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