Arylboronic Acid Pinacol Esters as Stable Boron Sources for Dihydrodibenzoborepin Derivatives and a Dibenzoborole

The general synthesis of boron-containing cyclic compounds (boracycles) necessitates toxic organotin precursors or highly reactive boron halides. Here, we report the synthesis of seven- and five-membered boracycles utilizing arylboronic acid pinacol esters (ArBpins) as stable boron sources. Grignard reagents generated from 2,2′-dibromodibenzyl or 2,2′-dibromobiphenyl reacted with ArBpins, where Ar = 9-anthryl (Anth), 2,4,6-trimethylphenyl (Mes), or 2,4,6-triisopropylphenyl (Tip), to give 10,11-dihydro-5H-dibenzo[b,f]borepins or dibenzoborole derivatives. This Bpin-based method was successfully applied to a one-shot double boracycle formation, providing a dihydrodibenzoborepin–anthracene–dihydrodibenzoborepin triad molecule in a good yield. The dihydrodibenzoborepin bearing the Anth group was directly converted to the unsaturated borepin by NBS/AIBN. All products were characterized by NMR, HRMS, and in some cases, single-crystal X-ray diffraction analysis. Additionally, the photophysical properties of the products are also reported.

Synthetic methods for boracycles can be roughly divided into three types: (1) tinboron transmetalation, (2) salt-elimination reaction, and (3) intramolecular CH borylation (Scheme 1) [11][12][13][14].The tin-boron transmetalation method has been a reliable route to many types of boracycles including dibenzoboroles (also known as 9-borafluorenes) and dibenzoborepins [8,[15][16][17][18][19]. Similarly to the synthesis of other heterocycles [20], the salt-elimination reaction between metalated carbons, e.g., organolithiums and Grignard reagents, and haloboranes (BX 3 and RBX 2 , where X = Cl, Br) is also widely employed [15].Additionally, intramolecular cyclization via CH borylation has been developed as a convenient approach, particularly for the synthesis of boron-containing PAHs (polycyclic aromatic hydrocarbons) in the last decade [21][22][23][24].However, the aforementioned methods rely on toxic organotin compounds and highly reactive haloboranes.Therefore, the development of alternative boracycle synthesis using less toxic chemicals is highly demanded from the viewpoint of sustainable chemistry.thesis of boracycles using ArBpin would enable facile access to various boracycles which could serve as acceptor units in donor-acceptor-type molecules.In this report, we present the synthesis of seven-and five-membered boracycles utilizing ArBpin as the boron source.This method enables the straightforward synthesis of donor-acceptor-and acceptor-π-acceptor-type molecules with borepin acceptors.The photophysical properties of the newly synthesized borepin derivatives are also documented.
One possible solution is using boronate esters [B(OR) 3 and R ′ B(OR) 2 ] as boron sources, and indeed, such boracycle formation has been reported.For example, the Yamaguchi's group has reported the synthesis of dibenzoboroles and dibenzoborepins using ArB(OMe) 2 as a boron source [10,25].Additionally, stepwise boracycle formations involving arylboronic acid esters have also been developed [7,[26][27][28].Given the widespread application of arylboronic acid pinacol esters (ArBpins) in cross-coupling chemistry owing to their stability and moderate reactivity [29], we envisage that ArBpins can be useful and stable boron sources for boracycle synthesis.However, to the best of our knowledge, ArBpins have never been used as boron sources for boracycles, although the usage of B 2 pin 2 for the synthesis of Mes 2 BBpin has been reported [30].An additional advantage of using ArBpin is that its synthetic methods have been well-established: Miyaura borylation [31,32], CH borylation [33,34], and nucleophilic borylation.Therefore, the synthesis of boracycles using ArBpin would enable facile access to various boracycles which could serve as acceptor units in donor-acceptor-type molecules.In this report, we present the synthesis of sevenand five-membered boracycles utilizing ArBpin as the boron source.This method enables the straightforward synthesis of donor-acceptor-and acceptor-π-acceptor-type molecules with borepin acceptors.The photophysical properties of the newly synthesized borepin derivatives are also documented.
Molecules 2024, 29, x FOR PEER REVIEW 3 of 14 chromatography, although it has a 9-anthryl group that is sterically less demanding compared to widely used protecting groups such as Mes (2,4,6-trimethylphenyl) and Tip (2,4,6-triisopropylphenyl).When AnthB(OMe)2 was employed as a boron source, the yield of 1-sp 3 decreased to 31% (entry 4), indicating that the bidentate character of the pinacol group stabilizes a reaction intermediate and/or suppresses undesired side reactions.Our attempts to synthesize 1-sp 2 by this method are unsuccessful because the preparation of Grignard reagent 2Mg-sp 2 from (Z)-2,2′-dibromostilbene and magnesium causes the concomitant formation of phenanthrene and the E-isomer (entry 5 and Table S1).This type of Z/E isomerization of stilbene by alkaline metals and an Fe I complex has been reported [35][36][37].a A mixture of 2Mg-sp 2 , its E-isomer and phenanthrene was used.
To explore the substrate scope of this ArBpin-based boracycle synthesis, other reagents were next subjected to the reaction (Scheme 2).When MesBpin [38] and TipBpin [39] were allowed to react with 2Mg-sp 3 in THF under reflux, the yields of the corresponding dihydrodibenzoborepins 3 and 4 were only 16 and 4%, respectively.However, using cyclopentyl methyl ether (CPME) as a solvent improved the yields (59% for 3 and 46% for 4).The higher boiling point of CPME (106 °C) compared to that of THF (66 °C) would be a key factor in the efficient reaction when bulky Ar groups are employed.The reaction using 9-Br-10-Bpin-anthracene [40] provided 10-bromoanthryl derivative 5-sp 3 (64% yield), the bromo substituent of which can be used for further functionalization.Moreover, the one-shot double boracycle formation was achieved when 9,10-(Bpin)2-anthracene was used as a substrate to generate a dihydrodibenzoborepin-anthracene-dihydrodibenzoborepin triad molecule 6-sp 3 in a 66% yield.On the contrary, our attempts to synthesize 6-sp 3 using tin-boron transmetalation were unsuccessful; the reactions of in situ generated 5-chloro-5H-dibenzo[b,f]borepin, which was prepared from 5,5-dimethyl-5Hdibenzo[b,f]stannepin and BCl3, and 9,10-dilithioanthracene provided a complex mixture, highlighting the usefulness of the Bpin-based method.a A mixture of 2Mg-sp 2 , its E-isomer and phenanthrene was used.

Entry
To explore the substrate scope of this ArBpin-based boracycle synthesis, other reagents were next subjected to the reaction (Scheme 2).When MesBpin [38] and TipBpin [39] were allowed to react with 2Mg-sp 3 in THF under reflux, the yields of the corresponding dihydrodibenzoborepins 3 and 4 were only 16 and 4%, respectively.However, using cyclopentyl methyl ether (CPME) as a solvent improved the yields (59% for 3 and 46% for 4).The higher boiling point of CPME (106 • C) compared to that of THF (66 • C) would be a key factor in the efficient reaction when bulky Ar groups are employed.The reaction using 9-Br-10-Bpin-anthracene [40] provided 10-bromoanthryl derivative 5-sp 3 (64% yield), the bromo substituent of which can be used for further functionalization.Moreover, the one-shot double boracycle formation was achieved when 9,10-(Bpin) 2 -anthracene was used as a substrate to generate a dihydrodibenzoborepin-anthracene-dihydrodibenzoborepin triad molecule 6-sp 3 in a 66% yield.On the contrary, our attempts to synthesize 6-sp 3 using tin-boron transmetalation were unsuccessful; the reactions of in situ generated 5-chloro-5Hdibenzo[b,f ]borepin, which was prepared from 5,5-dimethyl-5H-dibenzo[b,f ]stannepin and BCl 3 , and 9,10-dilithioanthracene provided a complex mixture, highlighting the usefulness of the Bpin-based method.
We next investigated the conversion of 1-sp 3 to the corresponding unsaturated one (1-sp 2 ) because the direct synthesis of 1-sp 2 from the reaction in Table 1 failed (Scheme 3).According to the literature, the bromination of a dihydroborepin with N-bromosuccinimide (NBS) and subsequent elimination reaction using a base would be a promising route [41].However, the bromination of 1-sp 3 using 1.1 equiv NBS and 0.25 equiv azobis(isobutyronitrile) (AIBN) did not yield the benzylic bromination product 1Br-sp 3 but 5-sp 3 in a 68% yield.Thus, the bromination of 5-sp 3 under the same conditions was next carried out, which provided a 3:2 mixture of 5-sp 3 and 5-sp 2 , and again, no 1Br-sp 3 was obtained.Increasing the amount of AIBN to 0.5 equiv allowed the isolation of 5-sp 2 with a 55% yield.Notably, one-pot synthesis of 5-sp 2 was also achieved by a treatment of 1-sp 3 with 2 equiv of NBS and 0.5 equiv of AIBN (73% yield).The bromo substituent in 5-sp 2 was replaced by a hydrogen atom via a lithiation/protonation process to afford 1-sp 2 in a 89% yield.We next investigated the conversion of 1-sp 3 to the corresponding unsaturated one (1-sp 2 ) because the direct synthesis of 1-sp 2 from the reaction in Table 1 failed (Scheme 3).According to the literature, the bromination of a dihydroborepin with N-bromosuccinimide (NBS) and subsequent elimination reaction using a base would be a promising route [41].However, the bromination of 1-sp 3 using 1.1 equiv NBS and 0.25 equiv azobis(isobutyronitrile) (AIBN) did not yield the benzylic bromination product 1Br-sp 3 but 5-sp 3 in a 68% yield.Thus, the bromination of 5-sp 3 under the same conditions was next carried out, which provided a 3:2 mixture of 5-sp 3 and 5-sp 2 , and again, no 1Br-sp 3 was obtained.Increasing the amount of AIBN to 0.5 equiv allowed the isolation of 5-sp 2 with a 55% yield.Notably, one-pot synthesis of 5-sp 2 was also achieved by a treatment of 1-sp 3 with 2 equiv of NBS and 0.5 equiv of AIBN (73% yield).The bromo substituent in 5-sp 2 was replaced by a hydrogen atom via a lithiation/protonation process to afford 1-sp 2 in a 89% yield.We next investigated the conversion of 1-sp 3 to the corresponding unsaturated one (1-sp 2 ) because the direct synthesis of 1-sp 2 from the reaction in Table 1 failed (Scheme 3).According to the literature, the bromination of a dihydroborepin with N-bromosuccinimide (NBS) and subsequent elimination reaction using a base would be a promising route [41].However, the bromination of 1-sp 3 using 1.1 equiv NBS and 0.25 equiv azobis(isobutyronitrile) (AIBN) did not yield the benzylic bromination product 1Br-sp 3 but 5-sp 3 in a 68% yield.Thus, the bromination of 5-sp 3 under the same conditions was next carried out, which provided a 3:2 mixture of 5-sp 3 and 5-sp 2 , and again, no 1Br-sp 3 was obtained.Increasing the amount of AIBN to 0.5 equiv allowed the isolation of 5-sp 2 with a 55% yield.Notably, one-pot synthesis of 5-sp 2 was also achieved by a treatment of 1-sp 3 with 2 equiv of NBS and 0.5 equiv of AIBN (73% yield).The bromo substituent in 5-sp 2 was replaced by a hydrogen atom via a lithiation/protonation process to afford 1-sp 2 in a 89% yield.This ArBpin-based method is also applied for the synthesis of a dibenzoborole.We selected a Tip borole 7 as the target molecule because this molecule can be purified by column chromatography owing to the bulky Tip group [25].Grignard reagent 8Mg [42] generated from 2,2 ′ -dibromobiphenyl reacted with TipBpin in THF under reflux to afford 7 in a 19% yield (Scheme 4).Although this yield is inferior to the reported method using 8Mg and TipB(OMe) 2 (45%) [25], it is worth noting that TipBpin can also be used as a stable boron source for dibenzoborole synthesis.In this case, the reaction in CPME instead of THF under reflux did not give 7 at all, probably due to the lower thermal stability of antiaromatic 7.
generated from 2,2′-dibromobiphenyl reacted with TipBpin in THF under reflux to afford 7 in a 19% yield (Scheme 4).Although this yield is inferior to the reported method using 8Mg and TipB(OMe)2 (45%) [25], it is worth noting that TipBpin can also be used as a stable boron source for dibenzoborole synthesis.In this case, the reaction in CPME instead of THF under reflux did not give 7 at all, probably due to the lower thermal stability of antiaromatic 7.

Single-Crystal X-ray Diffraction Analysis
Figure 1 illustrates the crystal structures of 3, 5-sp 3 and 6-sp 3 and that of 4 is shown in Figure S2.Each asymmetric unit of 3, 4 and 6-sp 3 contains two independent molecules which are structurally similar.The dihydrodibenzoborepin skeleton of 5-sp 3 is partially disordered over two positions with a ratio of 58:42.In the packing structure of 5-sp 3 , the intermolecular Br…Br distance is 3.321 Å, much shorter than the sum of the van der Waals radii (3.70 Å), as shown in Figure S3, suggesting the existence of the halogen bond categorized as type I [43,44].The packing structure of 6-sp 3 shows that the CH-π and halogenπ interactions between the co-crystallized chlorobenzene molecule and the anthryl units of the two independent molecules are important (Figure S3) [45].  3 (center) and 6-sp 3 (right) with thermal ellipsoid plots of a 50% probability.All hydrogen atoms and a co-crystalized chlorobenzene molecule in 6sp 3 are omitted for clarity.Only one of the two independent molecules are shown for 3 and 6-sp 3 .Only the major disordered structure of 5-sp 3 is shown.

Single-Crystal X-ray Diffraction Analysis
Figure 1 illustrates the crystal structures of 3, 5-sp 3 and 6-sp 3 and that of 4 is shown in Figure S2.Each asymmetric unit of 3, 4 and 6-sp 3 contains two independent molecules which are structurally similar.The dihydrodibenzoborepin skeleton of 5-sp 3 is partially disordered over two positions with a ratio of 58:42.In the packing structure of 5-sp 3 , the intermolecular Br. ..Br distance is 3.321 Å, much shorter than the sum of the van der Waals radii (3.70 Å), as shown in Figure S3, suggesting the existence of the halogen bond categorized as type I [43,44].The packing structure of 6-sp 3 shows that the CH-π and halogen-π interactions between the co-crystallized chlorobenzene molecule and the anthryl units of the two independent molecules are important (Figure S3) [45].
7 in a 19% yield (Scheme 4).Although this yield is inferior to the reported method 8Mg and TipB(OMe)2 (45%) [25], it is worth noting that TipBpin can also be use stable boron source for dibenzoborole synthesis.In this case, the reaction in CPME in of THF under reflux did not give 7 at all, probably due to the lower thermal stabi antiaromatic 7.

Single-Crystal X-ray Diffraction Analysis
Figure 1 illustrates the crystal structures of 3, 5-sp 3 and 6-sp 3 and that of 4 is s in Figure S2.Each asymmetric unit of 3, 4 and 6-sp 3 contains two independent mol which are structurally similar.The dihydrodibenzoborepin skeleton of 5-sp 3 is pa disordered over two positions with a ratio of 58:42.In the packing structure of 5-s intermolecular Br…Br distance is 3.321 Å, much shorter than the sum of the van der radii (3.70 Å), as shown in Figure S3, suggesting the existence of the halogen bond gorized as type I [43,44].The packing structure of 6-sp 3 shows that the CH-π and ha π interactions between the co-crystallized chlorobenzene molecule and the anthry of the two independent molecules are important (Figure S3) [45].Table 2 shows the selected bond lengths and angles for these dihydro zoborepins.Each boron atom has a planar three-coordinated structure with the sum C-B-C angles about 360°.These compounds have highly twisted structures with th B1-C15-C16 torsion angles (80.2(2)-89.80(14)°)being larger than those in related 9-d borylanthracenes and 9,10-bis(diarylboryl)anthracenes (ca.45-63°), where Ar = Me  3 (center) and 6-sp 3 (right) with thermal ellipsoid plots of a 50% probability.All hydrogen atoms and a co-crystalized chlorobenzene molecule in 6-sp 3 are omitted for clarity.Only one of the two independent molecules are shown for 3 and 6-sp 3 .Only the major disordered structure of 5-sp 3 is shown.

Photophysical Properties and Theoretical Calculations
Although the photophysical properties of aromatic dibenzoborepins are wellinvestigated [8,49], little is known about those of dihydrodibenzoborepins.Therefore, we explored the absorption and emission properties of 1-sp 3 and 6-sp 3 as well as 1-sp 2 .Figure 2 shows the absorption and emission spectra of 1-sp 3 and 1-sp 2 recorded in different solvents (hexane, toluene, THF, CHCl 3 and CH 2 Cl 2 ).Spectra for 6-sp 3 were recorded only in CH 2 Cl 2 due to the poor solubility in non-halogenated solvents (Figure S4).These photophysical data are summarized in Table 3.

Photophysical Properties and Theoretical Calculations
Although the photophysical properties of aromatic dibenzoborepins are well-investigated [8,49], little is known about those of dihydrodibenzoborepins.Therefore, we explored the absorption and emission properties of 1-sp 3 and 6-sp 3 as well as 1-sp 2 .Figure 2 shows the absorption and emission spectra of 1-sp 3 and 1-sp 2 recorded in different solvents (hexane, toluene, THF, CHCl3 and CH2Cl2).Spectra for 6-sp 3 were recorded only in CH2Cl2 due to the poor solubility in non-halogenated solvents (Figure S4).These photophysical data are summarized in Table 3.No significant solvent dependency was observed in the absorption spectra of 1-sp 3 and 1-sp 2 .Dihydrodibenzoborepin derivatives 1-sp 3 and 6-sp 3 show a broad and weak absorption ranging from ca. 450 to 400 nm, resulting from charge transfer (CT) from the anthracene unit to the dihydrodibenzoborepin acceptor, whereas the CT absorption is weak in 1-sp 2 probably due to the aromatic character of borepin, which reduces the Lewis acidity of the boron atom [50].Three absorption peaks of around 350-400 nm originating from the anthracene unit are slightly redshifted compared to those of anthracene by ca. 10 nm [51], the reason for which would be the inductive effect of the electropositive boron atoms (vide infra).As mentioned above, the dihydrodibenzoborepin units are almost perpendicular to the central anthracene core, which causes a less effective conjugation between them.Therefore, it is important to compare the photophysical properties of 1-sp 3 , 1-sp 2 , 6-sp 3  and related borylanthracenes.The absorption maxima of 9-[B(Mes) 2 ]anthracene and 9,10bis[B(Mes) 2 ]anthracene, whose anthracene unit tilts ca.53 • with respect to the boroncentered plane, are 420 and 455 nm [52,53], redshifted compared to those of 1-sp 3 and 6-sp 3  (390 and 398 nm).This difference is rationalized by the different degree of π(anthracene)p*(boron) conjugation.
In contrast to the absorption spectra, the emission spectra of 1-sp 3 and 1-sp 2 are highly dependent on the solvents, as commonly found in donor-acceptor-type molecules [54][55][56].Stokes shifts of 1-sp 3 varied from ca. 3500 to 6300 cm −1 , being larger than those of 1sp 2 , as the solvent polarity increases.These larger Stokes shifts in 1-sp 3 suggests that the dihydrodibenzoborepin skeleton is more flexible than the dibenzoborepin, allowing a greater structural relaxation in the excited state.Compound 1-sp 3 shows two types of emission peaks: (1) an anthracene-based emission with three peak tops around 360 to 430 nm and (2) a broadened CT emission peak ranging from 450 to 530 nm.Interestingly, the strength of these two emissions depends on the solvent; the anthracene-based emission is dominant in THF, whereas the CT emission is a major contributor in the other solvents.The lower contribution of the CT emission in THF can be rationalized by the coordination of THF to the vacant p orbital of the boron atoms.Although a similar trend is found in the spectra of 1-sp 2 , the anthracene-based emission peaks are broadened, the reason for which is not clear at this point.

General Considerations
All manipulations were performed under an argon atmosphere by using standard Schlenk techniques.Et2O, THF, hexane, benzene, toluene and CPME were dehydrated by 4A molecular sieves.All reagents were purchased from Sigma-Aldrich Japan (Tokyo, Japan), FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan), Tokyo Chemical Industry Co., LTD.(Tokyo, Japan), Kanto Chemical Co., Inc. (Tokyo, Japan) or Nacalai Tesque (Kyoto, Japan) and used as received unless otherwise stated.Column chromatography was carried out using Wakogel silica 60N (particle size: 40-100 µm).(Z)-2,2′-Dibromostilbene [8], 2,2′-dibromodibenzyl [60] q), septet (sept), multiplet (m) and broad (br).Labels for NMR assignments are shown in Figure S1.The HRMS data were obtained by a Bruker ultrafleXtreme using 9-nitroanthracene as a matrix.Diffraction data were collected on a Bruker APEX II (for 3 and 6-sp 3 ) or Bruker D8 QUEST (for 4 and 5-sp 3 ) with Mo Kα radiation (λ = 0.71075 Å) at -110 to −80 • C. The structures were solved by direct methods using SHELXS.The refinements were performed using SHELXL-2019/3 [65].The positions of the non-hydrogen atoms were determined by SHELXT 2018/2 [66].All non-hydrogen atoms were refined on F o 2 anisotropically by full-matrix least-square techniques.All hydrogen atoms were placed at the calculated positions with fixed isotropic parameters.UV-vis absorption and emission spectra were recorded using JASCO V-650 and JASCO FP-6600 spectrometers.Theoretical calculations were performed using the Gaussian 16 program [67].The optimized structures of 1-sp 3 and 6-sp 3 are in good agreement with the corresponding X-ray structures.All local minima were confirmed by vibrational frequency calculations showing zero imaginary frequencies.

Figure 1 .
Figure 1.The crystal structures of 3 (left), 5-sp3 (center) and 6-sp3 (right) with thermal ellipsoid plots of a 50% probability.All hydrogen atoms and a co-crystalized chlorobenzene molecule in 6sp3 are omitted for clarity.Only one of the two independent molecules are shown for 3 and 6-sp3 .Only the major disordered structure of 5-sp3 is shown.

Figure 1 .
Figure 1.The crystal structures of 3 (left), 5-sp3 (center) and 6-sp3 (right) with thermal el plots of a 50% probability.All hydrogen atoms and a co-crystalized chlorobenzene molecu sp3 are omitted for clarity.Only one of the two independent molecules are shown for 3 and Only the major disordered structure of 5-sp3 is shown.

Figure 1 .
Figure 1.The crystal structures of 3 (left), 5-sp3 (center) and 6-sp3 (right) with thermal ellipsoid plots of a 50% probability.All hydrogen atoms and a co-crystalized chlorobenzene molecule in 6-sp3 are omitted for clarity.Only one of the two independent molecules are shown for 3 and 6-sp3 .Only the major disordered structure of 5-sp3 is shown.

Table 3 .
Absorption and emission properties of 1