The α-alkylation of ketones with alcohols in pure water catalyzed by a water-soluble Cp?Ir complex bearing a functional ligand

Article abstract of DOI:10.1039/c9nj03345a

A water-soluble dinuclear Cp?Ir complex bearing 4,4′,6,6′-tetrahydroxy-2,2′-bipyrimidine as a bridging ligand was found to be a highly effective catalyst for the α-alkylation of ketones with alcohols in pure water. In the presence of catalyst (0.5 mol%), a series of desirable products were obtained with high reaction economy under environmentally benign conditions. The importance of the hydroxy group in the ligand for catalytic hydrogen transfer was confirmed by mechanism experiments. Furthermore, the application of this catalytic system for the synthesis of a biologically active molecule donepezil in pure water has been accomplished. Notably, this research would facilitate the progress of C-C bond-forming reactions in water catalyzed by water-soluble metal-ligand bifunctional catalysts.

Full text of DOI:10.1039/c9nj03345a

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The α-alkylation of ketones with alcohols in pure water catalyzed
by a water-soluble Cp*Ir complex bearing a functional ligand†
Chong Meng,‡a Jing Xu,‡a Yawen Tang,a Yao Ai,a and Feng Li*a,b
Received 00th January 20xx,
Accepted 00th January 20xx
A water-soluble dinuclear Cp*Ir complex bearing 4,4’,6,6’-tetrahydroxy-2,2’-bipyrimidine as a bridging ligand was found to
be a highly effective catalyst for the α-alkylation of ketones with alcohols in pure water. In the presence of catalyst (0.5
mol %), a series of desirable products were obtained with high reaction economy under environmentally benign conditions.
The importance of the hydroxy group in the ligand for catalytic hydrogen transfer was confirmed by mechanism
experiments. Furthermore, the application of this catalytic system for the synthesis of a biologically active molecule
donepezil in pure water has been accomplished. Notably, this research would facilitate the progress of C-C bond-forming
reactions in water catalyzed by water-soluble metal-ligand bifunctional catalysts.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
co-workers reported the only an example of α-alkylation of
ketones with alcohols in pure water. They used heterogeneous
The α-alkylation of ketones for the construction of C-C bond
presents one of the most important transformations in
synthetic chemistry. Traditionally, such reactions were
performed with highly toxic alkyl halides as alkylating reagents
in the presence of at least a stoichiometric amount of strong
base.1 In recent years, considerable effort has been paid to the
α-alkylation of ketones with the activation of alcohols as
alkylating agents based on hydrogen autotransfer process or
hydrogen-borrowing strategy catalyzed by various transition
metal catalysts,2 such as Ru,3 Ir,4 Pd,5 Os,6 Fe,7 Co,8 Mn9 and Ni
complexes.10 In this process, alcohols are initially
dehydrogenated to give aldehydes, followed by the cross-aldol
condensation between the resulting aldehydes and ketones
resulted in the formation of α,β-unsaturated ketones, which
undergo transfer hydrogenation by metal hydride species
generated in the step of the dehydrogenation of alcohols to
afford α-alkylated ketones. Such methodology is attractive
because of high atom efficiency and the formation of water as
the side product. Although significant advance has been made,
these procedures have usually performed in various organic
solvents, such as toluene and p-xylene, which might result in
the production of a large amount of auxiliary waster.
palladium species as a catalyst. This procedure suffer from
extremely harsh reaction conditions (180 oC), microwave
irradiation, the addition of 10 equiv of alcohols as alkylating
agents and the resulting large amount of by-products.12
Subsequently, Glorius and co-workers demonstrated the use of
[Cp*IrCl2]2 as a catalyst for the α-alkylation of ketones with
alcohols in water. Apart from 2 equiv of alcohols, the addition
of 25 mol% cetyltrimethylammonium bromide (CTAB) as a
cationic surfactant and THF as the co-solvent (THF : H2O = 1 : 4)
were also necessary for this approach.13 Therefore, the
development of a new type of organometallic catalyst for the
α-alkylation of ketones with alcohols in pure water under more
environmentally benign conditions is highly desirable from
both synthetic and environmental points of view.
Very recently, Fujita, Yamaguchi and co-workers reported a
series of Cp*Ir complexes bearing
a
functional α-
hydroxypyridine ligand, which exhibited high activity for the
acceptorless dehydrogenation of alcohols based on the
concept of “ligand promoted dehydrogenation” (Scheme 1).14
Especially, they developed a water-soluble Cp*Ir complex
bearing
a
functional bipyridine ligand [Cp*Ir(6,6'-
(OH)2bpy)(H2O)][OTf]2, which exhibits high activity for the
acceptorless dehydrogenation of alcohols in water.14c We have
also demonstrated that this complex is a highly effective
Because water is cheap, safe and environmentally benign
compared with various organic solvents, the development of
catalytic transformations in water has attracted much
attention.11 However, to the best of our knowledge, Mu and
catalyst for the activation of alcohols for the N-alkylation of
sulfonamides with alcohols in water.
A
mechanistic
investigation revealed that protic hydrogens of OH units in the
bpy ligand are crucially important for the catalytic activity, and
thus this complex is a metal-ligand bifunctional catalyst for the
hydrogen autotransfer process.15 As part of our continuing
effort in the development of iridium-catalyzed reactions,15-16
we herein wish to report the α-alkylation of ketones with
a.School of Chemical Engineering, Nanjing University of Science & Technology,
Nanjing 210094, P. R. China. Fax: (+)86-25-84431939; E-mail: fengli@njust.edu.cn
b.State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian
116024, P. R. China
†
Electronic Supplementary Information (ESI) available: 1H NMR and 13C NMR
spectra of all products. See DOI: 10.1039/x0xx00000x
These authors contributed equally to this work.
‡
This journal is © The Royal Society of Chemistry 20xx
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Table 2 The α-alkylation of acetophenone 1a with a variety of alcohols 2 a
.
alcohols in pure water catalyzed by a water-soluble dinuclear
Cp*Ir coumplex bearing 4,4’,6,6’-tetrahydroxy-2,2’-
View Article Online
DOI: 10.1039/C9NJ03345A
bipyrimidine as a bridging ligand.
O
O
cat. 8 (0.5 mol %)
KOH (1 equiv)
R
R
OH
+
H2O, 100 o
under air
C
Results and discussion
1a
2
3
Product
O
Yield (%)b
Entry
Alcohol
Me
To explore the feasibility of reaction, the α-alkylation of
acetophenone (1a) with benzyl alcohol (2a) was selected as a
model. Several different types of water-soluble Cp*Ir
complexes were examined for their catalytic ability towards
this model reaction. In the presence of a cationic complex
[Cp*Ir(Me2NCH2CH2NMe2)Cl]Cl (cat. 1) or [Cp*Ir(bpy)Cl]Cl (bpy
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Me
OH
OH
1
80
2b
2c
3ab
O
O
= 2,2’-bipyridine) (cat. 2) (1 mol %), and KOH (1 equiv), the
o
reaction was performed in water at 100 C for 12 h to afford
the product 3aa in < 16% yields (Table 1, entries 1-2). When a
2
3
80
82
Me
Me
3ac
MeO
OMe
Cp*Ir
[Cp*Ir(NH3)3][Cl]2 (cat.
more aqua ligands, such as [Cp*Ir(H2O)3][OTf]2 (cat.
[Cp*Ir(bpy)(H2O)][OTf]2 (cat. and [Cp*Ir(6,6'-
(OMe)2bpy)(H2O)][OTf]2 (cat. ), was used as a catalyst, the
product 3aa was obtained in 17-55% yields (Table 1, entries 3-
6). Using [Cp*Ir(6,6'-(OH)2bpy)(H2O)][OTf]2 (cat. ) as a catalyst,
complex
bearing
) or a Cp*Ir complex bearing one or
),
three
ammonia
ligands
OH
3
4
2d
2e
3ad
3ae
O
O
5
)
6
OH
OH
4
5
79
80
MeO
OMe
7
the reaction gave the product 3aa in 86% yield (Table 1, entry
MeO
MeO
OMe
OMe
2f
3af
Table 1 The α-alkylation of acetophenone 1a with benzyl alcohol 2a under
various conditions.a
O
O
F
F
OH
OH
6
7
83
84
O
O
Catal (x mol %)
KOH (y equiv)
2g
3ag
OH
+
H2O, reflux
under air
1a
2a
3aa
Entry
x
y
Yield (%)b
Catal.
Base
T (oC)
F
F
2h
3ah
3ai
3aj
1
cat.1
cat.2
cat.3
cat.4
cat.5
cat.6
cat.7
cat.8
cat.8
cat.8
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.5
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.3
1.0
1.0
1.0
1.0
100
100
100
100
100
100
100
100
100
100
n.d.
16
2
Cl
O
O
Cl
3
55
OH
OH
4
33
8
82
83
80
5
17
6
24
86
95(87c)
2i
7
8
9
51
9
10
26
Cl
Cl
Cl
11
12
13
14
cat.8
cat.8
cat.8
-
Cs2CO3
K2CO3
KOH
0.5
0.5
0.5
100
100
80
29
2j
16
Cl
O
O
O
O
Cl
80
OH
KOH
n.d.
-
100
10
2Cl-
[OTf]2
Cl-
Cl-
Cl
2k
2l
3ak
3al
Ir Cl
Ir Cl
Ir
Ir
H2O
H2O
H3N
H3N
N
N
OH2
NH3
N
N
OH
OH
11
12
13
78
79
80
Br
Br
cat. 1
cat. 2
cat. 3
cat. 4
[OTf]2
HO
[Cl]2
[OTf]2
MeO
[OTf]2
HO
OH
Cl
N
N
N
N
Cp*
Ir H2O
Ir H2O
Ir H2O
N
OMe
N
OH
Ir
N
Ir
F3C
CF3
N
N
N
Cl
Cp*
2m
2n
3am
3an
HO
OH
cat. 5
cat. 6
cat. 7
cat. 8
OH
a Reactions conditions: 2a (0.5 mmol), 1a (0.65 mmol, 1.3 equiv), catal (x mol %),
H2O (1 mL), base (y equiv), 100 oC, under air, 12 h. b Yield was determined based
on the 1H NMR spectrum of the crude reaction mixture. c Isolated yield.
F3CO
OCF3
2 | J. Name., 2012, 00, 1-3
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with benzyl alcohol 2a a
.
Table 2 (Continued)
Table 3. The α-alkylation of a series of ketones
1
View Article Online
DOI: 10.1039/C9NJ03345A
O
cat. 8 (0.5 mol %)
KOH (1 equiv)
Entry
Alcohol
Product
Yield (%)b
O
OH
R
O
+
R
H2O, 100 o
under air
C
OH
OH
1
2a
Ketone
3
14
15
16
82
81
83
Product
O
Yield (%)b
Entry
2o
3ao
3ap
3aq
O
O
O
N
N
S
10
11
12
13
14
15
16
17
18
19
20
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58
59
60
Me
O
Me
2p
2q
1
2
3
80
1b
3ba
S
OH
O
O
76
85
Me
Me
1c
3ca
OH
O
O
17
80
Fe
Fe
3ar
3as
3at
2r
2s
2t
MeO
F
MeO
F
O
O
3da
1d
O
O
OH
OH
18
19
65c
75c
4
5
55
67
3ea
1e
O
O
Cl
Cl
3fa
1f
O
O
a
Reactions conditions:
2
(0.5 mmol), 1a (0.65 mmol, 1.3 equiv), cat.
b
8
(0.5 mol
c
%), KOH (1 equiv), H2O (1 mL), 100 oC, under air, 12 h. Isolated yield. 1a (1.0
6
7
50
71
Br
Br
mmol).
3ga
1g
O
O
7). Obviously, the presence of OH units in the bpy ligand is
crucially important for the catalytic activity of iridium complex.
To our surprise, the yield of 3aa could be enhanced to 95%
when a dinuclear water-soluble iridium complex with 4,4’,6,6’-
O
O
NH2
NH2
3ha
1h
O
O
8
9
83
81
tetrahydroxy-2,2’-bipyrimidine (thbpym) as a bridging ligand
17
[(Cp*IrCl)2(thbpym)][Cl]2 (cat.
8
)
(0.5 mol %) was used as a
3ia
1i
catalyst (Table 1, entry 8). [(Cp*IrCl)2(thbpym)][Cl]2 was chosen
as the catalyst for further research. Attempts to reduce the
amount of KOH, or use of K2CO3 and Cs2CO3 instead of KOH,
and decrease temperature of reaction resulted in relatively
low yields (Table 1, entries 9-12). It was also found that no
reaction occurred when KOH was added lonely (Table 1, entry
O
O
1j
3ja
a
Reactions conditions: 2a (0.5 mmol), 1 (0.65 mmol, 1.3 equiv), cat. 8 (0.5 mol
%), KOH (1 equiv), H2O (1 mL), 100 oC, under air, 12 h. b Isolated yield.
13)
.
Encouraged by the promising result (Table 1, entry 8), we
investigated the generality of the reaction with respect of
alcohols and these results are shown in Table 2.
Transformations of 1a with benzylic alcohols bearing one or
two electron-donating substituents, such as methyl, methoxy
and dimethoxy groups, gave the desired products 3ab-3af in
79-82% yields (Table 2, entries 1-5). Similarly, benzylic
alcohols bearing one or two halogen atoms, such as fluorine,
chlorine, dichlorine and bromine, were converted to afford the
desired products 3ag-3al in 78-84% yields (Table 2, entries 6-
11). More serious electron-withdrawing trifluoromethyl and
trifluoromethoxy groups could be tolerated and the
corresponding products 3am and 3an were obtained in 79%
and 80% yields, respectively (Table 2, entries 12-13). In the
case of 1-naphthalenemethanol, 2-pyridinemethanol, 2-
thiophenemethanol and ferrocenemethanol, reactions
afforded the desired products 3ao-3ar in 80-83% yields (Table
2, entries 14-17). The aliphatic alcohols, such as
cyclohexylmethanol and 1-hexanol and were proven to be
suitable substrates and the corresponding products 3as and
3at were obtained in 65% and 75% yields, respectively (Table 2,
entries 18-19).
The scope of reaction with respect of ketones was then
examined (Table 3). The α-alkylation of acetophenones bearing
This journal is © The Royal Society of Chemistry 20xx
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an electron-donating group afforded the corresponding Noyori-Ikariya catalyst.19
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products 3ba-3da in 76-85% yields (Table 3, entries 1-3).
To support the proposed mechanisDmOI: 1o0f.10r3e9a/Cc9tiNoJn0,33t4h5eA
Acetophenones bearing an electron-withdrawing substituent catalytic hydrogen transfer between an α,β-unsaturated
were also converted to the desired products 3ea-3ha, albeit ketone and an alcohol was investigated (Scheme 2). In the
moderate yields were obtained (Table 3, entries 4-7). This presence of cat.
5 or cat. 6, the reaction of (E)-chalcone (4),
catalytic system was also successfully applied to non-methyl which is prepared by the condensation between
ketones and aliphatic ketones, giving the corresponding acetophenone and benzylaldehyde, with benzyl alcohol 2a as
o
products 3ha and 3ia in 83% and 81% yields, respectively a hydrogen source performed in water at 100 C for 12 h to
9
10
11
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13
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(Table 3, entries 8-9).
On the basis of the previous knowledge14-15 and When cat.
afford the product 3aa in 9% and 40% yields, respectively.
or cat. was used as an alternative catalyst, the
7
8
experimental results, a possible mechanism is proposed for the product 3aa could be obtained in 84% and 91% yields,
present α-alkylation of ketones with alcohols in water respectively. Apparently, OH groups in the ligand are crucially
catalyzed by [(Cp*IrCl)2(thbpym)][Cl]2 (Scheme 1). The initial important for catalytic hydrogen transfer. In addition, a peak
step of the reaction involved the formation of an unsaturated (δ -10.68) was observed from 1H NMR spectrum of the
species A by the reaction of cat.
8 with a base. Furthermore, substoichiometric reaction of cat. 8 with 2a (8 equiv) in D2O at
the ligand accepted two protons in the step of the activation of 100 oC for 15 min. It was speculated to be a characteristic
two molecular alcohols, resulting in the generation of dialkoxy signal of [Ir-H].20 Apparently, these experimental results
iridium species B, which underwent β-hydrogen elimination to supported the proposed mechanism shown in Scheme 1.
afford iridium hydride species
C and two molecular aldehydes.
O
O
A
base-promoted cross-aldol condensation between the
cat. 8 (0.5 mol %)
KOH (1 equiv)
resulting two molecular aldehydes and two molecular ketones
occurred to give two molecular α,β-unsaturated ketones.
Accompanied by simultaneous transfer of two hydrides on the
+
Ph
OH
H2O, 100 o
under air
C
4
2a
3aa
[OTf]2
[Cl]2
[OTf]2
MeO
iridium and two hydroxyl protons on the ligand of species
the C=C bonds of two molecular α,β-unsaturated ketones,
catalytic species were regenerated and two molecularα-
C
to
[OTf]2
HO
OH
Ir
HO
N
Cl
Ir H2O
N
N
N
N
N
Cp*
Cl
Ir H2O
N
Ir H2O
A
N
OMe
N
OH
Ir
N
alkylated ketones were liberated as the desirable products.
Similar mechanism for the simultaneous delivery of hydride
and proton to ketones or imines was proposed in other metal-
ligand bifunctional catalysts, such as Shvo’s catalyst18 and
Cp*
HO
OH
cat. 5, 9% yield
cat. 6, 40% yield
cat. 7, 84% yield
cat. 8, 91% yield
Scheme 2 The hydrogen transfer between an α,β-unsaturated ketone and an alcohol.
cat. 8
In order to demonstrate the practicality of this catalytic
system, the large-scale reaction was undertaken. The α-
alkylation of 1a (10 mmol) with 2a (1.3 equiv) in 5 mL was
o
carried out at 100 C in the presence of cat.
Base
O
-2HCl
2+
8 (0.5 mol %) and
OH
O
KOH (1 equiv) for 12 h to give the corresponding product 3aa
in 85% yield (Scheme 3). Furthermore, the application of the
present catalytic system for the synthesis of a biologically
active molecule donepezil (a well-known acetylcholinesterase
inhibitor used clinically to treat cognitive dysfunction in
Alzheimer’s disease) was undertaken (Scheme 4).21 Under
established conditions (Table 1, entry 8), the reaction of 5,6-
N
Ir
N
N
Cp*
2
x
R2
OH
2 x
R1
R2
Ir
N
Cp*
HO
O
A
2+
R2
R2
H
2+
HO
Ir
OH
Ir
O
Ir
OH
Ir
R2
O
N
N
Cp*
O
O
N
N
N
N
Cp*
H
R1
dimethoxy-2,3-dihydroinden-1-one
din-4-yl)-methyl)-5,6-dimethoxy-2,3-dihydroinden-1-one
carried out in water at 100 oC for 12 h to give the desired
5
with 2-((1-benzylpiperi-
H
N
N
Cp*
R1
6
was
Cp*
HO
OH
O
HO
O
H
R2
product 7 in 82% yield.
C
B
R2
+
2x
O
O
O
H2O
2
x
2+
cat. 8 (0.5 mol %)
KOH (1 equiv)
OH
HO
OH
Ir
+
O
H2O, 100 o
under air
C
N
N
N
Cp*
H
2
x
R1
Ir
1a (10 mmol)
2a
3aa, 85% yield
H
N
Cp*
R1, R2 = Aryl or aliphatic group
vacant site
HO
OH
Scheme 3 Large-scale reaction.
=
C
Scheme 1 Proposed reaction mechanism.
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Ph
purified by flash column chromatography with hexanes/ethyl
acetate to afford the corresponding productD. OI: 10.1039/C9NJ03345A
View Article Online
N
OH
O
O
MeO
MeO
cat. 8 (0.5 mol %)
MeO
MeO
1,3-Diphenylpropan-1-one (3aa).3e White solid; 87% yield (95 mg);
KOH (1 equiv)
+
o
1
H2O, 100 o
under air
C
mp 69-70 C; H NMR (500 MHz, CDCl3) δ 7.95 (d, J = 7.3 Hz, 2H,
ArH), 7.53 (t, J = 7.3 Hz, 1H, ArH), 7.43 (t, J = 7.8 Hz, 2H, ArH), 7.32-
7.22 (m, 4H, ArH), 7.19 (t, J = 7.3 Hz, 1H, ArH), 3.28 (t, J = 7.3 Hz, 2H,
CH2), 3.06 (t, J = 7.3 Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 199.2,
141.3, 136.9, 133.1, 128.7, 128.6, 128.5, 128.1, 126.2, 40.5, 30.2.
Ph
5
6
7
Scheme 4 Synthesis of a biologically active molecule Donepezi.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Phenyl-3-(o-tolyl)propan-1-one (3ab).6 White solid; 80% yield (90
mg); mp 47-48 oC; 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J = 8.3 Hz, 2H,
ArH), 7.55 (t, J = 7.5 Hz, 1H, ArH), 7.46 (t, J = 7.7 Hz, 2H, ArH), 7.24-
7.08 (m, 4H, ArH), 3.24 (t, J = 7.3 Hz, 2H, CH2), 3.04 (t, J = 8.3 Hz, 2H,
CH2), 2.34 (s, 3H, CH3); 13C NMR (125 MHz, CDCl3) δ 199.4, 139.5,
136.9, 136.1, 133.2, 130.4, 128.8, 128.7, 128.1, 126.4, 126.3, 39.2,
27.6, 19.5.
Conclusion
We have demonstrated that a water-soluble Cp*Ir complex bearing
4,4’,6,6’-tetrahydroxy-2,2’-bipyrimidine as a bridging ligand is highly
effective catalyst for the α-alkylation of ketones with alcohols in
pure water. In the presence of catalyst (0.5 mol %), a series of
desirable products were obtained with high reaction economy
under more environmentally benign conditions. The importance of
hydroxy groups in the ligand for catalytic hydrogen transfer was
also confirmed by mechanism experiments. Furthermore, the
application of this catalytic system for the synthesis of a biologically
active molecule donepezil in water has been accomplished. Notably,
this research would facilitate the progress of C-C bond-forming
reactions in water catalyzed by water-soluble metal-ligand
bifunctional catalysts.
1-Phenyl-3-p-tolylpropan-1-one (3ac).3e White solid; 80% yield (90
mg); mp 33-34 oC; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 7.3 Hz, 2H,
ArH), 7.56 (t, J = 7.6 Hz, 1H, ArH), 7.46 (t, J = 7.8 Hz, 2H, ArH), 7.20-
7.08 (m, 4H, ArH), 3.29 (t, J = 7.4 Hz, 2H, CH2), 3.04 (t, J = 8.1 Hz, 2H,
CH2), 2.33 (s, 3H, CH3); 13C NMR (125 MHz, CDCl3) δ 199.5, 138.3,
137.0, 135.8, 133.2, 129.3, 128.7, 128.4, 128.2, 40.7, 29.8, 21.1.
3-(3-Methoxyphenyl)-1-phenylpropan-1-one (3ad).28 White solid;
82% yield (99 mg); mp 64-65 oC; 1H NMR (500 MHz, CDCl3) δ 7.97 (d,
J = 8.0 Hz, 2H, ArH), 7.55 (t, J = 7.6 Hz, 1H, ArH), 7.45 (t, J = 7.5 Hz,
2H, ArH), 7.22 (t, J = 7.8 Hz, 1H, ArH), 6.70-6.90 (m, 3H, ArH), 3.79 (s,
3H, CH3), 3.30 (t, J = 7.6 Hz, 2H, CH2), 3.05 (t, J = 7.8 Hz, 2H, CH2); 13
C
NMR (125 MHz, CDCl3) δ 199.3, 159.9, 143.1, 137.0, 133.2, 129.6,
128.7, 128.2, 120.9, 114.3, 111.5, 55.3, 40.5, 30.3.
Experimental Section
3-(4-Methoxyphenyl)-1-phenylpropan-1-one (3ae).3e White solid;
79% yield (95 mg); mp 67-68 oC; 1H NMR (500 MHz, CDCl3) δ 7.97 (d,
J = 7.2 Hz, 2H, ArH), 7.56 (t, J = 7.4 Hz, 1H, ArH), 7.45 (t, J = 7.9 Hz,
2H, ArH), 7.19 (t, J = 8.5 Hz, 2H, ArH), 6.86 (d, J = 8.6 Hz, 2H, ArH),
3.79 (s, 3H, CH3), 3.28 (t, J = 7.9 Hz, 2H, CH2), 3.03 (t, J = 7.4 Hz, 2H,
CH2); 13C NMR (125 MHz, CDCl3) δ 199.5, 158.1, 137.0, 133.4, 133.1,
129.4, 128.7, 128.1, 114.0, 55.3, 40.8, 29.3.
General Experimental Details.
Melting points were measured on a X-6 micro-melting apparatus.
Proton nuclear magnetic resonance (1H NMR) spectra were
recorded at 500 MHz using a Bruker Avance 500 spectrometer.
Chemical shifts are reported in delta (δ) units, parts per million
(ppm) downfield from tetramethylsilane or ppm relative to the
center of the singlet at 7.26 ppm for CDCl3 and 2.50 ppm for
DMSO-d6. Coupling constants J values are reported in Hertz (Hz),
and the splitting patterns were designated as follows: s, singlet;
d, doublet; t, triplet; m, multiplet; b, broad. Carbon-13 nuclear
magnetic resonance (13C NMR) spectra were recorded at 125
MHz using a Bruker Avance 500 spectrometer. Chemical shifts
are reported in delta (δ) units, ppm relative to the center of the
triplet at 77.16 ppm for CDCl3 and 39.5 ppm for DMSO-d6. 13C
NMR spectra were routinely run with broadband decoupling.
3-(3,4-Dimethoxyphenyl)-1-phenylpropan-1-one (3af).29 White
solid; 80% yield (108 mg); mp 65-66 oC; 1H NMR (500 MHz, CDCl3) δ
7.95 (d, J = 7.3 Hz, 2H, ArH), 7.55 (t, J = 7.4 Hz, 1H, ArH), 7.45 (t, J =
7.9 Hz, 2H, ArH), 6.73-6.84 (m, 3H, ArH), 3.85 (d, J = 5.9 Hz, 6H,
2xCH3), 3.27 (t, J = 8.1 Hz, 2H, CH2), 3.01 (t, J = 7.9 Hz, 2H, CH2); 13C
NMR (125 MHz, CDCl3) δ 199.4, 148.9, 147.4, 136.9, 133.9, 133.0,
128.6, 128.0, 120.2, 111.8, 111.4, 55.9, 55.8, 40.7, 29.8.
3-(3-Fluorophenyl)-1-phenylpropan-1-one (3ag).3f White solid; 83%
o
1
yield (95 mg); mp 53-55 C; H NMR (500 MHz, CDCl3) δ 7.97 (d, J =
7.5 Hz, 2H, ArH), 7.56 (t, J = 7.3 Hz, 1H, ArH), 7.46 (t, J = 7.8 Hz, 2H,
ArH), 7.25 (q, J = 7.2 Hz, 1H, ArH), 7.04 (d, J = 7.6 Hz, 1H, ArH), 6.97
(d, J = 9.9 Hz, 1H, ArH), 6.93-6.84 (m, 1H, ArH), 3.30 (t, J = 7.5 Hz, 2H,
CH2), 3.07 (t, J = 7.7 Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 198.9,
163.1 (d, JC-F = 245.1Hz), 144.0, 136.9, 133.3, 130.1 (d, JC-F = 8.2Hz),
128.8, 128.2, 124.2, 115.5 (d, JC-F = 21.1Hz), 113.2 (d, JC-F = 21.1Hz),
40.1, 29.9.
[Cp*Ir(Me2NCH2CH2NMe2)Cl]Cl (cat.
2
1
),22 [Cp*Ir(bpy)Cl]Cl (cat.
),25
),23 [Cp*Ir(NH3)3][Cl]2 (cat. ),24 [Cp*Ir(H2O)3][OTf]2 (cat.
3
(cat.
(cat.
4
[Cp*Ir(bpy)(H2O)][OTf]2
(OMe)2bpy)(H2O)][OTf]2
(OH)2bpy)(H2O)][OTf]2 (cat.
5
),26
),27
[Cp*Ir(6,6'-
[Cp*Ir(6,6'-
6
7
),14c [(Cp*IrCl)2(thbpym)][Cl]2 (cat.
8
),17 were synthesized according the previous reports.
General procedure for the α-alkylation of ketones with alcohols in
water catalyzed by a water-soluble dinuclear Cp*Ir complex
[(Cp*IrCl)2(thbpym)][Cl]2 (cat. 8) (Tables 1-3).
3-(4-Fluorophenyl)-1-phenylpropan-1-one (3ah).30 White solid;
84% yield (96 mg); mp 65-66 oC; 1H NMR (500 MHz, CDCl3) δ 7.96 (d,
J = 7.2 Hz, 2H, ArH), 7.56 (t, J = 7.4 Hz, 1H, ArH), 7.46 (t, J = 7.5 Hz,
2H, ArH), 7.25-7.17 (m, 2H, ArH), 6.98 (t, J = 8.7 Hz, 1H, ArH), 3.29 (t,
J = 7.8 Hz, 2H, CH2), 3.05 (t, J = 7.5 Hz, 2H, CH2); 13C NMR (125 MHz,
CDCl3) δ 199.1, 161.5 (d, JC-F = 243.5Hz), 137.0, 136.9, 133.3, 130.0
(d, JC-F = 7.8 Hz), 128.8, 128.2, 115.4 (d, JC-F = 21.2Hz), 40.6, 29.4.
Under air atmosphere, alcohol (0.5 mmol), ketone (0.65 mmol, 1.3
equiv), cat. 8 (2.5 mg, 0.0025 mmol, 0.5 mol%), KOH (28 mg, 0.5
mmol, 1 equiv) and H2O (1 mL) were added to a 5 mL round-
bottomed flask with a condenser tube. The mixture of reaction was
heated under reflux in an oil bath for 12 h. The reaction mixture
was cooled to ambient temperature, concentrated in vacuo and
3-(2-Chlorophenyl)-1-phenylpropan-1-one (3ai).31 White solid; 82%
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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yield (100 mg); mp 45-46 oC; 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J = ArH), 7.14 (d, J = 5.1 Hz, 1H, ArH), 6.95-6.90 (m, 1H, ArH), 6.87 (d, J
7.2 Hz, 2H, ArH), 7.56 (t, J = 7.4 Hz, 1H, ArH), 7.46 (t, J = 7.8 Hz, 2H, = 3.1 Hz, 1H, ArH ) 3.37 (t, J = 7.5 Hz, 2H, CH2D),O3I:.3100.1(0t,3VJ9ie/=wC79A.Nr4tiJcHl0e3zO3,n42li5HnAe,
ArH), 7.36 (dd, J = 7.6 Hz and 1.5 Hz, 1H, ArH), 7.31 (dd, J = 7.3 Hz CH2); 13C NMR (125 MHz, CDCl3) δ 198.7, 144.0, 136.9, 133.3, 128.8,
and 1.9 Hz, 1H, ArH), 7.23-7.13 (m, 2H, ArH), 3.32 (t, J = 7.1 Hz, 2H, 128.2, 127.0, 124.8, 123.5, 40.7, 24.4.
CH2), 3.18 (t, J = 7.2 Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 199.2,
139.0, 136.9, 134.1, 133.3, 131.0, 129.7, 128.8, 128.2, 127.9, 127.1, 3-Ferrocenyl-1-phenylpropan-1-one (3ar).34 Yellow solid; 80% yield
o
1
38.6, 28.5.
(127 mg); mp 90-91 C; H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 7.7
Hz, 2H, ArH), 7.57 (t, J = 7.2 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H, ArH),
3-(4-Chlorophenyl)-1-phenylpropan-1-one (3aj).32 White solid; 83% 4.20-4.05 (m, 9H, ferrocene H), 3.20 (t, J = 7.8 Hz, 2H, CH2), 2.80 (t, J
yield (102 mg); mp 52-53 oC; 1H NMR (500 MHz, CDCl3) δ 7.94 (d, J = = 7.7 Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 199.6, 137.0, 133.1,
7.3 Hz, 2H, ArH), 7.54 (t, J = 7.4 Hz, 1H, ArH), 7.43 (t, J = 7.5 Hz, 2H, 128.7, 128.1, 88.1, 68.7, 68.2, 67.5, 40.5, 24.2.
ArH), 7.24 (d, J = 8.5 Hz, 2H, ArH), 7.17 (d, J = 8.5 Hz, 2H, ArH), 3.26
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
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53
54
55
56
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58
59
60
(t, J = 7.7 Hz, 2H, CH2), 3.02 (t, J = 7.4 Hz, 2H, CH2); 13C NMR (125 3-Cyclohexyl-1-phenylpropan-1-one (3as).3e White solid; 65% yield
MHz, CDCl3) δ 198.9, 139.8, 136.8, 133.2, 131.9, 129.9, 128.7, 128.6, (70 mg); mp 38-39 oC; 1H NMR (500 MHz, CDCl3) δ 7.96 (d, J = 7.2 Hz,
128.1, 40.2, 29.4.
2H, ArH), 7.54 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.8 Hz, 2H, ArH), 2.96 (t,
J = 7.8 Hz, 2H, CH2), 1.78-1.68 (m, 4H), 1.67-1.60 (m, 3H), 1.35-1.10
3-(2,4-Dichlorophenyl)-1-phenylpropan-1-one (3ak).30 White solid; (m, 4H), 1.01-0.89 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 200.9,
80% yield (112 mg); mp 63-64 C; H NMR (500 MHz, CDCl3) δ 7.96 137.2, 132.9, 128.6, 128.1, 37.5, 36.2, 33.3, 31.9, 26.7, 26.4.
o
1
(d, J = 7.3 Hz, 2H, ArH), 7.56 (t, J = 7.3 Hz, 1H, ArH), 7.46 (t, J = 7.6 Hz,
1
2H, ArH), 7.37 (d, J = 2.1 Hz, 1H, ArH), 7.26 (d, J = 8.2 Hz, 1H, ArH), 1-Phenyloctan-1-one (3at).35 Pale yellow oil; 75% yield (77 mg); H
7.20-7.15 (m, 1H, ArH), 3.29 (t, J = 7.8 Hz, 2H, CH2), 3.15 (t, J = 7.7 NMR (500 MHz, CDCl3) δ 7.96 (d, J = 7.1 Hz, 2H, ArH), 7.55 (t, J = 7.4
Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 198.8, 137.6, 136.8, 134.7, Hz, 1H, ArH), 7.45 (t, J = 7.9 Hz, 2H, ArH), 2.96 (t, J = 7.6 Hz, 2H, CH2),
133.4, 132.8, 131.8, 129.4, 128.8, 128.2, 127.3, 38.3, 27.8.
1.77-1.70 (m, 2H, CH2), 1.41-1.25 (m, 8H, 4xCH2), 0.88(t, J = 7.0 Hz,
3H, CH3); 13C NMR (125 MHz, CDCl3) δ 200.8, 137.2, 133.0, 128.7,
3-(4-Bromophenyl)-1-phenylpropan-1-one (3al).31 White solid; 78% 128.2, 38.8, 31.9, 29.5, 29.3, 24.5, 22.8, 14.2.
yield (113 mg); mp 63-64 oC; 1H NMR (500 MHz, CDCl3) δ 7.96 (d, J =
7.9 Hz, 2H, ArH), 7.56 (t, J = 7.5 Hz, 1H, ArH), 7.46 (t, J = 7.7 Hz, 2H, 3-Phenyl-1-o-tolylpropan-1-one (3ba).36 Pale yellow oil; 80% yield
1
ArH), 7.42 (d, J = 8.3 Hz, 2H, ArH), 7.14 (d, J = 8.3 Hz, 2H, ArH), 3.28 (90 mg); H NMR (500 MHz, CDCl3) δ 7.58 (d, J = 7.5 Hz, 1H, ArH),
(t, J = 7.7 Hz, 2H, CH2), 3.03 (t, J = 7.5 Hz, 2H, CH2); 13C NMR (125 7.35 (t, J = 7.5 Hz, 1H, ArH), 7.28 (t, J = 7.6 Hz,2H, ArH), 7.25-7.17 (m,
MHz, CDCl3) δ 198.9, 140.4, 136.8, 133.3, 131.7, 130.4, 128.8, 128.1, 5H, ArH), 3.22 (t, J = 7.8 Hz, 2H, CH2), 3.04 (t, J = 7.8 Hz, 2H, CH2),
120.0, 40.2, 29.5.
2.46 (s, 3H, CH3); 13C NMR (125 MHz, CDCl3) δ 203.5, 141.3, 138.2,
138.0, 132.1, 131.4, 129.1, 128.6, 128.5, 126.2, 125.8, 43.3, 30.5,
1-Phenyl-3-[4-(trifluoromethyl)phenyl]propan-1-one
White solid; 79% yield (110 mg); mp 47-48 C; H NMR (500 MHz,
(3am).32 21.4.
o
1
CDCl3) δ 7.96 (d, J = 7.7 Hz, 2H, ArH), 7.59-7.53 (m, 3H, ArH), 7.46 (t, 3-Phenyl-1-p-tolylpropan-1-one (3ca).37 White solid; 76% yield (85
J = 7.5 Hz, 2H, ArH), 7.46 (t, J = 7.9 Hz, 2H, ArH), 7.38 (d, J = 8.0 Hz, mg); mp 67-68 oC; 1H NMR (500 MHz, CDCl3) δ 7.87 (d, J = 8.2 Hz, 2H,
2H, ArH), 3.33 (t, J = 7.7 Hz, 2H, CH2), 3.14 (t, J = 7.4 Hz, 2H, CH2); 13
C
ArH), 7.35-7.15 (m, 7H, ArH), 3.27 (t, J = 7.4 Hz, 2H, CH2), 3.06 (t, J =
NMR (125 MHz, CDCl3) δ 198.6, 145.6, 136.8, 133.3, 128.9, 128.8, 7.5 Hz, 2H, CH2), 2.40 (s, 3H, CH3); 13C NMR (125 MHz, CDCl3) δ
128.5, 128.1, 125.5, 124.5(q, JC-F = 271.1 Hz), 39.9, 29.9.
199.0, 144.0, 141.5, 134.6, 129.4, 128.64, 128.56, 128.3, 126.2, 40.5,
30.4, 21.8.
1-Phenyl-3-[4-(trifluoromethoxy)phenyl]propan-1-one
(3an).16g
Pale yellow oil; 80% yield (118 mg); 1H NMR (500 MHz, CDCl3) δ 7.96 1-(4-Methoxyphenyl)-3-phenylpropan-1-one (3da).28 White solid;
o
1
(d, J = 7.3 Hz, 2H, ArH), 7.56 (t, J = 7.3 Hz, 1H, ArH), 7.46 (t, J = 7.8 Hz, 85% yield (102 mg); mp 95-96 C; H NMR (500 MHz, CDCl3) δ 7.93
2H, ArH), 7.28 (d, J = 8.6 Hz, 2H, ArH), 7.15 (d, J = 8.3 Hz, 2H, ArH), (d, J = 8.8 Hz, 2H, ArH), 7.29 (t, J = 7.3 Hz, 2H, ArH), 7.26-7.23 (m, 2H,
3.31 (t, J = 7.8 Hz, 2H, CH2), 3.08 (t, J = 7.4 Hz, 2H, CH2); 13C NMR ArH), 7.20 (t, J = 7.1 Hz, 2H, ArH), 6.91(d, J = 8.9 Hz, 2H, ArH), 3.85 (s,
(125 MHz, CDCl3) δ 198.9, 147.8, 140.2, 136.9, 133.3, 129.9, 128.8, 3H, CH3), 3.24 (t, J = 7.4 Hz, 2H, CH2), 3.05 (t, J = 7.4 Hz, 2H, CH2); 13
C
128.2, 121.2, 120.7(q, JC-F = 257.8 Hz), 40.3, 29.5.
NMR (125 MHz, CDCl3) δ 196.9, 162.5, 140.5, 129.4, 129.0, 127.6,
127.5, 125.1, 112.8, 54.5, 39.2, 29.1.
3-(Naphthalen-2-yl)-1-phenylpropan-1-one (3ao).28 White solid;
o
1
82% yield (107 mg); mp 65-66 C; H NMR (500 MHz, CDCl3) δ 8.10 1-(3-Fluorophenyl)-3-phenylpropan-1-one (3ea).38 Pale yellow oil;
(d, J = 8.2 Hz, 1H, ArH), 7.99 (d, J = 8.0 Hz, 2H, ArH), 7.91 (d, J = 7.9 55% yield (63 mg); H NMR (500 MHz, CDCl3) δ 7.73 (d, J = 7.7 Hz,
1
Hz, 1H, ArH), 7.77 (t, J = 4.2 Hz, 1H, ArH), 7.60-7.49 (m, 3H, ArH), 1H, ArH), 7.64 (d, J = 9.4 Hz, 1H, ArH), 7.46-7.40 (m, 1H, ArH), 7.34-
7.49-7.40 (m, 4H, ArH), 3.57 (t, J = 8.1 Hz, 2H, CH2), 3.44 (t, J = 8.3 7.28 (m, 2H, ArH), 7.26-7.19 (m, 4H, ArH), 3.29 (t, J = 8.0 Hz, 2H,
Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 199.4, 137.5, 136.9, 134.0, CH2), 3.07 (t, J = 7.9 Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 198.0,
133.2, 131.8, 129.0, 128.7, 128.1, 127.1, 126.24, 126.20, 125.7, 163.0 (d, JC-F = 248.3 Hz), 141.1, 139.0, 130.4 (d, JC-F = 7.5 Hz), 128.7,
123.6, 39.8, 27.3.
128.5, 126.3, 123.9, 120.2 (d, JC-F = 21.3 Hz), 114.9 (d, JC-F = 22.4 Hz),
40.7, 30.1.
1-Phenyl-3-(pyridin-2-yl)propan-1-one (3ap).33 Pale yellow oil; 81%
1
yield (86 mg); H NMR (500 MHz, CDCl3) δ 8.51 (d, J = 4.6 Hz, 1H, 1-(4-Chlorophenyl)-3-phenylpropan-1-one (3fa).32 White solid; 67%
o
1
ArH), 8.00 (d, J = 7.4 Hz, 2H, ArH), 7.62-7.49 (m, 2H, ArH), 7.44 (d, J yield (82mg); mp 72-73 C; H NMR (500 MHz, CDCl3) δ 7.89 (d, J =
= 7.8 Hz, 2H, ArH), 7.26 (d, J = 7.8 Hz, 1H, ArH), 7.12-7.06 (m, 1H, 8.6 Hz, 2H, ArH), 7.42 (d, J = 8.6 Hz, 2H, ArH), 7.30 (t, J = 7.5 Hz, 2H,
ArH) 3.51 (t, J = 7.3 Hz, 2H, CH2), 3.24 (t, J = 7.3 Hz, 2H, CH2); 13C ArH), 7.27-7.17 (m, 3H, ArH), 3.27 (t, J = 8.0 Hz, 2H, CH2), 3.06 (t, J =
NMR (125 MHz, CDCl3) δ 199.3, 160.8, 149.3, 137.0, 136.4, 133.0, 7.9 Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 198.1, 141.2, 139.7,
128.6, 128.1, 123.4, 121.3, 37.8, 32.1.
135.3, 129.6, 129.1, 128.7, 12.8.5, 126.4, 40.6, 30.2.
1-Phenyl-3-(thiophen-2-yl)propan-1-one (3aq).28 White solid; 83% 1-(4-Bromophenyl)-3-phenylpropan-1-one (3ga).39 White solid;
o
1
yield (90 mg); mp 47-48 C; H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 50% yield (72 mg); mp 98-99 oC; 1H NMR (500 MHz, CDCl3) δ 7.81 (d,
7.5 Hz, 2H, ArH), 7.57 (t, J = 7.3 Hz, 1H, ArH), 7.47 (d, J = 7.6 Hz, 2H, J = 8.5 Hz, 2H, ArH), 7.59 (d, J = 8.5 Hz, 2H, ArH), 7.30 (t, J = 7.4 Hz,
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2H, ArH), 7.26-7.19 (m, 3H, ArH), 3.26 (t, J = 7.9 Hz, 2H, CH2), 3.06 (t, purified by flash column chromatography with hexanes/ethyl
J = 7.8 Hz, 2H, CH2); 13C NMR (125 MHz, CDCl3) δ 198.2, 141.1, 135.6, acetate to afford the corresponding productD7OiIn: 1802.1%03Vy9iie/ewCld9ANr(t1iJc5l0e63O3mn4li5ngAe).
132.0, 129.6, 128.6, 128.5, 128.3, 126.3, 40.5, 30.1.
2-((1-Benzylpiperidin-4-yl)methyl)-5,6-dimethoxy-2,3-
1
4-(3-phenylpropanoyl)benzamide (3ha).39 Yellow solid; 71% yield dihydroinden-1-one (7).42 Pale yellow oil; 82% yield (156 mg); H
o
1
(90 mg); mp 188-189 C; H NMR (500 MHz, DMSO-d6) δ 8.13 (br s, NMR (500 MHz, DMSO-d6) δ 7.33-7.25 (m, 4H, ArH), 7.25-7.19 (m,
1H), 8.03 (d, J = 7.9Hz, 2H), 7.97 (d, J = 7.9 Hz), 7.54 (br s, 1H) 7.28 (s, 1H, ArH), 7.04 (s, 2H, ArH), 3.84 (s, 3H, CH3), 3.77 (s, 3H, CH3), 3.41
4H), 7.17 (s, 1H), 3.40 (t, J = 6.2 Hz, 2H), 2.94 (t, J = 7.3 Hz, 2H); 13C (s, 2H, CH2), 3.17 (dd, J = 17.6 Hz and 7.9 Hz, 1H, CH), 2.77 (t, J =
NMR (125 Hz, DMSO-d6) δ 199.1, 167.2, 141.2, 138.6, 138.1, 128.5, 12.5 Hz, 2H, CH2), 2.64-2.56 (m, 2H, CH2), 1.92-1.83 (m, 2H, CH2),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
128.4, 127.9, 127.8, 125.9, 39.8, 29.5.
1.73-1.64 (m, 2H, CH2), 1.57 (d, J = 12.7 Hz, 1H, CH), 1.46-1.33 (m,
1H, CH), 1.24-1.16 (m, 2H, CH2), 1.15-1.07 (m, 1H, CH); 13C NMR
2-Benzyl-2,3-dihydroinden-1-one (3ia).40 Yellow oil; 83% yield (92 (125 MHz, DMSO-d6) δ 206.6, 155.2, 149.1, 148.7, 138.6, 128.7,
mg); 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 7.6 Hz, 1H, ArH), 7.56 (t, 128.4, 128.1, 126.8, 108.1, 103.8, 62.5, 55.9, 55.5, 53.3, 44.8, 38.3,
J = 7.4 Hz,1H, ArH), 7.42-7.33 (m, 2H, ArH), 7.29 (t, J = 7.4 Hz, 2H, 33.9, 32.7, 31.4.
ArH), 7.26-7.17 (m, 3H, ArH), 3.39 (dd, J = 13.9 Hz and 4.2 Hz, 1H,
CH), 3.15 (dd, J = 17.2 Hz and 7.8 Hz, 1H, CH), 3.04-2.94 (m, 1H, CH),
2.85 (dd, J = 17.2 Hz and 4.0 Hz, 1H, CH), 2.66 (dd, J = 14.0 Hz and Acknowledgements
10.5 Hz, 1H, CH); 13C NMR (125 MHz, CDCl3) δ 207.9, 153.7, 139.7,
Financial support by National Natural Science Foundation of
136.6, 134.9, 129.0, 128.6, 127.5, 126.7, 126.4, 124.1, 49.0, 37.1,
China (21272115), Natural Science Foundation of Jiangsu
32.3.
Province (BK20161494) and the State Key Laboratory of Fine
1-Cyclopropyl-3-phenylpropan-1-one (3ja).41 Pale yellow oil; 81%
yield (71 mg); H NMR (500 MHz, CDCl3) δ 7.30-7.24 (m, 2H, ArH),
Chemicals (KF1704) is greatly appreciated.
1
7.23-7.14 (m, 3H, ArH), 2.95-2.85 (m, 4H, CH2), 1.95-1.86 (m, 1H,
CH), 1.06-0.98 (m, 2H, CH2), 0.88-0.81 (m, 2H, CH2); 13C NMR (125
Notes and reference
10.8.
MHz, CDCl3) δ 210.1, 141.3, 128.6, 128.4, 126.2, 45.1, 30.1, 20.7,
1
(a) D. Caine, in: Comprehensive Organic Synthesis, (Eds.: B.
M. Trost, I. Fleming,), Pergamon), Oxford, 1991, , 1; (b)
3
Procedure for hydrogen transfer between an α,β-unsaturated
ketone and an alcohol (Scheme 2).
Modern Carbonyl Chemistry (Ed.: J. Otera,), Wiley-VCH, W
einheim, 2000.
2
For selected reviews about hydrogen autotransfer process or
hydrogen-borrowing strateghy, see: (a) G. Guillena, D. J.
Ramon and M. Yus, Angew. Chem. Int. Ed., 2007, 46, 2358; (b)
M. H. S. A. Hamid, P. A. Slatford and J. M. J. Williams, Adv.
Synth. Catal., 2007, 349, 1555; (c) G. E. Dobereiner, R. H.
Grabtree, Chem. Rev., 2010, 110, 681; (d) G. Guillena, D.
Ramon and M. Yus, Chem. Rev., 2010, 110, 1611; (e) S. Bahn,
S. Imm, L. Neubert, M. Zhang, H. Neumann and M. Beller,
Under air atmosphere, 2a (54 mg, 0.5 mmol), 4 (135 mg, 0.65 mmol,
1.3 equiv), cat. 8 (2.5 mg, 0.0025 mmol, 0.5 mol %), KOH (28 mg, 0.5
mmol, 1 equiv) and H2O (1 mL) were added to a 5 mL round-
bottomed flask with a condenser tube. The mixture of reaction was
heated under reflux in an oil bath for 12 h. The reaction mixture
was cooled to ambient temperature, concentrated in vacuo and
purified by flash column chromatography with hexanes/ethyl
acetate to afford the corresponding product 3aa in 91% yield (96
mg).
ChemCatChem, 2011,
3
3, 1853; (f) S. Pan and T. Shibata, ACS
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Procedure for the confirmation of the formation of [Ir-H].
3
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2001, 66, 9020; (b) C. S. Cho, B. T. Kim, T. J. Kim and S. C.
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3608; (d) C. S. Cho, B. T. Kim, H. J. Choi, T. J. Kim and S. C.
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A J-Young NMR tube was charged with cat. 8 (5.1 mg, 0.005 mmol),
2a (4.3 mg, 0.04 mmol, 8 equiv) and D2O (1 mL), and was then
heated in oil bath at 100oC for 15 min. The NMR tube was cooled
and was put into the NMR probe. 1H NMR (500 MHz, D2O) δ -10.68.
,
Procedure for the large-scale reaction (Scheme 3).
Brand, D. J. Ramon and M. Yus, Tetrahedron Lett., 2005, 46
3683; (f) R. Martínez, D. J. Ramon and M. Yus, Tetrahedron,
,
Under air atmosphere, 2a (10 mmol), 1a (13 mmol, 1.3 equiv), cat. 8
(50 mg, 0.05 mmol, 0.5 mol %), KOH (560 mg, 10 mmol, 1 equiv)
and H2O (5 mL) were added to a 25 mL round-bottomed flask with a
condenser tube. The mixture of reaction was heated under reflux in
an oil bath for 12 h. The reaction mixture was cooled to ambient
temperature, concentrated in vacuo and purified by flash column
chromatography with hexanes/ethyl acetate to afford the
corresponding product 3aa with 85% yield.
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4
5
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Procedure for the Synthesis of Donepezil (Scheme 4).
Under air atmosphere, 6 (103 mg, 0.5 mmol), 5 (125 mg, 0.65 mmol,
1.3 equiv), cat. 8 (2.5 mg, 0.0025 mmol, 0.5 mol %), KOH (28 mg, 0.5
mmol, 1 equiv) and H2O (1 mL) were added to a 5mL round-
bottomed flask with a condenser tube. The mixture of reaction was
heated under reflux in an oil bath for 12 h. The reaction mixture
was cooled to ambient temperature, concentrated in vacuo and
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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8 | J. Name., 2012, 00, 1-3
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