2-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated ketones under ligand-free and neutral conditions

Article abstract of DOI:10.1021/jo4001367

A simple and efficient Ru-catalyzed conjugate addition reaction of arylboronic acids to α,β-unsaturated ketones under neutral conditions without any additional ligands has been developed. This Ru(II)-catalytic system both fulfilled the inhibition of the β-hydride elimination in the catalytic cycle and minimized the protonolysis of arylboronic acids.

Full text of DOI:10.1021/jo4001367

Note
pubs.acs.org/joc
[RuCl2(p-cymene)]2‑Catalyzed Conjugate Addition of Arylboronic
Acids to α,β-Unsaturated Ketones under Ligand-Free and Neutral
Conditions
Lei Zhang,†,‡ Xiaomin Xie,‡ Lei Fu,*,† and Zhaoguo Zhang*,‡
‡
†School of Pharmacy and School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road,
Shanghai 200240, China
S
* Supporting Information
ABSTRACT: A simple and efficient Ru-catalyzed conjugate addition
reaction of arylboronic acids to α,β-unsaturated ketones under neutral
conditions without any additional ligands has been developed. This
Ru(II)-catalytic system both fulfilled the inhibition of the β-hydride
elimination in the catalytic cycle and minimized the protonolysis of
arylboronic acids.
uring the past decades, the transition-metal-catalyzed 1,4-
conjugate addition reaction of organometallic reagents to
cymene)]2 (2.0 mol %) and PPh3 (5.0 mol %) as the catalyst in
dioxane/H2O (v/v = 100:1). As illustrated in Table 1, in the
presence of 1 equiv of KOH (10 M aqueous), the reaction gave
the desired product in only 21% yield, accompanied by Heck-
type product (14%) and a large amount of tert-butylbenzene
resulted from the protonolysis of (4-(tert-butyl)phenyl)boronic
D
α,β-unsaturated carbonyl compounds has emerged as a
powerful tool for the construction of carbon−carbon bonds.1
Among various organometallic reagents, organoboron reagents
were widely used due to their readily availability, stability, and
low toxicity.2 Rh(I)-catalyzed conjugate addition of arylboron
reagents to α,β-unsaturated carbonyl compounds has been well-
documented3 since the pioneering work of Miyaura and co-
workers.4 Recently, the enantioselective conjugate addition
using chiral dienes and olefin-heteroatom ligands were
extensively studied.5 More recently, the conjugate addition
was also catalyzed by Pd,6 Ni,7 and Pt8 complexes. Although
Ru-catalyzed addition reactions of arylboronic acids to
aldehydes and ketones have been reported since 2009,9 Ru-
catalyzed conjugate addition has been rarely explored. One
exception is the work by Hayashi et al,10 in which the
combination of [RuCl2(p-cymene)]2 and P(t-Bu)2(2-PhC6H4)
catalyzed the reaction of arylboronic acids with linear β-
substituted enones under basic conditions to give Michael
addition-type and Heck-type products. In 2011 Kochi and
Kakiuchi reported a Ru-catalyzed cross-coupling of organo-
boron reagents with 2- and 4-(2-methoxyethyl)pyridines, the
reaction proceeding via a kind of addition of organoboron
reagents with vinylpyridine intermediates formed by dehy-
dromethoxylation.11 Up to now, there have been no examples
for the Ru-catalyzed selective conjugate addition of arylboronic
acids to vinyl ketones to produce 1,4-addition products.12
In the transition-metal-catalyzed addition reaction of
arylboronic acids with α,β-unsaturated carbonyl compounds,
in order to facilitate the transmetalation of the catalyst
precursor [MX] with boronic acids, a base was often employed
to form the active catalyst [MOH]. However, the base was
usually unnecessary if [MOR] (OR  OH, OAc, acac, etc.)
was used as catalyst precursor.13 We initiated our studies by
investigating the reaction of pent-1-en-3-one (2a) with (4-(tert-
butyl)phenyl)boronic acid (1a) in the presence of [RuCl2(p-
a
Table 1. Ru-Catalyzed 1,4-Addition of 1a to 2a
yield
(%)
c
b
entry
catalyst
base
solvent
1
[RuCl2(p-cymene)]2 + PPh3 KOH
[RuCl2(p-cymene)]2 + PPh3 K2CO3
[RuCl2(p-cymene)]2 + PPh3 NO
dioxane/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
THF/H2O
21
17
91
95
92
88
92
93
92
20
ND
ND
2
3
4
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[Ru(benzene)Cl2]2
RuCl2(PPh3)3
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
5
6
toluene/H2O
DCE/H2O
7
8
acetone/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
9
10
11
12
13
14
[RuCl2(COD)]n
RuCl3·xH2O
d
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
89
e
93
a
All reactions were carried out with 1 (0.5 mmol), 2 (0.5 mmol), and
ruthenium complex (2.0 mol %) in a solvent (3 mL) at 90 °C under
N2 for 10 h. Yield determined by GC with durene as an internal
b
c
d
standard. v/v = 100:1. Base, 0.5 mmol; PPh3, 0.025 mmol. Reaction
e
at 50 °C. Reaction at 120 °C.
Received: January 23, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo4001367 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
acid. The weaker base K2CO3 did not improve the reaction
(Table 1, entries 1, 2). This result is similar to those reported
earlier by Hayashi.10 It was surprising to find that when the
reaction was carried out in the absence of a base, the conjugate
addition proceeded smoothly, together with a thimbleful of tert-
butylbenzene and no Heck-type product (Table 1, entry 3).
When the reaction is carried out under the acidic conditions,
tert-butylbenzene will be the major product. Other organo-
boron reagents such as Ph4BNa and 5,5-dimethyl-2-phenyl-
1,3,2-dioxaborinane were inefficient, no product was observed
when Ph4BNa was used, and the conversion was very low for
5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane. Replacing the cata-
lyst with RuCl2(PPh3)3, the reaction gave 3aa in only 20% yield
(Table 1, entry 10); [Ru(benzene)Cl2]2 as catalyst gave
comparable yields (Table 1, entries 4 vs 9).
Even better yield of the product was obtained when the
reaction was conducted in the absence of PPh3, implying that
PPh3 was not necessary for this reaction. Other solvents such as
THF, DCE, toluene, and acetone were all acceptable solvents in
our catalytic system (Table 1, entries 4−8). Other ruthenium
catalysts are inefficient, and[Ru(COD)Cl2]n and RuCl3·xH2O
are totally inert (Table 1, entries 11, 12). This reaction was
insensitive to the temperature. When the reaction was carried
out at 50 °C, the yield was slightly decreased, along with more
tert-butylbenzene being produced; when the reaction was
carried out at 120 °C, the yield was almost equal to that at 90
°C.
Table 2. Ru-Catalyzed 1,4-Addition of 1a to 2aa
entry
Ar
2
product
yield (%)
b
1
p-ButC6H4 (1a)
o-MeC6H4 (1b)
m-MeC6H4 (1c)
p-MeC6H4 (1d)
p-MeOC6H4 (1e)
1-naphthyl (1f)
p-CF3C6H4 (1g)
p-ClC6H4 (1h)
p-CF3OC6H4 (1i)
1,3-benzodioxol-5-yl (1j)
C6H5 (1k)
styryl (1l)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
3aa
3ba
3ca
3da
3ea
3fa
95 (91 )
c
2
64 (92 )
3
93
92
90
4
5
c
6
34 (94 )
7
3ga
3ha
3ia
90
92
94
94
89
8
9
10
11
12
13
14
15
16
17
18
3ja
3ka
3la
d
57
e
1a
3ab
3ac
3ad
3ae
3af
68 (92 )
1a
92
f
1a
75
c
1a
41 (77 )
c
1a
trace
c
1a
2g
3ag
trace
a
To investigate the substrate scope, we explored other
arylboronic acids as nucleophiles for this reaction. The reaction
tolerated various functional groups, such as OCF3, Cl, CF3, and
OCH3 at the para and/or meta position of the phenyl ring of
arylboronic acids 1 (Table 2, entries 1−10). These results
indicated that the reaction was not sensitive to the electronic
properties of the substituents. Arylboronic acids 1a−l can
efficiently react with 2a to afford the corresponding addition
products in excellent yields (Table 2, entries 1−13), albeit
vulnerable to the position of the substituent at the ortho
position of the phenyl rings. For example, 2-methylphenylbor-
onic acid (1b) and naphthalen-1-ylboronic acid (1f) gave 3ba
and 3fa in only 64% and 34% yield, respectively (Table 2,
entries 2, 6), with a large amount of arylboronic acids being
protonolyzed. To our delight, the yields were increased to 92%
and 94%, respectively, when 2.5 equiv of 1b and 1f was used.
Other vinyl ketones, such as 1-(p-tolyl)prop-2-en-1-one (2b)
and 5-phenylpent-1-en-3-one (2c), are acceptable reactants.
However, 2b reacted with 1a to give 3ab in 68% yield, because
2b polymerized easily during the reaction. This problem can be
solved by adding a polymerization inhibitor. As a result, the
yield was increased to 92% when 2,6-di-tert-butylphenol (5 mol
% relative to 2b) was added. It is worth noting that butyl
acrylate (2d), a difficult substrate for transition-metal-catalyzed
1,4-addition reaction, worked fairly well. When 2d reacted with
1a, product 3ad was obtained in 75% yield accompanied by
20% of Heck-type product.
All reactions were carried out with 1 (1.05 mmol), 2 (1.0 mmol), and
[RuCl2(p-cymene)]2 (2.0 mol %) in 3 mL of dioxane/H2O (3 mL, v/v
b
= 100:1) at 90 °C under N2 for 10 h. Reaction run at 50 mmol scale.
c
Reactions were carried out at 120 °C with 2.5 equiv of arylboronic
d
e
acid. With 10% Heck-type product. 2,6-Di-tert-butyl phenol (0.05
mmol) was added. With 20% Heck-type product.
f
both Hayashi’s work, in which vinyl ketones did not work with
[RuCl2(p-cymene)]2 and P(t-Bu)2(2-PhC6H4) as catalyst under
basic conditions,10 and Lu’s work, where in a palladium-
catalyzed conjugate reaction of aryl boronic acids with α,β-
unsaturated carbonyl compounds only sterically hindered α,β-
unsaturated ketones work efficiently.14
To understand the reaction and to explain the different
reactivity of α,β-unsaturated carbonyl compounds, a mecha-
nism was proposed according to the literature (Scheme 1).13
Transmetalation between [RuCl2(p-cymene)]2 and arylboronic
acid generates intermediate A. Insertion of the C−C double
bond of α,β-unsaturated ketones into the Ru−C bond of A
affords the intermediate C, which may undergo β-hydride
elimination to give product D or be in equilibrium with
intermediate E, which protonolyzes to give the product 3 and
regenerates the catalyst.
Once intermediate A is formed, the central metal will
coordinate with cymene and bind with an aromatic ring and a
halogen. Because of the bulkiness of the catalyst, it is difficult
for a bulky enone to coordinate to ruthenium, accounting for
the highly steric demanding of the reactants. Once the
coordination of enone and subsequent insertion of the C−C
double bond of enone into the Ru−C bond occurs, quick
enolization takes place to afford intermediate E, which upon
hydrolysis gives the 1,4-addition product and regenerates the
catalyst.
Furthermore, the reaction is very sensitive to the steric
hindrance of the alkenes 2. When cyclopentenone (2e) was
used as substrate, 3ae was obtained in only 41% yield; by
increasing 4-tert-butylphenylboronic acid loading from 1.05
equiv to 2.5 equiv relative to 2e, up to 77% yield was obtained
(Table 2, entry 16). Other more sterically hindered α,β-
unsaturated ketones, either cyclic or linear, such as cyclohex-2-
enone and benzalacetone, are not suitable substrates for this
reaction (Table 2, entries 17 and 18). This is complementary to
As for butyl acrylate, after the insertion of the CC bond of
butyl acrylate into the Ru−C bond, intermediate C does not
form O-bound enolate intermediate E easily and completely.15
B
dx.doi.org/10.1021/jo4001367 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(dd, J = 17.6, 10.4 Hz, 1H), 6.22 (dd, J = 17.6, 1.2 Hz, 1H), 5.84 (dd, J
= 10.4, 1.2 Hz, 1H), 2.99−2.90 (m, 4H). 13C NMR (100 MHz,
CDCl3) δ 199.8, 141.4, 136.7, 128.8, 128.7, 128.5, 126.4, 41.4, 30.0.
Typical Procedure for the Conjugate Addition of Arylbor-
onic Acids to Pent-1-en-3-one. To a Schlenk tube under N2 were
added arylboronic acid (1.05 mmol), [RuCl2(p-cymene)]2 (12.3 mg,
0.02 mmol), and pent-1-en-3-one (84.0 mg, 1.0 mmol) in 3.0 mL of
dioxane/H2O = 100:1 (v/v). The solution turned orange immediately,
and then the mixture was stirred at 90 °C for 10 h. The reaction
mixture was concentrated, and the residue was purified by silica gel
chromatography (PE/EA = 100:1) to give the product.
Scheme 1. Proposed Mechanism for [RuCl2(p-cymene)]2-
Catalyzed 1,4-Addition Reaction
a
1-(4-(tert-Butyl)phenyl)pentan-3-one (3aa, 208 mg, 95%.).
1
Light yellow liquid. H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.4
Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 2.87 (t, J = 7.6 Hz, 2H), 2.73 (t, J =
7.6 Hz, 2H), 2.42 (q, J = 7.2 Hz, 2H), 1.30 (s, 9H), 1.05 (t, J = 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 210.9, 149.1, 138.3, 128.2, 125.6,
44.1, 36.3, 34.6, 31.65, 29.5, 8.0. HRMS (QTOF-ESI) calcd for
C15H22ONa (M + Na) 241.1568, found 241.1555.
1-(o-Tolyl)pentan-3-one (3ba, 113 mg, 64%; 162 mg, 92%).
1
Colorless liquid. H NMR (400 MHz, CDCl3) δ 7.18−7.04 (m, 4H),
2.89 (t, J = 7.6 Hz, 2H), 2.69 (t, J = 7.6 Hz, 2H), 2.43 (q, J = 7.2 Hz,
2H), 2.31 (s, 3H), 1.06 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ 210.9, 139.5, 136.1, 130.5, 128.8, 126.5, 126.4, 42.8, 36.3,
27.4, 19.5, 8.1. HRMS (QTOF-ESI) calcd for C12H17O (M + H)
177.1279, found 177.1262.
a
Ligands cymene, benzene were omitted for clarity.
Therefore, part of intermediate C degrades to compound D via
β-hydride elimination.
1-(m-Tolyl)pentan-3-one (3ca, 164 mg, 93%). Colorless liquid.
1H NMR (400 MHz, CDCl3) δ 7.19−7.15 (m, 1H), 7.02 − 6.97 (m,
3H), 2.87 (t, J = 7.6 Hz, 2H), 2.72 (t, J = 7.6 Hz, 2H), 2.42 (q, J = 7.2
Hz, 2H), 2.32 (s, 3H), 1.05 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ 210.8, 141.4, 138.2, 129.4, 128.6, 127.1, 125.5, 44.2, 36.3,
30.0, 21.6, 8.0. HRMS (QTOF-ESI) calcd for C12H17O (M + H)
177.1279, found 177.1255.
In summary, we have developed the first simple and efficient
Ru-catalyzed conjugate addition reaction of arylboronic acids to
enones under neutral conditions without any additional ligands.
Comparing to other transition-metal-catalyzed conjugate
addition reaction conditions, this Ru(II)-catalyzed system
efficiently inhibited the β-hydride elimination and protonolysis
of arylboronic acids.
1-(p-Tolyl)pentan-3-one (3da, 162 mg, 92%).18 Colorless
1
liquid. H NMR (400 MHz, CDCl3) δ 7.08 (s, 4H), 2.86 (t, J = 7.6
Hz, 2H), 2.71 (t, J = 7.6 Hz, 2H), 2.40 (q, J = 7.2 Hz, 2H), 2.31 (s,
3H), 1.04 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 210.8,
138.3, 135.7, 129.4, 128.4, 44.2, 36.3, 29.7, 21.2, 8.0.
EXPERIMENTAL SECTION
■
General. Commercially available reagents were used throughout
without further purification other than those detailed below. The
solvents were pretreated by the following procedures: tetrahedronfur-
an, toluene, and dioxane were distilled over sodium benzopheneone
ketyl under nitrogen. 1,2-Dichloroethane was distilled over calcium
hydride. Acetone was distilled over calcium sulfate anhydrous under
nitrogen. All reactions were carried out under an atmosphere of
nitrogen using standard Schlenk techniques or in a nitrogen-filled
1-(4-Methoxyphenyl)pentan-3-one (3ea, 173 mg, 90%).19
Pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.09 (d, J = 8.4 Hz,
2H), 6.82 (d, J = 8.8 Hz, 2H), 3.78 (s, 3H), 2.84 (t, J = 8.0 Hz, 2H),
2.69 (t, J = 7.2 Hz, 2H), 2.39 (q, J = 7.2 Hz, 2H), 1.03 (t, J = 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 211.0, 158.2, 133.4, 129.4, 114.1,
55.4, 44.4, 36.3, 29.2, 8.0.
1
1-(Naphthalen-1-yl)pentan-3-one (3fa, 72 mg, 34%; 199 mg,
94%).20 Colorless viscous oil. 1H NMR (400 MHz, CDCl3) δ 8.00 (d,
J = 8.0 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H),
7.55−7.46 (m, 2H), 7.43 − 7.32 (m, 2H), 3.37 (t, J = 7.6 Hz, 2H),
2.86 (t, J = 7.6 Hz, 2H), 2.42 (q, J = 7.2 Hz, 2H), 1.06 (t, J = 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 210.9, 137.5, 134.1, 131.8, 129.1,
127.2, 126.3, 125.8, 125.8, 123.7, 43.4, 36.4, 27.1, 8.1.
1-(4-(Trifluoromethyl)phenyl)pentan-3-one (3ga, 208 mg,
90%). Pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J =
8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 2.96 (t, J = 7.6 Hz, 2H), 2.75 (t,
J = 7.6 Hz, 2H), 2.41 (q, J = 7.2 Hz, 2H), 1.05 (t, J = 7.2 Hz, 3H). 13C
NMR (100 MHz, CDCl3) δ 210.1, 145.6, 128.9, 128.7, 128.4, 125.9,
125.5, 125.5, 123.2, 43.4, 36.2, 29.6, 7.8. HRMS (QTOF-ESI) calcd for
C12H14F3O (M + H) 231.0997, found 231.0988.
glovebox, unless otherwise noted. H NMR spectra were recorded at
400 MHz, with TMS as internal standard. 13C NMR spectra were
obtained at 100 MHz and referenced to the central peak of 77.0 ppm
for CDCl3. Coupling constants (J) are reported in hertz and refer to
apparent peak multiplications. Flash column chromatography was
performed on silica gel (300−400 mesh).
Procedures for the Preparation of 2b and 2c. A solution of N-
methoxy-N,4-dimethylbenzamide (895.0 mg, 5.0 mmol) in THF (30.0
mL) was cooled to −78 °C. Vinyl magnesium bromide (1 M solution
in THF, 5.5 mL, 5.5 mmol) was slowly added, and the mixture was
stirred at −78 °C for 10 min. Then the mixture was stirred for a
further 5 h at −50 °C, and the reaction was quenched with saturated
aqueous NH4Cl (10 mL). After the removal of the organic solvent and
extraction with ethyl acetate (2 × 20 mL), the combined organic phase
was washed with brine (30 mL), then dried over MgSO4, and
concentrated in vacuo. The product was purified by silica gel
chromatography (PE/EA = 50:1) to give 2b (452 mg, 62%) as a
colorless liquid. Similarly, 2c (481 mg, 5 mmol scale) was synthesized
in 60% yield.
1-(4-Chlorophenyl)pentan-3-one (3ha, 180 mg, 92%).21
Colorless liquid. 1H NMR (400 MHz, CDCl3) δ 7.25−7.21 (m,
2H), 7.13−7.08 (m, 2H), 2.86 (t, J = 7.2 Hz, 2H), 2.70 (t, J = 7.2 Hz,
2H), 2.40 (q, J = 7.2 Hz, 2H), 1.04 (t, J = 7.2 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 210.3, 139.9, 131.9, 129.9, 128.7, 43.7, 36.3, 29.3, 7.9.
1-(4-(Trifluoromethoxy)phenyl)pentan-3-one (3ia, 232 mg,
94%). Colorless liquid. 1H NMR (400 MHz, CDCl3) δ 7.21−7.18 (m,
2H), 7.12−7.10 (m, 2H), 2.90 (t, J = 7.2 Hz, 2H), 2.72 (t, J = 7.2 Hz,
2H), 2.41 (q, J = 7.2 Hz, 2H), 1.04 (t, J = 7.2 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 210.2, 147.7, 140.2, 129.8, 124.5, 122.0, 121.1, 119.4,
116.9, 43.6, 36.2, 29.1, 7.8. HRMS (QTOF-ESI) calcd for C12H14F3O2
(M + H) 247.0946, found 247.0936.
1-(p-Tolyl)prop-2-en-1-one (2b).16 Colorless liquid. 1H NMR
(400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.0 Hz,
2H), 7.15 (dd, J = 17.2, 10.4 Hz, 1H), 6.42 (dd, J = 17.2, 1.6 Hz, 1H),
5.87 (dd, J = 10.4, 1.6 Hz, 1H), 2.39 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 190.6, 144.1, 134.9, 132.5, 129.9, 129.5, 129.0, 21.9.
5-Phenylpent-1-en-3-one (2c).17 Colorless liquid. 1H NMR
(400 MHz, CDCl3) δ 7.32−7.27 (m, 2H), 7.22−7.18 (m, 3H), 6.36
C
dx.doi.org/10.1021/jo4001367 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1-(Benzo[d][1,3]dioxol-5-yl)pentan-3-one (3ja, 194 mg,
REFERENCES
1
■
94%). Colorless liquid. H NMR (400 MHz, CDCl3) δ 6.71 (d, J =
(1) (a) Perlmutter, P. Conjugate Addition Reactions in Organic
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VCH: Weinheim, Germany, 2010; Chapter 1, p 1.
(2) (a) Suzuki, A. Acc. Chem. Res. 1982, 15, 178. (b) Miyaura, N.;
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(3) (a) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169.
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7.6 Hz, 1H), 6.67−6.66 (m, 1H), 6.63−6.61 (m, 1H), 5.91 (s, 2H),
2.81 (t, J = 7.4 Hz, 2H), 2.68 (t, J = 7.4 Hz, 2H), 2.39 (q, J = 7.2 Hz,
2H), 1.04 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 210.8,
147.8, 146.0, 135.2, 121.2, 109.0, 108.4, 101.0, 44.3, 36.3, 29.8, 8.0.
HRMS (QTOF-ESI) calcd for C12H14O3Na (M + Na) 229.0841,
found 229.0801.
1-Phenylpentan-3-one (3ka, 143 mg, 89%).22 Colorless liquid.
1H NMR (400 MHz, CDCl3) δ 7.30−7.26 (m, 2H), 7.22−7.14 (m,
3H), 2.91 (t, J = 7.6 Hz, 2H), 2.73 (t, J = 7.6 Hz, 2H), 2.41 (q, J = 7.2
Hz, 2H), 1.05 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ
210.8, 141.4, 128.7, 128.6, 126.3, 44.1, 36.3, 30.1, 8.0.
(E)-7-Phenylhept-6-en-3-one (3la, 108 mg, 57%).23 Colorless
(4) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16,
4229.
1
liquid. H NMR (400 MHz, CDCl3) δ 7.35−7.27(m, 4H), 7.22−7.18
(m, 1H), 6.41 (d, J = 15.6 Hz, 1H), 6.24−6.18 (m, 1H), 2.64−2.57
(m, 2H), 2.51−2.42 (m, 4H), 1.07 (t, J = 7.4 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 211.0, 137.7, 130.9, 129.3, 128.8, 127.3, 126.2, 42.0,
36.3, 27.4, 8.1.
(5) (a) Tian, P.; Dong, H.-Q.; Lin, G.-Q. ACS Catal. 2012, 2, 95.
(b) Chen, G.; Gui, J.; Li, L.; Liao, J. Angew. Chem., Int. Ed. 2011, 50,
7681. (c) Thaler, T.; Guo, L.-N.; Steib, A. K.; Raducan, M.;
Karaghiosoff, K.; Mayer, P.; Knochel, P. Org. Lett. 2011, 13, 3182.
(d) Gosiewska, S.; Raskatov, J. A.; Shintani, R.; Hayashi, T.; Brown, J.
M. Chem.Eur. J. 2012, 18, 80. (e) Jin, S.-S.; Wang, H.; Zhu, T.-S.;
Xu, M.-H. Org. Biomol. Chem. 2012, 10, 1764. (f) Sasaki, K.;
Nishimura, T.; Shintani, R.; Kantchev, E. A. B.; Hayashi, T. Chem. Sci.
2012, 3, 1278. (g) Nishimura, T.; Noishiki, A.; Tsui, C. G.; Hayashi, T.
J. Am. Chem. Soc. 2012, 134, 5056.
3-(4-(tert-Butyl)phenyl)-1-(p-tolyl)propan-1-one (3ab, 190
mg, 68%; 258 mg, 92%). White solid (mp 63.6−64.0 °C). 1H
NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.0 Hz, 2H), 7.35−7.32 (m,
2H), 7.27−7.19 (m, 4H), 3.28 (t, J = 7.6 Hz, 2H), 3.04 (t, J = 7.6 Hz,
2H), 2.41 (s, 3H), 1.32 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
199.3, 149.1, 144.0, 138.6, 134.7, 129.5, 128.4, 128.4, 125.7, 40.6, 34.6,
31.7, 29.9, 21.9. HRMS (QTOF-ESI) calcd for C20H25O (M + H)
281.1905, found 281.1869.
(6) (a) Gutnov, A. Eur. J. Org. Chem. 2008, 4547. (b) Miyaura, N.
Synlett 2009, 2039.
1-(4-(tert-Butyl)phenyl)-5-phenylpentan-3-one (3ac, 270
(7) (a) Shirakawa, E.; Yasuhara, Y.; Hayashi, T. Chem. Lett. 2006, 35,
768−769. (b) Hirano, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9,
1541. (c) Hirano, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9,
5031. (d) Lin, P.-S.; Jeganmohan, M.; Cheng, C.-H. Chem.Asian J.
2007, 2, 1409.
(8) (a) Bedford, R. B.; Betham, M.; Charmant, J. P. H.; Haddow, M.
F.; Orpen, A. G.; Pilarski, L. T.; Coles, S. J.; Hursthouse, M. B.
Organometallics 2007, 26, 6346. (b) Hayashi, T.; Sasaki, K. Chem. Lett.
2008, 37, 842. (c) Liao, Y.-X.; Xing, C.-H.; He, P.; Hu, Q.-S. Org. Lett.
2008, 10, 2509.
(9) (a) Yamamoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem., Int.
Ed. 2009, 48, 4414. (b) Fukuyama, T.; Okamoto, H.; Ryu, I. Chem.
Lett. 2011, 40, 1453. (c) Li, H.; Xu, Y.; Shi, E.; Wei, W.; Suo, X.; Wan,
X. Chem. Commun. 2011, 47, 7880. (d) Yamamoto, Y.; Shirai, T.;
Miyaura, N. Chem. Commun. 2012, 48, 2803.
1
mg, 92%). Colorless viscous oil. H NMR (400 MHz, CDCl3) δ
7.32−7.26 (m, 4H), 7.22−7.15 (m, 3H), 7.13−7.08 (m, 2H), 2.91−
2.84 (m, 4H), 2.73−2.69 (m, 4H), 1.31 (s, 9H). 13C NMR (100 MHz,
CDCl3) δ 209.6, 149.2, 141.3, 138.2, 128.8, 128.6, 128.2, 126.4, 125.6,
44.8, 34.6, 31.7, 30.0, 29.5. HRMS (QTOF-ESI) calcd for C21H26ONa
(M + Na) 317.1881, found 317.1868.
n-Butyl 3-(4-(tert-Butyl)phenyl)propanoate (3ad, 196 mg,
1
75%). Colorless oil. H NMR (400 MHz, CDCl3) δ 7.33−7.29 (m,
2H), 7.24−7.20 (m, 3H), 4.09 (t, J = 8.0 Hz, 2H), 2.98 (t, J = 8.0 Hz,
2H), 2.65 (t, J = 8.0 Hz, 2H), 1.57−1.62 (m, 2H), 1.33−1.39 (m, 2H),
0.92 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.4, 149.2,
128.2, 126.1, 125.6, 64.5, 36.2, 31.6, 31.4, 30.9, 30.7, 19.4, 14.0. HRMS
(QTOF-ESI) calcd for C17H26O2Na (M + Na) 285.1831, found
285.1837.
3-(4-(tert-Butyl)phenyl)cyclopentanone (3ae, 89 mg, 41%;
166 mg, 77%). Beige solid (mp 79.9−80.3 °C). 1H NMR (400 MHz,
CDCl3) δ 7.40−7.34 (m, 2H), 7.23−7.15 (m, 2H), 3.44−3.35 (m,
1H), 2.69−2.63 (m, 1H), 2.50−2.43 (m, 2H), 2.38−2.45 (m, 2H),
2.04−1.93 (m, 1H), 1.32 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
218.7, 149.8, 140.3, 126.7, 125.8, 46.1, 42.0, 39.2, 34.7, 31.7, 31.5.
HRMS (QTOF-ESI) calcd for C15H21O (M + H) 217.1592, found
217.1573.
(10) Shintani, R.; Hayashi, T. Chem. Lett. 2008, 37, 724.
(11) Ogiwara, Y.; Kochi, T.; Kakiuchi, F. Org. Lett. 2011, 13, 3254.
(12) When we were preparing our manuscript, Ito and Nishiyanma
reported a Ru-catalyzed addition of alkynes to vinyl ketones: Ito, J.-i.;
Fujii, K.; Nishiyama, H. Chem.Eur. J. 2013, 19, 601.
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ASSOCIATED CONTENT
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(15) (a) Hartwig, J. F.; Andersen, R. A.; Bergman, R. G. J. Am. Chem.
Soc. 1990, 112, 5670. (b) Hartwig, J. F.; Bergman, R. G.; Andersen, R.
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S
* Supporting Information
NMR and/or HPLC spectra of compounds 1−3. This material
is available free of charge via the Internet at http://pubs.acs.org.
(16) Bodwell, G. J.; Li, J.; Miller, D. O. Tetrahedron 1999, 55, 12939.
(17) Molander, G. A.; Jean-Gerard, L. J. Org. Chem. 2009, 74, 1297.
́
AUTHOR INFORMATION
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Corresponding Author
*E-mail: zhaoguo@sjtu.edu.cn; leifu@hotmail.com.
(18) Jana, R.; Tunge, J. A. Org. Lett. 2009, 11, 971.
(19) Molander, G. A.; Petrillo, D. E. Org. Lett. 2008, 10, 1795.
(20) Shen, Z.-L.; Lai, Y.-C.; Wong, C. H. A.; Goh, K. K. K.; Yang, Y.-
S.; Cheong, H.-L.; Loh, T.-P. Org. Lett. 2010, 13, 422.
(21) Chen, M.; Wang, J.; Chai, Z.; You, C.; Lei, A. Adv. Synth. Catal.
2012, 354, 341.
Notes
The authors declare no competing financial interest.
(22) Lee, D.-Y.; Hong, B.-S.; Cho, E.-G.; Lee, H.; Jun, C.-H. J. Am.
Chem. Soc. 2003, 125, 6372.
(23) Jana, R.; Tunge, J. A. Org. Lett. 2009, 11, 971.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
for financial support.
D
dx.doi.org/10.1021/jo4001367 | J. Org. Chem. XXXX, XXX, XXX−XXX