Organic Letters
Letter
Investigation of Mechanism. Previous literature reports
assisted us in the optimization of the cocatalyst system12 and
allowed us to derive a balanced chemical equation. To verify
this balanced equation (Figure 2a), we first validated the
necessity of water in the reaction. As suspected the reaction
stalls in dried solvents. Inversely, the reaction was seemingly
insensitive to excess water, coupling well in 1:1 H2O/DMSO.
The generation of H2O2 was tested with a commercially
available peroxide test kit (Figure S1) which revealed H2O2
being produced as the reaction proceeded. An obvious source
of H2O2 is as the product of Cu(I) oxidation by molecular
oxygen (Figure 1b upper left). Another source of H2O2 could
be the transmetalation from an arylboronate to the Pd(O2)
complex,13 followed by hydrolysis (Figure 1b in the cycle).
Broadening the Substrate Scope. After screening several
solvents (Table S2), DMSO was chosen due to its solvating
and coordinating properties, and the anticipation it would help
to solubilize our ultimate polymer products (see below).
Similar to previously reported results,14 electron-withdrawing
substituents reacted with yields of 50%−quant. (Scheme 1).
However, in stark contrast to previous homocoupling
strategies, electron-donating groups were even more successful
with yields of 85%−quant. (9−11).14 In addition, most of the
ortho-substituted structures coupled with good to moderate
yields of 65%−quant. (12−16). Unfortunately, the dimeriza-
tion did not work with the diortho substituted substrate (17);
however, the dimeta substituted substrate coupled in
quantitative yield (18).
Figure 1. Proposed mechanism of bimetallic reaction where copper is
oxidized by oxygen which in turn oxidizes Pd(0) to Pd(II) (adapted
from previous literature).13 The aryl group is transmetalated to
palladium. Subsequently, the Pd(II) forms the biaryl dimer through
reductive elimination. Palladium(0) is oxidized by copper(I) to restart
the catalytic cycle. The Cu ligands (L) would be combinations of
acetic acid, water, and DMSO.
Next, we examined the tolerance of the method to more
challenging functional groups. Both 3- and 4-hydroxyphenyl-
boronic acids coupled with greater than 90% yield (24−25).
The anilines behaved differently. While 3-amino phenyl
boronic acid coupled well (23), 4-amino phenyl boronic acid
was almost completely proteodeborylated, presumably due to
the more nucleophilic nature of the aromatic ring (22). The
nucleophilic 2-thiophenyl boronic acid also homocoupled with
acceptable yields considering its challenging nature (19).
However, the carboxylic acid failed to react (21). The presence
of the carboxylic acid appears to stop the reaction. To access
carboxylic acids, the aldehydes 7 and 15 could be subsequently
oxidized post-reaction. Interestingly, aldehyde oxidation to
carboxylic acid did not occur in any detectable amounts (7,15)
under the oxidative reaction conditions. Next, we investigated
the reaction in the presence of metal coordinating π-
nucleophiles, such as terminal olefins. Gratifyingly, only
aryl−aryl coupling was observed (20). Finally, being inspired
by a previous study12 we explored the cross-coupling of
boronic acids in our bimetallic system. However, initial
attempts resulted in statistical mixtures of the homo- and
heterodimers, and this idea was not further pursued.
Benchtop Synthesis of Polymers. Being satisfied by the
broad functional scope and coupling efficiency of this method,
we turned our attention to the original goalbenchtop
synthesis of conjugated polymers. Our first attempt involved
coupling the simple commercially available 1,4-phenyldibor-
onic acid. Self-reinforced poly paraphenylenes (SRPs) have
been commercially useful in hard thermoplastics because of
their rigid rod structure and high thermal stability.3 With our
approach, the resulting reaction affords 5−8-mers of
polyparaphenylene. We were able to observe their mass
distribution by MALDI-TOF MS, and their physical
appearance and fluorescence matched well with literature
reports.3
Figure 2. Palladium and copper react with phenyl boronic acid (0.5
M) for 14 h at different catalyst concentrations. (a) Reaction scheme.
(b) Ratio of starting material to product as seen by GC-MS in varying
concentration of Pd(OAc)2 (x-axis). The reaction conversion without
copper (blue) and with 5 mol % Cu(OAc)2 (red) in acetone.
percent conversion (Figure 2b, Red). The reaction with 2%
Pd(II) and 5% Cu(II) proceeds to completion within 1 h,
while the reaction with only 2 mol % Pd(II) requires over 24 h.
Complete reactions were observed with Pd(II) amounts as low
as 1 mol % in the presence of Cu(II) (Figure 2b). These
results supported our design hypothesis that the Cu(II)
facilitated the redox cycle of Pd(0) to Pd(II) enhancing the
turnover rate. In fact, we found that the dimerization reactions
do not even occur under an inert atmosphere and
deoxygenated solvents. Hence, similar to the Wacker
oxidation,13 Pd(0) is generated then reoxidized by Cu(II) to
Pd(II), which performs the homocoupling. Cu(II) is quickly
regenerated by atmospheric oxygen, resuming the catalytic
cycle (Figure 1).
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Org. Lett. 2021, 23, 2873−2877