8 ‐ [4 ‐ (2 ‐ Hydroxypropane ‐ 2 ‐ yl)Phenyl] ‐ 1,3,4,4,5,7 ‐ Hexamethyl ‐ 4 ‐ Boron ‐ 3 a ,4 a ‐ Diaza ‐ S ‐ Indacene

: During recent years, the BODIPY core became a popular scaffold for designing photo ‐ removable protecting groups (PPG). In this paper, we report the synthesis of a new mole ‐ cule—8 ‐ [4 ‐ (2 ‐ hydroxypropane ‐ 2 ‐ yl)phenyl] ‐ 1,3,4,4,5,7 ‐ hexamethyl ‐ 4 ‐ boron ‐ 3 a ,4 a ‐ diaza ‐ S ‐ indacene —by the treatment of meso ‐ (4 ‐ CO 2 Me ‐ phenyl) ‐ BODIPY with excess of MeMgI. The product was characterized by 1 H, 13 C NMR and HRMS. The combination of BODIPY core with tertiary benzilyc alcohol might be promising for utilizing this molecule as visible light removable PPG.

Since seminal work of Winstein's and Winter's groups in 2015 [2,3], meso-CH2OH-BODIPY photoremovable protecting groups (PPGs) gained much popularity for the design of caged compounds, which enable the light-controlled release of small molecules, including those that are biologically relevant [4][5][6]. For biological applications, the light dose should be minimized due to potential phototoxic effects, emphasizing the need for high quantum yield (QY) of photorelease. However, for BODIPY-based PPG, low QYs are commonly observed but could be increased by the introduction of heavy iodine atoms or by changing fluorine atoms with methyl groups ( Figure 1A) [7,8]. The mechanism of photorelease is suggested to proceed from the formation of cation 1 [2] by heterolysis of C-X bond in an excited state of BODIPY ( Figure 1B). We hypothesized that additional stabilization of the carbocationic center by phenyl conjugation or the addition of methyl groups could be favorable for increasing the effectiveness of the photorelease.

Results and Discussion
One of the common approaches to the construction of BODIPY core is the one pot procedure starting with the condensation of pyrroles and aldehydes under acidic catalysis, subsequent oxidation with DDQ or chloranil and, finally, treatment with NEt3 or DIPEA followed by the addition of BF3•Et2O [9]. We started our work with the synthesis of aldehyde 3 by reactions of MeMgI with dimethylacetal 2, which was prepared from 4-formylbenzoic acid and methanol/SOCl2 (Scheme 1). Nevertheless, the application of the above-mentioned procedure of BODIPY synthesis to aldehyde 3 resulted in a complex mixture of products according to 19 F spectrum. The problems may arise from dehydration of tertiary alcohol with the formation of carbocation, which also might be active in reactions with pyrrole.

Scheme 1. Attempt to synthesis of meso-4-(2-hydroxyprop-2-yl)phenylBODIPY.
At the next step, we synthesized BODIPY 4 according to the literature procedure [10]. The reaction of BODIPY 4 with excess of MeMgI resulted in the exchange of fluorines to methyl groups and the transformation of CO2Me to 2-hydroxyprop-2-yl fragments (Scheme 2). BODIPY 5 was obtained in good yield. The structure of BODIPY 5 was confirmed by NMR studies (Supplementary Materials). In 1 H NMR, spectrum signals of 1,4-disubstituted benzene were observed at 7.25 and 7.57 ppm with coupling constant J = 8.3 Hz. Pyrrole fragments produce singlet signals at 5.96 ppm for C-H and at 1.32 and 1.62 ppm for CH3-groups. Moreover, the signals of CH3 groups of C(CH3)2OH fragment are observed at 2.47 ppm, and B-CH3 groups have up-field shifted signals at 0.27 ppm. The OH-group produced a broad singlet signal at 1.27 ppm. In the 13 C NMR spectrum, all signals of aromatic and heterocyclic fragments could be observed in range of 121-153 ppm, and alkyl fragments produce signals at 14-73 ppm region. However, the signals of B(CH3)2 fragment are not visible in the 13 C spectrum. The same peculiarity was previously described for other BODIPY containing B-C bond [11].
To characterize optical properties of 5, we first measured the absorption spectrum of its 1 μM solution in DMSO. Figure 2A shows the obtained result. The maximum absorption wavelength in DMSO is λmax = 503 nm, with the absorbance 0.093, producing the molar extinction coefficient ε(λmax) = 93,000 M −1 cm −1 . In water with 1% DMSO, the absorption peak is blue-shifted and wider, probably indicating the formation of aggregates [12,13].  Figure 2B shows the emission spectra of the same solutions excited at 500 nm. For comparison, we also show a fluorescence spectrum of Rhodamine 6G solution in DMSO, with the absorption at 500 nm matched to the sample of 5 in DMSO. The known fluo-rescence QY of Rhodamine 6G (0.56; [14]) allows us to estimate the fluorescence QY of 5 in DMSO to be 0.33.

Materials and Methods
All chemicals were purchased from commercial sources and used without additional purification unless otherwise noted. The progress of reactions was monitored by thin-layer chromatography (TLC) on Sorbfil Silica 60 F254 on aluminum sheets with UV visualization. Column chromatography was performed by using 100-200 mesh silica gel. NMR spectra were recorded on Bruker Avance-300 (300.13 MHz for 1 H) and Avance-400 (400.13 MHz for 1 H, 100.62 MHz for 13 C) spectrometers; chemical shifts of 1 H and 13 C{ 1 H} are provided in ppm, with solvent signals serving as the internal standard ( 1 H = 7.24 ppm and 13 C = 77.16 ppm for CDCl3). The masses of molecular ions were determined by high-resolution mass spectrometry (HRMS) by means of a DFS Thermo Scientific instrument (EI, 70 eV). The UV-Vis spectrum was registered with a Shimadzu UV-1900 spectrophotometer, and fluorescence spectra were obtained on a Shimadzu RF-6000 fluorometer for 10 −5 -10 −6 M solutions in DMSO. 
A solution of 1.20 g (12.6 mmol) of pyrrole and 1.00 g (6.1 mmol) of aldehyde 2 in 200 mL of dry CH2Cl2 was degassed with the "freeze-pump-thaw" technique, and then 2 drops of TFA was added. The resultant solution was stirred ~2 h until full consumption of aldehyde according TLC was achieved. Then, 1.67 g (7.3 mmol) of DDQ was added in small portions, and the mixture was additionally stirred for 30 min. After that, the mixture was cooled to 0 °C, and 20 mL of NEt3 was added followed with 20 mL BF3•Et2O. The resultant solution was kept at RT overnight with stirring. Then, it was quenched with 100 mL of H2O, and the organic phase was separated, washed with 100 mL H2O, 100 mL 5% HCl in H2O and 100 mL of saturated Na2CO3 and dried over Na2SO4. After the removal of CH2Cl2, the residue was analyzed by 19 F NMR. The complex mixture of BODIPY derivatives was observed. The analysis of isolated fractions has not revealed any useful products.   To a solution of 0.0320 g (0.084 mmol) of BODIPY 4 in 20 mL of dry diethyl ether, 0.28 mL (0.84 mmol) of 3M solution of MeMgI in diethyl ether was added under argon atmosphere. The mixture was stirred for 4 h and then quenched with a saturated solution of NH4Cl in water. The ether was separated and dried over Na2SO4 and removed. The resultant residue was dissolved in CH2Cl2 and passed through a pad of Al2O3. The evaporation of solvent produced dark red crystals, 0.0210 g (67%). Decomposition was >143 °C. 1