Asymmetric catalytic synthesis of boron chiral BODIPYs

Recently, He Chuan’s research group in the Department of Chemistry of Southern University of Science and Technology realized the first asymmetric catalytic synthesis of boron chiral BODIPYs through theoretical guidance and experimental confirmation of the model. On March 17, 2023, Beijing time, this result was published in Nature Synthesis under the title “Catalytic enantioselective synthesis of boron-stereogenic BODIPYs”. The first authors of the article are Dr. Zu Bing and Dr. Guo Yonghong of Southern University of Science and Technology, and the calculation part was completed by Dr. Li Yingzi.

Boron dipyrrole (BODIPYs) are bis-pyrrole-chelated N,N π-conjugated tetracoordinated organoboronic compounds, which have the advantages of high fluorescence quantum yield, high sensitivity, high molar extinction coefficient, high photostability and insensitivity to acids and bases, and are widely used in fluorescent probes, biological imaging, optoelectronic materials and photocatalysts. In view of the importance of chiral chemistry in the field of biomedicine and functional materials, chemists have also tried to introduce chiral elements, such as carbon center chirality, axial chirality and helical chirality, into the backbone of BODIPYs, and these new chiral BODIPYs fluorescent molecules have shown good application prospects in the fields of chiral functional materials and chiral catalysts. It is worth mentioning that the structure of BODIPYs tetracoordination, if the four substituents are different, can also form the corresponding boron center chirality. However, to date, only two cases of boron chiral BODIPYs have been reported, both obtained by chiral dissection (Figure 1a). In view of the importance of chiral organoboronic compounds and the excellent photoelectric properties of BODIPYs, it is of great significance to develop an efficient method to synthesize boronchiral BODIPYs.

Figure 1: Synthesis of boron chiral BODIPYs

He Chuan’s research group of Southern University of Science and Technology has been carrying out systematic research on the synthesis and application of heteroatoms (silicon, boron, sulfur, etc.) chiral compounds. In 2021, the catalytic asymmetric synthesis of boron-centered chiral compounds was realized for the first time with high efficiency and high enantioselectivity by using the intermolecular asymmetric CuAAC reaction (J. Am. Chem. Soc. 2021, 143, 16302)。 Based on these works, the authors envisage the construction of boron chiral BODIPYs by attempting to desymmetry the a-carbon-hydrogen bonds of the double pyrrole rings by using the equivalent properties of the two pyrrole rings in the delocalized structure of BODIPYs (Figure 2b). The authors specifically used prechiral ARYL bromide-substituted BODIPYs as substrates to synthesize a series of novel boron-centered chiral N2O-BODIPYs with high enantioselectivity through intramolecular hydrocarbon aromatation (Figure 2c).

Figure 2: DFT-guided ligand screening

In order to accurately identify boron stereocenters and construct boron chiral BODIPYs, the authors used chiral pocket ligands with steric hindrance effect and synergistic regulation of interaction forces to achieve enantioselective intramolecular C−H arylation under transition metal catalytic conditions. In order to efficiently screen ligands, the authors predicted common chiral phosphine ligands by means of theoretical calculations such as topographic steric maps and percentage of buried volume (%V_Bur) (Figure 2). Topological stereogram comparison shows Pd/L1-L3There is no strong steric hindrance region in these three palladium-phosphine complexes that does not provide an effective spatial effect. After comparison, the authors further determined the TADDOL class (L5The ligand effectively controls enantioselectivity and has been experimentally verified. Subsequently, the mechanism and selectivity of the reaction were studied in depth by DFT calculation, showing that oxidative addition is a key step in inducing chiral production. At the same time, by comparing the energies of the key transition states of the four quadrants, it is shown that its enantioselectivity is controlled by steric hindrance effect and the interaction between ligand and substrate.

Next, under optimal reaction conditions, the authors examined the substrate range of the reaction system. The results show that the reaction has good compatibility with functional groups such as halogen atoms, methoxy groups, amine groups, and trifluoromethyl groups. In addition, substrates containing heterocycles such as thiophene and carbazole are also suitable for this reaction. It is worth mentioning that in addition to the boronchial N2O-BODIPYs of the six-membered ring, the asymmetric catalytic reaction can also obtain the target products of the seventh, eighth and nine-membered rings with good enantioselectivity (Figure 3).

Figure 3: Substrate application

Subsequently, the authors studied the optical properties of boron chiral BODIPYs obtained. Among them, the maximum emission of the six-membered ring product was 614 nm, which was significantly redshifted compared with the raw material. With the gradual increase of the product ring, the maximum absorption and maximum emission have undergone a significant blue shift (Figure 4a). After simple modification of the six-membered ring, the maximum emission can reach 666 nm, showing the potential application of the product in fluorescence imaging and photodynamic therapy (Figure 4b). Finally, the authors found that the synthesized bromoboron chiral BODIPY can be used as a chiral fluorescent probe to achieve enantioselective identification of chiral 1,2-cyclohexanediamine (Figure 4c).

Figure 4: Optical properties studies and applications

He Chuan’s research group in the Department of Chemistry of Southern University of Science and Technology achieved the first asymmetric catalytic synthesis of boron chiral BODIPYs through theoretical guidance and experimental confirmation of the model. These new boron chiral BODIPYs exhibit good optical properties and show good application prospects in the field of chiral recognition. This method provides a new way for the synthesis of boron chiral BODIPYs, and also opens up a new development direction for the study of chiral boron chemistry. (Source: Science Network)

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