Asymmetric 1,4-addition of organoboronic acids to α,β-unsaturated ketones and 1,2-addition to aldehydes catalyzed by a palladium complex with a ferrocene-based phosphine ligand

Article abstract of DOI:10.1016/j.tetasy.2009.11.025

A combination of palladium with ferrocene-based phosphine ligand with a carbon-bromine bond was found to be a good catalyst for the 1,4-addition of arylboronic acids to α,β-unsaturated ketones and the 1,2-addition to aldehydes. Using Pd(dba)₂ and (S,R_p)-[1-(2-bromoferrocenyl)ethyl]diphenylphosphine (S,R_p)-1, 3-phenylcyclohexanone was obtained from the reaction of 2-cyclohexen-1-one with phenylboronic acid in the presence of K₂CO₃ in toluene at room temperature after 3 h in 92% yield with 76% ee. In the 1,2-addition of 4-methylphenylboronic acid to benzaldehyde, 96% of (4-methylphenyl)phenylmethanol was afforded after 24 h, while the enantiomeric excess was only 6%.

Full text of DOI:10.1016/j.tetasy.2009.11.025

Tetrahedron: Asymmetry 20 (2009) 2751–2758
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Tetrahedron: Asymmetry
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Asymmetric 1,4-addition of organoboronic acids to a,b-unsaturated ketones
and 1,2-addition to aldehydes catalyzed by a palladium complex with a
ferrocene-based phosphine ligand
Yoshinori Suzuma , Shoko Hayashi , Tetsuya Yamamoto , Yohei Oe , Tetsuo Ohta b,*, Yoshihiko Ito a
a
a
b
b
a
Department of Molecular Science and Technology, Faculty of Engineering, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan
Department of Biomedical Information, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A combination of palladium with ferrocene-based phosphine ligand with a carbon–bromine bond was
Received 19 October 2009
Accepted 17 November 2009
Available online 5 January 2010
found to be a good catalyst for the 1,4-addition of arylboronic acids to
the 1,2-addition to aldehydes. Using Pd(dba) and (S,R )-[1-(2-bromoferrocenyl)ethyl]diphenylphosphine
S,R )-1, 3-phenylcyclohexanone was obtained from the reaction of 2-cyclohexen-1-one with phenylbo-
ronic acid in the presence of K CO in toluene at room temperature after 3 h in 92% yield with 76% ee. In
a,b-unsaturated ketones and
2
p
(
p
2
3
the 1,2-addition of 4-methylphenylboronic acid to benzaldehyde, 96% of (4-methylphenyl)phenylmeth-
anol was afforded after 24 h, while the enantiomeric excess was only 6%.
Ó 2009 Elsevier Ltd. All rights reserved.
1
. Introduction
Transformations using an organometallic nucleophile catalyzed
is a crucial activation reagent for conventional palladium species.
We also developed a new catalyst system combined with a palla-
dium precursor with a phosphine having a carbon–bromine bond
by utilizing the chloroform effect and reported the preliminary
by transition metal complexes are indispensable techniques in
present organic syntheses. Among them, various kinds of reactions
using organoboronic acid have been developed.1 An asymmetric
carbon–carbon bond-forming reaction using organoboronic acid
is especially useful for making a skeleton of optically active organic
compounds because of their commercial availability, stability, non-
toxicity, and allowance for many functional groups.2
The combination of rhodium catalysts and organoboronic acids
has emerged as a powerful and ideal catalytic system in carbon–
carbon bond-forming reactions. The 1,4-additions of aryl- and
1
0f
results. Herein, we report the addition reaction of organoboronic
acid to ,b-unsaturated ketones and to aldehydes catalyzed by a
combination of palladium and ferrocene-based phosphine ligands.
a
2
2
. Results and discussion
.1. Design of ferrocene ligand
In our previous research, conventional palladium complexes
were activated by the addition of a catalytic amount of chloroform
in the presence of triphenylphosphine for the reaction of 1,2- and
1
-alkenylboron compounds to a,b-unsaturated carbonyl com-
3
,4
aldehydes,5 and aldimines have been developed. In
6
pounds,
the last few years, various groups have reported the use of inex-
pensive metals in comparison to rhodium, such as nickel, ruthe-
1
,4-additions of arylboronic acids to
a
,b-unsaturated carbonyl
7
1
0e,15b
compounds and aldehydes.
The best catalytic activity was
8
9
10
nium, platinum, and palladium catalysts for the 1,4-additions
to ,b-unsaturated carbonyl compounds with organoboron com-
pounds. Additionally, copper, iron, platinum, ruthenium,
palladium, and nickel have been reported to catalyze the 1,2-
additions of organoboron compounds to aldehydes, ketones,
imines, and nitriles. However, these addition reactions with orga-
noboron compounds by metals other than rhodium are still under
development.
achieved using one equimolar amount of triphenylphosphine to a
palladium atom. The oxidative addition of chloroform to palladium
is considered essential for the activation (Scheme 1). From these
hypotheses, a ferrocene-based phosphine with a carbon–bromine
a
11
12
13
14
1
5
16
CHCl
CHCl
2
2
OH-
CHCl3
Pd0
PdII
PdII
L
L
L
- Cl-
We have also developed a new palladium catalyst system for
,2- and 1,4-addition reactions.10e,15b In our system, chloroform
Cl
L = Phosphine Ligand
OH
1
*
Corresponding author. Tel.: +81 774 65 6548; fax: +81 774 65 6789.
E-mail address: tota@mail.doshisha.ac.jp (T. Ohta).
Scheme 1. Plausible formation of catalytically active species.
0
957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.11.025

2
752
Y. Suzuma et al. / Tetrahedron: Asymmetry 20 (2009) 2751–2758
Br
Br
NMe2
NMe2
PPh2
Fe
Fe
Fe
(S)-4
(S,R )-3
(S,R )-1
p
p
Fe
+
NMe2
PPh2
Fe
Fe
(R)-4
(S)-2
Scheme 2. Preparation of compounds 1–4.
bond 1 was selected. Ferrocene-based ligand 1 was readily accessi-
(Table 1, entry 6). On the other hand, the yield was dramatically de-
creased with ligand 2 which had no carbon–bromine bond (Table 1,
entry 7). The reaction did not proceed when using ligand 3 which
has no phosphine substituent but a carbon–bromine bond (Table 1,
entry 8). Moreover, the combination of triphenylphosphine and
ligand 3 gave no reaction at all. These results indicate that the effec-
tive ligand for this addition reaction should simultaneously have a
carbon–bromine bond and a phosphine substituent. In addition,
ble by a reported procedure (Scheme 2).17
2
.2. Palladium-catalyzed addition reaction of phenylboronic
acid to 2-cyclohexen-1-one
We screened the use of phosphine and ferrocene-based ligands
1–4 in the palladium-catalyzed addition reaction of phenylboronic
acid 7a to 2-cyclohexen-1-one 6a (Eq. 1). All the reactions were
performed with 5 mol% of Pd source and racemic ligand. The re-
sults are summarized in Table 1.
we examined other Pd sources such as PdCl
entries 11–13). However, the combination of PdCl
ligand 1 or 2 did not give good results.
2
and Pd(OAc)
2
(Table 1,
2
, Pd(OAc) , and
2
O
O
2
.3. Plausible reaction mechanism
From the above results, we propose this reaction’s catalytic cy-
Pd source / Ligand (5.0 mol%)
+
PhB(OH)2
Cs CO3
2
Ph
Toluene, 80 oC, 24 h
cle in Scheme 3. First, palladacycle A, which is generated by the
oxidative addition of a carbon–bromine bond in ligand 1 to
Pd(dba) , is converted to hydroxypalladium species B by ligand ex-
2
6a
7a
8aa
ð1Þ
In the presence of triphenylphosphine, the reaction did not pro-
ceed (Table 1, entry 1). Bidentate phosphine ligands such as DPPP,
DPPB, DPPF, and BINAP were not effective at all (Table 1, entries
–5). The reaction progressed when a ferrocene-based phosphine
ligand with a carbon–bromine bond [1-(2-bromoferrocenyl)ethyl]-
change with a hydroxide anion. Then the transmetallation between
phenylboronic acid 7a and hydroxypalladium species B occurs to
generate phenylpalladium intermediate C. The coordination and
the insertion of the 2-cyclohexen-1-one 6a into the carbon–palla-
dium bond afford intermediate E which is hydrolyzed by water
generated from boronic acid and the base to give the correspond-
ing carbonyl compound 3-phenylcyclohexanone 8aa to regenerate
the hydroxypalladium species B
2
diphenylphosphine 1 was employed, and 1,4-addition product
-phenylcyclohexanone 8aa was obtained in 82% isolated yield
3
Table 1
Palladium-catalyzed 1,4-addition reaction of phenylboronic acid to 2-cyclohexen-1-
2
.4. Optimization of the reaction conditions
onea
Entry
Ligand
PPh
DPPPc
Pd source
Yieldb (%)
p
We optimized the reaction conditions using chiral ligand (S,R )-
1
2
3
4
5
6
7
8
9
3
Pd(dba)
Pd(dba)
Pd(dba)
Pd(dba)
Pd(dba)
Pd(dba)
Pd(dba)
Pd(dba)
Pd(dba)
Pd(dba)
2
2
2
2
2
2
2
2
2
2
0
0
0
0
1 (Table 2). First, the reaction was carried out in the presence of
Cs CO at 80 °C for 24 h, and the desired product 8aa was obtained
2
3
d
DPPB
in 82% yield with 42% ee. The product 8aa was gained in identical
yield with similar ee at 60 °C, and higher enantioselectivity was re-
corded at room temperature even with a similar yield of the prod-
uct (Table 2, entries 1–3). At a lower temperature (0 °C), the
reaction did not proceed at all. We found that the reaction was rel-
atively quick, that is, when the reaction time was shortened from
DPPFe
rac-BINAP
rac-1
f
0
82g
rac-2
rac-3
rac-3 + PPh
rac-4
rac-1
3
0
0
0
8
3
10
11
12
13
2
4 h to 6, 3, and 1 h, it proceeded smoothly to give the product
PdCl
Pd(OAc)
PdCl
2
rac-1
rac-2
2
18
17
in 81%, 80%, and 60% yields, respectively, with the same enantiose-
lectivities (Table 2, entries 3–6). These results allowed us to con-
duct the reaction for 3 h. In the experiments to determine the
solvent effect, toluene, ethanol, and 1,4-dioxane were good sol-
vents with regard to yield and enantioselectivity (Table 2, entries
2
a
The reaction was carried out with 2-cyclohexen-1-one (1.0 mmol), phenylbo-
ronic acid (2.0 mmol), a Pd source (0.05 mmol), ligand (0.05 mmol), and Cs CO
2
3
(
1.0 mmol) in 2 mL of toluene at 80 °C for 24 h.
b
Determined by 1H NMR.
5
, 9, and 10). When DMF and acetonitrile were used as solvents,
c
1
1
1
2
,3-Bisdiphenylphosphinopropane.
,4-Bisdiphenylphosphinobutane.
d
e
f
both yield and enantioselectivity decreased (Table 2, entries 8
and 11). When phenylboronic acid was examined, the kind of base
was crucial for reactivity and selectivity. Therefore, we examined
the base effect. Bases which included potassium usually gave
0
,1 -Bisdiphenylphosphinoferrocene.
0
0
,2 -Bis(diphenylphosphino)-1,1 -binaphthyl.
g
Isolated yield.

Y. Suzuma et al. / Tetrahedron: Asymmetry 20 (2009) 2751–2758
2753
Pd(dba)2
2 DBA
PPh2
PPh2
Br
Fe
Fe Pd
Br
A
4
OH-
O
Br-
PhB(OH)2
Ph
PhB(OH) + Base
2
8aa
7
a
PPh2
Fe Pd
OH
B(OH)3
H O
2
B
PPh2
O
PPh2
Fe Pd
Fe Pd
Ph
Ar
C
E
O
PPh2
Fe Pd
Ph
O
6a
D
Scheme 3. Plausible reaction mechanism.
Table 2
a
lower. The use of CaCO
use of Ca(OH) afforded the product in better yield. The optimum
reaction conditions were finalized when the reaction was carried
out in toluene in the presence of K CO at room temperature for
3
made the reaction sluggish, while the
Optimization of reaction condition
2
Entry Temp (°C) Time (h) Solvent
Base
Yieldb (%) eec (%)
1
2
3
4
5
6
7
8
9
1
80
60
rt
rt
rt
rt
rt
rt
rt
rt
24
24
24
6
3
1
3
3
3
3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
DMF
Ethanol
1,4-
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
3
3
3
3
3
3
3
3
3
3
82
83
79
81
80
60
70
32
77
80
42 (S)
46 (S)
66 (S)
67 (S)
66 (S)
65 (S)
62 (S)
49 (S)
66 (S)
61 (S)
2
3
3
h.
2
.5. 1,4-Addition of arylboronic acid to a,b-unsaturated
ketones
After the determination of the optimized reaction conditions,
the scope of this palladium-catalyzed asymmetric 1,4-addition of
0
Dioxane
Acetonitrile Cs
arylboronic acid 7 to
(Scheme 4). The results are summarized in Table 3. First, 2-cycloh-
exen-1-one 6a was used as an ,b-unsaturated ketone, and the
a,b-unsaturated ketones 6 was examined
1
1
1
1
1
1
1
1
1
2
3
4
5
6
7
8
rt
rt
rt
rt
rt
rt
rt
rt
3
3
3
3
3
3
3
3
2
CO
3
48
92
52
17
85
91
64
69
30 (S)
76 (S)
73 (S)
75 (S)
72 (S)
75 (S)
76 (S)
66 (S)
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
K
2
CO
Na CO
CaCO
PO
KOH
3
a
2
3
substituent effects on 4-carbon in phenylboronic acid were tested.
When such substrates with electron-donating groups such as
methyl, methoxy, and tert-butyl were employed for this reaction,
almost identical yields and enantioselectivities were recorded (Ta-
ble 3, entries 1–4). The enantioselectivity increased to 79% from
the reaction with 4-tert-butylphenylboronic acid 7d. The reaction
with 4-trifluoromethylphenylboronic acid 7e proceeded smoothly
in 81% yield with very low enantioselectivity, 4% ee, and the reac-
tion with 4-fluorophenylboronic acid 7f proceeded slowly with
good enantioselectivity, 68% ee. 2-Naphthylboronic acid 7g was
examined for this reaction and converted to 3-(2-naphthyl)cyclo-
hexanone 8ag in 80% yield with 42% ee. Then several cyclic and
3
K
3
4
Ca(OH)
2
t
KO Bu
a
The reaction was carried out with 2-cyclohexen-1-one (1.0 mmol), phenylbo-
ronic acid (2.0 mmol), Pd(dba) (0.05 mmol), ligand (0.05 mmol), and base
2
1
(
1.0 mmol) in 2 mL of solvent.
Isolated yield.
Determined by HPLC.
b
c
better enantioselectivities than the common base Cs
reaction using phenylboronic acid. Among the bases tested,
2 3
CO for the
acyclic a,b-unsaturated ketones were allowed to react with phen-
ylboronic acid. In comparison with 2-cyclohexen-1-one 6a, the
reaction of 2-cyclophenten-1-one 6b and 2-cycloepten-1-one 6c
K
5
2
CO
3
gave the best yield and enantioselectivity (Table 2, entries
CO was used, the product yield became
and 12–18). When Na
2
3

2
754
Y. Suzuma et al. / Tetrahedron: Asymmetry 20 (2009) 2751–2758
O
Ar
O
Pd(dba) / (S,R )-1 (5.0 mol%)
2
p
R1
R2
+
ArB(OH)2
R1
R2
K CO (1.0 equiv.)
2
3
6
7
Toluene, rt, 3 h
8
O
O
O
R1
R2
O
1
2
6
6
6
6
d: R =Me, R =Me
1
2
e: R =Me, R =Et
1
i
2
f: R = Pr, R =Me
6
a
6b
6c
1
2
g: R =n-C H , R =Me
5
11
Scheme 4. 1,4-Additon of arylboronic acids 7 to
p
a,b-unsaturated ketones 6 catalyzed by palladium-(S,R )-1.
Table 3
,4-Addition of arylboronic acids
palladium-(S,R )-1
p
Table 4
1
7
to
a
,b-unsaturated ketones
6
catalyzed by
1,2-Additon of arylboronic acids 7 to aldehydes 9 catalyzed by palladium-1a
a
Entry Aldehyde
R=
Boronic acid
Product Yieldb (%) eec (%)
Entry Substrate 6 Boronic acid 7
Ketone 8 Yieldb (%) eec (%)
R=
1
2
3
4
5
6
7
8
9a
9a
9a
9a
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
C
C
C
C
C
6
6
6
6
6
H
H
H
H
H
5
5
5
5
5
7a
7b
7c
7d
7g
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
10aa
10ab
10ac
10ad
10ag
10ba
10ca
10da
10ea
10fa
10ga
10ha
10ia
95
96
81
92
71
78
93
80
83
>99
51
91
90
78
54
19
68
61
—
6 (R)
8 (R)
4 (ꢀ)
11 (R)
5 (S)
9 (S)
8 (S)
11 (S)
5 (S)
7 (S)
6 (S)
11 (S)
3 (R)
4 (R)
2 (R)
3 (R)
6 (R)
1
2
3
4
6a
6a
6a
6a
7a
C
6
H
5
8aa
8ab
8ac
8ad
92
89
83
92
76 (S)
78 (S)
76 (S)
79 (S)
7b 4-CH
7c 4-CH
7d 4-tert-
3
C
OC
6
H
4
3
6
H
4
C
4
H
9
C
6
H
4
4-CH
4-CNC
4-NO
4-CH
4-ClC
4-BrC
1-Naphthyl
2-Naphthyl
Cyclohexyl
3 6 4
C H
H
6 4
5
6
7
8
9
1
1
1
1
6a
6a
6a
6b
6c
6d
6e
6f
7e 4-CF
7f 4-FC
7g 1-Naphthyl
3
C
6
H
4
8ae
8af
8ag
8ba
8ca
8da
8ea
8fa
8ga
81
45
80
94
90
53
62
70
99
4 (S)
68 (S)
42 (S)
54 (S)
38 (S)
44 (S)
47 (S)
52 (S)
42 (S)
6
H
4
2
C
6
H
4
9
3
OC
6
H
4
7a
7a
7a
7a
7a
7a
C
C
C
C
C
C
6
H
6
H
6
H
6
H
6
H
6
H
5
5
5
5
5
5
10
11
12
13
14
15
6 4
H
H
6 4
0
1
2
3
10ja
10ka
10la
10ma
10na
6g
tert-C
3 7
iso-C H
4
H
9
16
17
18
a
The reaction was carried out with
ylboronic acid (2.0 mmol), Pd(dba) (0.05 mmol), ligand 1 (0.05 mmol), and K
1.0 mmol) in 2 mL of toluene at rt for 3 h.
a
,b-unsaturated ketone (1.0 mmol), phen-
9m 2-Furyl
9n 2-Thiophenyl
2
2
CO
3
(
b
c
a
Isolated yield.
Determined by HPLC.
The reaction was carried out with an aldehyde (1.0 mmol), phenylboronic acid
(2.0 mmol), Pd(dba) (0.05 mmol), ligand 1 (0.05 mmol), and K CO (1.0 mmol) in
2
2
3
2
mL of toluene at rt for 24 h.
Isolated yield.
Determined by HPLC.
b
c
gave the corresponding products in similar yields with lower
enantioselectivities of 54% and 38% ee, respectively. Acyclic sub-
strates 6d–6g also smoothly reacted with phenylboronic acid 7a
to give the desired products 8da–8ga in moderate to good yields
but with lower enantioselectivities than cyclic 6a but with similar
selectivities to the five- and seven-membered substrates 6b and
and the product had an opposite configuration (Table 4, entries 2
and 6). Similarly, 10ea and 10ha had the opposite configurations
of 10ac and 10ag (Table 4, entries 3 and 9, 5, and 12). Ligand 1
has the potential to control the configuration of the products. A
high yield was also observed from the reaction of cyclohexanecarb-
aldehyde 9j (Table 4, entries 14). Acyclic alkylaldehydes 9k and 9l
produced the 10ka and 10la in moderate to low yields (Table 4,
entries 15 and 16). In addition, furan-2-carbaldehyde 9m and thi-
ophene-2-carbaldehyde 9n were converted to the desired products
in moderate yields (Scheme 5).
6
c.
2
.6. 1,2-Addition of arylboronic acid to aldehydes
This catalyst system was applied to the 1,2-addition of arylbo-
ronic acids to aldehydes, and the results are summarized in Table 4.
First, the addition of phenylboronic acid 7a to benzaldehyde 9a
was tested under the standard reaction condition described in
the 1,4-addition reaction. The reaction proceeded successfully to
give the desire product diphenylmethanol 10aa in high yield
O
OH
Ar
Pd(dba) / (S,R )-1 (5.0 mol%)
2
p
+
ArB(OH)
2
R
H
R
(Table 4, entry 1), but slower than the 1,4-addition. Therefore,
K CO (1.0 equiv.)
2
3
the reaction time was prolonged to 24 h as a standard reaction con-
dition. The addition of arylboronic acids 7b–d and 7g was pro-
ceeded smoothly to give the corresponding diarylmethanols
Toluene, rt
9
7
10
Scheme 5. 1,2-Addition of arylboronic acids 7 to aldehydes 9 catalyzed by palla-
dium-1.
1
0ab–10ad and 10ag in high yield (Table 4, entries 2–5). Unfortu-
nately, enantioselectivity was quite low. Various arylaldehydes
b–9i underwent the addition reaction of phenylboronic acid 7a.
9
3. Conclusion
All products 10ba–10ia were obtained in high yield with low
enantioselectivity (Table 4, entries 6–13). Even with low enanti-
oselectivity, the reaction of aldehyde 9b and boronic acid 7a pro-
duced the product 10ba with the same structure as that of 10ab,
We have achieved an efficient addition reaction to a,b-unsatu-
rated ketones and aldehydes with an arylboronic acid catalyzed
by palladium complex having a ferrocene-based phosphine ligand,

Y. Suzuma et al. / Tetrahedron: Asymmetry 20 (2009) 2751–2758
2755
which has an oxidative addition ability to the palladium center.
The asymmetric 1,4-addition of arylboronic acids to ,b-unsatu-
enantiomeric ratio was determined by HPLC using a chiral column
(Daicel Chiralpak AD-H), hexane/2-propanol 98:2, 0.5 mL/min,
a
2
5
rated ketones proceeded smoothly at room temperature for 3 h
to give the addition products in good yields with good enantiose-
lectivities. For the 1,2-addition of arylboronic acids to aldehydes,
the products were obtained in high yields but the enantioselectiv-
ities were low. Further applications and the development of effi-
cient ligands continue.
254 nm, 13.0 min (major), 14.6 min (minor). ½
a
ꢁ
¼ ꢀ12:0 (c 1.00,
D
2
D
3
CHCl
3
) for 78% ee [lit.: ½
a
ꢁ
¼ ꢀ15:0 (c 1.09, CHCl
3
) for 94% ee in
the (S)-isomer].
4.6. (S)-3-(4-Methoxyphenyl)cyclohexanone 8ac18
1H NMR (300 MHz, CDCl
3
) d 1.69–1.86 (m, 2H), 2.01–2.15 (m,
H), 2.30–2.58 (m, 4H), 2.89–2.98 (m, 1H), 3.76 (s, 3H), 6.82–
2
6
3
4
4
. Experimental
1
3
.87 (m, 2H), 7.09–7.14 (m, 2H). C NMR (75 MHz, CDCl
3
) d 25.7,
3.2, 41.5, 44.3, 49.3, 55.5 126.7, 136.7, 158.3 211.2. GC–MS (M/
.1. General procedure
Z) 204. The enantiomeric ratio was determined by HPLC using a
chiral column (Daicel Chiralpak AD-H), hexane/2-propanol 90:10,
All reactions with air- or moisture-sensitive materials were car-
0
.5 mL/min, 254 nm, 13.7 min (major), 14.6 min (minor).
ried out under argon using standard Schlenk techniques. All com-
pounds are commercially available, and are used without
purification. All solvents were dried by standard methods and
distilled under argon. Nuclear magnetic resonance spectra were
2
5
23
D
½
a
ꢁ
¼ ꢀ11:0 (c 1.00, CHCl
3
) for 76% ee [lit.: ½
a
ꢁ
¼ ꢀ14:2 (c 1.02,
D
CHCl
3
) for 92% ee in the (S)-isomer].
4.7. (S)-3-(4-t-Butylphenyl)cyclohexanone 8ad19
1
measured on a Varian MERCURY plus 300-4N spectrometer ( H:
1
3
3
00 MHz, C: 75 MHz). Exact mass spectrometry was performed
1H NMR (300 MHz, CDCl
) d 1.31 (s, 9H), 1.74–1.89 (m, 2H),
.06–2.18 (m, 2H), 2.31–2.63 (m, 4H), 2.93–3.04 (m, 1H), 7.13–
3
on a JEOL JMS-700 (FAB-MS, matrix: m-NBA, reference: PEG-400).
All substrates are commercially available and are used without
2
7
2
2
1
3
3
.16 (m, 2H), 7.33–7.35 (m, 2H). C NMR (75 MHz, CDCl ) d
purification. N,N-Dimethy-1-ferrocenylethylamine 4, (S,R
methyl-1-(2-bromoferrocenyl)ethylamine (S,R )-3, (S,R
Bromoferrocenyl)ethyl]diphenylphosphine (S,R )-1, and (S,R
)-2) were prepared
p
)-N,N-di-
)-[1-(2-
)-(1-
5.9, 31.8, 33.2, 34.8, 41.6, 44.6, 49.3, 125.8, 126.4, 141.5, 149.6,
11.3. GC–MS (M/Z) 230. The enantiomeric ratio was determined
p
p
p
p
by HPLC using a chiral column (Daicel Chiralpak AS-H), hexane/
2-propanol 98:2, 0.5 mL/min, 254 nm, 22.9 min (minor), 30.5 min
ferrocenylethyl)diphenylphosphine ((S,R
p
according to the literature.17
2
D
5
20
D
(
major). ½
aꢁ
¼ ꢀ12:0 (c 1.00, CHCl
3
) for 79% ee [lit.: ½
a
ꢁ
¼
þ11:9 (c 0.68, CHCl
3
) for 99% ee in the (R)-isomer].
4
.2. 1,4-Addition of organoboronic acid to
a,b-unsaturated
ketone
4
.8. (S)-3-(4-Trifluoromethylphenyl)cyclohexanone 8ae18
In a 80 mL Schlenk tube were placed the
tone (1.0 mmol), arylboronic acid (2.0 mmol), Pd(dba)
.05 mmol), ligand (0.0239 g, 0.05 mmol), K CO
2 3
.0 mmol), and solvent (2 mL). The resulting solution was stirred
at room temperature for 3 h. The analytically pure ketone was ob-
tained by chromatography on silica gel.
a,b-unsaturated ke-
1H NMR (300 MHz, CDCl
) d 1.77–1.94 (m, 2H), 2.07–2.18 (m,
3
2
(0.0288 g,
2
7
4
H), 2.34–2.62 (m, 4H), 3.05–3.12 (m, 1H), 7.32–7.25 (m, 2H),
0
1
(0.1382 g,
1
3
3
.56–7.59 (m, 2H). C NMR (75 MHz, CDCl ) d 25.7, 32.8, 41.4,
1
9
4.8, 48.8, 126.0, 127.2, 129.1, 148.3, 210.6. F NMR (282 MHz,
CDCl
3
) d ꢀ62.98. GC–MS (M/Z) 242. The enantiomeric ratio was
determined by HPLC using a chiral column (Daicel Chiralcel OD-
H), hexane/2-propanol 98:2, 0.5 mL/min, 254 nm, 18.7 min (min-
4
.3. 1,2-Addition of organoboronic acid to aldehyde
2
D
5
or), 19.9 min (major). ½
aꢁ
¼ ꢀ1:0 (c 1.00, CHCl
3
) for 4% ee [lit.:
2
3
½
a
ꢁ
¼ ꢀ11:4 (c 0.95, CHCl
3
) for 95% ee in the S-isomer].
D
In a 80 mL Schlenk tube were placed the aldehyde (1.0 mmol),
arylboronic acid (2.0 mmol), Pd(dba)
2
(0.0288 g, 0.05 mmol),
4
.9. (S)-3-(4-Fluorophenyl)cyclohexanone 8af20
1H NMR (300 MHz, CDCl
ligand (0.0239 g, 0.05 mmol), K CO (0.1382 g, 1.0 mmol), and sol-
2
3
vent (2 mL). The resulting solution was stirred at room tempera-
ture for 24 h. The analytically pure alcohol was obtained by
chromatography on silica gel.
3
) d 1.72–1.88 (m, 2H), 2.04–2.18 (m,
H), 2.31–2.59 (m, 4H), 2.93–3.02 (m, 1H), 6.99 (m, 2H), 7.13–
.19 (m, 2H). C NMR (75 MHz, CDCl ) d 25.7, 33.2, 41.4, 44.3,
3
2
7
4
1
3
1
9
3
9.4, 115.6, 128.1, 140.2, 161.6, 210.8. F NMR (282 MHz, CDCl )
4
.4. (S)-3-Phenylcyclohexanone 8aa4a
1H NMR (300 MHz, CDCl
d ꢀ161.6. GC–MS (M/Z) 192. The enantiomeric ratio was deter-
mined by HPLC using a chiral column (Daicel Chiralpak AD-H), hex-
3
, TMS) d 1.69–1.90 (m, 2H), 2.07–2.17
m, 2H), 2.31–2.60 (m, 4H), 2.94–3.05 (m, 1H), 7.19–7.23 (m, 3H),
ane/2-propanol 99:1, 0.5 mL/min, 254 nm, 20.3 min (major),
2
(
25
D
7.1 min (minor). ½
a
ꢁ
¼ ꢀ17:7 (c 0.51, CHCl
3
) for 68% ee [lit.:
) for 88% ee in the (S)-isomer].
1
3
7
.29–7.34 (m, 2H). C NMR (75 MHz, CDCl
3
) d 25.9, 33.1, 41.5,
20
D
½a
ꢁ
¼ ꢀ21:3 (c 0.50, CHCl
3
4
5.1, 49.3, 126.8, 126.9, 128.9, 144.5, 211.2. GC–MS (M/Z) 174.
The enantiomeric ratio was determined by HPLC using a chiral col-
umn (Daicel Chiralcel OD-H), hexane/2-propanol 98:2, 0.5 mL/min,
.10. (S)-3-(1-Naphthyl)cyclohexanone 8ag18
4
25
2
CHCl
the (S)-isomer].
54 nm, 30.6 min (major), 33.0 min (minor). ½
a
ꢁ
¼ ꢀ17:2 (c 1.05,
1
D
3
H NMR (300 MHz, CDCl ) d 1.86–2.08 (m, 2H), 2.15–2.30 (m,
2
D
0
3
) for 76% ee [lit.: ½
aꢁ
¼ ꢀ21 (c 0.96, CHCl
3
) for 97% ee in
2H), 2.41–2.82 (m, 4H), 3.81–3.92 (m, 1H), 7.38–7.57 (m, 4H),
7
1
.76 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 8.9 Hz, 1H), 8.05 (d, J = 8.4 Hz,
H). C NMR (75 MHz, CDCl ) d 25.7, 32.5, 39.6, 41.7, 48.8,
3
1
3
4
.5. (S)-3-(4-Methyphenyl)cyclohexanone 8ab18
1H NMR (300 MHz, CDCl
122.8, 125.8, 126.4, 127.4, 129.3, 131.1, 134.1, 140.2, 211.3. GC–
MS (M/Z) 224. The enantiomeric ratio was determined by HPLC
using a chiral column (Daicel Chiralpak AD-H), hexane/2-propanol
99:1, 0.5 mL/min, 230 nm, 33.1 min (major), 36.2 min (minor).
3
) d 1.69–1.86 (m, 2H), 2.00–2.14 (m,
H), 2.30 (s, 3H), 2.30–2.58 (m, 4H), 2.89–2.99 (m, 1H), 7.06–7.13
2
1
3
25
D
23
D
(
m, 4H). C NMR (75 MHz, CDCl
3
) d 21.4, 25.9, 33.2, 41.5, 44.7,
½
aꢁ
¼ ꢀ39:0 (c 1.00, CHCl ) for 42% ee [lit.: ½
a
ꢁ
¼ ꢀ31:7 (c 0.97,
3
4
9.4, 126.6, 129.5, 136.3, 141.6, 211.1. GC–MS (M/Z) 188. The
3
CHCl ) for 52% ee in the (S)-isomer].

2
756
Y. Suzuma et al. / Tetrahedron: Asymmetry 20 (2009) 2751–2758
4
.11. (S)-3-Phenylcyclopentanone 8ba4a
1H NMR (300 MHz, CDCl
a chiral column (Daicel Chiralcel OD-H), hexane/2-propanol 95:5,
2
5
0
.5 mL/min, 210 nm, 7.2 min (major), 7.5 min (minor). ½
a
ꢁ
¼
D
3
) d 1.88–2.02 (m, 2H), 2.19–2.47 (m,
þ20:0 (c 0.50, CHCl
3
) for 42% ee.
4
7
3
1
H), 2.63 (dd, J = 18.6 Hz, 7.5 Hz, 1H), 3.32–3.44 (m, 1H), 7.18–
.23 (m, 3H), 7.29–7.33 (m, 2H). 13C NMR (75 MHz, CDCl
4.17. Diphenylmethanol 10aa
3
) d
1.5, 39.2, 42.5, 46.1, 126.9, 128.8, 143.2, 218.5. GC–MS (M/Z)
1
60. The enantiomeric ratio was determined by HPLC using a chiral
3
H NMR (300 MHz, CDCl ) d 2.35 (br s, 1H), 5.80 (s, 1H), 7.20–
1
3
column (Daicel Chiralcel OB-H), hexane/2-propanol 99.5:0.5,
3
7.43 (m, 10H). C NMR (75 MHz, CDCl ) d 76.3, 126.6, 127.6,
0
.7 mL/min, 210 nm, 37.0 min (major), 40.2 min (minor).
128.5, 143.8. GC–MS (M/Z) 184.
2
5
20
D
½
a
ꢁ
¼ ꢀ45:5 (c 1.01, CHCl
3
) for 54% ee [lit.: ½
aꢁ
¼ ꢀ92 (c 0.96,
D
CHCl
3
) for 97% ee in the (S)-isomer].
4.18. (R)-4-Methylphenyl(phenyl)methanols 10ab and 10ba
1
4
.12. (S)-3-Phenylcycloheptanone 8ca20
3
H NMR (300 MHz, CDCl ) d 2.21 (br s, 1H), 2.32 (s, 3H), 5.79 (s,
1
3
1
3
H), 7.11–7.38 (m, 9H). C NMR (75 MHz, CDCl ) d 21.5, 76.4,
126.65, 126.72, 127.6, 128.6, 129.4, 137.5, 141.1 144.1. GC–MS
(M/Z) 198. The enantiomeric ratio was determined by HPLC using
a chiral column (Daicel Chiralcel OD-H), hexane/2-propanol
1H NMR (300 MHz, CDCl
H), 1.96–2.14 (m, 3H), 2.86–2.99 (m, 2H), 7.16–7.24 (m, 3H),
3
) d 1.43–1.58 (m 1H), 1.66–1.82 (m,
2
7
4
1
3
.26–7.31 (m, 2H). C NMR (75 MHz, CDCl
3
) d 24.3, 29.4, 39.4,
2.9, 44.1, 51.4, 126.5, 128.8, 147.1, 213.5. GC–MS (M/Z) 188. The
90:10, 0.5 mL/min, 254 nm, 19.4 min (minor), 21.2 min (major).
enantiomeric ratio was determined by HPLC using a chiral column
(
2
Daicel Chiralcel OD-H), hexane/2-propanol 95:5, 0.7 mL/min,
4.19. (R)-4-Methoxyphenyl(phenyl)methanols 10ac and 10ea
25
10 nm, 10.7 min (major), 11.8 min (minor). ½
a
ꢁ
¼ ꢀ28:2 (c 1.10,
D
2
D
0
1H NMR (300 MHz, CDCl
1H), 6.83 (d, J = 8.4, 2H), 7.20–7.35 (m, 7H). C NMR (75 MHz,
CDCl ) d 55.6, 76.1, 114.1, 126.6, 127.6, 128.1, 128.6, 136.4,
CHCl
the (S)-isomer].
3
) for 38% ee [lit.: ½
aꢁ
¼ ꢀ61:3 (c 1.00, CHCl
3
) for 90% ee in
3
) d 2.34 (br s, 1H), 3.75 (s, 3H), 5.74 (s,
1
3
3
4
.13. (S)-4-Phenyl-2-pentanone 8da21
144.2, 159.2. GC–MS (M/Z) 214. The enantiomeric ratio was deter-
mined by HPLC using a chiral column (Daicel Chiralcel OJ), hexane/
2-propanol 90:10, 0.7 mL/min, 254 nm, 50.5 min (major), 63.6 min
(minor).
1H NMR (300 MHz, CDCl
3
) d 1.23 (d, J = 6.9 Hz, 3H), 2.01 (s, 3H),
2
3
2
.61 (dd, J = 16.2 Hz, 7.9 Hz, 1H), 2.71 (dd, J = 16.2 Hz, 6.5 Hz, 1H),
.26 (m, 1H), 7.16–7.25 (m, 5H). 13C NMR (75 MHz, CDCl
) d
1.9, 30.4, 35.3, 51.9, 126.2, 126.6, 128.4, 146.0, 207.6. GC–MS
3
4.20. (ꢀ)-4-t-Butylphenyl(phenyl)methanol 10ad
(M/Z) 162. The enantiomeric ratio was determined by HPLC using
a chiral column (Daicel Chiralcel OJ-H), hexane/2-propanol 99:1,
1H NMR (300 MHz, CDCl
3
) d 1.30 (s, 9H), 2.15 (br s, 1H), 5.81 (s,
0
.5 mL/min, 210 nm, 24.9 min (major), 26.4 min (minor).
1H), 7.20–7.44 (m, 9H). GC–MS (M/Z) 240. The enantiomeric ratio
was determined by HPLC using a chiral column (Daicel Chiralpak
AD-H), hexane/2-propanol 95:5, 0.7 mL/min, 254 nm, 15.4 min
2
5
20
D
½a
ꢁ
¼ 14:0 (c 0.50, CHCl
3
) for 44% ee [lit.: ½
aꢁ
¼ 38:8 (c 0.4,
D
CHCl
3
) for 97% ee in the (S)-isomer].
(
minor), 17.5 min (major).
4
.14. (S)-5-Phenyl-3-hexanone 8ea22
4
.21. (R)-1-Naphthyl(phenyl)methanols 10ag and 10ha
1H NMR (300 MHz, CDCl
) d 2.39 (br s, 1H), 5.98 (s, 1H), 7.25–
3
1H NMR (300 MHz, CDCl
) d 0.96 (t, J = 7.2 Hz, 3H), 1.24 (d,
3
J = 6.9 Hz, 3H), 2.21–2.38 (m, 2H), 2.57–2.74 (m, 2H), 3.25–3.37
m, 1H), 7.13–7.29 (m, 5H). 13C NMR (75 MHz, CDCl
) d 8.01,
2.2, 35.8, 37.1, 51.3, 126.4, 127.0, 128.7, 146.4, 210.4. GC–MS
M/Z) 176. The enantiomeric ratio was determined by HPLC using
a chiral column (Daicel Chiralpak AD-H), hexane/2-propanol
13
(
2
(
3
3
7.55 (m, 8H), 7.78–7.93 (m, 4H). C NMR (75 MHz, CDCl ) d
73.3, 124.0, 124.5, 125.3, 125.5, 125.8, 127.0, 127.5, 127.6, 128.4,
128.6, 130.4, 133.6, 138.8, 143.2. GC–MS (M/Z) 234. The enantio-
meric ratio was determined by HPLC using a chiral column (Daicel
Chiralcel OJ), hexane/2-propanol 80:20, 0.7 mL/min, 254 nm,
22.9 min (minor), 36.9 min (major).
9
9:1, 0.5 mL/min, 210 nm, 9.2 min (major), 9.9 min (minor).
2
D
5
25
D
½a
ꢁ
¼ þ26:0 (c 0.50, CHCl
3
) for 47% ee [lit.: ½
a
ꢁ
¼ ꢀ49:5 (c 1.00,
CHCl
3
) for 98% ee in the (R)-isomer].
4
.22. (S)-4-Cyanophenyl(phenyl)methanol 10ca
1H NMR (300 MHz, CDCl
4
.15. (S)-5-Methyl-4-phenyl-2-hexanone 8fa18
3
) d 2.63 (br s, 1H), 5.78 (s, 1H), 7.23–
1H NMR (300 MHz, CDCl
J = 6.6 Hz, 2H), 1.79–1.83 (m, 1H), 1.95 (s, 3H), 2.77–2.79 (m, 2H),
2
13
3
) d 0.73 (d, J = 6.6 Hz, 3H), 0.93 (d,
3
7.35 (m, 5H), 7.43–7.55 (m, 4H). C NMR (75 MHz, CDCl ) d
75.81, 113.13, 119.11, 127.08, 123.45, 129.06, 132.46, 143.00,
149.26. GC–MS (M/Z) 209. The enantiomeric ratio was determined
by HPLC using a chiral column (Daicel Chiralcel OD-H), hexane/2-
propanol 85:15, 0.5 mL/min, 254 nm, 23.8 min (minor), 26.5 min
(major).
1
3
.88–2.95 (m, 1H), 7.11–7.18 (m, 3H), 7.22–7.27 (m, 2H).
C
3
NMR (75 MHz, CDCl ) d 20.3, 20.7, 30.6, 33.3, 47.6, 48.0, 126.2,
1
28.1, 128.4, 143.3, 208.3. GC–MS (M/Z) 176. The enantiomeric ra-
tio was determined by HPLC using a chiral column (Daicel Chiralcel
OJ-H), hexane/2-propanol 99:1, 0.5 mL/min, 210 nm, 14.2 min
2
D
5
(
major), 17.3 min (minor). ½
a
ꢁ
¼ ꢀ16:0 (c 0.50, CHCl
3
) for 52%
4.23. (S)-4-Nitrophenyl(phenyl)methanol 10da
2
D
2
ee [lit.: ½
aꢁ
¼ ꢀ26:3 (c 1.18, CHCl
3
) for 77% ee in the S-isomer].
1H NMR (300 MHz, CDCl
7.38 (m, 5H), 7. 59 (d, J = 6.9 Hz, 2H), 8.21 (d, J = 6.9 Hz, 2H).
NMR (75 MHz, CDCl ) d 75.5, 123.6, 126.7, 127.0, 128.4, 128.7,
142.7, 150.5. GC–MS (M/Z) 229. The enantiomeric ratio was deter-
mined by HPLC using a chiral column (Daicel Chiralpak AD-H), hex-
ane/2-propanol 80:20, 0.5 mL/min, 254 nm, 14.6 min (minor),
18.0 min (major).
3
) d 2.39 (br s, 1H), 5.93 (s, 1H), 7.33–
.16. (S)-4-Phenyl-2-nonanone 8ga23
13
C
4
3
1H NMR (300 MHz, CDCl
3
) d 0.81 (t, J = 6.7 Hz, 3H), 1.05–1.27
(
3
(
m, 6H), 1.50–1.67 (m, 2H), 2.01 (s, 3H), 2.71 (d, J = 7.2 Hz, 2H),
.04–3.16 (m, 1H), 7.14–7.21 (m, 3H), 7.25–7.31 (m, 2H). GC–MS
M/Z) 218. The enantiomeric ratio was determined by HPLC using

Y. Suzuma et al. / Tetrahedron: Asymmetry 20 (2009) 2751–2758
2757
4
.24. (S)-4-Chlorophenyl(phenyl)methanol 10fa
1H NMR (300 MHz, CDCl
OD-H), hexane/2-propanol 95:5, 0.5 mL/min, 254 nm, 9.3 min
minor), 10.4 min (major).
(
3
) d 2.34 (s, 1H), 5.76 (s, 1H), 7.24–7.29
1
3
(
m, 5H), 7.31–7.33 (m, 4H). C NMR (75 MHz, CDCl
27.8, 128.5, 128.6, 133.2, 142.1, 143.4. GC–MS (M/Z) 218. The
enantiomeric ratio was determined by HPLC using a chiral column
Daicel Chiralcel OB-H), hexane/2-propanol 90:10, 0.7 mL/min,
3
) d 75.5, 126.4,
4.31. (R)-Phenyl(2-thiophenyl)methanol 10na
1
1H NMR (300 MHz, CDCl
J = 2.9 Hz, 1H), 6.92–6.94 (m,1H), 6.96–6.98 (m, 1H), 7.28–7.49
3
) d 2.43 (d, J = 2.9 Hz, 1H), 6.12 (d,
(
1
3
2
54 nm, 32.5 min (minor), 47.7 min (major).
(m, 6H). C NMR (75 MHz, CDCl
3
) d 72.7, 125.2, 125.7, 126.5,
1
26.9, 128.3, 128.8, 142.2. GC–MS (M/Z) 190. The enantiomeric ra-
4
.25. (S)-4-Bromophenyl(phenyl)methanol 10ga
tio was determined by HPLC using a chiral column (Daicel Chiralcel
OD-H), hexane/2-propanol 98:2, 0.7 mL/min, 254 nm, 30.3 min
(minor), 34.4 min (major).
1H NMR (300 MHz, CDCl
J = 2.9 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.22–7.31 (m, 5H), 7.42 (d,
3
) d 2.30 (d, J = 2.9 Hz, 1H), 5.77 (d,
1
3
J = 8.4 Hz, 2H). C NMR (75 MHz, CDCl
28.1, 128.6, 128.9, 131.9, 143.0, 143.6. GC–MS (M/Z) 262. The
enantiomeric ratio was determined by HPLC using a chiral column
Daicel Chiralcel OB-H), hexane/2-propanol 90:10, 0.7 mL/min,
3
) d 75.8, 121.7, 126.8,
Acknowledgment
1
This work was partially supported by a grant to RCAST at Dosh-
isha University the Ministry of Education, Culture, Sports, Science,
and Technology, Japan.
(
2
54 nm, 19.1 min (minor), 27.6 min (major).
4
.26. (S)-2-Naphthyl(phenyl)methanol 10ia
References
1H NMR (300 MHz, CDCl
3
.49 (m, 8H), 7.76–7.88 (m, 4H). C NMR (75 MHz, CDCl ) d
6.7, 125.2, 126.2, 126.4, 126.9, 127.9, 128.3, 128.5, 128.8, 133.1,
) d 2.36 (br s, 1H), 5.98 (s, 1H), 7.23–
3
1. (a) Suzuki, A. Acc. Chem. Res. 1982, 15, 178; (b) Miyaura, N.; Suzuki, A. Chem.
Rev. 1995, 95, 2457; (c) Suzuki, A. J. Organomet. Chem. 1998, 576, 147.
13
7
7
1
2
3
.
.
Hall, D. G. Boronic Acids; John Wiley & Sons: New York, 2005.
(a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16, 4229; (b)
Batey, R. A.; Thadani, A. N.; Smil, D. V. Org. Lett. 1999, 1, 1683; (c) Ogasawara,
M.; Yoshida, K.; Hayashi, T. Organometallics 2000, 19, 1568; (d) Ramnaulth, J.;
Poulin, O.; Bratovanov, S. S.; Rakhit, S.; Maddaford, S. P. Org. Lett. 2001, 3, 2571;
33.4, 141.3, 143.8. GC–MS (M/Z) 234. The enantiomeric ratio
was determined by HPLC using a chiral column (Daicel Chiralcel
OJ), hexane/2-propanol 80:20, 0.7 mL/min, 254 nm, 31.1 min (ma-
jor), 39.3 min (minor).
(
e) Itooka, R.; Iguchi, Y.; Miyaura, N. Chem. Lett. 2001, 722; (f) Amengual, R.;
Michelet, V.; Genêt, J.-P. Tetrahedron Lett. 2002, 43, 5905; (g) Pucheault, M.;
Darses, S.; Genêt, J.-P. Tetrahedron Lett. 2002, 43, 6155; (h) Yamamoto, Y.;
Fujita, M.; Miyaura, N. Synlett 2002, 767.
4
.27. (R)-Cyclohexyl(phenyl)methanol 10ja
1H NMR (300 MHz, CDCl
4.
(a) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N. J. Am. Chem.
Soc. 1998, 120, 5579; (b) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron
Lett. 1998, 39, 8479; (c) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron Lett.
3
) d 0.90–1.36 (m, 5H), 1.38–1.48 (m,
H), 1.60–1.76 (m, 3H), 1.78–1.87 (m, 2H), 2.00 (m, 1H), 4.39 (d,
1999, 40, 6957; Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.; Hayashi,
1
13
T. Tetrahedron: Asymmetry 1999, 4070, 10; (e) Sakuma, S.; Sakai, M.; Itooka, R.;
Miyaura, N. J. Org. Chem. 2000, 65, 5951; (f) Senda, T.; Ogasawara, M.; Hayashi,
T. J. Org. Chem. 2001, 66, 6852; (g) Kuriyama, M.; Tomioka, K. Tetrahedron Lett.
J = 7.4 Hz, 1H), 7.20–7.38 (m, 5H). C NMR (75 MHz, CDCl
3
) d
2
6.0, 26.1, 26.4, 28.8, 29.3, 44.9, 79.4, 126.6, 127.4, 128.2, 142.2.
2
001, 42, 921; (h) Reet, M. T.; Moulin, D.; Gosberg, A. Org. Lett. 2001, 3, 4083; (i)
GC–MS (M/Z) 190. The enantiomeric ratio was determined by
HPLC using a chiral column (Daicel Chiralcel OD-H), hexane/2-
propanol 99:1, 0.5 mL/min, 254 nm, 29.1 min (minor), 40.1 min
Sakuma, S.; Miyaura, N. J. Org. Chem. 2001, 66, 8944; (j) Kuriyama, M.; Nagai, K.;
Yamada, K.; Miwa, Y.; Taga, T.; Tomioka, K. J. Am. Chem. Soc. 2002, 124, 8932;
(k) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002,
124, 5052; (l) Boiteau, J.-G.; Imbos, R.; Minnaard, A. J.; Feringa, B. L. Org. Lett.
(
major).
2003, 5, 681; (m) Ma, Y.; Song, C.; Ma, C.; Sun, Z.; Chai, Q.; Andrus, M. B. Angew.
Chem., Int. Ed. 2003, 42, 5871; (n) Kurihara, K.; Sugishita, N.; Oshita, K.; Piao, D.;
Yamamoto, Y.; Miyaura, N. J. Organomet. Chem. 2007, 692, 428; (o) Monti, C.;
Gennari, C.; Piarulli, U. Chem. Eur. J. 2007, 13, 1547; (p) Mariz, R.; Briceño, A.;
Dorta, R.; Dorta, R. Organometallics 2008, 27, 6605; (q) Gendrineau, T.; Chuzel,
O.; Eijsberg, H.; Genet, J.-P.; Darses, S. Angew. Chem., Int. Ed. 2008, 47, 7669.
(a) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem., Int. Ed. 1998, 37, 3279; (b)
Ueda, M.; Miyaura, N. J. Org. Chem. 2000, 65, 4450; (c) Fürstner, A.; Krause, H.
Adv. Synth. Catal. 2001, 343.
Ueda, M.; Saito, A.; Miyaura, N. Synlett 2000, 1637.
(a) Shirakawa, E.; Yasuhara, Y.; Hayashi, T. Chem. Lett. 2006, 35, 198; (b) Hirano,
K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9, 1541.
Shintani, R.; Hayashi, T. Chem. Lett. 2008, 37, 724.
Hayashi, T.; Sasaki, K. Chem. Lett. 2008, 37, 842.
4
.28. (R)-t-Butyl(phenyl)methanol 10ka
1H NMR (300 MHz, CDCl
3
) d 0.93 (s, 9H), 1.83 (d, J = 3.0 Hz, 1H),
13
4
CDCl
1
.40 (d, J = 3.0 Hz, 1H), 7.25–7.35 (m, 5H). C NMR (75 MHz,
) d 25.9, 35.6, 82.4, 127.2, 127.5, 127.6, 142.2. GC–MS (M/Z)
64. The enantiomeric ratio was determined by HPLC using a chiral
5
.
3
6
7
.
.
column (Daicel Chiralcel OD-H), hexane/2-propanol 99:1, 0.5 mL/
min, 254 nm, 24.1 min (minor), 32.6 min (major).
8
9
1
.
.
4
.29. (R)-Phenyl(i-propyl)methanol 10la
0. (a) Cho, C. S.; Motofusa, S.; Ohe, K.; Uemura, S.; Shim, S. C. J. Org. Chem. 1995,
0, 883; (b) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Angew, Chem., Int. Ed.
003, 42, 2768; (c) Gini, F.; Hessen, B.; Minnaard, A. J. Org. Lett. 2005, 7, 5309;
d) Lu, X.; Lin, S. J. Org. Chem. 2005, 70, 9651; (e) Yamamoto, T.; Iizuka, M.;
6
2
(
1H NMR (300 MHz, CDCl
J = 6.9 Hz, 3H), 1.81 (br s, 1H), 1.96 (m, 1H), 4.36 (d, J = 6.9 Hz,
3
) d 0.80 (d, J = 6.9 Hz, 3H), 1.00 (d,
Ohta, T.; Ito, Y. Chem. Lett. 2006, 35, 198; (f) Suzuma, Y.; Yamamoto, T.; Ohta, T.;
Ito, Y. Chem. Lett. 2007, 36, 470; (g) Nishikata, T.; Yamamoto, Y.; Miyaura, N.
Adv. Synth. Catal. 2007, 349, 1759; (h) He, P.; Lu, Y.; Dong, C.-G.; Hu, Q.-S. Org.
Lett. 2007, 9, 343; (i) Horiguchi, H.; Turugi, H.; Satoh, T.; Miura, M. J. Org. Chem.
1
3
H), 7.24–7.37 (m, 5H). 13C NMR (75 MHz, CDCl
4.2, 79.0, 125.5, 126.4, 127.2, 142.6. GC–MS (M/Z) 150. The enan-
3
) d 17.2, 18.0,
tiomeric ratio was determined by HPLC using a chiral column (Dai-
cel Chiralcel OD-H), hexane/2-propanol 98:2, 0.7 mL/min, 254 nm,
1
2
008, 73, 1590.
1. Tomita, D.; Kanai, M.; Shibasaki, M. Chem. Asian J. 2006, 1, 161.
12. Zou, T.; Pi, S.-S.; Li, J.-H. Org. Lett. 2009, 11, 435.
1
2.0 min (minor), 15.3 min (major).
1
1
1
3. Lial, Y.-X.; Xing, C.-H.; He, P.; Hu, Q.-S. Org. Lett. 2008, 10, 2509.
4. Yamamoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem., Int. Ed. 2009, 48, 4414.
5. (a) Gibson, S.; Foster, D. F.; Eastham, G. R.; Tooze, R. P.; Cole-Hamilton, D. J.
Chem. Commun. 2001, 779; (b) Yamamoto, T.; Ohta, T.; Ito, Y. Org. Lett. 2005, 7,
4153; (c) Suzuki, K.; Arao, T.; Ishii, S.; Maeda, Y.; Kondo, K.; Aoyama, T.
Tetrahedron Lett. 2006, 47, 5789; (d) Zhao, B.; Lu, X. Tetrahedron Lett. 2006, 47,
4
.30. (R)-2-Furyl(phenyl)methanol 10ma
1H NMR (300 MHz, CDCl
3
) d 2.54 (br s, 1H), 5.82 (br s, 1H), 6.11
(
dd, J = 3.1, 0.8 Hz, 1H), 6.32 (dd, J = 3.2, 2.1 Hz, 1H), 7.30–7.47 (m,
6
765; (e) He, P.; Lu, X. J. Am. Chem. Soc. 2006, 128, 16509; (f) He, P.; Lu, X.; Hu,
H). 1 C NMR (75 MHz, CDCl
3
) d 70.1, 107.3, 110.2, 126.5, 127.9,
6
1
3
Q.-S. Tetrahedron Lett. 2007, 48, 5283; (g) Qin, C.; Wu, H.; Chang, J.; Chen, X.;
Liu, M.; Zhang, W.; Su, W.; Ding, J. J. Org. Chem. 2007, 72, 4102; (h) Kuriyama,
M.; Shimazawa, R.; Shirai, R. J. Org. Chem. 2008, 73, 1597.
28.4, 140.8, 142.4, 155.9, GC–MS (M/Z) 174. The enantiomeric ra-
tio was determined by HPLC using a chiral column (Daicel Chiralcel

2
1
758
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2
Arao, T.; Kondo, K.; Aoyama, T. Tetrahedron Lett. 2007, 48, 4115; (d) Bouffard, J.;
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1
1
8
279; (c) Barbaro, P.; Bianchini, C.; Giambastiani, G. Synthesis 2005, 2445.
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