Rhodium-catalyzed Heck-type reaction of arylboronic acids with
a,b-unsaturated esters: tuning b-hydrogen elimination vs. hydrolysis of
alkylrhodium species
Gang Zou,* Zhiyong Wang, Junru Zhu and Jie Tang
Department of Chemistry, East China Normal University, 3663 North Zhongshan Rd., Shanghai, 200062, P.
R. China. E-mail: gzou@chem.ecnu.edu.cn; Fax: 86-21-62232100; Tel: 86-21-62232764
Received (in Cambridge, UK) 22nd May 2003, Accepted 12th August 2003
First published as an Advance Article on the web 20th August 2003
The elusive rhodium-catalyzed Heck-type coupling of ar-
ylboronic acids with a,b-unsaturated esters is effected using
rhodium chloride as catalyst, indicating the hydrolysis of
Rh–C bond could be finely tuned by the steric environment
around rhodium.
Addition of phosphine ligands, such as PPh
increased the yields of 3aa (from 20% to 50%) while P(O Pr)
gave a mixture of 3aa and butyl 3-phenylpropanoate (3Aaa)
(Table 1, entries 2–4). K CO was found to accelerate the
reaction, but was not essential. Use of water as co-solvent was
necessary, but aqueous/polar solvents such as dioxane, gave a
3
and dppf,
i
3
2
3
Rhodium(
I)-catalyzed conjugate addition of arylboronic acids
similar result to toluene/H
catalyst, Rh(PPh Cl, worked similarly to the direct combina-
tion of RhCl and PPh (Table 1, entry 7). Using excess
PhB(OH) (2.0 eq.) increased the yield (Table 1, entry 5).
2
O (Table 1, entry 8). Wilkinson’s
to a,b-unsaturated carbonyl compounds has attracted much
3 3
)
1–4
attention since it was reported in 1997. The reaction has been
proposed to proceed through a mechanism that begins with
3
3
2
transmetalation from organoboron to rhodium(
insertion of the electron-deficient CNC bond to Rh–Csp and
I
), followed by
However, in contrast to the conjugate addition of arylboronic
acids to a,b-unsaturated esters, which always requires a large
excess of arylboronic acids to achieve good yields due to
protodeborylation, use of 2 eq. butyl acrylate gave 3aa in a
higher yield (Table 1, entry 6). This is consistent with the
production of the conjugate reduction product, butyl propanoate
2
3
subsequent protonolysis of the resulting Rh–Csp or Rh–O of
5
rhodium enolate after migration. The mechanistically related
Heck-type olefination products were not detected since they
were found to be more reactive than the parent substrates.6
Aqueous conditions were also reported to favor the conjugate
addition due to the ready hydrolysis of alkylrhodium inter-
mediates.7 However, Lautens et al. reported that, with a
substrate incapable of enolization, such as styrene, Heck-type
reaction occurred even in water that was expected to facilitate
hydrolysis of the resulting Rh–C intermediates, the key-step for
conjugate addition, while ortho- or para-vinylpyridines pro-
vided conjugate adducts under otherwise identical conditions
through tautomerization of the Rh–C bond to Rh–N.4 All these
reports implied that Rh-catalyzed Heck-type reaction of
arylboronic acids with a,b-unsaturated esters could not be
effected, especially under aqueous conditions. Thus recent
efforts have been devoted to non-rhodium catalysts for Heck-
(up to 40%, GC and GC-Mass). In all cases, except for the
i
ligand P(O Pr)
3
, only minor conjugate addition products were
1
detected by GC and H NMR
Typical a,b-unsaturated compounds were tested under the
3 3
optimized condition of 3% eq. RhCl , 12% eq. PPh in toluene/
water with a 2 : 1 ratio of olefins to boronic acids (Table 2).†
The olefin structure had a marked effect on the reaction. Parent
acrylates reacted smoothly, but substituted acrylates, such as
methyl methylacrylate, gave 3ad in low yield (7% by GC-MS)
while butyl trans-cinnamate remained untouched, indicating
steric factors played a critical role in the reaction (Table 2,
entries 1, 2 and 4). Electron donor or withdrawing groups
,8
3 3
(CH O or CH OOC) on the arylboronic acid component had
type coupling of arylboronic acids with a,b-unsaturated
little effect on the reaction (Table 2, entries 5 and 6).
Acrylonitrile reacted smoothly to offer the desired product 3ac,
while acrylamide looked likely to destroy the catalyst. 2-Cyclo-
hexenone (2e), the a,b-unsaturated ketone that is often used as
a model substrate in studies of Rh-catalyzed conjugate addition,
reacted with 1a to give both Heck-type coupling product 3ae
and conjugate adduct 3Aae in low yields.
esters.9
–11
Herein, we report the elusive rhodium-catalyzed
Heck-type coupling of arylboronic acids with a,b-unsaturated
esters.
The key for conjugate addition vs. Heck-type reaction of
arylboronic acids with a,b-unsaturated esters lies in the
competition of hydrolysis or tautomerization with b-H elimina-
tion of the alkylrhodium intermediates. From the organome-
Table 1 Rhodium-catalyzed Heck-type reaction of PhB(OH)
2
with butyl
3
tallic chemistry point of view, hydrolysis of Rh–Csp preferably
acrylatea
I
occurs through oxidative addition (OA) of water to RRh ,
III
generating species R(H)(OH)Rh , followed by reductive
elimination (RE) to give formal protonolysis products R–H
although direct hydrolysis of Rh–C is also possible.12 Both
tautomerization and hydrolysis through the OA/RE sequence
require a strict steric and electronic environment around the
metal, thus leaving a chance for development of rhodium-
catalyzed Heck-type reaction by tuning rhodium catalysts. In
b
Entry
1a/2a
Ligand
—
Solvents (v/v)
Yield (%)
1
2
3
4
5
6
7
8
9
1/1
1/1
1/1
1/1
2/1
1/2
1/2
1/1
1/1
1/1
Tol/H
Tol/H
Tol/H
Tol/H
2
O (3/1)
2
O (3/1)
2
O (3/1)
2
O (3/1)
21
50
49
21
75
85
78
45
PPh
3
dppf
fact, when equivalent amounts of PhB(OH)
acrylate (2a) were subjected to 3% eq. of RhCl
2
(1a) and butyl
(H O) in a
i
c
P(O Pr)
3
3
2
3
PPh3
2
Tol/H O (3/1)
toluene/water mixture (3 : 1, v/v) the desired Heck-type product
butyl trans-cinnamate (3aa) formed albeit in low yield (20%)
while the conjugate adduct was only formed in trace amounts
PPh
PPh
PPh
PPh
3
3
3
3
Tol/H
Tol/H
2
O (3/1)
O (3/1)
d
2
Dioxane/H
DMF/H O (3/1)
Tol/H O (3/1)
2
O (3/1)
2
trace
trace
(
< 3%) (Table 1, entry 1). Biphenyl was detected implying that
1
0
TPPTS
2
III
I
Rh was reduced to Rh species in situ through reductive
elimination of Rh (Ph)
a
III
2 3
When the reaction was conducted in the presence of K CO it completed
within 8 h, but yield decreased slightly due to increase of protodeborylation
2
. Other metal chlorides, such as PdCl
2
or RuCl , failed to catalyze the reaction of 1a with 2a under
3
b
of PhB(OH)
various amounts. 10% conjugate adduct 3Aaa was also detected. d 3% eq.
RhCl(PPh was used.
3
. Determined by GC and butyl propanoate was detected in
otherwise identical conditions. These initial results, although
not satisfactory, clearly indicated that the reaction course could
be tuned by properly choosing the rhodium source.
c
3 3
)
2
438
CHEM. COMMUN., 2003, 2438–2439
This journal is © The Royal Society of Chemistry 2003