Background and Originality Content
Green chemistry is a pressing concern for chemists, as the increasing pollution and waste generated during chemical processes have become a major environmental issue. The demand for environmentally-friendly processes in organic synthesis has spurred interest in developing efficient and sustainable reactions for the synthesis of valuable organic compounds. Since the discovery of boron dipyrromethenates (BODIPYs) in 1968,[1] organic difluoroboron complexes have occupied an increasingly important position in organic chemistry and material science owing to their superior photophysical properties, such as high fluorescent quantum yield, tunable structure and emission, as well as robust photo- and chemical stability.[2-5] Especially in the last decade, a large number of difluoroboron complexes have been explored and applied in fluorescent sensing, laser dyes, organic light-emitting devices, bioconjugates components, bio-imaging,[6-10] and even singlet-oxygen generators for photodynamic therapy.[11, 12] According to the difference of the ligands, organic difluoroboron complexes can be categorized into three types: N,N-bidentate type, O,O-bidentate type, and N,O-bidentate type. BODIPYs,[3, 13, 14] including azo-BODIPYs,[15] and 1,3-dioxa-2-borine have been well studied with plenty of publications,[16]which could be regarded as the typical representatives of the prior two types of organic difluoroboron complexes compounds. Whereas, the research on N,O-bidentate organic difluoroboron complexes is relatively lagging behind.[17, 18] The scope and function of N,O-bidentate organic difluoroboron complexes are still rarely involved but promising region worthy further exploration.
Compared to the significant progresses in the expansion of the structure and application for organic difluoroboron complexes, the innovation in the synthetic strategy for these compounds is few and far between. Generally, the process to prepare an organic difluoroboron complex can be divided into two stages: 1) synthesis of corresponding organic bidentate ligand; 2) complexation with boron sources, in most cases is boron trifluoride diethyl etherate (Scheme 1a).[19-26] Despite of the drawbacks of tedious synthetic steps and low efficiency,[23-26] the structural diversity of the organic difluoroboron complexes is also limited by the deficiency in effective synthetic methods with broad functional groups tolerance. Recently, as the prosperity of transition-metal-catalyzed C-H bond activation reactions, Glorius group developed two pioneering samples to construct the organic ligands and difluoroboron complexes in one shot via copper-mediated C-H bond activation strategy (Scheme 1b).[27, 28] These protocols not only provided efficient and rapid assemble solution for organic difluoroboron complexes, but also enriched the inventory of N,O-bidentate products. Apart from the copper tetrafluoroborate (Cu(BF4)2·6H2O) employed as catalyst and boron source, stoichiometric silver salts were also necessary as oxidant, which impaired the green chemical scores of these protocols in some extent. With the attention to expand the scope and function of N, O-bidentate organic difluoroboron complexes further, and also from the perspective of green chemistry and sustainable development, novel efficient synthetic method is always of continuing interest.[29-31] In this paper, we have established a straightforward synthesis of N,O-bidentate organic difluoroboron chromophores from quinoxalin-2(1H)-ones and readily available ketones (Scheme 1c). The reaction showcases excellent step and atom economy, broad functional group tolerance and operational convenience. A vast array of N, O-bidentate organic difluoroboron complexes are synthesized via our protocol. Furthermore, the photophysical properties and application of these compounds in bio-imaging are also explored in several dimensions.
Scheme 1 Progress in the synthesis of organic difluoroboron complexes.
Results and Discussion
At first, the reaction was conducted between 1-methylquinoxalin-2(1H)-one (1a ) and acetophenone (2a ) as shown in Table 1. The desired product 3aacould be obtain with 0.5 equiv of Cu(BF4)2·6H2O as catalyst and BF2 source (Table 1, Entry 1). The yield could be increased to 65% with 2.0 equiv of Cu(BF4)2·6H2O (Table 1, Entry 2-3). When we increased the amount of Cu(BF4)2·6H2O to 2.5 equiv, no better outcomes was obtained (Table 1, Entry 4). Next, we turn to examine the combination of Cu(BF4)2·6H2O and other BF2 sources, and 82% product was generated with 0.5 equiv of Cu(BF4)2·6H2O and 2 equiv of HBF4 (Table 1, Entry 5-7). A series of solvents were also tested and the results indicated that DCE is the proper choice (Table 1, Entry 8-15). When we conducted the reaction at lower temperature, the yield was reduced to 59% (Table 1, Entry 16). To our delight, even 58% of product could be generated without the use of Cu(BF4)2·6H2O. The amount of HBF4 and the reaction temperature were screened in the absence of Cu salt, and the highest yield was obtained with 2 equiv. of HBF4 at 80 oC (Table 1, Entry 19-23).
Table 1 Optimization of the reaction conditionsa