Following the general procedure, the reaction of 9a (29.0 mg, 0.069 mmol) with InI₃ (6.8 mg, 0.014 mmol) and 3-ethynylthiophene (0.10 mL, 0.96 mmol) in DCE (1 mL) was heated at 80 °C for 23 h. After purification by chromatography (3–10% EtOAc/hexanes), compound 10a (26.3 mg, 73%) was obtained as a pink solid: mp = 102–104 °C; λ^abs_max (CHCl₃) = 524 nm (ε = 51,560 M^–1 cm^–1); λ^em_max (CHCl₃) = 544 nm; Φ_F (CHCl₃) = 0.77; IR (ATR) ν_max = 2955, 2922, 2851, 1536, 1463 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 7.36–7.41 (m, 3H), 7.27–7.32 (m, 1H), 7.22–7.26 (m, 1H), 7.17–7.19 (m, 1H), 7.10–7.12 (m, 1H), 6.84 (dd, J = 1.3, 3.0 Hz, 1H), 5.97 (q, J = 1.5 Hz, 1H), 5.71 (d, J = 1.5 Hz, 1H), 4.93 (d, J = 1.5 Hz, 1H), 3.52 (s, 3H), 2.38 (s, 3H), 2.36 (s, 3H), 1.92 (s, 3H), 1.16 (s, 3H), 1.15 (s, 3H); ¹³C{1H} NMR (75 MHz, CDCl₃) δ 165.4 (C), 154.3 (C), 153.1 (C), 148.5 (C), 142.2 (C), 141.8 (C), 140.0 (C), 138.3 (C), 135.9 (C), 135.2 (2 × C), 133.2 (C), 132.3 (C), 131.0 (C), 129.1 (CH), 129.1 (CH), 129.0 (CH), 128.2 (CH), 128.1 (CH), 126.0 (CH), 125.4 (CH), 122.6 (CH), 121.3 (CH), 115.9 (CH₂), 51.2 (CH₃), 26.2 (2 × CH₃), 13.1 (CH₃), 12.7 (CH₃), 12.6 (CH₃); ¹⁹F{1H} NMR (282 MHz, CDCl₃) δ −145.97 (dq, J_F–F = 262.9, J_B–F = 33.2 Hz, 2F); HRMS (ESI) m/z: [M + Na]⁺ calculated for C₃₀H₂₉BF₂N₂O₂SNa, 553.1909, found, 553.1909.

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.3c02951.

• Copies of ¹H NMR, ¹³C NMR, and ¹⁹F NMR spectra of all compounds; NOE and 2D NMR spectra for compounds 6a, 7a, 8a, and 9a; and UV–vis and emission spectra for all compounds (PDF)

The authors declare no competing financial interest.