Heck-type coupling vs. conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with α,β-unsaturated carbonyl compounds: A systematic investigation

Article abstract of DOI:10.1039/b615473e

The competition between Heck-type coupling and conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with α,β-unsaturated carbonyls has been systematically investigated in a toluene-H₂O biphasic system. Aside from the intrinsic nature of rhodium and the enolization of carbonyls, the phosphine supporting ligand on rhodium, the ratio of aryl boronic acid to α,β-unsaturated carbonyl and the pH value of the aqueous phase were found to affect the competition significantly. Highly selective rhodium-based catalyst systems have therefore been developed for both Heck-type coupling and conjugate addition by synergistically tuning the supporting ligand, the boronic acid to olefin ratio and other reaction conditions. Conjugate addition with selectivity >99% and Heck-type coupling with selectivity of up to 100%, 98% and 84% for acrylates, acrylamides and methyl vinyl ketone, respectively, could be achieved in the rhodium-catalyzed reactions of aryl boronic acids with α,β- unsaturated carbonyls using the corresponding optimized rhodium-based catalyst systems. The Royal Society of Chemistry.

Full text of DOI:10.1039/b615473e

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Heck-type coupling vs. conjugate addition in phosphine–rhodium catalyzed
reactions of aryl boronic acids with a,b-unsaturated carbonyl compounds: a
systematic investigation†
Gang Zou,* Jianping Guo, Zhiyong Wang, Wen Huang and Jie Tangb
a
a,b
a
a,b
Received 25th October 2006, Accepted 17th April 2007
First published as an Advance Article on the web 14th May 2007
DOI: 10.1039/b615473e
The competition between Heck-type coupling and conjugate addition in phosphine–rhodium catalyzed
reactions of aryl boronic acids with a,b-unsaturated carbonyls has been systematically investigated in a
toluene–H O biphasic system. Aside from the intrinsic nature of rhodium and the enolization of
2
carbonyls, the phosphine supporting ligand on rhodium, the ratio of aryl boronic acid to
a,b-unsaturated carbonyl and the pH value of the aqueous phase were found to affect the competition
significantly. Highly selective rhodium-based catalyst systems have therefore been developed for both
Heck-type coupling and conjugate addition by synergistically tuning the supporting ligand, the boronic
acid to olefin ratio and other reaction conditions. Conjugate addition with selectivity >99% and
Heck-type coupling with selectivity of up to 100%, 98% and 84% for acrylates, acrylamides and methyl
vinyl ketone, respectively, could be achieved in the rhodium-catalyzed reactions of aryl boronic acids
with a,b-unsaturated carbonyls using the corresponding optimized rhodium-based catalyst systems.
Introduction
be tunable in the rhodium-catalyzed C–C bond forming reactions
of aryl boronic acids with a,b-unsaturated carbonyls. In fact, in
closely related rhodium-catalyzed reactions of aryl silicons with
a,b-unsaturated esters, Heck-type coupling arose under anhydrous
conditions while conjugate addition occurred favorably in the
presence of water, demonstrating that the competition between
hydrolysis and b-H elimination of a-rhodium carbonyls could be
The rhodium-catalyzed conjugate addition (CA) of aryl boronic
acids to a,b-unsaturated carbonyl compounds is often reported as
1
a highly selective procedure, although, according to the currently
2
accepted mechanism, there is a mechanistically competitive side
reaction, Heck-type coupling (HC), which results from b-H
elimination of the a-rhodium carbonyl intermediates (Scheme 1).
4
controlled by reaction conditions. Owing to the covalent property
of a Rh–C bond, the favored pathway for hydrolysis of the Rh–
C bond consists of an oxidative addition–reductive elimination
(
OA–RE) sequence with H
2
O instead of direct hydrolysis as a
5
carbon anion. The OA–RE process is strongly dependent on
ligands bound to the metal, including the r-bonded carbon group
as well as the coordinatively bound supporting ligands. Thus,
it is possible to coordinatively control the hydrolysis vs. b-H
elimination competition of an organorhodium species. Lautens
and co-workers have reported a rhodium-catalyzed Heck-type
Scheme 1 The competition of b-H elimination vs. hydrolysis ofa-rhodium
carbonyls.
Considering that the Heck-type coupling of aryl boronic acids
with a,b-unsaturated carbonyl compounds is well known for non-
rhodium transition metal catalysts, such as Ir, Ru and Pd, it looks
reasonable to attribute the bias in favor of conjugate addition with
rhodium catalysts to the intrinsic nature of rhodium metal that
6
coupling of aryl boronic acids with styrene in an aqueous system,
proving that hydrolysis of the Rh–C could be blocked even in the
presence of water. For a-rhodium carbonyls in particular, there
is one more hydrolysis path, enolization–hydrolysis. Therefore, it
would be more difficult to achieve rhodium-catalyzed Heck-type
coupling of aryl boronic acids with a,b-unsaturated carbonyls by
blocking the hydrolysis of a-rhodium carbonyls in the presence of
a proton source, such as water (Scheme 2).
3
disfavors b-H elimination for the Heck-type coupling. However,
from an organometallic chemistry point of view, the reactivity of
an organorhodium species is not only determined by the intrinsic
nature of rhodium, but also tuned by supporting ligands and
reaction conditions. That is to say the HC : CA selectivity should
Fortunately, the C–metal tautomer is favored over the O–metal
enolate, in the metal tautomerism of a-rhodium carbonyls owing to
7
a
the soft property of the rhodium ion. Therefore, there should still
Laborotary of Advanced Materials and Department of Fine Chemicals, East
China University of Science and Technology, 130 Meilong Road, Shanghai,
China 200237. E-mail: zougang@ecust.edu.cn
Department of Chemistry, East China Normal University, 3663 North
Zhongshan Rd., Shanghai, China 200062
be a chance to control the competition between b-H elimination
and hydrolysis of the a-rhodium carbonyl species even in the
presence of water, especially for carbonyls with a low enolization
tendency. Based on this conjecture, we attained highly selective
rhodium-catalyzed Heck-type coupling of arylboronic acids with
acrylates using a biphasic system of water–toluene consisting of
b
†
Electronic supplementary information (ESI) available: Experimen-
tal data on screening the reaction conditions in detail. See DOI:
0.1039/b615473e
1
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(silica gel) to afford Heck-type coupling product (or a mixture
with a small amount of conjugate addition product).
General procedure for the conjugate addition of aryl boronic acids
to a,b-unsaturated amides
To a suspension of aryl boronic acid (2.0 mmol), RhCl
3
(H
2
O)
3
(
(
9 mg, 0.03 mmol) and dppp (41 mg, 0.10 mmol) in toluene–water
15 ml : 5 ml) was added a,b-unsaturated amide (1.0 mmol). The
◦
mixture was stirred at 80 C (bath temperature) under nitrogen.
Progress of the reaction was monitored by GC or TLC until
complete consumption of a,b-unsaturated amide occurred. A
work-up procedure similar to that for Heck-type coupling afforded
conjugate addition product (or a mixture with a small amount of
Heck-type coupling product).
Scheme 2 Hydrolysis paths of a-rhodium carbonyls.
–PR or (PR RhCl and K CO , thereby demonstrating
RhCl
3
3
3
)
3
2
3
tunability of the competition of b-H elimination vs. hydrolysis
of a-rhodium carbonyls in the presence of water for the first
8
time. Shortly after this, a b-hydroxy elimination reaction against
the hydrolysis of a-rhodium, b-hydroxy carbonyls was described
General procedure for the conjugate addition of aryl boronic acids
to a,b-unsaturated esters
to control the reaction direction in the rhodium-catalyzed reac-
9
tions of boronic acids with Baylis–Hillmann adducts. Recently,
To a suspension of aryl boronic acid (2.0 mmol), RhCl
3
(H
2
O)
3
Lautens and co-workers have further reported the impact of
steric effects of both ligands and substrates on the HC : CA
selectivity in the rhodium-catalyzed reactions of aryl boronic
acids with unsaturated carboxylic acid derivatives in emulsion
systems. Herein we report in detail our systematic investigation
of the influence of phosphine ligands, carbonyls and reaction
conditions on the competition of b-H elimination vs. hydrolysis
of a-rhodium carbonyl intermediates in the rhodium-catalyzed
reactions of aryl boronic acids with a,b-unsaturated carbonyls.
This investigation allowed the development of highly selective
rhodium-based catalyst systems for both the Heck-type coupling
and conjugate addition for a,b-unsaturated esters, amides and
ketones.
(
9 mg, 0.03 mmol) and (± )binap (90 mg, 0.15 mmol) in toluene–
water (15 ml : 5 ml) was added a,b-unsaturated ester (1.0 mmol).
The mixture was stirred at 80 C (bath temperature) under
◦
nitrogen. Progress of the reaction was monitored by GC until
complete consumption of a,b-unsaturated ester occurred. A work-
up procedure similar to that for Heck-type coupling of esters
afforded conjugate addition product (or a mixture with a small
amount of Heck-type coupling product)
10
General procedure for the Heck-type coupling of aryl boronic acids
with a,b-unsaturated ketones
To a suspension of aryl boronic acid (1.0 mmol) and RhCl(PPh
3
)
3
(28 mg, 0.03 mmol) in toluene–water (15 ml : 5 ml) was added a,b-
◦
unsaturated ketone (4.0 mmol). The mixture was stirred at 120 C
bath temperature) under nitrogen. Progress of the reaction was
Experimental
(
monitored by TLC until the complete consumption of aryl boronic
acid occurred. A work-up procedure similar to that for Heck-type
coupling of esters afforded the Heck-type coupling product as a
mixture with the conjugate addition product.
General
All reactions were performed in N atmosphere unless otherwise
indicated. All commercially available chemicals were used as
received. Aryl boronic acids, dppp, dppf, dppe, dppb, dppm,
2
(
± )binap and methyl vinyl ketone (MVK) were purchased from
General procedure for the conjugate addition of aryl boronic acids
to a,b-unsaturated ketones
Sigma-Aldrich or Acros. Vinyl phenyl ketone was prepared
according to the previously reported procedure. H NMR spectra
were recorded on a Bruker 500 spectrometer (500 MHz) using the
residue of deuterated solvent (CDCl ) as the internal standard.
GC/GC-MS analysis was performed using a Hewlett Packard
Model HP 6890 Series with HP-5 column.
11 1
To a suspension of aryl boronic acid (2.0 mmol) RhCl
3
(H
2
O)
3
(
9 mg, 0.03 mmol) and (± )binap (90 mg, 0.15 mmol) in toluene–
3
water (15 ml : 5 ml) was added a,b-unsaturated ketone (1.0 mmol).
The mixture was stirred at 80 C (bath temperature) under
◦
nitrogen. Progress of the reaction was monitored by GC until
the complete consumption of a,b-unsaturated ketone occurred. A
work-up procedure similar to that for Heck-type coupling afforded
the conjugate addition product.
General procedure for the Heck-type coupling of aryl boronic acids
with a,b-unsaturated amides and esters
To a suspension of aryl boronic acid (1.0 mmol), RhCl
9 mg, 0.03 mmol), PPh (33 mg, 0.12 mmol) and K CO
mmol) in toluene–water (15 ml : 5 ml) was added a,b-unsaturated
3
(H
(0.45 g,
2
O)
3
(
3
3
2
3
Results and discussion
◦
amide or ester (2.0 mmol). The mixture was stirred at 120
C
In order to systematically investigate the influence of supporting
ligands and reaction conditions on the competition between b-H
elimination and hydrolysis of a-rhodium carbonyl intermediates,
namely HC : CA selectivity, in the rhodium-catalyzed reactions
of aryl boronic acids with a,b-unsaturated carbonyl compounds,
a proper model had to be established. The reactions of phenyl
(
bath temperature) under nitrogen. Progress of the reaction was
monitored by TLC until complete consumption of aryl boronic
acid occurred. After cooling to room temperature, the organic
phase of the reaction mixture was separated from the aqueous
phase, concentrated and purified by column chromatography
3
056 | Dalton Trans., 2007, 3055–3064
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Table 1 Establishment of the model reaction
than that of esters. Thus, the reaction of N,N-dimethyl acrylamide
with phenyl boronic acid was chosen as the model. The influence
of reaction conditions on the HC : CA selectivity was investigated
at first and the results are compiled in Table 2.
When N,N-dimethyl acrylamide was used in excess (2 and 4
equiv.), the Heck-type coupling proceeded with high selectivity
a
b
Entry
X
B : O
HC : CA
Yield (%)
to the conjugate addition using 3% RhCl
3
–12% PPh
3
as a
catalyst in the presence of 3 equiv. K CO , (Table 2, entries 1
2
3
1
2
3
4
5
OBu
NMe
Me
1 : 2
1 : 2
1 : 2
2 : 1
2 : 1
100 : 0
95 : 5
—
93 : 7
53 : 47
86
and 2). The beneficial effects of excess terminal olefin used in
Heck-type coupling reactions have been reported to originate
from the consumption of the Rh–H species generated from b-
2
80c
—
OBu
NMe
66
75
4
2
H elimination. However, even when an equivalent amount of
a
b
1
N,N-dimethyl acrylamide was used the HC : CA selectivity was
still as high as 92 : 8 with 60% overall yield (Table 2, entry 11),
supporting the existence of alternative routes for the conversion
of Rh–H species into Rh–Ar.
Determined by H NMR; no cis isomer of the HC products detected.
c
Isolated yield (%). Complicated mixture.
boronic acid with butyl acrylate, N,N-dimethyl acrylamide and
vinyl methyl ketone (MVK), catalyzed by our previously estab-
Basic conditions looked to be crucial to the b-H elimination of
a-rhodium amides. For example, the HC : CA selectivity reversed
lished biphasic catalyst system of RhCl
3
–PPh
3
–K
2
CO
3
in toluene–
from favoring Heck-type coupling in the presence of K
to favor conjugate addition (20 : 80) in the absence of K
2
CO
CO
3
,
,
water, were screened in a parallel fashion to find the most suitable,
using criteria of good chemical yield, easily monitored progress
and proper HC : CA selectivity (Table 1).
The reactions of both butyl acrylate and N,N-dimethyl acryl-
amide proceeded cleanly while the reaction of MVK gave a
complicated mixture. However, the HC : CA selectivity in the
reaction of N,N-dimethyl acrylamide was sensitive to the ratio
of boronic acid (B) to olefin (O), decreasing from 95 : 5 to 53 :
2
3
although the reaction became much slower giving only a 32%
yield after 30 h (Table 2, entries 1 and 3). Since the 3% RhCl –12%
PPh system is assumed to work through in situ formation of Rh(I)
species, e.g. RhCl(PPh , the decrease of reaction rate could be
attributed to the difficulty in the formation of Rh(I) species in the
absence of base. In fact, when the Wilkinson catalyst, RhCl(PPh
was used in place of 3% RhCl –12% PPh the reaction rate did
improve, but the HC : CA selectivity was poor (Table 2, entry 4),
implying differences between the RhCl –PPh system and the
Wilkinson catalyst. However, in the presence of K CO , the
HC : CA selectivity with RhCl(PPh compared favorably to
that obtained with the combination of 3% RhCl and 12% PPh
confirming the necessity of a basic condition for b-H elimination
3
3
)
3 3
3
) ,
3
3
3
4
7 with the B : O ratios increasing from 1 : 2 to 2 : 1 (mol)
(
Table 1, entries 2 and 5). Meanwhile the HC : CA selectivity
3
3
12
in the reaction of butyl acrylate consistently and overwhelmingly
favored the Heck-type coupling regardless of the B : O ratios
2
3
)
3 3
(
Table 1, entries 1 and 4). Obviously, the competition between b-H
3
3
,
elimination and hydrolysis of a-rhodium amides is easier to tune
Table 2 HC : CA selectivity in the model reaction of acrylamide with phenyl boronic acid under various conditions
a
◦
b
c
Entry
B : O
Catalyst
Base
T/ C
t/h
HC : CA
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
1 : 2
1 : 4
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
3% RhCl
3% RhCl
3% RhCl
3% RhCl(PPh
3% RhCl(PPh
3% RhCl(PPh
3% RhCl(PPh
3% RhCl(PPh
3% RhCl(PPh
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3
3
3
–12% PPh
–12% PPh
–12% PPh
3
3
3
K
K
—
—
K
K
NH
B(OH)
—
K
K
K
K
—
—
—
—
—
2
2
CO
CO
3
3
120
120
120
120
120
80
120
120
120
120
120
120
120
120
80
5
5
30
5
5
8
48
5
5
5
8
5
5
30
48
48
5
95 : 5
98 : 2
78
80
32
73
79
86
70
60
78
71
60
80
77
43
61
76
70
86
20 : 80
51 : 49
93 : 7
86 : 14
42 : 58
33 : 67
40 : 60
96 : 4
3
3
3
3
3
3
)
)
)
)
)
)
3
3
3
3
3
3
2
CO
CO
3
3
2
d
4
Cl
3
e
–PPh
3
f
1
1
1
1
1
1
1
1
1
3
3
3
3
3
3
3
–12% PPh
–12% PPh
–12% PPh
–30% PPh
–12% PPh
–12% PPh
–30% PPh
3
3
3
3
3
3
3
2
2
2
2
CO
CO
CO
CO
3
3
3
3
92 : 8
55 : 45
31 : 69
6 : 94
8 : 92
8 : 92
16 : 84
4 : 96
80
80
80
3% RhCl(PPh
3% RhCl(PPh
3
)
)
3
e
3
3
–PPh
3
5
a
b
1
c
d
e
f
3
equiv. used. Determined by HNMR; no cis isomer of HC product detected. Isolated yield (%). Saturated NH
4
Cl(aq.). 15% PPh
3
added. Run in
air.
This journal is © The Royal Society of Chemistry 2007
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of a-rhodium amides (Table 2, entries 5 and 6). In comparison to
the HC : CA selectivity obtained under neutral conditions, further
with a,b-unsaturated amides could be tuned by properly choosing
reaction conditions.
lowering the pH value of the aqueous phase by using NH
4
Cl or
It is reasonable to anticipate that the chelate effects of
bidentate phosphine ligands could increase the CA selectivity
since they depress the formation of a coordinatively unsaturated
rhodium species, thus slowing down the b-H elimination for
B(OH) (3 equiv.) solution just slightly increases the conjugate
3
addition selectivity (Table 2, entries 4, 7 and 8). Lower reaction
temperature increased the overall yield, but decreased the HC :
CA selectivity slightly (Table 2, entry 6). Although most of the
ꢀ
Heck-type coupling. Therefore, diphosphine ligands, 1,1 -bis-
experiments were conducted in N
2
atmosphere, a similar result
(diphenylphosphino)ferrocene (dppf), 1,1-bis(diphenylphos-
with respect to both yield and HC : CA selectivity could also be
obtained in air (Table 2, entry 10).
phino)methane
(dppm),
1,2-bis(diphenylphosphino)ethane
(dppe), 1,4-bis(diphenylphosphino)butane (dppb), 1,3-bis(di-
ꢀ
The dependence of the HC : CA selectivity on the B : O ratio
and the pH value of the aqueous phase in the reaction of phenyl
boronic acid with N,N-dimethyl acrylamide was further confirmed
by experiments using excess phenyl boronic acid. The HC : CA
selectivity decreased to 55 : 45 with excess (2 equiv.) phenyl boronic
acid from 95 : 5 with excess olefin (2 equiv.), even in the presence
phenylphosphino)propane (dppp) and (± )2,2 -bis(diphenyl-
ꢀ
phosphino)-1,1 -binaphthalene (binap), were tested in the model
reaction of phenyl boronic acid with N,N-dimethyl acrylamide
under the optimized conditions for Heck-type coupling and
conjugate addition, respectively (Table 3).
As expected, the CA selectivity in the model reaction upon
using diphosphines increased compared to the same reaction
of 3 equiv. K
type coupling (Table 2, entries 1 and 12). Furthermore, in the
absence of K CO , the CA selectivity increased to 94 : 6 with
2
CO
3
which was found to be beneficial to Heck-
with PPh
diphosphine showed remarkable influence on both the chemical
yields and CA : HC selectivity. In the absence of K CO , the
CA product was obtained in excellent selectivity and yield with
3
under otherwise identical conditions. The structure of
2
3
excess phenyl boronic acid (2 equiv.) from 80 : 20 with excess N,N-
dimethyl acrylamide (2 equiv.) (Table 2, entries 3 and 14). Again,
lower reactiontemperature showed a beneficialeffecton theoverall
yields. Although the CA selectivity did not further increase, the
chemical yield of the model reaction increased from 61% to 76%
2
3
◦
◦
large bite angle diphosphines, dppf (98.74 ), dppp (91.56 ), dppb
◦
◦
(97.07 ) and binap (92.77 ), using just a slight excess (1.2 equiv.)
of phenyl boronic acid; while both the yields and CA selectivity
were comparatively low with small bite angle diphosphines, dppm
upon increasing the PPh
entries 15 and 16). Using the Wilkinson catalyst, RhCl(PPh
in place of the direct combination of 3% RhCl and 12% PPh
3
loading from 12% to 30% (mol) (Table 2,
◦
◦
3
)
3
,
,
(71.53 ) and dppe (82.55 ) (Table 3, entries 3, 5, 7, 9, 11 and
1
3, 14
3
3
13).
CA selectivity with diphosphines noticeably increased compared
with that using PPh , except for dppm, which performed similarly
to PPh (Table 3, entries 1, 4, 6, 8 and 10). It is noteworthy that
Even under conditions favoring Heck-type coupling, the
gave slightly lower CA selectivity. But good CA selectivity could
be restored by using extra PPh along with (PPh RhCl, which
3
3
)
3
3
was expected to depress the b-H elimination of the a-rhodium
carbonyl intermediate (Table 2, entries 17 and 18). Based on these
experiments, it could be concluded that basic aqueous, excess olefin
and higher temperature promote the b-H elimination while non-
basic conditions, excess aryl boronic acid and lower temperature
benefit hydrolysis of a-rhodium amides. That is to say the HC : CA
selectivity in the rhodium-catalyzed reactions of aryl boronic acids
3
when binap was used as the supporting ligand for rhodium, the
CA product was obtained in high yield and selectivity, regardless
of the reaction conditions, B : O ratio, pH value and temperature
◦
(80–120 C) (Table 3, entries 12 and 13). For example, the CA :
HC selectivity reached 97 : 3 with a 91% yield using 2 equiv. N,N-
dimethyl acrylamide, 3% RhCl
3
, 6% binap and 3 equiv. K
2
CO ,
3
Table 3 Chelate effects of diphosphines on the HC : CA selectivity in the model reaction
a
◦
b
c
Entry
B : O
Phosphine
Base
T/ C
t/h
HC : CA
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
1 : 2
2 : 1
1.2 : 1
1 : 2
1.2 : 1
1 : 2
1.2 : 1
1 : 2
1.2 : 1
1 : 2
1.2 : 1
1 : 2
1.2 : 1
1.2 : 1
1.2 : 1
1.2 : 1
6% dppf
10% dppf
10% dppf
6% dppe
K
—
—
K
—
K
—
K
—
K
—
K
—
—
—
—
2
CO
3
120
80
80
120
80
120
80
120
80
120
80
120
80
80
5
10
10
25
70
20
70
25
10
5
10
5
15
30
10
20
81 : 19
0 : 100
1 : 99
55 : 45
21 : 79
92 : 8
25 : 75
61 : 39
0 : 100
77 : 23
4 : 96
96
93
92
17
65
83
18
86
93
93
91
91
93
93
94
66
2
CO
CO
CO
CO
CO
3
3
3
3
3
10% dppe
6% dppm
10% dppm
6% dppp
10% dppp
6% dppb
10% dppb
6% binap
10% binap
3% binap
6% dppp
3% dppp
2
2
1
1
1
1
1
1
1
2
2
3 : 97
2 : 98
3 : 97
2 : 98
80
80
20 : 80
a
b
1
c
3
equiv. used. Determined by H NMR; no cis isomer of HC product detected. Isolated yield (%).
3
058 | Dalton Trans., 2007, 3055–3064
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conditions that were found to disfavor conjugate addition for
the other tested phosphine ligands, especially PPh , with which
Unlike the aryl group, the carbonyl moiety can coordinate
with the rhodium ion and is the root of enolization of the a-
rhodium b-aryl carbonyl intermediate, thus significantly affecting
the b-H elimination vs. hydrolysis competition. In fact, during
our screening for the model reaction, the HC : CA selectivity
in the reaction of butyl acrylate with phenyl boronic acid was
found to be less sensitive to the B : O ratio than that of
acrylamide (see Table 1). Thus, the tunability of the hydrolysis
vs. b-H elimination competition of a-rhodium ester intermediates
in the reactions of aryl boronic acids with a,b-unsaturated esters,
was explored using the reaction of butyl acrylate as the model
(Table 5).
3
high HC : CA selectivity (95 : 5) was obtained. Since binap has
a comparable bite angle and the same diphenyl phosphine units
as dppp, it is clear that the HC : CA selectivity in the rhodium-
catalyzed process is also affected by the rigidness of the chelate
ligands. Decrease of the ratio of diphosphine to Rh markedly
decreased the reaction rate and even the CA selectivity with some
ligands, such as dppp, resembling the results obtained with PPh
3
.
◦
For example, using 3% RhCl
3
at 80 C, a longer reaction time
was required for the reaction to go to completion — 3% binap
loading (30 h) compared to 10% loading (15 h) —although the
CA selectivity and yields remained unchanged (Table 3, entries 13
In sharp contrast to results obtained with a,b-unsaturated
amides, the pH value of the aqueous phase and B : O ratio
showed few effects on the HC : CA selectivity in the reaction
of butyl acrylate with phenyl boronic acid catalyzed by the
and 14). The conjugate addition of PhB(OH)
dimethyl acrylamide went to completion within 10 h giving 93%
yield and 100% CA selectivity with 10% dppp and 3% RhCl
Table 3, entry 9). However, when the dppp loading was reduced
3
(1.2 equiv) to N,N-
3
(
Rh–PPh toluene–water system. The HC : CA selectivity is
3
to 3% both the CA : HC selectivity and yield decreased significantly
to 80 : 20 and 66%, respectively, with longer reaction time (Table 3,
entry 16). These results indicated that phosphine ligands play
an important role in the formation and reactivity of a-rhodium
amides.
Electronic effects of the boronic acid aryl group on the HC : CA
selectivity in the reactions with acrylamides were also investigated
and the results are listed in Table 4. Clearly, electronic effects from
aryl boronic acids on both Heck-type coupling and conjugate
addition were negligible. For example, under conditions favoring
conjugate addition with dppp as the ligand, all the tested aryl
boronic acids, including p-methoxy and p-acetyl phenyl boronic
acids, reacted to provide CA products with >99% selectivity
consistently high (98% or higher) with excess (2 equiv.) butyl
acrylate albeit the yields and reaction rate varied with the change of
reaction conditions (Table 5, entries 1–4). Even with excess phenyl
boronic acid (2–4 equiv.), the Heck-coupling was still favored
(Table 5, entries 5 and 6). These results clearly indicated that the
carbonyl structures could significantly affect the b-H elimination
vs. hydrolysis competition of the a-rhodium carbonyls. With the
stronger donating ligand tricyclohexyl phosphine, PCy , the CA
3
selectivity increased significantly, but the Heck-type coupling was
still favored (Table 5, entries 7 and 8).
The chelate effects of most of the bidentate phosphine ligands
on the HC : CA selectivity were smaller in the reaction of butyl
acrylate than those observed with acrylamides under similar
conditions. For example, the CA selectivity increased to 20–45%
with bidentate ligands of dppm, dppe, dppf, dppb and dppp using
(
Table 4, entries 1, 2, 4, 6 and 8). Heck-type coupling also
proceeded with high HC : CA selectivity ranging from 85 : 15
for 3,5-bis(trifluoromethyl)phenyl boronic acid to 99 : 1 for p-
methoxy and p-acetyl phenyl boronic acids under the HC-favored
conditions (Table 4, entries 3, 5, 7 and 9). The poor yields in the
reactions of 3,5-bis(trifluoromethyl)phenyl boronic acid may be
attributed to deboronation since 1,3-bis(trifluoromethyl) benzene
was detected as a component in the product mixtures.
2 equiv. phenyl boronic acid without K
2
CO , while the Heck-
3
type coupling still proceeded with >92% selectivity with bidentate
ligands dppm, dppf, dppb and dppp, except for dppe, with excess
(2 equiv.) butyl acrylate and 3 equiv. K
2
CO (Table 5, entries 9–
3
18). These were obviously different to the selectivities observed
in the reactions of acrylamides (see Table 3). However, similar
to the reactions of acrylamides, when binap was used as the
supporting ligand for rhodium, the CA product was obtained in
high selectivity and yields under both the HC- and CA-favored
conditions (Table 6, entries 19–22). For example, 92 : 8 CA :
HC selectivity and 85% yield were observed in the reaction of
Table 4 Electronic effects of aryl boronic acids on the HC : CA selectivity
in the reactions with acrylamides
PhB(OH)
2
with excess acrylate (2 equiv.), in the presence of 3%
CO . The CA : HC selectivity
RhCl , 6% binap and 3 equiv. K
3
2
3
further increased to 99 : 1 using excess phenyl boronic acid (2
a
b
c
Entry Ar
R
Cond. t/h HC : CA Yield (%)
◦
equiv.) in the absence of K
2
CO
3
at 80 C. When the loading of
binap was decreased from 15% to 3–6% mol, the reaction became
slower albeit the CA selectivity and yields were not markedly
affected (Table 6, entries 21–24).
1
2
3
4
5
6
7
8
9
p-CH
3
3
3
3
3
C
OC
OC
COC
COC
6
H
4
CH
CH
CH
CH
CH
H
H
CH
CH
3
3
3
3
3
A
A
B
A
B
A
B
A
B
5
5
5
6
7
6
6
6
7
0 : 100 90
0 : 100 93
p-CH
p-CH
p-CH
p-CH
Ph
6
H
4
6
H
4
98 : 2
<1 : 99
>99 : 1
<1 : 99
91 : 9
79
71
73
90
69
43
49
6
H
H
4
4
Since esters and amides display comparable enolization ten-
dencies, the rationale for the comparatively lower tendency of
a,b-unsaturated esters than the corresponding amides towards
conjugate addition may lie in the lower rhodium coordinating
capability of O compared to N. The coordination of N to Rh would
disfavor the b-H elimination in the a-rhodium carbonyl form and
enhance the enolization by formation of chelating structure in the
enolate form, thus increasing the tendency to conjugate addition
6
Ph
3,5-(CF
3,5-(CF
3
3
)
)
2
2
C
C
6
6
H
H
3
3
3
3
<1 : 99
85 : 15
a
◦
A: Boronic acid : olefin = 1.2 : 1 (mol), L = dppp (10% mol), 80 C;
(12% mol), 3equiv. K CO
B: Boronic acid : olefin = 1 : 2, L=PPh
3
,
3
2
◦
b
1
1
20 C. Determined by H NMR; no cis isomer of HC products detected.
c
Isolated yield (%).
(
Scheme 3).
This journal is © The Royal Society of Chemistry 2007
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a
Table 5 HC : CA selectivity in the reaction of butyl acrylate with phenyl boronic acid under various conditions
b
◦
c
d
Entry
B : O
Catalyst
Base
T/ C
t/h
HC : CA
Yield (%)
1
2
3
1 : 2
1 : 2
1 : 2
1 : 2
2 : 1
4 : 1
1 : 2
2 : 1
1 : 2
2 : 1
1 : 2
2 :1
1 : 2
2 : 1
1 : 2
2 : 1
1 : 2
2 : 1
1 : 2
2 : 1
1.5 : 1
2 : 1
2 : 1
2 : 1
3% RhCl
3% RhCl
3% RhCl(PPh
3%RhCl(PPh
3% RhCl –12% PPh
3% RhCl(PPh
3
3
–12% PPh
–12% PPh
3
3
K
—
—
NH
—
K
K
—
K
—
K
—
K
—
K
—
K
—
2
CO
3
120
120
120
120
80
80
120
80
120
80
120
80
120
80
120
80
5
20
6
48
20
8
3
10
5
10
6
20
25
25
6
25
6
10
5
100 : 0
100 : 0
99 : 1
85
89
90
78
63
75
80
54
89
68
55
30
35
20
81
40
91
69
85
89
91
95
96
89
3
)
3
e
4
3
)
3
4
Cl
98 : 2
5
6
7
8
9
3
3
91 : 9
74 : 26
70 : 30
55 : 45
97 : 3
67 : 33
92 : 8
80 : 20
73 : 27
55 : 45
93 : 7
60 : 40
93 : 7
55 : 45
8 : 92
1 : 99
4 : 96
2 : 98
2 : 98
3 : 97
3
)
3
2
CO
CO
3
3
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
–12% PCy
–30% PCy
–6% dppf
–15% dppf
–6% dppm
–15% dppm
–6% dppe
–15% dppe
–6% dppp
–15% dppp
–6% dppb
–15% dppb
–6% binap
–15% binap
–15% binap
–15% binap
–6% binap
–3% binap
3
3
2
2
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
2
2
2
2
120
80
120
80
80
80
K
—
—
K
—
—
2
10
15
20
30
36
2
CO
3
80
80
a
b
c
1
d
See ESI for more data on screening the reaction condition.† 3 equiv. used. Determined by H NMR; no cis isomer of HC product detected. Isolated
e
4
yield (%). Saturated NH Cl (aq.) used.
Table 6 Influence of substrate structures on the HC : CA selectivity in reactions of acrylates with aryl boronic acids
ꢀ
ꢀꢀ
a
b
c
Entry
Ar
R/R /R
Cond.
t/h
HC : CA
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
p-CH
p-CH
p-CH
p-CH
p-CH
3,5-(CF
3,5-(CF
Thiophene-3
3
3
3
3
3
C
OC
OC
COC
COC
6
H
4
Bu/H/H
Bu/H/H
Bu/H/H
Bu/H/H
Bu/H/H
Bu/H/H
Bu/H/H
Bu/H/H
Bu/H/H
Me/H/H
Me/H/Me
Me/H/Me
Et/Me/H
Et/Me/H
B
B
C
B
C
B
C
B
C
B
B
C
B
C
4
4
12
5
15
6
12
4
12
5
15
30
18
30
100 : 0
100 : 0
0 : 100
99 : 1
0 : 100
96 : 4
25 : 75
99 : 1
0 : 100
100 : 0
95 : 5
89
90
96
70
95
65
27
48
67
78
18
65
21
78
6
H
4
6
H
4
6
H
H
H
H
4
4
6
3
)
)
2
C
C
6
3
3
3
2
6
Thiophene-3
1
1
1
1
1
Ph
Ph
Ph
Ph
Ph
0 : 100
37 : 63
0 : 100
a
b
, 120 ◦C; C: Boronic acid : olefin = 1.2 : 1 (mol), L = binap (10% mol), 80 ◦C.
B: Boronic acid : olefin = 1 : 2, L = PPh
3
(12% mol), 3 equiv. K CO
Determined by H NMR; no cis isomer of HC products detected. Isolated yield (%).
2
3
1
c
As with amides, the electronic effects of aryl moieties on the
2, 4 and 6). Both electron-rich and -poor aryl boronic acids,
b-H elimination vs. hydrolysis competition of a-rhodium esters
were negligible in most cases. High HC selectivity was consistently
obtained for the reactions of both electron-rich and -poor aryl
boronic acids under the HC-favored conditions (Table 6, entries 1,
p-methoxy and p-acetyl phenyl boronic acids offered conjugate
addition products in excellent yields and selectivity under the op-
timized conditions for the conjugate addition using binap (Table 6,
entries 3 and 5), except for 3,5-bis(trifluoromethyl) phenyl boronic
3
060 | Dalton Trans., 2007, 3055–3064
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much better than those in the Heck-type coupling for substituted
a,b-unsaturated esters, consistent with the sensitivity of Heck-type
coupling to steric hindrance of olefins.
Due to the ready enolization of ketones, rhodium-catalyzed
reactions of aryl boronic acids with a,b-unsaturated ketones which
gave exclusively conjugate addition products were previously
1,10
reported.
Encouraged by the observation of the substantial
effects of supporting ligands and reaction conditions on the b-H
elimination vs. hydrolysis competition of the a-rhodium carbonyl
intermediates in the Rh-catalyzed reactions of aryl boronic acids
with a,b-unsaturated esters and amides, we further explored the
possibility to effect rhodium-catalyzed Heck-type coupling of a,b-
unsaturated ketones with aryl boronic acids using the reaction
of methyl vinyl ketone (MVK) with phenyl boronic acid as a
model. Considering that MVK was unstable under basic (K
2
CO )
3
conditions for the reactions of a,b-unsaturated esters and amides,
non-basic conditions were used. To our surprise, Heck-type
coupling occurred with good HC selectivity and overall yields
Scheme 3 Rationale for the increased tendency to conjugate addition of
a,b-unsaturated amides compared to esters.
using the Wilkinson catalyst, (PPh ) RhCl, in the toluene–water
3
3
acid which gave lower HC : CA selectivity (25 : 75) and poor
yield (27%) due to deboronation (Table 6, entry 7). Thiophene-
biphasic system. Similar to a,b-unsaturated esters and amides, the
dependence of the HC : CA selectivity on the B : O ratio was again
observed in the reaction of MVK (Table 7).
3
-boronic acid also provided Heck-type coupling and conjugate
addition products with excellent selectivity in modest yields under
HC- and CA-favored conditions, respectively (Table 6, entries 8
and 9) while complete deboronation occurred for thiophene-2-
boronic acid under both sets of conditions. The b-methyl substi-
tuted a,b-unsaturated ester, crotonate, gave the conjugate addition
product as the major product even under HC-favored conditions;
while the a-methyl a,b-unsaturated ester, methyl methacrylate, still
favored the Heck-type coupling (95 : 5) albeit the reaction became
slower than with the unsubstituted acrylate (Table 6, entries 11
and 13). Not surprisingly, the CA selectivity for the reactions of
both crotonate and methyl methacrylate under the CA-favored
condition was exclusive (Table 6, entries 12 and 14). Besides the
selectivity, the chemical yields in the conjugate addition were also
Using equivalent to excess MVK, Heck-type coupling occurred
with HC : CA selectivity varying from 46 : 54 (1 equiv. MVK) to
73 : 27 (2 equiv. MVK) and 84 : 16 (4 equiv. MVK). However, the
HC selectivity did not significantly increase further with 8 equiv.
MVK (Table 7, entries 1–4). However, exclusive conjugate addition
was observed when 2 equiv. phenyl boronic acid was used under
otherwise identical conditions. A similar result was obtained with
respect to both HC : CA selectivity and chemical yield using the
combination of RhCl
3
and PPh
3
in place of RhCl(PPh
3
3
) although
the reaction rate decreased (Table 7,entries 5 and 6). Chelate effects
of diphosphines were also observed in the competition between
b-H elimination and hydrolysis of the a-rhodium ketone. The
conjugate addition occurred favorably with all tested diphosphines
Table 7 HC : CA selectivity in the reaction of phenyl boronic acid with MVK under various conditions
◦
a
b
Entry
B : O
Catalyst
T/ C
t/h
HC : CA
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
1 : 2
1 : 4
1 : 8
1 : 1
2 : 1
2 : 1
1 : 4
1 : 4
1 : 4
1 : 4
1 : 4
1 : 4
1 : 1
2 : 1
3% RhCl(PPh
3% RhCl(PPh
3% RhCl(PPh
3% RhCl(PPh
3% RhCl(PPh
3
3
3
3
3
)
)
)
)
)
3
3
3
3
3
120
80
80
80
80
15
15
15
15
15
36
24
24
24
24
24
24
36
36
73 : 27
84 : 16
87 : 13
46 : 54
0 : 100
0 : 100
1 : 99
30 : 70
1 : 99
39 : 61
1 : 99
89
94
93
58
56
55
65
38
75
46
75
51
56
84
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3% RhCl
3
3
3
3
3
3
3
3
3
–20% PPh
–6% dppf
–6% dppe
–6% dppb
–6% dppm
–6% dppp
–6% binap
–15% binap
–15% binap
3
80
120
120
120
120
120
120
80
1
1
1
1
1
0 : 100
1 : 99
0 : 100
c
80
a
1
b
c
Determined by H NMR; no cis isomer of HC product detected. Isolated yield (%). Use of dppf, dppm, dppe, dppb and dppp as the supporting
ligand also gave exclusive conjugate addition product but in much lower yields (11–31% by GC), see ESI for data in detail.†
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Dalton Trans., 2007, 3055–3064 | 3061

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regardless of the B : O ratios. The bite angle effects of chelating
diphosphine ligands on the HC : CA selectivity were also
remarkable. Although the conjugate addition was favored, the
Heck-type coupling product was observed with 30–39% selectivity
using excess olefin (4 equiv. MVK) with bidentate ligands having
entry 9). These results indicated that the aryl electron-donating
groups exerted little influence on the competition between b-H
elimination and hydrolysis of the a-rhodium ketones. However, p-
acetyl phenyl boronic acid gave a near 1 : 1 mixture of Heck-type
coupling and conjugate addition products in repeated runs under
the HC-favored condition with 3–6 equiv. MVK (Table 8, entry 5).
To investigate whether or not an electron-withdrawing or carbonyl
group on the phenyl moiety would affect the b-H elimination of the
corresponding a-rhodium ketones, the reactions of p-fluoro and
p-methoxycarbonyl phenyl boronic acids were conducted under
otherwise identical conditions. However, both displayed better
HC : CA selectivity than p-acetyl phenyl boronic acid (Table 8,
entries 6 and 7). The reason for the loss of selectivity in the reaction
of p-acetyl phenyl boronic acid is not clear at present.
◦
◦
small bite angles, dppm (71.53 ) and dppe (82.55 ) (Table 7,
entries 8 and 10). However, high CA selectivity (>99%) was
obtained with bidentate ligands having large bite angles, dppf
◦
◦
◦
◦
(
98.74 ), dppp (91.56 ), dppb (97.07 ) and binap (92.77 ) under
otherwise identical conditions (Table 7, entries 7, 9, 11 and 12). It
has to be pointed out that the structural influence of the bidentate
phosphine ligands on the HC : CA selectivity was only observed
with excess MVK (4 equiv.). Using excess boronic acid (2 equiv.)
the conjugate addition product was obtained exclusively in various
yields.
The influence of structures of aryl boronic acids and a,b-
unsaturated ketones on the b-H elimination vs. hydrolysis compe-
tition of the a-rhodium ketone intermediates was also investigated
Considering that basic conditions (aq. K
to favor Heck-type coupling in the reactions of a,b-unsaturated es-
ters and amides and the instability of MVK to K CO (aq.), phenyl
vinyl ketone (PVK) was used to explore if the presence of K CO
could increase HC selectivity in the reactions of a,b-unsaturated
ketones with aryl boronic acids catalyzed by (PPh RhCl in the
2
CO
3
) have been found
2
3
2
3
(
Table 8). Under the CA-favored condition, conjugate addition
products were obtained in >99 : 1 CA : HC selectivity in all the
reactions of the tested aryl boronic acids with MVK, such as p-
methyl, p-methoxy and p-acetyl phenyl boronic acids (Table 8,
entries 2, 4 and 8). The heterocyclic boronic acid, thiophene-
)
3 3
toluene–water biphasic system. The HC selectivity in the reaction
of PVK was lower than that of MVK, consistent with the stronger
enolization tendency of the a-rhodium ketone resulting from PVK
than that from MVK. However, almost no change of HC : CA
selectivity was observed for the reactions of PVK in the presence
3
-boronic acid, also reacted similarly to the phenyl analogues,
givingexclusively conjugate additionproduct in 73%yield (Table 8,
entry 10). The conjugate addition of phenyl boronic acid to phenyl
vinyl ketone (PVK) and 2-cyclohexen-1-one (CEO) also occurred
with exclusive CA selectivity and modest yields (Table 8, entries 14
and 16). Under the HC-favored conditions, the reactions of p-
methyl and p-methoxy phenyl boronic acids with MVK showed
HC : CA selectivity comparable to that of phenyl boronic acid
of 3 equiv. K
2
CO (Table 8, entries 11–13). Probably due to
3
the depression of the b-substituent to b–H elimination of the a-
rhodium ketone intermediate, conjugate addition was still favored
even with excess cyclohexen-1-one (CEO) albeit the yield was very
poor. No reaction was observed for benzylidene acetone under
15
Heck-type coupling conditions. By effecting rhodium-catalyzed
Heck-type coupling of aryl boronic acids with a,b-unsaturated
ketones, it is further confirmed that the competition between
(
Table 8, entries 1 and 3). Thiophene-3-boronic acid even displayed
the highest HC selectivity (90 : 10) with 70% yield (Table 8,
Table 8 Influence from substrate structures on the HC : CA selectivity in the reactions of a,b-unsaturated ketones with aryl boronic acids
a
a
c
Entry
Ar
Olefin
Cond.
t/h
HC : CA
Yield (%)
1
2
3
4
p-CH
p-CH
p-CH
p-CH
p-CH
p-CH
3
3
3
3
3
3
C
C
OC
OC
COC
CO
6 4
H
6
6
H
H
4
MVK
MVK
MVK
MVK
MVK
MVK
MVK
MVK
MVK
MVK
PVK
D
E
D
E
D
D
D
E
D
E
D
D
D
E
D
E
20
50
15
40
12
12
12
40
10
40
25
20
20
40
40
40
80 : 20
0 : 100
73 : 27
0 : 100
49 : 51
77 : 23
71 : 29
1 : 99
90 : 10
0 : 100
47 : 53
43 : 57
47 : 53
0 : 100
25 : 75
0 : 100
93
80
88
83
87
89
83
91
70
73
79
80
85
52
<10
65
4
6
H
4
6
H
4
d
5
6
H
4
6
7
8
9
0
1
2
3
4
5
6
2
C
6
H
4
p-FC
p-CH
3
6 4
COC H
Thiophene-3
1
1
1
1
1
1
1
Thiophene-3
Ph
Ph
Ph
Ph
Ph
Ph
e
PVK
PVK
PVK
CEO
e,f
CEO
a
◦
D: 3% Rh(PPh
3
)
3
Cl, 4 equiv. olefin, in toluene : H
2
O (3 : 1, v/v), 120 C; E: 3% RhCl
3
-15% (± )-binap, 2 equiv. aryl boronic acid, in toluene : H
2
O (3 : 1,
◦
b
1
c
d
v/v), 80 C. Determined by H NMR; no cis isomer of HC products detected. Isolated yield (%). The reaction was repeated 3 times giving HC : CA
e
f
2 3
selectivity 45 : 55, 52 : 48, 49 : 51. In the presence of 3 equiv. K CO . 8 equiv. PVK used.
3
062 | Dalton Trans., 2007, 3055–3064
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Scheme 4 A slightly modified mechanism for the rhodium-catalyzed reactions of aryl boronic acids with a,b-unsaturated carbonyls.
hydrolysis and b-H elimination of a-rhodium carbonyls could be
tunable, even for the most enolizable a-rhodium ketones.
The competition of Heck-type coupling vs. conjugate addition
observed in the rhodium-catalyzed reactions of aryl boronic acids
with a,b-unsaturated carbonyls could be reasonably explained
by the previously proposed mechanism with slight modifications
esters and amides, is consistent with the OA–RE hydrolysis path
for Rh–H instead of direct hydrolysis like ionic metal hydrides.
However, the increase of CA selectivity in the presence of excess
aryl boronic acids is obscure in the currently accepted enolization–
hydrolysis–transmetallation mechanism. For a given type of
a,b-unsaturated carbonyl, the increase in CA selectivity upon
increasing the concentration of aryl boronic acids means that the
presence of excess aryl boronic acids in the reaction mixture would
push the reaction to CA direction, implying that aryl boronic acids
should be involved in the rate-determining steps in the cycle for
conjugate addition. This would require a pre-condition for the
enolization–hydrolysis–transmetallation mechanism of conjugate
addition to work. That is, the transmetallation between aryl
boronic acids and rhodium hydroxide, Rh–OH, has to be involved
in the rate-determining steps in the conjugate addition, but not
in the Heck-type coupling, since both cycles consist of the same
step. Alternatively, we tentatively propose a direct transmetallation
between the enolate 5 (instead of Rh–OH) and aryl boronic
acids generating Rh–Ar species 1 and a boron enolate to explain
the increase of the CA selectivity in the presence of excess aryl
boronic acids, considering that boron enolates have been widely
proposed in the reactions of carbonyl compounds promoted by
(
Scheme 4).
The b-H elimination of the a-rhodium carbonyl 2 required
for Heck-type coupling to occur necessitates that the rhodium
ion is unsaturatedly coordinated with respect to both steric and
electronic aspects, which is closely related to the supporting ligand,
phosphines. Thus, comparing with PPh , a chelating diphosphine,
3
depressing the formation of an open coordinate site on rhodium
ion of 2, disfavors the Heck-type coupling, in other words, favoring
the conjugate addition. The further increased CA selectivity with
large bite angle diphosphines is obviously consistent with the
shrinking of the coordination sphere available for approach of
14
the b-H of alky moiety. Structural effects of the carbonyls on the
competition of hydrolysis vs. b-H elimination could be understood
on the basis of carbonyl enolization and coordination. With
carbonyls reluctant to enolize, for example, esters and amides,
the Heck-type coupling could easily be promoted. For a substrate
with readily enolizable carbonyl group, such as ketones, the Heck-
type coupling is less favored than the conjugate addition. The
beneficial effects of the presence of excess of a terminal olefin on
Heck-type coupling come from the conversion of Rh–H species
generated from b-H elimination into 3, which is readily converted
into Rh–Ar 1 through the OA–RE hydrolysis path followed by
transmetallation, thus, favoring the Heck-type coupling. The co-
existing OA–RE hydrolysis of the rhodium hydride with water,
generating a rhodium hydroxide, Rh–OH, which is then converted
into 1 through the transmetallation with aryl boronic acid,
accounts for reasonable Heck-type coupling selectivity and yields
in the reactions with one equivalent of a,b-unsaturated esters and
amides. Higher HC selectivity under basic conditions, as opposed
to neutral or acidic conditions, in the reactions of a,b-unsaturated
16
dialkyl boronates. Of course, increasing the proportion of aryl
boronic acids means reduction of the proportion of olefins, which
depressed the consumption of Rh–H via the conjugate reduction
path, in other words, increased the conjugate addition selectivity.
Conclusions
In conclusion, through a systematic investigation of the factors
affecting the selectivity of Heck-type coupling vs. conjugate
addition, (discounting the intrinsic nature of rhodium and the
enolization of carbonyls), we have found that the supporting lig-
ands on rhodium, the ratio of aryl boronic acid to a,b-unsaturated
carbonyl and the pH value of aqueous phase play important roles,
even decisive in some cases, in the hydrolysis vs. b-H elimination
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competition of the a-rhodium carbonyl intermediates in the
phosphine–rhodium catalyzed C–C bond forming reactions of
aryl boronic acids with a,b-unsaturated carbonyls in the toluene–
2 (a) T. Hayashi, M. Takahashi, Y. Takaya and M. Ogasawara, J. Am.
Chem. Soc., 2002, 124, 5052–5058; (b) A. Kina, H. Iwamura and T.
Hayashi, J. Am. Chem. Soc., 2006, 128, 3904–3905.
For Ru: (a) E. J. Farrington, J. M. Brown, C. F. J. Barnard and E.
Rowsell, Angew. Chem., Int. Ed., 2002, 41, 169–171; For Ir: (b) T. Koike,
X. Du, T. Sanada, Y. Danda and A. Mori, Angew. Chem., Int. Ed., 2003,
3
H O biphasic system. Subsequently, the reactions of aryl boronic
2
acids with a,b-unsaturated esters, amides and ketones have been
directed to favor both conjugate addition and Heck-type coupling
by synergistically tuning the supporting ligands on rhodium, the
boronic acid : olefin ratio and the other reaction conditions. In fact,
the Heck-type coupling was carried out for acrylates, acrylamides
and methyl vinyl ketone (MVK) with selectivity up to 100%,
4
1
2, 89–92; For Pd: (c) C. S. Cho and S. Uemura, J. Organomet. Chem.,
994, 465, 85–92; (d) X. Du, M. Suguro, K. Hirabayashi, A. Mori, T.
Nishikata, N. Hagiwara, K. Kawata, T. Okeda, H. F. Wang, K. Fugami
and M. Kosugi, Org. Lett., 2001, 3, 3313–3316; (e) M. M. S. Andappan,
P. Nilsson and M. Larhed, Chem. Commun., 2004, 218–219.
A. Mori, Y. Danda, T. Fujii, K. Hirabayashi and K. Osakada, J. Am.
Chem. Soc., 2001, 123, 10774–10775.
T. Yoshida, T. Okano, Y. Ueda and S. Otsuka, J. Am. Chem. Soc., 1981,
103, 3411–3422.
4
5
6
7
9
8% and 84%, respectively, using PPh
with excess olefins in the presence of K
9% conjugate addition selectivity was obtained using bidentate
ligands with a large bite angle, such as dppp and binap, with excess
boronic acids in the absence of K CO . These results clearly imply
3
as the supporting ligand
2
CO , while higher than
3
M. Lautens, A. Roy, K. Fukuoka, K. Fagnou and B. Mart ´ı n-Matute,
J. Am. Chem. Soc., 2001, 123, 5358–5359.
9
For examples of structurally characterized a-rhodium carbonyls: (a) C.
Bianchini, C. Mealli, A. Meli, D. M. Proserpio, M. Peruzzini, F.
Vizza and P. Frediani, J. Organomet. Chem., 1989, 369, C6–C10; (b) J.
Ott, L. M. Venanzi, C. A. Ghilardi, S. Midollini and A. Orlandini,
J. Organomet. Chem., 1985, 291, 89–100.
2
3
that high conjugate addition selectivity should not be assumed in
the rhodium-catalyzed reactions of aryl boronic acids with a,b-
unsaturated carbonyl compounds.
8
9
G. Zou, Z. Wang, J. Zhu and J. Tang, Chem. Commun., 2003, 2438–
2
439.
(a) L. Navarre, S. Darses and J.-P. Genet, Chem. Commun., 2004, 1108–
Acknowledgements
1
2
109; (b) L. Navarre, S. Darses and J.-P. Genet, Adv. Synth. Catal.,
006, 348, 317–322.
We thank National Natural Science Foundation of China
10 M. Lautens, J. Mancuso and H. Grover, Synthesis, 2004, 2006–2014.
11 J. L. Gras, K. J. Gombatz and G. Buchi, Org. Synth., 1981, 60,
(
20402006) for financial support.
8
8–90.
1
2 It was reported that RhCl showed much better performance as a
3
catalyst precursor than Rh(I) precursors, such as RhCl(cod), in the
rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes: A.
F u¨ rstner and H. Krause, Adv. Synth. Catal., 2001, 343, 343–350.
References
1
For reviews: (a) K. Yoshida and T. Hayashi, in: Modern Rhodium-
Catalyzed Organic Reactions, ed. P. A. Evans, Wiley-VCH, Weinheim,
13 For the bite angle data of phosphines see: (a) P. Dierkes and P. W. N. M.
Leeuwen, J. Chem. Soc., Dalton Trans., 1999, 1519–1529; (b) Z. Freixa
and P. W. N. M. Leeuwen, Dalton Trans., 2003, 1890–1901.
14 One of the reviewers suggests that the low activity of the smaller
bidentates may be a consequence of forming coordinatively saturated
tetraphosphine complexes of rhodium.
2
005, pp. 55-78; (b) K. Yoshida and T. Hayashi, in Boronic Acids, ed.
D. G. Hall, Wiley-Vch Verlag GmbH & Co. KGaA, Weinheim, 2005,
pp. 171-203; (c) T. Hayashi, Pure Appl. Chem., 2004, 76, 465–475;
(
(
d) T. Hayashi and K. Yamasaki, Chem. Rev., 2003, 103, 2829–2844;
e) K. Fagnou and M. Lautens, Chem. Rev., 2003, 103, 169–196; (f) T.
Hayashi, Synlett, 2001, 879–887; For representative examples: (g) M.
15 For cinnamaldehyde, instead of conjugate addition or Heck-type
coupling, a new type of coupling-conjugate reduction cascade reaction
Sakai, H. Hayashi and N. Miyaura, Organometallics, 1997, 16, 4229–
4
231; (h) Y. Takaya, M. Ogasawara, T. Hayashi, M. Sakai and N.
3
occurred with the Rh–PPh biphasic system. Z. Wang, G. Zou and
J. Tang, Chem. Commun., 2004, 1192–1193.
16 (a) A. Abiko, Acc. Chem. Res., 2004, 37, 387–395; (b) Y. Mori,
K. Manabe and S. Kobayashi, Angew. Chem., Int. Ed., 2001, 40,
2815–2818; (c) Y. Mori, J. Kobayashi, K. Manabe and S. Kobayashi,
Tetrahedron, 2002, 58, 8263–8268; (d) K. Yoshida, M. Ogasawara and
T. Hayashi, J. Org. Chem., 2003, 68, 1901–1905.
Miyaura, J. Am. Chem. Soc., 1998, 120, 5579–5580; (i) M. Kuriyama,
K. Nagai, K. Yamada, Y. Miwa, T. Taga and K. Tomioka, J. Am.
Chem. Soc., 2002, 124, 8932–8939; (j) J.-F. Paquin, C. Defieber, C. R. J.
Stephenson and E. M. Carreira, J. Am. Chem. Soc., 2005, 127, 10850–
1
0851; (k) R. Shintani, W. Duan, T. Nagano, A. Okada and T. Hayashi,
Angew. Chem., Int. Ed., 2005, 44, 4611–4614.
3
064 | Dalton Trans., 2007, 3055–3064
This journal is © The Royal Society of Chemistry 2007