R.M. Appa et al.
Molecular Catalysis 501 (2021) 111366
temperature. The progress of the reaction was monitored by thin layer
chromatography (TLC) and after the completion the reaction, the reac-
tion mixture was added 10 mL of distilled water and 5 mL of EtOAc. The
EtOAc portion was then separated and the aqueous part was further
extracted with EtOAc (2 × 8 mL) and the combined EtOAc portions were
dried over anhydrous Na2SO4. The organic portion was then evaporated
under reduced pressure to obtain pure biaryl, 2. In some instances the
products were purified by using column chromatography. Similar
experimental procedure was used for the cross-coupling of arylboronic
acids.
their position provided high yields of symmetrical biaryls (85–95 %) in
15–30 min (Table 3, products 2ap–2aw).
The disubstituted 2-methoxy-5-fluorophenylboronic acid (1az) with
a combination of ER and ED groups provided biaryl, 2az with 88 % yield
in 30 min (Table 3, product 2az). For an instance, the yields are reported
as low (35 %) in 16 h using 1az as the substrate and CuII-β-cyclodextrene
[Cu(BDC)] as catalyst [54]. Disubstituted ABAs, 3,4-dichlorophenylbor-
onic acid (1ba) and 3-cyano-5-fluorophenylboronic acid (1bb) with
both the ED functionalities were also converted into biaryls in 10 min to
give excellent yields of 2ba and 2bb (Table 3, products 2ba & 2bb). It is
noteworthy to specify that the base sensitive functional groups such as
ester (1 ag, 1ak & 1 al) and cyano (1ai & 1bb) were unaffected in this
process.
The symmetrical and unsymmetrical biaryls were characterized by
the analysis of their spectral (NMR and MS) data. The 1H and 13C NMR
data of all the compounds was aggregated the reported data.
Heteroarylboronic acids were also identified as good substrates
under current conditions. 3- & 2-pyridineboronic acids (1bc & 1bd), 2-
methoxy-5-pyridineboronic acid (2be) and 2-bromo-5-pyridineboronic
acid (2bf) were easily transferred into bipyridines, 2bc–2bf in 30–40
min with good yields (81–89 %) (Table 3, products 2bc–2bf). 2-Thio-
pheneboronic acid (1bg) and 5-formyl-2-thiopheneboronic acid (2bh)
were formed 2,2’-bithiophenes, 2bg and 2bh in 30 min with 92 % and
89 % yields (Table 3, products 2bg & 2bh). Interestingly, 5-acetyl-2-thi-
opheneboronic acid (1bi) forms protodeborylated product; 2-acetylthio-
phene (3) under WEPA-mediated conditions.
3. Result and discussion
Initially, we inspected the homocoupling of 4-formylphenylboronic
acid (1aa) in WEPA (Table 2). It conveyed the formation of symmetri-
cal biaryl, 2aa in 32 % (in 3 h) at rt using 0.5 mol% of Pd(OAc)2 and 1
mL of WEPA (Table 2, entry 1). The yield was improved to 43 %, 63 %
and 62 % by increasing WEPA to 2 mL, 3 mL and 4 mL (Table 2, entries
2–4), indicating, 3 mL of WEPA is crucial. By the increase of Pd(OAc)2 to
1.0 mol%, 2aa was formed in 95 % yield (Table 2, entry 5) and further
increase of catalyst to 1.5 mol% has no effect on the yield (Table 2, entry
6). We then screened other palladium complexes; PdCl2, Pd(PPh3)4,
PdCl2(CH3CN)2, Pd(PPh3)2Cl2, Pd2(dba)3 (Table 2, entries 7–11) and
observed that the Pd2(dba)3 is also suitable for the present conversion,
but, Pd(OAc)2 is the best amongst. Indication of no reaction in the
absence of catalyst or WEPA (Table 2, entries 12 and 13) insinuates the
necessity of Pd(OAc)2 and WEPA for the present transformation.
With these tuned conditions we explored the present exercise to an
array of ABAs with diverse functional groups (Table 3). Monosubstituted
ABAs with electron deficient (ED) groups such as acetyl, chloro, fluoro,
nitro, ester, cyano, formyl and trifluoromethyl been converted effec-
tively into corresponding biaryls (Table 3, products 2ac–2ao). The ABAs
with the substituents at para, meta and ortho were observed to give high
yields indicating negligible effect of position of functional groups on
present conversion. Nevertheless, ortho substituted ABAs seems to offer
low yields of biaryls in several reported procedures [37,44–47,54,58].
Phenylboronic acid (1ab), biphenyl-4-boronic acid (1ax) and
phenanthracene-9-boronic acid (1ay) were noted as good substrates for
this transformation (Table 3, products 2ab, 2ax & 2ay), but, only 27 %
of 2ay was reported from 1ay using Pd[(Phbz)(OAc)(PPh3)] in 24 h
[37]. ABAs containing electron rich (ER) functional groups such as
bromo, methyl, methoxy, tert-butyl, phenolic and methylthio despite
Intriguingly, no trace of Suzuki cross-coupling product was observed
with the ABAs bearing chlorine (1ad, 1 ah, 1an & 1ba) and bromine
(1ap & 1bf) evidences high chemoselectivity for boronic acids over
halogens under current development. However, the cross-coupled
product was reported as major with 1ap using Pd(OAc)2⋅2PPh3–K2CO3
[43] and Pd(PPh3)2Cl2–Bu4NF⋅H2O [21] systems.
Further, screened the arylboron compounds for homocoupling using
potassium phenyltrifluoroborate (4), diethanolamine phenylboronate
(5), N-methyldiehtanolamine phenylboronate (6), pinacol phenyl-
boronate (7) and neopentyl glycolato phenylboronate (8) (Table 4). All
the arylboronates showed excellent yields of biaryl, 2ab (85–95 %) in
0.25–5 h (Table 4, entries 1–5). Phenyltrifluoroborate, 4 was the best
amongst (Table 4, entry 1) and provided similar results as phenylboronic
acid (1ab). Diehtanolamine phenylboronate (5) and its N-methyl
analogue (6) were also gave very good yields of 2ab (Table 4, entries 2 &
3), while pinacol and neopentyl glycolato phenylboronates (7 and 8)
were found to form 2ab with slow rate. This trend may be due to free
solubility of 1ab, 4, 5 and 6 in WEPA (aqueous media) than 7 and 8.
The mechanism of homocoupling of ABAs is believed to resemble the
˜
suggested one by Moreno-Manas et al. [83]. and Domingos et al. [84], as
outlined in the Scheme 1. The reduction (A) of PdII of Pd(OAc)2 to Pd0
species (I) might happens in the first mechanistic step [15]. The for-
mation of Pd0 has been confirmed by the X-ray photoelectron spec-
troscopy (XPS) analysis (Fig. 1a) of solid formed during the
homocoupling reaction of 1aa. The Pd0 species involves in trans-
metallation (B) with the intermediate, V formed between ABA and base
of WEPA, results PdII intermediate, II via an intermediatory perox-
opalladium species [83,84]. Intermediate II participates in further
transmetallation (C) with V to produce diarylpalladium intermediate, III
and it involves in reductive elimination (IV) in WEPA to generate biaryls
(2) and Pd0 active principle (I). Towards further understanding about
the nature of base that is present in WEPA, an X-ray fluorescence (XRF)
study of pale yellow powder obtained after the evaporation of water of
WEPA (Fig. 1b) showed the presence of large quantity of K2O and Cl
along with the minor quantities of Na2O, MgO, Al2O3, SiO2, CaO and
SO3, and trace amounts of other metallic and non-metallic substances.
The K2O present in dried WEPA may exist in water as KOH due to the
high reactivity of K2O towards water and is assumed to be responsible
for the high basic property of WEPA (pH was observed between 11.7 and
12.1 [15]). The presence of K, Mg, O, Ca and Cl was also ascertained
from our previous XPS and EDS analysis [15] and the presence of similar
quantities of the elements in WEPA using different methods indicates the
results obtained are assumed to be accurate.
Table 2
Optimization Studiesa.
Entry
Catalyst (mol%)
Media (mL)
Time (h)
Isolated yield (%)
1
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (1.0)
Pd(OAc)2 (1.5)
PdCl2 (1.0)
WEPA (1)
WEPA (2)
WEPA (3)
WEPA (4)
WEPA (3)
WEPA (3)
WEPA (3)
WEPA (3)
WEPA (3)
WEPA (3)
WEPA (3)
Water (3)
WEPA (3)
3.0
32
43
63
62
95
94
52
28
58
63
91
–
2
3.0
3
3.0
4
3.0
5
0.25
0.25
2.0
6
7
8
PdCl2(CH3CN)2 (1.0)
Pd(PPh3)4 (1.0)
Pd(PPh3)2Cl2 (1.0)
Pd2(dba)3 (1.0)
Pd(OAc)2 (1.0)
–
5.0
9
1.0
10
11
12
13
0.5
0.5
10.0
10.0
–
a
Reaction conditions: 1aa (1 mmol) at rt in open-air.
3