Communication
of isolated product (Table 4, entries 1–6). Aryl chlorides with
substituents at the para- and meta-positions were successfully
converted into the corresponding boronate esters in 88–99%
yields (Table 4, entries 1,2 and 4,5). Although ortho-substituted
aryl halides are known to be particularly challenging sub-
strates, the yields for compounds 4e and 4g (Table 4, entries 3
and 6) are quite acceptable, 88 and 62%, respectively. The
Pd(OAc)2/Xphos system efficiently transformed 3,4-dimethyl-
chlorobenzene 2h into the corresponding boronate ester 4h
in good yield (81%, Table 4, entry 8). In addition, 3-chlorophe-
nylmethylsulfane 2i and the heterocyclic chloride 2j were also
efficiently transformed into the desired products 4i and 4j in
99 and 90% yield, respectively (Table 4, entries 7 and 9). Sur-
prisingly, the system proved to be highly active in the boryla-
tion of 1-chloro-4-fluorobenzene 2k, an electron-poor aryl
chloride, and the desired pinacol boronate ester 4k was isolat-
ed in 99% yield (Table 4, entry 10). As observed in Table 4,
yields were lower when trifluoromethyl-substituted aryl chlor-
ides were used. Indeed, the boronates resulting from the reac-
tion of 1-chloro 4-trifluoromethylbenzene 2c and 1-chloro-3,5-
difluorobenzene 2l were isolated in poor yields (60 and 33%
respectively, entries 11 and 12, Table 4,). Therefore, we sought
to investigate a system that could efficiently improve yields
when these substrates are used as starting materials.
2c. The influence was completely reversed; KBr, NaCl, and KCl
showed a moderate activating effect (see kinetic studies in the
Supporting Information). However, KI led to complete conver-
sion after 3 h, compared with 80% conversion after 10 h in the
absence of salts. In both cases, KI showed the largest effect on
kinetics. Therefore, we investigated the influence of potassium
iodide on the yield of isolated products from the reactions of
1-chloro-4-(trifluoromethyl)benzene 2c and 1-chloro-4-me-
thoxybenzene 2b. The reactions were performed in EtOAc, at
508C for 16 h, in the presence of aminoborane (2 equiv),
Pd(OAc)2 (2 mol%), XPhos (6 mol%), triethylamine (3 equiv),
and with different amount of KI (Table 5). The quantity of po-
Table 5. Variation of potassium iodide in the borylation of chloro-4-tri-
fluoromethylbenzene.
Entry
Aryl chloride
KI [mol%]
Yield [%][a]
1
2
3
4
5
6
7
8
9
0
2
3
60
73
94
81
78
77
99
61
Intrigued by the effect of potassium iodide addition to
attain good yields, we investigated further the influence of
halide salts. As demonstrated by the good reactivity of 4-chol-
oranisole 2b at room temperature, it seems unlikely that oxi-
dative addition into the CÀCl bond is the rate-determining
step. This corroborates the general observation that electron-
poor substrates react more slowly than the electron-rich sub-
strates.[16a] Potassium iodide could, therefore, be involved in
the second step of the catalytic cycle,[16a] that is, the rate-deter-
mining reaction of the ArPdX complex with the aminoborane.
The beneficial effect can be explained by a halide exchange on
the palladium species or an over stabilization of this palladi-
um(II) intermediate. However, it has been shown, for example,
that for Tsuji–Trost allylation in the presence of chloride ions,
the oxidative addition may become irreversible and the rate of
isomerization reduced due to the formation of neutral [(h1-
allyl)PdCl(PPh3)2] complexes.[18] We investigated various halide
salts in the reaction of 4-chloroanisole 2b under optimized
conditions (see the Supporting Information). Although calcula-
tions[16a] have shown that a cationic palladium species would
arise from dissociation of a ArPdX complex (promoted by base
addition), this cationic species being the intermediate in the
borylation mechanism with aminoborane, we never observed
such an intermediate in solution (see NMR spectroscopy stud-
ies in the Supporting Information). This finding may be due to
intrinsic differences between the calculated system (PMe3,
BH2NMe2, no solvent) and the real catalytic systems (PAr3,
BH2NiPr2, AcOEt) Similarly, NMR studies on the effect of the ad-
dition of halide ions to this complex remain inconclusive.
Some halide ions have little influence on the reaction kinetics
(NaCl, KBr, LiNTf2, CsCl, and NaBF4), whereas others showed
a marked slowing effect (KCl, NaPF6, LiCl, and KI). The same re-
action was performed with 1-chloro-4-trifluoromethylbenzene
20
50
100
200
0
2
50
[a] Yield of product isolated after purification.
tassium iodide had an important effect on the yields of 4b
and 4c (Table 5). In the absence of salt, the desired boronate
product 4c, resulting from the borylation of 4-chlorobenzotri-
fluoride 2c, was obtained in only 3% yield (entry 1). By increas-
ing the quantity of potassium iodide from 0 to 50 mol%, the
yields of compound 4c increased substantially (entries 2–4).
We were pleased to obtain the desired product 4c in 94%
yield with 50 mol% of KI (entry 4). Further increase in the
amount of KI led to a slight decrease in the yields; 81% in the
presence of one equivalent of KI and 78% with two equiva-
lents (entries 6 and 7). The iodide ions may be involved in a cat-
alytic step, which is not possible in their absence. On the con-
trary, potassium iodide displayed the opposite effect on elec-
tron-rich aryl chlorides, such as 4-chloroanisole 2b (Table 5). In
the absence of KI, the boronate 4b was obtained in 77% yield
(entry 7), whereas a 99% yield was obtained in the presence of
2 mol% of KI (entry 8), found to be the optimum conditions
for electron-rich aryl chlorides. On increasing the amount of
salt to 50 mol%, there was a significant drop in yield, the de-
sired product being obtained in 61% (entry 9). Lower yields
are probably due to the formation of side products (10–20%
dehalogenation product).
Chem. Eur. J. 2014, 20, 5573 – 5579
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