1082
Chemistry Letters 2001
Palladium-Catalyzed Benzylic C–H Borylation of Alkylbenzenes
with Bis(pinacolato)diboron or Pinacolborane
Tatsuo Ishiyama,* Kousaku Ishida, Jun Takagi, and Norio Miyaura*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628
(Received July 19, 2001; CL-010679)
Borylation at the benzylic C–H bond of alkylbenzenes with
ligand-free metallic palladium. Although commercial palladi-
um black did not catalyze the reaction, a palladium on carbon
(10% Pd/C) finally achieved the selective coupling in high
yields. Very interestingly, two boryl groups in 1 participated in
the reaction to provide 74% yield of the product based on the
boron atom.10 Other heterogeneous catalysts such as Pt/C,
Rh/C, and Ru/C were totally ineffective.
bis(pinacolato)diboron [(Me4C2O2)B–B(O2C2Me4)] or pina-
colborane [(Me4C2O2)B–H] was carried out at 100 °C in the
presence of a catalytic amount of 10% Pd/C. The reaction
selectively afforded pinacol benzylboronates in good yields
directly from various alkylbenzenes.
In order to obtain further information on the formation of
two moles of benzylboronate from one mole of the diboron, the
Pd/C-catalyzed reaction of 1 with toluene at 100 °C was fol-
lowed by GC analysis. The diboron was completely consumed
after 2.5 h, but the yield of benzylboronate was 49%. Further
prolongation of the reaction time increased the yield even after
the complete consumption of the diboron. Finally, the reaction
gave 74% yield of benzylboronate after 9 h. The results indi-
cated a two-step process involving a very fast and quantitative
reaction of toluene with the diboron 1, followed by a slow reac-
tion with pinacolborane 2 generated by the former process. A
52% yield of pinacol benzylboronate was obtained indeed when
pinacolborane was treated with toluene at 100 °C in the pres-
ence of Pd/C (3 mol%).10
The transition metal-catalyzed C–C and C–X bond forma-
tion accompanied with activation of inactive C–H bonds has
emerged as an interesting and important alternative to the con-
ventional bond-forming reactions involving functionalized sub-
strates.1 Since organoboron compounds are versatile intermedi-
ates in organic synthesis,2 an extension of the methodology to
borylation reactions would have significant synthetic value.
Indeed, several pioneering studies have been made on the cou-
pling reactions of bis(pinacolato)diboron (1) or pinacolborane
(2). The direct borylation of alkanes and benzene with the
diboron 1 was catalyzed by Cp*Re(CO)3 under photochemical
conditions3 or by Cp*Rh(η4-C6Me6) under thermal conditions.4
The latter complex,5 Cp*Ir(PMe3)(H)[B(O2C2Me4)],5,6 and
7
(Cp*RhCl2)2 have been successfully used for aromatic C–H
The representative results are summarized in Table 1. All
reactions of bis(pinacolato)diboron 1 or pinacolborane 2 were
carried out at 100 °C in the presence of 10% Pd/C (3–6
mol%).10 Not only toluene (Entry 1), but also polymethylated
benzenes are viable substrates. o-, m-, and p-Xylenes smoothly
underwent the selective monoborylation to provide the corre-
sponding benzylboronates 4 in good yields in the presence of 3
mol% catalyst (Entries 2–4), while mesitylene required 6 mol%
of catalyst to achieve a satisfactory yield (Entry 5).
Ethylbenzene yielded a 3:1 mixture of the benzylboronate and
the homobenzyl derivative. The latter product can be derived
from positional isomerization of the benzylpalladium interme-
diate to a homobenzylpalladium species via the β-hydride elim-
ination–insertion process (Entry 6).11 Another probable path-
way involving a direct C–H activation at the β-carbon should
be ruled out by the fact that no reaction was observed for tert-
butylbenzene. Isopropylbenzene exclusively afforded the
homobenzyl derivative due to large steric hindrance at the ben-
zylic carbon (Entry 7). On the other hand, the borylation of 4-
isopropyltoluene selectively occurred at the methyl group,
though the reaction was accompanied with a small amount of 2-
(4-methylphenyl)-1-propylboronate (Entry 8). In all reactions,
the diboron 1 gave higher yields than pinacolborane 2.
borylation with pinacolborane 2, and RhCl[P(i-Pr)3]2(N2)7 for
benzylic C–H borylation. In the course of our studies on the
transition metal-catalyzed reactions of diboron compounds,8 we
recently found that Pd/C is an efficient catalyst for selective
benzylic C–H borylation of alkylbenzenes (3) with the diboron
1 or pinacolborane 2 to produce the corresponding pinacol ben-
zylboronates (4) in good yields (eq 1).9
The borylation of toluene (60 mmol) with
bis(pinacolato)diboron 1 (1.0 mmol) was carried out at 100 °C
for 16 h in the presence of various metal complexes (3 mol%)
to optimize the catalyst system. Pd(OAc)2 and PdCl2 produced
pinacol benzylboronate as the sole product in 11% and 33%
yields, respectively. In contrast, NiCl2, PtCl2(COD), RhCl3,
IrCl3, and RuCl3 exhibited no catalytic activity at all.
Instantaneous formation of palladium black observed for
Pd(OAc)2 and PdCl2 prompted us to use ligands; however, the
addition of PPh3, P(c-Hex)3, P(OPh)3, AsPh3, and SbPh3 com-
pletely retarded the reaction, thus suggesting the superiority of
In contrast to the results of unfunctionalized alkylbenzenes,
the reaction was highly sensitive to the presence of het-
eroatoms. For example, 4-methylanisole and 4-fluorotoluene
resulted in 13% and 26% yields, respectively, even at higher
catalyst loading or prolongation of reaction time. All attempts
at the borylation of 4-methylacetophenone, 2-methylthiophene,
and 2-methylfuran were unsuccessful.
Copyright © 2001 The Chemical Society of Japan
Ishiyama, Tatsuo
