<figure><img src="image_1.png" /></figure>

# Synthesis of BODIPY Organophotocatalysts by Boron Functionalization with Quinine Derivatives and Applications in Asymmetric Photoxygenation

Corinne Coutant,[a] Jérôme Fischer,[a] Pierrick Nun,[a] and Vincent Coeffard*[a]

Boron dipyrromethene (BODIPY) derivatives are key dyes owing to their interesting (electro)chemical and spectroscopic properties. These features have been exploited in various scientific domains such as materials science, biomedicine or organic synthesis. In particular, heavy-atom containing BODIPY photocatalysts have found widespread applications in photoredox and energy transfer catalysis. The covalent attachment of heavy atoms to the boron dipyrromethene core enables the population of the triplet state through intersystem crossing (ISC), which is involved in the generation of singlet oxygen via triplet-triplet energy transfer. While the functionalization of the

dipyromethene core has been extensively studied, investigations on boron substitution is far less described. In this work, boron functionalization of diiodo-BODIPY dyes has enabled the grafting of quinine derivatives leading to a new family of chiral photosensitizers. The photophysical properties and the photo-stability of these photocatalysts have been investigated in dichloromethane and methanol. Preliminary investigations in asymmetric photooxidative processes have demonstrated the synthetic potential of these BODIPY-quinine dyes in photo-organocatalysis.

## Introduction

Boron-dipyrrromethene (BODIPY) dyes have been widely used in light-driven processes owing to their ease of synthesis, modularity, tunable photophysical and electrochemical properties, stability, and strong absorption of visible light.[1] Depending on the substitution pattern of the BODIPY core structure, singlet and triplet excited states can be preferentially populated upon photon absorption leading to different applications. For instance, the fluorescence properties of BODIPY have been exploited in life sciences for biosensing applications or for imaging activities.[2] Accessing the long-lived triplet state of BODIPY dyes spans applications such as photodynamic therapy, photon upconversion via triplet-triplet annihilation, or photocatalysis.[3] The covalent attachment of heavy atoms (i. e. Br, I, Au, Pt, Ru) to the BODIPY core structure is a common approach to promote the population of the triplet state through spin-orbit coupling (SOC) induced intersystem crossing.[4] The applications of these heavy atom-containing dyes in photoredox catalysis and energy transfer processes have flourished in the literature over the past decade.[5] For instance, halogen-containing BODIPY catalysts have been used in photoredox organic reactions such as functionalization of N-substituted tetrahydroisoquinolines,[6] arylation of furans and

thiophenes with diazonium salts,[6c] atom-transfer radical additions[7] or the synthesis of amides by reaction of aldehydes with amines to cite only some examples.[8] Halogen-containing BODIPY dyes are also relevant molecules for promoting singlet oxygen generation through triplet-triplet energy transfer between the triplet excited state of BODIPY and ground-state molecular oxygen.[9] Singlet oxygen is a metastable and highly reactive oxygen species that found relevant applications in organic synthesis.[10] Recently, we and others reported the applications of diiodo-BODIPY dyes in singlet oxygen-mediated organic transformations encompassing the photooxygenation of phenol derivatives,[11] the oxidation of amines[11c] and the hydroxylation of β-dicarbonyl compounds.[12] Despite the increasing interest in organophotocatalysis involving BODIPY dyes, asymmetric processes remain scarce in the literature. In 2013, the group of Zhao reported the BODIPY-catalyzed alkylation of N-aryl tetrahydroisoquinolines with acetone using L-Proline as a co-catalyst to activate acetone (Scheme 1).[6c] The products were isolated in good yields but with low enantiomeric excesses. In our own group, we have reported the combination of a photooxidative dearomatization of 1-naphthol with asymmetric aminocatalyzed functionalization of dienals in a single vessel.[11b] The procedure involving the diiodo-BODIPY B2 enabled the formation of enantioenriched naphthoquinone derivatives in moderate yields. In 2019, the use of BODIPY dyes in asymmetric organocatalyzed processes was extended to the photooxygenation of β-dicarbonyl compounds.[12] To this aim, the bifunctional BODIPY B3, composed of a photosensitizer part for singlet oxygen generation and a quinine moiety to interact with the substrate, was prepared through a multi-step route. Upon green LED illumination, photooxygenation of β-dicarbonyl compounds with 5 mol% of BODIPY B3 led to the desired products in 18–86% yields and enantiomeric excesses up to

<footnote>[a] C. Coutant, Dr. J. Fischer, Dr. P. Nun, Dr. V. Coeffard
Nantes Université, CNRS, UMR 6230, F-44000 Nantes, France
E-mail: vincent.coeffard@univ-nantes.fr</footnote>

<footnote>Supporting information for this article is available on the WWW under
https://doi.org/10.1002/slct.202303316</footnote>

<footnote>© 2023 The Authors. ChemistrySelect published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.</footnote>
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State of the art

a) Alkylation of N-aryl tetrahydroisoquinolines

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b) Synthesis of 1,4-naphthoquinone-derived polycycles

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c) Hydroxylation of β-dicarbonyl compounds

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BODIPY catalysts:

<figure><img src="image_6.png" /><figcaption>Scheme 1. Asymmetric organophotocatalysis involving BODIPY dyes.</figcaption></figure>

40%. Expansive efforts to include unprecedented light-driven asymmetric organocatalytic transformations require the design of new chiral organophotocatalysts. To this aim, we surmised that boron functionalization could be a relevant strategy to graft chiral organocatalysts on the BODIPY framework. While the functionalization of the dipyrrin core of BODIPY dyes has been widely investigated, the B–F substitution has received less attention in the literature.[13] Until now, the functionalization of the boron atom has mainly concerned the fluorescent properties of the BODIPY dyes. In this article, we report the preparation of photocatalysts **B4-5** composed of a BODIPY platform and two quinine units separated by ether linkages, and their investigations in singlet-oxygen mediated processes (Figure 1).

We surmised that increasing the number of quinine sites could influence the reaction kinetics and the stereoselectivities of asymmetric processes by impacting the interactions between the catalyst and the substrate.[14] Different linkage lengths between the photosensitizer part and the quinine moiety will be investigated to study their influence on the properties of BODIPY dyes **B4-5**. In addition to boron functionalization, two iodine atoms were directly attached to the BODIPY core to enhance the intersystem crossing, therefore enabling efficient singlet oxygen generation. To the best of our knowledge, there have been no reports about the investigation of B–F substitution on BODIPY dyes for applications in asymmetric organophotocatalysis.

<figure><img src="image_7.png" /><figcaption>Figure 1. BODIPY photosensitizers investigated in this work.</figcaption></figure>

Results and Discussion

The BODIPY dyes **B4-5** were prepared through the synthetic route shown in Scheme 2. The synthesis began with the desymmetrization of diethylene and tetraethylene glycol with tosyl chloride furnishing the compounds **1** and **2** in 90% and 98% yields, respectively. The tosylate groups underwent an efficient azide displacement in ethanol under reflux, leading to the desired products **3** and **4** in good yields. Boron functionalization of BODIPY **B2** was carried out using alcohols **3–4** in the
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<figure><img src="image_9.png" /><figcaption>**Scheme 2.** Synthetic route towards BODIPY photosensitizers **B4-5**: a) TsCl, NaOH, THF/H₂O, 5 °C; b) NaN₃, EtOH, 78 °C; c) **B2**, AlCl₃, CH₂Cl₂, 40 °C then TBDMSCl, imidazole, CH₂Cl₂, 20 °C; d) CuSO₄·5H₂O, sodium ascorbate, Et₃N, CH₂Cl₂/H₂O/MeOH, 20 °C.</figcaption></figure>

presence of anhydrous aluminium chloride in dichloromethane. [15]

An inseparable mixture of starting alcohols **3–4** and the corresponding BODIPY dyes **5–6** was obtained after purification, regardless of the purification method used. To address this issue, the crude reaction mixture was treated with TBDMSCl and imidazole allowing the protection of the remaining alcohol. Under these conditions, the formation of monosubstituted B–O derivatives could not be confirmed and the BODIPY dyes **5–6** were obtained in good yields (65–72%) after rapid purification by column chromatography on silica gel. Attempts to functionalize the boron atom with ethylene glycol derivatives bearing longer chains (n=4 or 5) failed to give pure BODIPY derivatives. The quinine unit was then connected to the BODIPY framework through a copper-catalyzed Huisgen cycloaddition. The quinine-BODIPY structures **B4** and **B5** were isolated in 84% and 72% yields after purification by column chromatography on silica gel. The photophysical properties of BODIPY dyes **B2-5** were then investigated in dichloromethane and methanol (Table 1). Regardless of the iodinated photosensitizers, the absorption band hardly changed in dichloromethane and methanol. For instance, the absorption spectrum of diiodo-BODIPY **B2** displays a band at 535 nm in dichloromethane and at 532 nm in methanol. Similar features were observed for functionalized BODIPY **B3-5** ($\lambda_{abs}$ between 531 and 535 nm) indicating that the functionalization of the boron atom has no influence on the longest wavelength absorption band. Switching from dichloromethane to methanol resulted in a decrease of the molar absorptivity, and this trend was observed for all BODIPY dyes. The highest absorption coefficients were obtained with the BODIPY dye **B2**, while a decrease in values was observed with the quinine derivatives **B3-5**.

<table><caption>**Table 1.** Photophysical properties of BODIPY dyes **B2-5**.</caption><thead><tr><th>Dye</th><th>Solvent</th><th>λ<sub>max</sub> [nm]<sup>[a]</sup></th><th>ε [M<sup>-1</sup>.cm<sup>-1</sup>]<sup>[b]</sup></th><th>Φ<sub>Δ</sub><sup>[c]</sup></th></tr></thead><tbody><tr><td rowspan="2">B2</td><td>CH<sub>2</sub>Cl<sub>2</sub></td><td>535</td><td>83719</td><td>0.86</td></tr><tr><td>MeOH</td><td>532</td><td>71772</td><td>0.72</td></tr><tr><td rowspan="2">B3</td><td>CH<sub>2</sub>Cl<sub>2</sub></td><td>535</td><td>66596</td><td>0.65</td></tr><tr><td>MeOH</td><td>531</td><td>65397</td><td>0.80</td></tr><tr><td rowspan="2">B4</td><td>CH<sub>2</sub>Cl<sub>2</sub></td><td>534</td><td>64224</td><td>0.88</td></tr><tr><td>MeOH</td><td>532</td><td>55044</td><td>0.61</td></tr><tr><td rowspan="2">B5</td><td>CH<sub>2</sub>Cl<sub>2</sub></td><td>535</td><td>53757</td><td>0.93</td></tr><tr><td>MeOH</td><td>531</td><td>44708</td><td>0.88</td></tr></tbody></table>

[a] Maximum absorption wavelength. [b] Molar extinction coefficient. [c] Singlet oxygen quantum yield (see Supporting Information for further details).

For example, BODIPY **B5** showed a 1.5-fold reduction in the molar extinction coefficient compared to its counterpart **B2**. The compounds are nearly non-emissive due to the presence of iodine atoms enhancing the intersystem crossing, and these results were confirmed by determining the singlet oxygen quantum yields. In dichloromethane, high singlet oxygen quantum yields ($\Phi_{\Delta} \ge 0.86$) were measured for **B2**, **B4** and **B5**, while dye **B3** was less prone to generate singlet oxygen upon illumination ($\Phi_{\Delta} = 0.65$).

The lower absorption coefficient and singlet oxygen quantum yields of **B3** explains the increase of catalytic activity of **B2** compared to **B3** towards the photoxygenation of anthracene under green-light irradiation.[12] Except for **B3**, a decrease in singlet oxygen quantum yields was observed when switching from dichloromethane to methanol but the values remain high enough for applications in photoxygenation. Reactive oxygen species such as singlet oxygen are oxidizing
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agents that can be responsible of the photobleaching of dyes.[16] Therefore, the photochemical alteration of dyes B2-5 in air-equilibrated dichloromethane solutions was then investigated by monitoring the variations of absorbance at λmax under green light illumination (Figure 2). Under these conditions, BODIPY B2 turned out to be photostable, and no change in absorbance was observed after 1 h of irradiation (Figure 2a). The introduction of a quinine moiety on the meso-substituent of BODIPY led to a slight alteration of the photostability as shown in Figure 2b. Boron functionalization with the quinine derivative led to less stable dyes compared to the native BODIPY B2 (Figures 2c–d). The linkage length influenced the photostability with B5 being more stable than B4 under green light illumination. Taking all the photophysical data together (singlet oxygen quantum yields and photostability), the BODIPY-Quinine dye B5 was selected for applications in a series of asymmetric photoxygenation reactions in order to show the synthetic potential of the photocatalyst (Scheme 3). The BODIPY dye B5 was first applied to the photoxygenation of 1,3-dicarbonyl compound 8 under the optimized conditions previously reported by our group (Scheme 3a).[12] Irradiation of 8 in the presence of 5 mol% of photocatalyst B5 led to the formation of 9 in 62% yield with an enantiomeric ratio (er) of 64:36. Running the reaction with 5 mol% of BODIPY B2 and 10 mol% of 7 under the same reaction conditions afforded 9 in 78% yield with a similar selectivity (er = 62:38). The discovery of new strategies to transform phenols in para-quinol derivatives is deemed worthy of investigation in light of the importance of these frameworks in natural products.[17] Phenolic compounds are known to interact with Cinchona derived catalysts, and this combination has been successfully applied in asymmetric dearomative processes.[18] In addition, the photo-oxygenation of 10 to generate the corresponding para-quinol

has also been reported, making this phenol a suitable candidate for asymmetric processes.[19] The photooxygenation of phenol 10 in the presence of B5 resulted to the formation of para-quinol 11 in 29% yield and an enantiomeric ratio (er) of 59:41 after the reduction of the hydroperoxide intermediate with triphenylphosphine (Scheme 3b). As a comparison, a higher yield of 11 (47%) was obtained with the catalytic system BODIPY B2 (5 mol%) and 7 (10 mol%). Nevertheless, the product was slightly enriched with the opposite enantiomer (er = 47:53). Therefore, the spatial structuration of the quinine units in B5 influences the enantioselection for this transformation. To the best of our knowledge, this is the first example of a singlet-oxygen mediated asymmetric photocatalyzed oxygenation of phenols to generate enantioenriched para-quinols. These results are promising and support further investigations to achieve higher levels of yields and enantioselections.

In the previous examples, the electrophilicity of singlet oxygen was harnessed in asymmetric processes. A conceptual leap in singlet oxygen chemistry would involve its use in the asymmetric oxidation of electron-poor substrates.[20] At the heart of our strategy is the *in-situ* preparation of the nucleophilic hydroperoxide **13** by photooxygenation of an excess of 2,3-dimethyl-2-butene **12** with B5. The alkene **12** has been selected for the *in-situ* generation of an hydroperoxide through photooxygenation due to the high quenching rate constant of **12** with singlet oxygen (k = 5.6 10⁷ L mol⁻¹ s⁻¹ in CHCl₃) and the selective formation of **13** by ¹O₂-mediated oxidation of **12**.[21] In 2022, the group of Chauhan reported an efficient organocatalytic strategy for the synthesis of enantioenriched isochromans *via* a desymmetrization process employing an hydroperoxide and *Cinchona* derivatives as catalysts.[22] Similarly, we surmised that the *in-situ* hydroperoxide **13** could

<figure><img src="image_11.png" /><figcaption>**Figure 2.** Absorption spectra variations of a solution of B2 (a), B3 (b), B4 (c) and B5 (d) in air-equilibrated dichloromethane (1.0 10⁻⁵ M) under green light illumination (525 nm, 10 mW cm⁻²).</figcaption></figure>
<figure><img src="image_12.png" /></figure>

<figure><img src="image_13.png" /><figcaption>b) Dearomative photooxygenation</figcaption></figure>

<figure><img src="image_14.png" /><figcaption>c) One-pot synthesis of a cyclohexenone-derived isochroman</figcaption></figure>

<figure><img src="image_15.png" /><figcaption>**Scheme 3.** Applications of dye B5 in asymmetric photooxygenation.</figcaption></figure>

react with the dienone **14** to afford the enantioenriched isochroman derivative **15** (Scheme 3c). A sequential one-pot process was implemented involving the photooxygenation of 2,3-dimethyl-2-butene **12** for 2 hours under green light illumination to ensure full conversion into **13** and then addition of the dienone **14**.[23] Using 5 mol% of B5, the product **15** was isolated in 26% yield with an enantiomeric ratio (er) of 87:13. In order to increase the reaction yield, the catalytic amount of B5 was increased to 15 mol% providing the desired product B5 in 64% yield and an enantiomeric ratio of 92:8. Similar results were obtained by running the reaction with 15 mol% of BODIPY B2 and 30 mol% of 7 (64%, er = 94:6). A higher amount of photocatalyst B5 (25 mol%) had no effect on the reaction yield while the enantiomeric ratio reached 95:5.

Conclusions

In summary, the synthesis of two BODIPY-quinine photosensitizers has been achieved by boron functionalization and azide-alkyne Huisgen cycloaddition as key steps. Photophysical analyses showed that the introduction of quinine units had no influence on the absorption spectra, while a decrease of the absorption coefficients was observed after B–F substitution with quinine derivatives in dichloromethane and methanol. The diiodo-BODIPY-quinine dyes exhibited high singlet oxygen quantum yields and variable photostabilities depending on the length of ether chains between the BODIPY framework and the quinine unit. The most promising photosensitizer, based on singlet oxygen quantum yield and photostability, was tested in a selective set of asymmetric photooxidative transformations, resulting in promising enantioselectivities. We believe that fine-tuning the substrate-catalyst interactions could pave the way to new possibilities for light-induced singlet oxygen-mediated asymmetric processes.

Experimental Section

**General Information:** ¹H NMR and ¹³C spectra were recorded on a BRUKER Avance 300 (300 MHz for ¹H and 75 MHz for ¹³C), BRUKER Avance III 400 (400 MHz for ¹H and 100 MHz for ¹³C) or BRUKER Avance III 500 (500 MHz for ¹H and 125 MHz for ¹³C) at room temperature on samples dissolved in CDCl₃ or acetone-d6. Chemical shifts (δ) are given in parts per million and coupling constants are given as absolute values expressed in Hertz. Multiplicities are indicated by *s* (singlet), *d* (doublet), *t* (triplet), *q* (quartet), *m* (multiplet) and *br*. (broad). High-resolution mass spectrometry (HRMS) analyses were recorded on a XEVO G2-XS QTOF (Waters). Infrared spectra were recorded with a Bruker Tensor 27 FT ATR spectrometer. UV-Visible spectra were recorded on an Analytik Jena specord 210. Thin-layer chromatography (TLC) was carried out on aluminium sheets precoated with silica gel 60 F₂₅₄ (Merck). Column chromatography separations were performed using Merck Kieselgel 60 (0.040–0.060 mm). The chemicals and solvents were purchased from commercial suppliers without further purification. The diiodo-BODIPY photosensitizer B2,[24] Quinine-BODIPY B3,[12] 10,11-didehydroquinine 7,[25] and the cyclohexadienone derivative 14[22] were prepared according to literature procedures.

BODIPY (5). To a solution of B2 (150.8 mg, 0.262 mmol, 1 eq.) under argon in anhydrous dichloromethane (16 mL) at 40 °C was added AlCl₃ (112 mg, 0.841 mmol, 3 eq.). The solution was stirred at 40 °C for 5 min. After cooling, a solution of 3 (123 mg, 0.938 mmol, 3.6 eq.) in anhydrous dichloromethane (10 mL) was added drop-wise. The solution was stirred at 40 °C for 1 h and controlled by TLC. After reaction completion and cooling, the solution was washed with water (3×30 mL). The aqueous layer was extracted with dichloromethane (30 mL). The organic layers were combined, dried under anhydrous Na₂SO₄, filtered and concentrated under vacuum. The crude residue was dissolved in anhydrous dichloromethane (10 mL) and imidazole (114 mg, 1.57 mmol, 6 eq.) followed by TBDMSCI (148 mg, 0.984 mmol, 4 eq.) were added. The solution was stirred at 20 °C in the dark for 18 h. The solution was washed with water (2×30 mL) and the aqueous layer was extracted with dichloromethane (30 mL). The organic layers were combined, dried under anhydrous Na₂SO₄, filtered and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel (CH₂Cl₂/MeOH, 99.5:0.5) to afford the desired product 5 as a
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pink oil in 65% yield (136 mg). The product needs to be stored in a freezer to avoid degradation. Rf = 0.39 (CH₂Cl₂/methanol, 99.5:0.5). ¹H NMR (CDCl₃, 400 MHz) δ (ppm): 7.53–7.48 (m, 3H), 7.28–7.22 (m, 2H), 3.58–3.49 (m, 8H), 3.36–3.30 (m, 4H), 3.18–3.11 (m, 4H), 2.67 (s, 6H), 1.37 (s, 6H). ¹³C NMR (CDCl₃, 100 MHz) δ (ppm): 157.1 (2 C), 144.1 (2 C), 141.3, 135.4, 132.7 (2 C), 129.4 (3 C), 128.2 (2 C), 86.0 (2 C), 72.5, 72.4, 70.2, 69.8, 62.0, 61.0, 51.0, 50.9, 17.2 (2 C), 16.1 (2 C). HRMS (ES⁺): m/z calculated for C₂₇H₃₃N₈O₄Br₂Na [M+Na]⁺: 820.0741 found 820.0747. IR (ATR, cm⁻¹): 2962, 2922, 2855, 2097, 1712, 1524, 1338, 1293, 1161, 1081, 985, 713, 519.

**BODIPY (6).** To a solution of B2 (150.4 mg, 0.261 mmol, 1 eq.) under argon in anhydrous dichloromethane (16 mL) at 40°C was added AlCl₃ (287 mg, 2.08 mmol, 8 eq.). The solution was stirred at 40°C for 5 min. After cooling, a solution of 4 (281 mg, 1.30 mmol, 5 eq.) in anhydrous dichloromethane (20 mL) was added dropwise. The solution was stirred at 40°C for 1 h and controlled by TLC. After reaction completion and cooling, the solution was washed with water (2×50 mL). The aqueous layer was extracted with dichloromethane (50 mL). The organic layers were combined, dried with anhydrous Na₂SO₄, filtered and concentrated under vacuum. The crude residue was dissolved in anhydrous dichloromethane (8 mL) and imidazole (140.1 mg, 2.05 mmol, 8 eq.) followed by TBDMSCl (197 mg, 1.31 mmol, 5 eq.) were added. The solution was stirred at 20°C in the dark for 18 h. The solution was washed with water (2×25 mL) and the aqueous layer was extracted with dichloromethane (25 mL). The organic layers were combined, dried with anhydrous Na₂SO₄, filtered and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel (CH₂Cl₂/MeOH, 99.5:0.5 and then 99:1) to afford the desired product 6 as a pink oil in 72% yield (183 mg). The product needs to be stored in a freezer to avoid degradation. Rf = 0.2 (CH₂Cl₂/MeOH, 99.5:0.5). ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 7.53–7.49 (m, 3H), 7.26–7.21 (m, 2H), 3.68–3.49 (m, 24H), 3.40–3.34 (m, 4H), 3.16–3.10 (m, 4H), 2.66 (s, 6H), 1.36 (m, 6H). ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): 157.1 (2 C), 144.0 (2 C), 141.2, 135.4, 132.7 (2 C), 129.5 (3 C), 128.1 (2 C), 86.1 (2 C), 72.2 (2 C), 70.9 (4 C), 70.8 (4 C), 70.6 (2 C), 60.8 (2 C), 50.8 (2 C), 17.1 (2 C), 16.1 (2 C). HRMS (ASAP⁻): m/z calculated for C₃₅H₄₈BN₈O₈Br₂ [M-H⁻]: 973.1778 found: 973.1799. IR (ATR, cm⁻¹): 2858, 1094, 1528, 1340, 1294, 1155, 1082, 714, 520.

**Photosensitizer Quinine-BODIPY (B4).** To a solution of 5 (121 mg, 0.152 mmol, 1 eq.) in dichloromethane (3 mL) was added 7 (97 mg, 0.303 mmol, 2 eq.). A solution of CuSO₄·5H₂O (8 mg, 0.030 mmol, 0.2 eq.) and sodium ascorbate (13 mg, 0.061 mmol, 0.4 eq.) in a mixture of H₂O/MeOH (0.7 mL/0.7 mL) was added followed by Et₃N (25.4 µL, 0.182 mmol, 1.2 eq.). The solution was stirred at 20°C in the dark for 16 h. After reaction completion, water (7 mL) was added and the solution was extracted with dichloromethane (2×10 mL). The combined organic layers were washed with a solution of EDTA (60 mg, 0.205 mmol) in water (20 mL), dried with anhydrous Na₂SO₄, filtered and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel (MeOH/EtOAc, 3:1 then 100% MeOH and finally MeOH + 1% Et₃N) to afford the desired product B4 as a red solid in 84% yield (184 mg). Rf = 0.46 (MeOH + 1% Et₃N). ¹H NMR (CDCl₃, 500 MHz) δ (ppm): 8.48 (d, 2H, *J* = 4.5 Hz), 7.84 (d, 2H, *J* = 9.1 Hz), 7.50–7.48 (m, 3H), 7.45 (d, 2H, *J* = 4.5 Hz), 7.24–7.19 (m, 8H), 5.58 (s, 2H), 4.29 (t, 4H, *J* = 5.2 Hz), 3.83 (s, 6H), 3.61–3.52 (m, 6H), 3.35–3.22 (m, 10H), 3.03–2.95 (m, 6H), 2.70–2.64 (m, 2H), 2.57 (s, 6H), 2.06–2.02 (m, 2H), 1.85–1.77 (m, 2H), 1.76–1.70 (m, 2H), 1.61–1.54 (m, 2H), 1.41–1.35 (m, 8H). ¹³C NMR (CDCl₃, 125 MHz) δ (ppm): 157.8 (2 C), 157.0 (2 C), 150.1 (2 C), 147.7 (2 C), 147.4 (2 C), 144.2 (2 C), 144.1 (2 C), 141.5, 135.0, 132.6 (2 C), 131.3 (2 C), 129.7 (2 C), 129.6, 128.0 (2 C), 126.9 (2 C), 121.8 (2 C), 121.7 (2 C), 118.7 (2 C), 101.6 (2 C), 86.0 (2 C), 72.4 (2 C), 70.9 (2 C), 69.2 (2 C), 60.8 (2 C), 59.7 (2 C), 56.0 (2 C), 55.9 (2 C), 50.3 (2 C), 43.3 (2 C), 32.2 (2 C), 28.0 (2 C), 27.6 (2 C), 22.5 (2 C), 17.1 (2 C), 16.1 (2 C). HRMS (ES⁺): m/z calculated for C₇₅H₉₅N₁₂Br₂ [M + 2H]⁺: 1619.5451 found: 1619.5424. IR (ATR, cm⁻¹): 3280, 2920, 2863, 1620, 1531, 1454, 1341, 1295, 1240, 1165, 1084, 995, 716, 520.

50.3 (2 C), 43.3 (2 C), 32.9 (2 C), 27.9 (2 C), 27.3 (2 C), 21.9 (2 C), 17.2 (2 C), 16.1 (2 C).

HRMS (ES⁺): m/z calculated for C₆₇H₇₈N₁₂O₈Br₂ [M + H]⁺: 1443.4248 found: 1443.4261. IR (ATR, cm⁻¹): 3254, 2925, 1620, 1530, 1454, 1165, 1084, 996, 716, 520.

**Photosensitizer Quinine-BODIPY (B5).** To a solution of 6 (209 mg, 0.227 mmol, 1 eq.) in dichloromethane (3 mL) was added 7 (146.5 mg, 0.455 mmol, 2 eq.). A solution of CuSO₄·5H₂O (15.1 mg, 0.045 mmol, 0.2 eq.) and sodium ascorbate (18.2 mg, 0.091 mmol, 0.4 eq.) in a mixture of H₂O/MeOH (1 mL/1 mL) was added. Et₃N (38 µL, 0.272 mmol, 1.2 eq.) was added. The solution was stirred at 20°C in the dark for 16 h. After reaction completion, water (10 mL) was added and the solution was extracted with dichloromethane (2×20 mL). The combined organic layers were washed with a solution of EDTA (60 mg, 0.205 mmol) in water (20 mL), dried with anhydrous Na₂SO₄, filtered and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel (MeOH/EtOAc, 3:1 then 100% MeOH and finally MeOH + 1% Et₃N) to afford the desired product B5 as a red solid in 72% yield (264 mg). Rf = 0.22 (MeOH + 1% Et₃N). ¹H NMR (CDCl₃, 400 MHz) δ (ppm): 8.64 (d, 2H, *J* = 4.5 Hz), 7.93 (d, 2H, *J* = 9.9 Hz), 7.54–7.49 (m, 5H), 7.40 (s, 2H), 7.30–7.27 (m, 4H), 7.23–7.19 (m, 2H), 5.64 (br, s, 2H), 4.39 (app, t, 4H, *J* = 5.6 Hz), 3.90 (s, 6H), 3.75–3.71 (m, 4H), 3.55–3.38 (m, 28H), 3.13–3.09 (m, 4H), 3.07–3.01 (m, 2H), 2.80–2.73 (m, 2H), 2.64 (s, 6H), 2.11 (app, s, 2H), 1.89–1.82 (m, 2H), 1.79–1.73 (m, 2H), 1.68–1.61 (m, 2H), 1.52–1.45 (m, 2H), 1.35 (s, 6H). ¹³C NMR (CDCl₃, 100 MHz) δ (ppm): 157.8 (2 C), 157.1 (2 C), 150.6 (2 C), 147.8 (2 C), 147.6 (2 C), 144.4 (2 C), 144.1 (2 C), 141.3, 135.3, 132.7 (2 C), 131.6 (2 C), 129.5 (3 C), 128.1 (2 C), 127.0 (2 C), 121.8 (2 C), 121.6 (2 C), 118.7 (2 C), 101.8 (2 C), 86.0 (2 C), 72.3 (2 C), 71.8 (2 C), 70.7 (2 C), 70.6 (2 C), 70.5 (4 C), 69.6 (2 C), 60.9 (2 C), 59.8 (2 C), 56.4 (2 C), 55.9 (2 C), 50.2 (2 C), 43.3 (2 C), 33.2 (2 C), 28.0 (2 C), 27.6 (2 C), 22.5 (2 C), 17.1 (2 C), 16.1 (2 C). HRMS (ES⁺): m/z calculated for C₇₅H₉₅N₁₂Br₂ [M + 2H]⁺: 1619.5451 found: 1619.5424. IR (ATR, cm⁻¹): 3280, 2920, 2863, 1620, 1531, 1454, 1341, 1295, 1240, 1165, 1084, 995, 716, 520.

## Supporting Information Summary

The Supporting Information includes experimental procedures and spectroscopic data of the substrates and products, absorption spectra, singlet oxygen quantum yield measurements, HPLC traces, additional experimental details. The authors have cited additional references within the Supporting Information.[26–30]

## Acknowledgements

This work was supported by The Région Pays de la Loire (NANO2 project) which financed a Ph.D. grant for J. F. and C. C. thanks Nantes Université for a Ph.D. grant. We also thank CNRS for financial support. The authors greatly acknowledge AMaCC platform team (CEISAM UMR CNRS 6230, Nantes University) for their contribution in chiral chromatography and mass spectrometry to this work. This work includes NMR experiments carried out on the CEISAM NMR. This work received financial assistance from the State within the framework of the EUR LUMOMAT project and the Investissements d'Avenir program ANR-18-EURE-0012.
<figure><img src="image_17.png" /></figure>

Conflict of Interests

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available
from the corresponding author upon reasonable request.

Keywords: asymmetric catalysis · BODIPY · organocatalysis · photocatalysis · singlet oxygen

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Manuscript received: August 21, 2023