Ligand-free nickel-catalysed 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1002/adsc.201400761

A simple and efficient ligand-free nickel-based catalytic system has been developed for the 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds. With catalyst loadings of 1-2 mol%, a series of 1,4-adducts from chalcones and cinnamates was obtained in moderate to excellent yields within 5-30 min under a nitrogen atmosphere and microwave irradiation. The 1,4-addition of arylboronic acids to acrylates is less efficient.

Full text of DOI:10.1002/adsc.201400761

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DOI: 10.1002/adsc.201400761
Ligand-Free Nickel-Catalysed 1,4-Addition of Arylboronic Acids
to a,b-Unsaturated Carbonyl Compounds
Wen Chen,a Lu Sun,a Xi Huang,a Jiayi Wang,a Yanqing Peng,a
and Gonghua Songa,*
a
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology,
Shanghai 200237, Peopleꢀs Republic of China
Fax: (+86)-21-6425-2603; e-mail: ghsong@ecust.edu.cn
Received: August 10, 2014; Revised: February 3, 2015; Published online: April 23, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400761.
Abstract: A simple and efficient ligand-free nickel- and microwave irradiation. The 1,4-addition of aryl-
based catalytic system has been developed for the boronic acids to acrylates is less efficient.
1,4-addition of arylboronic acids to a,b-unsaturated
carbonyl compounds. With catalyst loadings of 1–
2 mol%, a series of 1,4-adducts from chalcones and Keywords: 1,4-addition; arylboronic acids; ligand-
cinnamates was obtained in moderate to excellent free conditions; nickel; a,b-unsaturated carbonyl
yields within 5–30 min under a nitrogen atmosphere compounds
Introduction
trifluoroacetic anhydride (TFA) as the only catalyst
for the 1,4-addition of organoboranes to a,b-unsatu-
The transition metal-catalysed 1,4-addition of organo- rated carbonyl compounds. Unfortunately, for the 1,4-
metallic reagents to a,b-unsaturated carbonyl com- addition reaction of phenylboronic acid to chalcone,
pounds is a useful method for the construction of b- 1 equivalent of TFA and an 18-hour reaction time
substituted carbonyl compounds in modern organic were required to obtain the target compound in mod-
synthesis. Within the context of the addition of orga- erate yield (75%).[9] Therefore, an inexpensive, effec-
noboron reagents, rhodium complexes have been tive and ligand-free catalytic system for such a trans-
widely used as effective catalysts since the first report formation is still in high demand.
by Miyaura et al. in 1997.[1] Extensive studies have
Herein, we report for the first time a simple,
been conducted on rhodium complexes with a variety ligand-free nickel salt catalytic system for the 1,4-ad-
of asymmetric ligands to yield enantioenriched prod- dition of arylboronic acids to a,b-unsaturated carbon-
ucts.[2] Over the past decade, palladium,[3] nickel,[4] yl compounds. With catalyst loadings of only 1–
ruthenium,[5] platinum,[6] copper[7] and cobalt[8] com- 2 mol%, various 1,4-adducts of chalcones and cinna-
plexes have also been used to catalyse the 1,4-addi- mates were obtained in moderate to excellent yields
tion of organoboranes to a,b-unsaturated carbonyl under a nitrogen atmosphere and microwave irradia-
compounds. In most cases, however, specific organo- tion. Reactions of arylboronic acids with acrylates
metallic reagents, complex ligands and long reaction were generally less efficient.
times were necessary to achieve satisfactory results.
For example, a nickel-based catalytic system for the
conjugate addition of arylboronates to a,b-unsaturat- Results and Discussion
ed ketone compounds was originally reported by Hay-
ashiꢀs group.[4a] Nevertheless, 20 mol% of diphenyl- Initially, we investigated the potential catalytic activi-
acetylene was needed as the co-catalyst and the reac- ty of several transition metals, including Co, Cu, Fe
tion mixture had to be maintained at 608C for 24 h. and Ni, in various oxidation states for the model reac-
One of the two exceptions was reported by Hayashi tion of chalcone with phenylboronic acid (Table 1, en-
and Sasaki, who used K2PtCl4, an expensive noble- tries 1–10). Only nickel(II) salts showed positive re-
metal reagent, as the ligand-free metal catalyst.[6b] An- sults. Thus, further optimizations were evaluated
other example was reported by Csµkþ et al., who used using Ni(OAc)2·4H2O as the catalyst. Interestingly,
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Ligand-Free Nickel-Catalysed 1,4-Addition of Arylboronic Acids
Table 1. 1,4-Addition of phenylboronic acid to chalcone in
Table 2. 1,4-Addition of phenylboronic acid to chalcone in
the presence of different metal catalysts.[a]
the presence of various nickel catalysts.[a]
Yield [%][b]
Entry
Catalyst
Yield [%][b]
Entry
Metal
1
2
3
4
5
Ni(OH)2·H2O
NiSO4·6H2O
Ni(acac)2·2H2O
NiCl2·6H2O
5
1
2
3
4
5
6
7
8
Co(OAc)2·4H2O
Nano Cu(0) (80–100 nm)
CuCl2·2H2O
Cu(OAc)2·H2O
Nano Fe(0) (80 nm)
FeCl3·6H2O
Nano Ni(0) (20–100 nm)
NiCl2·6H2O
Ni(acac)2·2H2O
Ni(OAc)2·4H2O
Ni(OAc)2·4H2O
Ni(OAc)2·4H2O
<1
<1
<1
<1
<1
<1
<1
7
2
9
32
80
29
40
78
85
Ni(NO3)2·6H2O
[a]
Reaction conditions: 0.5 mmol of chalcone (1a), 1.5 equiv.
of phenylboronic acid (2a), 1 mol% of nickel catalyst,
1 equiv. of KOH, 2.0 mL of toluene under reflux for
40 min under nitrogen.
9
10
11[c]
12[c,d]
[b]
GC yield (dodecane as internal standard).
[a]
Table 3. Optimization of reaction conditions.[a]
Reaction conditions: 0.5 mmol of chalcone (1a), 1.5 equiv.
of phenylboronic acid (2a), 10 mol% of metal, 1 equiv. of
KOH, 1.0 mL of toluene, heated in an oil bath under
reflux for 24 h.
GC yield (dodecane as internal standard).
Under nitrogen.
[b]
[c]
[d]
Entry Cat.
[mol%]
Base/equiv.
Equiv. Solvent
2a
Yield
Vol. [mL] [%][b]
1 mol% of catalyst was used, and the reaction time was
40 min.
1
2
3
4
5
6
7
8
5
2
1
0.5
0.25
1
1
1
1
1
1
1
1
1
1
1
KOH/1
KOH/1
KOH/1
KOH/1
KOH/1
KOH/1
Et3N/1
K2CO3/1
Cs2CO3/1
K3PO4·3H2O/1 1.5
NaOH/1
CsOH·H2O/1
KOH/0.75
KOH/1.25
KOH/1.5
KOH/1
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2.0
2.0
2.0
2.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
60
92
85
83
80
90
when the reaction was performed under a nitrogen at-
mosphere, the yield increased from 9% to 32%
(entry 11). Furthermore, when the catalyst loading
was decreased from 10 mol% to 1 mol%, the product
yield increased dramatically to 80% when the reac-
tion time was 40 min (entry 12).
With these results in hand, we tested other nickel
sources (Table 2). After analysis of the reaction re-
sults, Ni(NO3)2·6H2O was chosen as the reaction cata-
lyst for further research (entry 5).
As shown in Table 3, the highest yield (92%) was
achieved with a catalyst amount of 2 mol% (entry 2).
An increase of the catalyst amount to 5 mol% result-
ed in a decrease in yield to 60% (entry 1), which was
consistent with the previous result for 10 mol% cata-
lyst (Table 1). With 1 mol% of Ni(NO3)2·6H2O, a high
yield of 90% was obtained when the volume of tolu-
ene was decreased to 1.0 mL (entry 6). Different
bases were also tested. Et3N, K2CO3 and Cs2CO3
failed in the nickel-based catalytic system (entries 7–
9). K3PO4·3H2O and NaOH did promote the reaction
(entries 10 and 11), but they were less efficient than
KOH. Moreover, the yield of 1,4-adduct was observed
<1
<1
<1
42
9
10
11
12
13
14
15
16
17
18
19
1.5
1.5
1.5
1.5
1.5
1
1.25
1.75
2
26/58[c]
<1
65
88
72
49
65
81
60
1
1
1
KOH/1
KOH/1
KOH/1
[a]
Reaction conditions: 0.5 mmol of chalcone (1a), phenyl-
boronic acid (2a), Ni(NO3)2·6H2O as catalyst, base, tolu-
ene as solvent, under reflux for 40 min in an oil bath
under nitrogen.
GC yield (dodecane as internal standard).
Reaction time was 2 h.
[b]
[c]
to decrease when either excessive or insufficient follows: a mixture of 0.5 mmol of chalcone (1a),
amounts of KOH and 2a were used (entries 13–19). 1.5 equiv. of phenylboronic acid (2a), 1 mol% of
When 1.5 equiv. of KOH were used, the decomposi- Ni(NO3)2·6H2O, 1.0 mL of toluene and 1 equiv. of
tion products of chalcone (benzaldehyde and aceto- KOH heated under reflux for 40 min under nitrogen.
phenone) were detected in the reaction mixture.
Furthermore, we studied the effects of solvent and
Thus, the final optimised reaction conditions were as microwave irradiation. No improvement was observed
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Table 4. Effects of solvent and microwave irradiation.[a]
(except for -CN) negatively affected the reaction (3g,
3h, 3n and -NO2). In particular, no desired product
was obtained when an -NO2 group was introduced
either on the enone or on the arylboronic acid. Simi-
lar deactivation phenomena were also observed by
other groups when a nickel catalyst co-existed with
a nitro group.[10] In addition, 1,4-adducts were ob-
tained with conventional heating. Results of certain
representative substrates under conventional heating
are shown in Tables 5, Table 6 and Table 7. In general,
the yields of reactions performed in oil baths were
comparatively lower than their microwave-irradiated
counterparts.
The conjugate addition of arylboronic acid to a,b-
unsaturated esters, such as cinnamates and acrylates,
was also explored. The addition of phenylboronic
acids to cinnamates proceeded smoothly, except in
the case of 5g, where a Suzuki reaction by-product
was obtained (Table 7). No obvious substituent effects
on the arylboronic acid were observed.
The result of the 1,4-addition reaction of phenyl-
boronic acid to n-butyl acrylate was complicated.
Both a reduced product (5j’) and a Heck-type product
(5j’’) were found in association with the target prod-
uct 5j (Scheme 1 and Table 8, entry 1). When the re-
action solvent was changed to toluene, both the con-
version and selectivity improved obviously, although
the ratio of 5j to 5j’’ was still approximately 12:1
Entry
Solvent
Temp.
[8C]
Time
[min]
Yield
[%][b]
1
2
3
4
5
6
7
toluene
p-xylene
DMF
DMSO
n-propanol
n-butanol
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
110
110
110
110
bp
40
40
40
40
40
40
40
40
10
5
90
67
10
9
66
29
82
98
98
98
39
99
110
bp
8[c]
9[c]
10[c]
11[c]
12[c]
110
110
110
100
140
5
5
[a]
Reaction conditions: 0.5 mmol of chalcone (1a), 1.5 equiv.
of phenylboronic acid (2a), 1 mol% of Ni(NO3)2·6H2O,
1 equiv. of KOH, 1.0 mL of solvent and under nitrogen.
bp=boiling point.
GC yield (Internal standard method, dodecane as inter-
nal standard).
[b]
[c]
The reaction was carried out under microwave irradia-
tion.
with other solvents at 1108C or at their boiling tem- (entry 2). Further investigation of reaction media
perature (Table 4, entry 2–7). However, as the yield demonstrated that p-xylene was beneficial to the se-
with 1,4-dioxane at its normal boiling temperature lectivity (entry 3). Because of the inefficient micro-
(1018C) (entry 7) was comparable to that with tolu- wave adsorption of p-xylene, the reactions with acryl-
ene at 1108C (entry 1), further studies were carried ates were subsequently carried out in oil baths. The
out with 1,4-dioxane as the solvent and in a sealed formation of by-products was observed to be inhibited
tube at 1108C with the assistance of microwave irradi- to some extent at lower temperatures (80–1108C).
ation. Full conversion of 1a was achieved, and the se-
Thus, reactions of different arylboronic acid with
lectivity of 3a was 98% (entry 8). When the micro- acrylates were performed at individually optimised
wave reaction time was shortened to 5 min at 1108C, temperatures (Table 9). The reactions with acrylates
the reaction still proceeded smoothly (entry 10). were less efficient than those with chalcones or cinna-
However, a significant decrease in yield was observed mate derivatives. Moreover, some efforts were dedi-
when the reaction was carried out at 1008C, even cated to increasing the yield. For example, the addi-
with microwave heating (entry 11).
tion of an extra 1 mol% of Ni(NO3)2·6H2O and
The scope of the conjugate addition was then ex- 0.5 equiv. of KOH to the reaction mixture after the
plored with various enones and arylboronic acids reaction had proceeded for 1.5 h (Supporting Infora-
(Table 5 and Table 6). In most cases, the desired prod- tion, Table S1) increased the yields of 5l and 5o
ucts were obtained in good to excellent isolated yields (Table 9). Unfortunately, similar increases in catalyst
within very short reaction times. As expected, the re- loadings did not increase the yields of other adducts.
actions of chalcones with electron-donating substitu-
A plausible reaction mechanism is shown in
ents on the 1-phenyl or 3-phenyl positions proceeded Scheme 2, where substrate n-butyl acrylate is used as
efficiently (3a–3f). Whereas the chalcones with a 4- the example. The catalytic reaction is initiated by the
fluorophenyl substituent (R1 or R2) still gave excellent formation of OH-[Ni(II)]NO3 species 6 through
results (3i, 3j), a longer reaction time was required the substitution of coordinated nitrate in Ni(NO3)2
for enones with other electron-withdrawing groups with
a
strong base. Transmetallation between
(3k–3o). The enones with an alkyl/cycloalkyl group OH-[Ni(II)]NO3 and phenylboronic acid generates in-
resulted in low yields (3q, 3r). For arylboronic acids, termediate 7. Insertion of the C=C double bond of n-
À
no obvious substituent effects were observed butyl acrylate into the Ni C bond of 7 gives the inter-
(Table 6). The presence of N-containing substituents mediate 8. Subsequent rearrangement of 8 leads to
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Ligand-Free Nickel-Catalysed 1,4-Addition of Arylboronic Acids
Table 5. Scope of the conjugate addition of phenylboronic acids to enones.[a]
[a]
Reaction conditions: 0.5 mmol of a,b-unsaturated ketone, 1.5 equiv. of phenylboronic acid (2a), 1 mol% of
Ni(NO3)2·6H2O, 1 equiv. of KOH, 1.0 mL of 1,4-dioxane in a sealed microwave tube at 1108C with the assis-
tance of microwave irradiation under nitrogen (General procedure C). Y=isolated yield; t=reaction time,
the heating-up time to 1108C was not included.
[b]
Reaction conditions: 0.5 mmol of a,b-unsaturated ketone, 1.5 equiv. of phenylboronic acid (2a), 1 mol% of
Ni(NO3)2·6H2O, 1 equiv. of KOH, 1.0 mL of 1,4-dioxane under reflux in oil bath under nitrogen (General
procedure D).
2 mol% of Ni(NO3)2·6H2O were used.
The reaction was carried out at 1108C for 30 min. No target compound was detected.
With 2 equiv. of arylboronic acid; the corresponding Heck-type product was detected.
[c]
[d]
[e]
the O-bound nickel enolate 9. The enolate 9 affords bond reductive product 5j’ and Heck-type product 5j’’
the 1,4-addition product 5j in the presence of is proposed as well. b-H elimination of intermediate 8
PhB(OH)2 and KOH, and the catalyst species 6 is re- affords nickel hydride species 7’ along with Heck-type
generated and ready for further transmetallation. A product 5j’’. Insertion of another n-butyl acrylate mol-
À
plausible mechanism for the formation of double- ecule into the Ni H bond of 7’ gives intermediate 8’,
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Table 6. Scope of the conjugate addition of arylboronic acid
Table 7. Scope of the conjugate addition of arylboronic acids
to chalcones.[a]
to cinnamates.[a]
[a]
Reaction conditions: 0.5 mmol of chalcone 1a, 1.5 equiv.
of arylboronic acid, 1 mol% of Ni(NO3)2·6H2O, 1 equiv.
of KOH, 1.0 mL of 1,4-dioxane in a sealed microwave
tube at 1108C with the assistance of microwave irradia-
tion under nitrogen (General procedure C). Y=isolated
yield; t=reaction time, the heating-up time to 1108C was
not included.
[a]
Reaction conditions: 0.5 mmol of cinnamate, 1.5 equiv. of
arylboronic acid, 1 mol% of Ni(NO3)2·6H2O, 1 equiv. of
KOH, 1.0 mL of 1,4-dioxane in a sealed microwave tube
at 1108C with the assistance of microwave irradiation
under nitrogen (General procedure C). Y=isolated
yield; t=reaction time, the heating-up time to 1108C was
not included.
[b]
Reaction conditions: 0.5 mmol of chalcone 1a, 1.5 equiv.
of arylboronic acid, 1 mol% of Ni(NO3)2·6H2O, 1 equiv.
of KOH, 1.0 mL of 1,4-dioxane under reflux in an oil
bath under nitrogen (General procedure D).
Conducted at 1108C for 30 min. No target compound
was detected.
[c]
[b]
Reaction conditions: 0.5 mmol of cinnamate, 1.5 equiv. of
arylboronic acid, 1 mol% of Ni(NO3)2·6H2O, 1 equiv. of
KOH, 1.0 mL of 1,4-dioxane under reflux in an oil bath
under nitrogen (General procedure D).
Reaction temperature was 1308C.
1.5 equiv. KOH.
[c]
followed by the rearrangement of 8’ to O-bound
nickel enolate 9’. With the help of PhB(OH)2 and
KOH, the active species 6 is regenerated from 9’ and
the hydrogenation product butyl propionate 5j’ is si-
multaneously produced. As trace amounts of the cor-
responding Heck-type and reductive products (less
[d]
than 2% in total) were detected in the products of the ic acids to a,b-unsaturated carbonyl compounds. The
1,4-addition of organoboranes to chalcones and cinna- use of 1–2 mol% of Ni(NO3)2·6H2O as the sole cata-
mates, this plausible reaction mechanism is consistent lyst resulted in the 1,4-adducts from chalcones and
with the experimental evidence.
cinnamates being obtained in moderate to excellent
yields within 5–30 min under a nitrogen atmosphere
and under microwave irradiation. The reaction of an
arylboronic acid with an acrylate was generally less
efficient.
Conclusions
In conclusion, we have developed a highly efficient
ligand-free nickel-catalysed 1,4-addition of arylboron-
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Ligand-Free Nickel-Catalysed 1,4-Addition of Arylboronic Acids
Table 9. Scope of the conjugate addition of arylboronic to
some acrylates.[a]
Scheme 1. The product and by-products of the reaction be-
tween n-butyl acrylate and phenylboronic acid.
Table 8. The addition of phenylboronic acid to n-butyl acryl-
ate.[a,b]
Entry
Solvent
5j [%]
5j’ [%]
5j’’ [%]
1
2
1,4-dioxane
toluene
p-xylene
p-xylene
p-xylene
26.5
60.3
59.7
64.8
47.0
4.5
5.1
2.5
1.5
0.7
4.4
5.3
2.5
1.7
0.8
3
4[c]
5[d]
[a]
Reaction conditions: 0.5 mmol of n-butyl acrylate,
1.5 equiv. of phenylboronic acid (2a), 1 mol% of
Ni(NO3)2·6H2O, 1 equiv. of KOH, 1.0 mL of solvent in
a sealed microwave tube for 20 min at 1108C with the as-
sistance of microwave irradiation and under nitrogen.
Analysed by GC.
[a]
Reaction conditions: 0.5 mmol of acrylate, 1.5 equiv. of
phenylboronic acid, 1 mol% of Ni(NO3)2·6H2O, 1 equiv.
of KOH, 1.0 mL of p-xylene in an oil bath under nitro-
gen. Y=isolated yield; T=reaction temperature.
[b]
[c]
[d]
In an oil bath at 1008C for 3 h.
In an oil bath at 808C for 6 h.
[b]
Extra 1 mol% of Ni(NO3)2·6H2O and 0.5 equiv. of KOH
were added after 1.5 h of reaction.
Experimental Section
DMSO-d6 was used as the NMR solvent for a,b-unsaturated
ketone substrates in most cases. Chemical shifts were re-
corded in parts per million (d) relative to DMSO-d6 at 2.5
General Remarks
1
and H2O at 3.3 for H NMR and 39 for 13C NMR. CDCl3
All reagents were of analytical grade and obtained from
commercial suppliers; unless stated otherwise, all reagents
were used without further purification. Chalcones were syn-
thesised and confirmed by GC-MS. The crude products
were all recrystallised from 95% ethanol. Toluene and 1,4-
dioxane were dried by standard methods prior to being used
and degassed. Nickel catalysts were grounded and well-kept.
The microwave generator used in the experiments was a Bi-
otage Initiator (max power 300 W, Biotageꢂ from Uppsala,
Sweden). The preparative thin-layer chromatography plates
used were HSGF 254 plates (thickness of coating: 0.4–
0.5 mm, 20 cm”20 cm, Huanghaiꢂ from Yantai, Shandong
was used as the NMR solvent for a,b-unsaturated ester sub-
strates in most cases. Chemical shifts were recorded in parts
1
per million (d) relative to CDCl3 at 7.26 for H NMR and
77.23 for 13C NMR. Gas chromatography-mass spectrometry
(GC-MS) was performed on an Agilent 7890 A/5975C. Gas
chromatograms were recorded on an Agilent 7890A. The
melting points were measured with an SRS EZ MELT-120
from USA.
General Procedures for 1,4-Addition of Arylboronic
Acids to a,b-Unsaturated Ketones/Esters
1
province, China). The H NMR and 13C NMR spectra were
General procedure A (conventional heating) for optimiza-
recorded on a Bruker AM-400 spectrometer (400 MHz and
100 MHz, respectively) using TMS as internal standard.
tion of the 1,4-addition:
(104.1 mg, 0.5 mmol), phenylboronic acid (91.4 mg,
A mixture of the chalcone
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Scheme 2. A plausible reaction mechanism.
0.75 mmol), catalyst, base and solvent were placed in a 10-
mL reaction tube with a magnetic stirring bar. After being
sealed with a cap and septum, the reaction tube was purged
with nitrogen for 10 min. The reaction tube was then placed
into an oil bath and heated under reflux for the indicated
period of time. After the reaction was finished, dodecane
(50.0 mg) was added into the mixture as an internal stan-
dard. The resulting suspension was diluted with water
(2.0 mL) and extracted with ethyl acetate (6.0 mL). The
upper clear mixture (0.5 mL) was collected for GC analysis.
General procedure B (microwave heating) for optimiza-
tion: A mixture of the chalcone (104.1 mg, 0.5 mmol), phe-
nylboronic acid (91.4 mg, 0.75 mmol), Ni(NO3)2·6H2O
(1.5 mg, 0.005 mmol), KOH (28.0 mg, 0.5 mmol) and 1,4-di-
oxane (1.0 mL) was placed in a 10-mL microwave tube with
a magnetic stirring bar. After being sealed with a cap and
a septum, the reaction tube was purged with nitrogen for
10 min. The tube was then placed into the microwave syn-
thesiser, and the reaction was run at 1108C for several mi-
nutes. After the reaction was finished, dodecane (50.0 mg)
was added to the mixture as an internal standard. The re-
sulting suspension was diluted with water (2.0 mL) and ex-
tracted with ethyl acetate (6.0 mL). The upper clear mixture
(0.5 mL) was collected for GC analysis.
(6.0 mL ” 3). The combined organic layers were washed
with brine and dried over MgSO4, and the solvents were re-
moved under vacuum. The resulting crude residue was puri-
fied by preparative thin-layer chromatography to give the
product 3 (eluent: ethyl acetate/cyclohexane=from 1:2.5 to
1:200). The products were further characterised by GC/MS,
1H NMR and 13C NMR.
General procedure D (conventional heating) for 1,4-ad-
dition of arylboronic acids to b-substituent of a,b-unsatu-
rated ketones/esters (Supporting Information, Table S1): A
mixture of the a,b-unsaturated ketone/ester (0.5 mmol), ar-
ylboronic acid (0.75 mmol), Ni(NO3)2·6H2O (1.5 mg,
0.005 mmol), KOH (28.0 mg, 0.5 mmol) and 1,4-dioxane
(1.0 mL) was placed in a 10-mL reaction tube with a magnet-
ic stirring bar. After being sealed with a cap and a septum,
the reaction tube was purged with nitrogen for 10 min. The
tube was then placed into an oil bath, and the reaction was
conducted under reflux for several hours. The resulting sus-
pension was diluted with water (2.0 mL) and extracted with
ethyl acetate (6.0 mL ” 3). The combined organic layers
were washed with brine and dried over MgSO4, and the sol-
vents were removed under vacuum. The resulting crude resi-
due was purified by preparative thin-layer chromatography
to give the product (eluent: ethyl acetate/cyclohexane=
from 1:15 to 1:100). The products were further identified by
General procedure C (microwave heating) for the 1,4-ad-
dition of arylboronic acids to b-substituent of a,b-unsatu-
rated ketones/esters: A mixture of the a,b-unsaturated
1
GC/MS, H NMR and 13C NMR.
General procedure E (conventional heating) for 1,4-addi-
ketone
(0.5 mmol),
arylboronic
acid
(0.75 mmol),
tion of arylboronic acids to acrylates: A mixture of the ac-
Ni(NO3)2·6H2O (1.5 mg, 0.005 mmol), KOH (28.0 mg,
0.5 mmol) and 1,4-dioxane (1.0 mL) was placed in a 10-mL
microwave tube with a magnetic stirring bar. After being
sealed with a cap and a septum, the reaction tube was
purged with nitrogen for 10 min. The tube was then placed
into the microwave synthesiser, and the reaction was run at
1108C for 5–30 min. The resulting suspension was diluted
with water (2.0 mL) and extracted with ethyl acetate
rylate
(0.5 mmol),
arylboronic
acid
(0.75 mmol),
Ni(NO3)2·6H2O (1.5 mg, 0.005 mmol), KOH (28.0 mg,
0.5 mmol)and p-xylene (1.0 mL) was placed in a 10-mL re-
action tube with a magnetic stirring bar. After being sealed
with a cap and a septum, the reaction tube was purged with
nitrogen for 10 min. The tube was then placed into an oil
bath, and the reaction was conducted at 80–1308C for 3 h.
The resulting suspension was diluted with water (2.0 mL)
1480
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Ligand-Free Nickel-Catalysed 1,4-Addition of Arylboronic Acids
and extracted with ethyl acetate (6.0 mL ” 3). The combined
organic layers were washed with brine and dried over
MgSO4, and the solvents were removed under vacuum. The
resulting crude residue was purified by preparative thin-
layer chromatography to give the product (eluent: ethyl ace-
tate/cyclohexane=from 1:100 to 1:200). The products were
further characterised by GC/MS, 1H NMR and 13C NMR.
General procedure F (conventional heating) for 1,4-addi-
tion of arylboronic acids to acrylates (supplement of cata-
lyst and base): A mixture of the acrylate (0.5 mmol), aryl-
boronic acid (0.75 mmol), Ni(NO3)2·6H2O (1.5 mg,
0.005 mmol), KOH (28.0 mg, 0.5 mmol) and p-xylene
(1.0 mL) was placed in a 10-mL reaction tube with a magnet-
ic stirring bar. After being sealed with a cap and a septum,
the reaction tube was purged with nitrogen for 10 min. The
tube was placed into an oil bath and heated at 1008C for
1.5 h. When the mixture was cooled to room temperature,
a supplement of Ni(NO3)2·6H2O (1.5 mg, 0.005 mmol) and
KOH (14.0 mg, 0.25 mmol) was added. After the tube was
sealed with a cap and a septum, the reaction tube was
purged with nitrogen for 10 min. The tube was then placed
into an oil bath and heated at 1008C for another 1.5 h. The
resulting suspension was diluted with water (2.0 mL) and ex-
tracted with ethyl acetate (6.0 mL ” 3). The combined or-
ganic layers were washed with brine and dried over MgSO4,
and the solvents were removed under vacuum. The resulting
crude residue was purified by preparative thin-layer chroma-
tography to give the product (eluent: ethyl acetate/cyclohex-
ane=from 1:100 to 1:200). The products were further char-
acterised by GC/MS, 1H NMR and 13C NMR.
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Acknowledgements
Financial support for this study from the National Key Tech-
nology R&D Program (Grant No. 2011BAE06B05-4) is
gratefully acknowledged.
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1482
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ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 1474 – 1482