New studies of Rh-catalyzed addition of boronic acids under basic conditions in aqueous medium

Article abstract of DOI:10.1016/S0040-4039(02)01274-1

Rh-catalyzed C-C bond formation in neat water under basic conditions has been efficiently performed. The addition of various boronic acids to styrene, 2-vinylpyridine, and cyclic α,β-unsaturated ketones has been realized with high selectivity and yield. We have shown that m-TPPTC (tris(m-carboxyphenyl)phosphane trilithium salt) exhibited a higher reactivity compared to TPPTS. These couplings could also be conducted very efficiently under basic and phosphaneless conditions to give functionalized aryl derivatives. The benefits of the additional anionic ligand m-TPPTC lied in the successful recycling experiments of 1,4-addition of phenylboronic acid to cyclohexenone, with no loss of the water-soluble catalyst.

Full text of DOI:10.1016/S0040-4039(02)01274-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5905–5908
New studies of Rh-catalyzed addition of boronic acids under
basic conditions in aqueous medium
Re´mi Amengual, Ve´ronique Michelet* and Jean-Pierre Geneˆt*
Laboratoire de Synthe`se Se´lective Organique et Produits Naturels, E.N.S.C.P., UMR 7573, 11 rue P. et M. Curie, F-75231
Paris Cedex 05, France
Accepted 28 June 2002
Abstract—Rh-catalyzed CꢀC bond formation in neat water under basic conditions has been efficiently performed. The addition
of various boronic acids to styrene, 2-vinylpyridine, and cyclic a,b-unsaturated ketones has been realized with high selectivity and
yield. We have shown that m-TPPTC (tris(m-carboxyphenyl)phosphane trilithium salt) exhibited a higher reactivity compared to
TPPTS. These couplings could also be conducted very efficiently under basic and phosphaneless conditions to give functionalized
aryl derivatives. The benefits of the additional anionic ligand m-TPPTC lied in the successful recycling experiments of 1,4-addition
of phenylboronic acid to cyclohexenone, with no loss of the water-soluble catalyst. © 2002 Elsevier Science Ltd. All rights
reserved.
Carbonꢀcarbon bond formation is fundamentally
important in organic synthesis. Recent years witnessed
tremendous growth in a number of reactions and
reagents for CꢀC bond formation. Among them, the
transition metal-catalyzed reactions and specifically
phenyl)phosphane trilithium salt).8 Preliminary studies
showed that, the reactivity of m-TPPTC was similar to
TPPTS in palladium-catalyzed reactions, but no reac-
tion mediated by rhodium was tested so far with this
ligand. We wish therefore to describe herein the appli-
cations of our new hydrophilic ligand 1 in rhodium-cat-
alyzed reactions.
homogeneous catalysis have given
a considerable
impetus to the progress of the area of organometallic,
organic and industrial chemistry.1 The development of
efficient environmentally safe systems has given the
ability to combine the high activity and selectivity of
the catalyst with the easier product separation and
possible catalyst recycling.2 We have been engaged for a
long time in a program devoted to reactions in
organoaqueous media using TPPTS ligand (tris(m-sul-
fonatophenyl)phosphane trisodium salt), such as palla-
dium-catalyzed reactions,3,4 nickel-catalyzed cross-
couplings5 and palladium, rhodium or nickel-catalyzed
ene-reaction.6
We first turned our attention to the coupling of boronic
acids with either styrene or 2-vinylpyridine (Scheme 1).
Boronic acids may be engaged in Rh-catalyzed reac-
tions via a Heck-type reaction (addition–elimination) or
via an addition–hydrolysis. In the literature, the use of
the disulfonated water-soluble ligand TPPDS 3 (bis(p-
sulfonatophenyl)phenylphosphane dipotassium salt)9
associated with a surfactant (sodium dodecyl sulfate
Heck-type
Reaction
O
Ph
Ph
Ar
[Rh], L, H2O
O
New CꢀC bond formations have recently been reported
in water using rhodium catalysts.7 The addition of
boronic acids to either styrene derivatives7a or a,b-
unsaturated ketones7c resulted in low yields using Rh/
TPPTS system (Scheme 1). We have reported very
recently the easy preparation of the new highly water-
Ar B(OH)2
[Rh], L, H2O
Ar
N
1,4-Addition
Ar
N
Addition -
Hydrolysis
soluble
ligand
m-TPPTC
1
(tris(m-carboxy-
PPh
2
LiO2C
=
P
3
NaO3S
P
3
KO3S
Keywords: water-soluble ligand; boronic acids; a,b-unsaturated
ketones; styrene derivatives; recyclable rhodium/m-TPPTC system.
* Corresponding authors. E-mail: michelet@ext.jussieu.fr; genet@
ext.jussieu.fr
m- TPPTC 1
TPPTS 2
TPPDS 3
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01274-1

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R. Amengual et al. / Tetrahedron Letters 43 (2002) 5905–5908
Stilbene derivatives were obtained with 84–99% isolated
yields (entries 3, 6, 9). In the case of the addition–
hydrolysis pathway, the corresponding functionalized
aryl derivatives could also be isolated in good yield
(entries 11, 13).
SDS) appeared to be necessary for the couplings in
water.7a As we experimentally observed a surfactant
effect for the m-TPPTC ligand, we conducted the reac-
tion directly in water without SDS (Table 1). Indeed,
the coupling of phenylboronic acid with styrene using 2
mol% of rhodium dimer, 8 mol% of m-TPPTC in neat
water at 80°C gave stilbene 7a with 79% yield (entry 1).
The reaction was very clean and after an easy work up
that consists in two extractions and a filtration of the
organic phase on a silica gel pad, stilbene was isolated
in high purity (gas chromatography).10 The same reac-
tion conducted with TPPTS ligand was very sluggish
and gave only 31% of the desired compound (entry 2).
In the case of 4-bromophenylboronic acid 6b (entry 4),
the reaction occurred with an excellent chemoselectiv-
ity. Electro-donating group was also tolerated as illus-
trated by the addition of 4-methoxyphenylboronic acid
6c (entry 7). Our system with m-TPPTC 1 was therefore
extremely efficient without the use of SDS. Stilbene
derivatives 7b and 7c were isolated with 96 and 71%
yield, respectively (entries 4, 7). In contrary, TPPTS 2
ligand gave poor results in these reactions (entries 5, 8).
The catalytic cycle of either CꢀC bond couplings
involves a transmetallation between ArB(OH)2 and the
Rh catalyst, and insertion of the alkene and finally a
Rh–H elimination of the rhodium intermediate. The
higher efficiency of m-TPPTC compared to TPPTS
may be then explained in terms of basicity of the
phosphanes that would favor the transmetallation
step.11 The addition of boronic acids on 2-vinylpyridine
was also efficiently performed using m-TPPTC ligand.
The heteroaryl compounds were respectively isolated
with 67 and 66% yield (entries 10, 12). Suspected that
the reaction might be catalyzed only by Rh(I),7c we
performed the couplings of boronic acids on styrene
derivatives 4 and 5 without additional phosphane
ligand. Indeed, the boron partners still reacted very
smoothly in the standard basic conditions.
Then, we turned our attention to the 1,4-addition of
boronic acids to a,b-unsaturated ketones.12,13 Encour-
aged by the previous good results in neat water, we
decided to use 2 mol% of [Rh(cod)Cl]2, 8 mol% ligand,
2 equiv. of Na2CO3 at 80°C. As documented in Table 2,
the addition of phenylboronic acid 6a to cyclohexenone
9 led very efficiently to the arylated cyclohexanone with
99% isolated yield (entry 1). The reaction was much
faster than the one with 2-vinylpyridine, because a,b-
unsaturated ketones are excellent Michael acceptors.
Under the same conditions, the use of TPPTS ligand
gave this time an excellent result too: the reaction was
complete within 1 h at 80°C in neat water (entry 2).
Without additional phosphane ligand, the addition of
6a was much faster (0.25 h versus 1 h) and the desired
1,4-adduct 12a was isolated with 99% yield (entry 3).
We then checked the generality of this phosphaneless
reaction under standard basic conditions. Either elec-
tro-donating boronic acid 6c (entry 4) or electro-with-
drawing boronic acid 6d (entry 5) could react in short
reaction time leading to 99% isolated compounds.
The highly hindered boronic acid 6e could also be a
good partner (entry 6). Other enones like cyclopen-
tenone 10 or cycloheptenone 11 (entries 7, 8) afforded
the corresponding adducts 13a and 14c with quantita-
tive yield. All compounds were characterized by NMR
and GC/mass spectroscopy. The addition of boronic
acids on a,b-unsaturated ketones was therefore
efficiently realized in short time at 80°C with or without
additional ligand, in neat water and in the presence of
a base. It has to be noticed that the presence of a base
accelerates the reaction compared to previous reports.
Table 1. Rh-catalyzed addition of boronic acids to styrene derivatives
2 mol% [Rh(cod)Cl]2
X
8 mol% L
Ph
C5H4N
+
B(OH)2
6a-c
Ar
or
Ar
Ar
Na2CO3 (2 equiv.), 80°C
H2O, 12 h
4, X = C
5, X = N
7a-c, X = C
8a-c, X = N
Entry
Styrene
Boronic acid
Ligand
Product
Yield (%)a
1
2
3
4
5
6
7
8
4
4
4
4
4
4
4
4
4
5
5
5
5
PhB(OH)2 6a
PhB(OH)2 6a
PhB(OH)2 6a
4-BrC6H4B(OH)2 6b
4-BrC6H4B(OH)2 6b
4-BrC6H4B(OH)2 6b
4-MeO-C6H4B(OH)2 6c
4-MeO-C6H4B(OH)2 6c
4-MeO-C6H4B(OH)2 6c
PhB(OH)2 6a
m-TPPTC 1
TPPTS 2
/
m-TPPTC 1
TPPTS 2
/
m-TPPTC 1
TPPTS 2
/
m-TPPTC 1
/
m-TPPTC 1
/
7a
7a
7a
7b
7b
7b
7c
7c
7c
8a
8a
8c
8c
79
31
99
96
24
99
71
32
84
67
80
66
77
9
10
11
12
13
PhB(OH)2 6a
4-MeO-C6H4B(OH)2 6c
4-MeO-C6H4B(OH)2 6c
a Isolated yield.

R. Amengual et al. / Tetrahedron Letters 43 (2002) 5905–5908
Table 2. Rh-catalyzed addition of boronic acids to enones
5907
O
O
2 mol% [Rh(cod)Cl]2
+
Ar B(OH)2
Na2CO3 (2 equiv.), 80°C
Ar
n
n
H2O, t
9, n = 1
10, n = 0
11, n = 2
12, n = 1
13, n = 0
14, n = 2
6a-e
Entry
Enone
Boronic acid
Ligand
Product
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
9
9
9
9
9
10
11
PhB(OH)2 6a
PhB(OH)2 6a
PhB(OH)2 6a
4-MeO-C6H4B(OH)2 6c
4-CF3-C6H4B(OH)2 6d
2,6-Me2-C6H3B(OH)2 6e
PhB(OH)2 6a
m-TPPTC 1
TPPTS 2
12a
12a
12a
12c
12d
12e
13a
14c
1
1
0.25
2
1
3
1
1
99
99
99
99
99
99
99
99
/
/
/
/
/
/
4-MeO-C6H4B(OH)2 6c
a Isolated yield.
A major advantage of water-soluble phosphane lie in
the recycling possibility of the catalyst, that is therefore
preserved in water. Thus, we envisaged improving our
catalyst system Rh(I)/m-TPPTC by recycle experi-
ments. We have conducted the 1,4-addition of phenyl-
boronic acid to cyclohexenone using 0.5 mol%
[Rh(cod)Cl]2, 1 mol% m-TPPTC 1 under our standard
basic conditions. As shown in Fig. 1, we were pleased
to find that the benefits of the water-soluble ligand 1
lied in the successful recycling of the expensive
rhodium. Indeed, after completion of the reaction, the
water phase (containing the catalyst and the product)
was extracted two times with cyclohexane and reloaded
with substrates. The reaction time was still very short
for each recycling (between 1 and 1.5 h). The arylated
ketone was isolated with 87–100% yield and with excel-
lent purity (98%). It is noteworthy that during the
continuous recycle experiments, no deposition of
rhodium metal on the glass was observed.
styrene gave, via a Heck-type reaction, stilbene deriva-
tives. Poor Michael acceptor such as 2-vinylpyridine
selectively underwent 1,4-addition of an aryl group.
We have shown that, in those cases, the use of an
additional phosphane was not necessary. Nevertheless,
a better reactivity was observed when using m-TPPTC
compared to TPPTS, presumably due to a difference of
basicity of the ligands.11 We have also realized Rh-cat-
alyzed couplings on a,b-unsaturated ketones under
basic conditions with or without additional water-solu-
ble ligand, which may be a drawback for asymmetric
catalysis.12,13 We have shown that the water-soluble
Rh/m-TPPTC could be easily recycled for the first time
in water with no loss of the selectivity. We are cur-
rently looking for optimized conditions to perform
asymmetric CꢀC bond formation using chiral water-
soluble ligands.
Acknowledgements
In conclusion, Rh-catalyzed CꢀC bond formation in
neat water under basic conditions has been efficiently
performed. The addition of various boronic acids to
R. Amengual is grateful to the Ministe`re de l’Educa-
tion et de la Recherche for a grant (1999–2002).
Figure 1. Addition of phenylboronic acid to cyclohexenone.

5908
R. Amengual et al. / Tetrahedron Letters 43 (2002) 5905–5908
8. Amengual, R.; Genin, E.; Michelet, V.; Savignac, M.;
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10. Typical procedure: To
a
mixture of degassed
[Rh(cod)Cl]2 (4.3 mg, 2 mol%) and m-TPPTC (14.5 mg, 8
mol%) at room temperature was successively added water
(2.2 mL), phenylboronic acid (133 mg, 1.09 mmol),
Na2CO3 (92 mg, 0.86) and styrene (50 mL, 0.43 mmol).
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