Palladium-catalyzed arylation of aldehydes with bromo-substituted 1,3-diaryl-imidazoline carbene ligand

Article abstract of DOI:10.1016/j.tet.2014.11.051

The combination of 0 valent palladium precursor and bromo-substituted 1,3-diaryl-imidazoline carbene ligand precursor such as 1-(2-bromophenyl)-3-(2,6-diisopropylphenyl)-imidazolinium chloride 1a exhibited high catalytic activity for the 1,2-addition of arylboronic acids to aldehydes including aqueous formaldehyde.

Full text of DOI:10.1016/j.tet.2014.11.051

Tetrahedron 71 (2015) 19e26
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Tetrahedron
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Palladium-catalyzed arylation of aldehydes with bromo-substituted
1,3-diaryl-imidazoline carbene ligand
,
b
,
a
a
a,
Tetsuya Yamamoto a , Takuma Furusawa , Azamat Zhumagazin , Tetsu Yamakawa
*
*
,
Yohei Oe b, Tetsuo Ohta b
,
*
a Catalysis Group, Sagami Chemical Research Institute, Hayakawa 2743-1, Ayase, Kanagawa 252-1193, Japan
b Department of Biomedical Information, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 October 2014
Received in revised form 18 November 2014
Accepted 19 November 2014
Available online 22 November 2014
The combination of 0 valent palladium precursor and bromo-substituted 1,3-diaryl-imidazoline carbene
ligand precursor such as 1-(2-bromophenyl)-3-(2,6-diisopropylphenyl)-imidazolinium chloride 1a ex-
hibited high catalytic activity for the 1,2-addition of arylboronic acids to aldehydes including aqueous
formaldehyde.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Palladium catalysis
1,2-Addition
Arylation
Aldehyde
Arylboronic acid
N-Heterocyclic carbene
1. Introduction
(2-ferrocenyl)ethyldiphenylphosphine that have no bromine atom
was ineffective as a ligand.6g This indicates the phosphapallada-
Functionalized benzylic alcohols are important intermediates
for bioactive compounds1 and functionalized materials.2 So far,
these alcohols were synthesized through the nucleophilic addition
using aryllithium or magnesium reagents.3 Recent development in
the catalytic 1,2-addition of arylboron compounds to carbonyl
compounds with the transition metals such as Rh,4,5 Pd,6 Ni,7 Ru,8
Pt,9 Co,10 Cu11 or Fe12 has made possible the preparation of these
alcohols with wide range of functional groups. Therefore, this cat-
alytic 1,2-addition is one of the most useful methods for the
preparation of various substituted benzylic alcohols, which are
difficult to synthesize from the classical nucleophilic addition. Rh
catalysts have been chiefly used in this 1,2-addition and various
ligands and complexes were developed. In contrast, the reports of
other metal catalysts including palladium are relatively rare.
Previously, we demonstrated that the combination of Pd(0)
precursors and chiral [2-(2-bromoferrocenyl)ethyl] diphenyphos-
phine as a ligand catalyzed the asymmetric 1,2-addition of aryl-
boronic acids to aldehydes with moderate catalytic activity, while
cycle generated via oxidative addition of CeBr bond to Pd(0) would
be catalytically active Pd(II) complex (Scheme 1, eq. 1), as Hu and
co-workers independently reported Pd-catalyzed addition using
the similar racemic phosphapalladacycle catalyst.6o On the other
hand, most of NHCs are stronger electron-donating ligands than
phosphine ligands.13 This suggests that replacing the phosphorous
ligand with N-heterocyclic carbene (NHC) ligand improves the
PPh2
PPh2
Pd(II)
Br
Br
Pd(0)
oxidative addition
Fe
Fe
(eq. 1)
(eq. 2)
Br
N
base
N
N
Pd(0)
N
N
C
N
C
oxidative
addition
Pd(II)
Cl
Br
Br
* Corresponding authors. Tel.: þ81 467 77 4112; fax: þ81 467 77 4113 (T.Y.); tel.:
þ81 467 76 9268 (T.Y.); tel.: þ81 774 65 6548; fax: þ81 774 65 6789 (T.O.); e-mail
addresses: t-yamamoto@sagami.or.jp (T. Yamamoto), t_yamakawa@sagami.or.jp (T.
Yamakawa), tota@mail.doshisha.ac.jp (T. Ohta).
1a
1a'
Scheme 1. Strategy of in situ generation of palladacycle catalyst.
http://dx.doi.org/10.1016/j.tet.2014.11.051
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

20
T. Yamamoto et al. / Tetrahedron 71 (2015) 19e26
catalytic activity of the phosphapalladacycle-catalyzed 1,2-
addition. Therefore, we have envisaged that the cyclometallated
NHC Pd(II) complex generates from Pd(0)precursor with imidazo-
linium salt with bromo-substituted aryl moiety in the side chain
such as 1-(2-bromophenyl)-3-(2,6-diisopropylphenyl)-imidazoli-
nium chloride 1a and this Pd(II) complex must act as a catalyst in
the addition (Scheme 1, eq. 2). Herein, we report the Pd-catalyzed
1,2-addition of (hetero)arylboronic acids to aldehydes with imida-
zolinium salt 1a as an imidazoline carbene ligand precursor.
afforded moderate catalytic activity (entry 9): this yield is higher
than that with the combination of 1d and [CpPd(
3-allyl)] (entry 9).
h
In this reaction condition, there was a possibility that the bromine
atom on 1a is reacted with a phenylboronic acid 3a to give 1d. The
results in entries 4 and 9 indicates that the Pd species formed with
1d is not essential active species in the reaction with 1a though 1d
form in this way. Therefore, the generation of the cyclometallated
NHC palladium species through the insertion of CeBr bond would
be an important step in this catalytic reaction. The other Pd source,
Pd(acac)2, afforded very small yield (entry 10). Hereinafter, all the
reactions under various conditions were carried out using the
2. Results and discussion
combination of [PdCl(
catalyst.
h
3-allyl)]2 and imidazolinium salt 1a as
Table 1 shows the results of Pd-catalyzed 1,2-addition of phe-
nylboronic acid 3a to 4-tert-butylbenzaldehyde 2a using Pd(0)
precursors and imidazolinium salts as NHC ligand precursor. Pre-
The optimization of reaction condition of Pd-catalyzed phenyl-
ation of 4-tert-butylbenzaldehyde 2a is summarized in Table 2. By
the use of Cs2CO3, CsF and K2CO3, the corresponding product 4a was
obtained in excellent yields (entries 1e3), while KF and Na2CO3
were less effective for this addition (entries 4 and 5). THF as a sol-
vent provided a similar yield as 1,4-dioxane (entry 6). The yield was
declined in toluene solvent (entry 7) and polar solvents such as tert-
butyl alcohol and acetonitrile (entries 8 and 9).
dictably, the combination of [CpPd(h
3-allyl)] as Pd(0) precursor and
imidazolinium salt 1a provided the corresponding alcohol 4a in
86% yield (entry 1). In contrast, the replacement of 1a with 1bee
afforded very low activity (entries 2e5). As for 1b, 1d and 1e, the
formed amount of the catalytically active cyclometallated NHC
palladium complex is very small due to the difficulty of the in-
sertion of Pd(0) to sp2 and sp3-CeH bond in this reaction condition.
Low activity of entry 3 suggests that the bulky phenyl group on NHC
is important for the catalysis. Pd2(dba)3 showed similar effect to
Table 2
The optimization of reaction condition of Pd-catalyzed phenylation of 4-tert-bu-
tylbenzaldehyde 2a
[CpPd(
allyl)]2 that acted as Pd(0) precursor and 1a also exhibited excellent
yield (entry 7). Interestingly, the combination of 1b and [PdCl(h3
allyl)]2 showed good catalytic activity (entry 8). In this case,
[PdCl(
3-allyl)]2 probably acted not only as Pd(0) precursor but also
h -
3-allyl)] (entry 6). Moreover, the combination of [PdCl(h3
-
h
as Pd(II) species. Thus, the reasonable amount of the catalytically
active cyclometallated NHC palladium complex for this reaction
would have generated via the insertion of Pd(II) to CeH bond.14 On
Entry
Base
Solvent
Yield (%)a
96 (89)b
96
94
37
<5
94
69
51
15
1
2
3
4
5
6
7
8
9
Cs2CO3
CsF
K2CO3
KF
Na2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
THF
Toluene
tert-Butyl alcohol
Acetonitrile
the other hand, the combination of 1d and [PdCl(h
3-allyl)]2
Table 1
Survey of Pd source and NHC ligand in the phenylation of 4-tert-butylbenzaldehyde
3a
a
Yields were determined by 1H NMR.
Isolated yield.
b
The scope and limitation of the Pd-catalyzed phenylation of
various aldehydes are listed in Table 3. The reactions proceeded
smoothly with aryl aldehydes having various functional groups
such as alkyl, alkoxy, alkoxycarbonyl, cyano and chloro groups in
excellent yields (entries 1e8). The reaction with 4-
bromobenzaldehyde 2j afforded a mixture of desired alcohol 4j,
benzhydrol and 4-phenylbenzhydrol probably due to the Pd(0)
precursor catalyzed side reactions such as Suzuki-Miyaura coupling
and debromination before the generation of the palladacycle spe-
cies (entry 9). Heteroaryl aldehydes such as thiophenecarbox-
yaldehydes 2k and 2l reacted cleanly in satisfactory yields (entries
10 and 11). Also the phenylation of aliphatic aldehyde such as
cyclohexanecarbaldehyde 2m obtained desired alcohol 4m in 92%
yield (entry 12).
Entry
Pd(0) precursor
Ligand
Yield (%)a
1
2
3
4
5
6
7
8
9
10
[CpPd(
[CpPd(
[CpPd(
[CpPd(
[CpPd(
h
h
h
h
h
3-allyl)]
3-allyl)]
3-allyl)]
3-allyl)]
3-allyl)]
1a
1b
1c
1d
1e
1a
1a
1b
1d
1a
86
6
The metal catalyzed addition of arylboron compounds to
formaldehyde provides the various functionalized mono-arylme-
thanols, which are key intermediates for bioactive compounds in-
cluding natural products. Very recently, we reported the first
instance of the dinuclear palladacycle catalyzed hydrox-
ymethylation of (hetero)arylboronic acids using aqueous formal-
dehyde.6s Therefore, we examined the present catalyst system of
18
19
<5
83
95
73
38
<5
Pd2(dba)3
[PdCl(
[PdCl(
[PdCl(
h
h
h
3-allyl)]2
3-allyl)]2
3-allyl)]2
the combination of [PdCl(h
3-allyl)]2 and imidazolinium salt 1a to
the addition of arylboronic acids to aqueous formaldehyde. Table 4
shows the results of the hydroxymethylation of naphthalen-2-
Pd(acac)2
a
Yields were determined by 1H NMR.

T. Yamamoto et al. / Tetrahedron 71 (2015) 19e26
21
Table 4
The optimization of reaction condition of Pd-catalyzed hydroxymethylation of
naphthalen-2-ylboronic acid 3b
Table 3
The scope and limitation of the Pd-catalyzed phenylation of aldehydes
Entry
1
Aldehyde 2
Product 4
Yield (%)a
96
Entry
Base
Solvent
Yield (%)a
1
2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CsF
1,4-Dioxane
THF
THF
THF
THF
68
91(83)b
<5
<5
9
3c
4d
5e
6f
7
2
99
THF
THF
89
86
8
9
10
11
K3PO4
K2CO3
KF
THF
THF
THF
THF
89
64
13
20
3
4
99
94
Na2CO3
a
Yields were determined by 1H NMR.
Isolated yield.
1b was used instead of 1a.
1c was used instead of 1a.
1f was used instead of 1a.
Reaction temperature was 80 ꢀC.
b
c
d
e
f
5
6
95
97
ylboronic acid 3b using aqueous formaldehyde under various re-
action conditions. THF was more suitable solvent than 1,4-dioxane
(entries 1 and 2). In this reaction, the combination of [PdCl(
lyl)]2 and 1b or 1c exhibited little catalytic activity (entries 3 and 4).
This suggests that [PdCl(
3-allyl)]2, which acted as Pd(0) precursor
on this reaction condition as well as [CpPd(
3-allyl)]2 in entry 3 in
Table 1. Interestingly, the combination of [PdCl(
3-allyl)]2 and 1f
h
3-al-
h
h
h
also afforded the low yield (entry 5). Kuriyama and co-workers
reported that this combined catalyst system exhibited high activ-
ity for the addition of arylboronic acid to aromatic and aliphatic
aldehydes and concluded that the catalytic active species is C,S-
hetero-bidentated NHC Pd(II) complex.6c Thus, the result in entry
5 strongly indicates that the present cyclometallated NHC Pd (II)
7b
8b
9b
10
94
complex, which was generated from [PdCl(h
3-allyl)]2 as Pd(0)
97
precursor and 1a is exclusively effective in the addition of aryl-
boronic acid to aqueous formaldehyde. The reaction in THF at 80 ꢀC
provided the slight decrease in the yield (entry 6). The yields were
remarkably depended on a base used. Thus, CsF and K3PO4
exhibited virtually the same effect as Cs2CO3 (entries 7 and 8). The
reaction using K2CO3 as a base afforded the corresponding product
in a moderate yield (entry 9), while the yields were remarkably low
using KF or Na2CO3 (entries 10 and 11).
N.d.c
89
The scope and limitation of arylboronic and heteroarylboronic
acids in the Pd-catalyzed arylation of 2-naphthaldehyde 2b and
formaldehyde 2n are summarized in Table 5. Naphthyl and
electron-rich arylboronic acids were converted to the correspond-
ing arylmethanols in excellent yields with low catalyst loading
(entries 1e4, 8 and 10), while electron-poor arylboronic acid such
as 3,5-bis(trifluoromethyl)phenylboronic acid 3l required 2 mol %
of catalyst (entry11). The reactions proceeded smoothly with sub-
strates bearing various reactive functional groups such as fluoro,
chloro, nitro, carbonyl and protected boryl groups in good to ex-
cellent yields under 1e2 mol % catalyst loading (entries 5, 6 and
12e14). The chlorine atom on the aromatic ring remained intact in
this reaction condition (entry 6). Naphthalen-1-ylboronic acid and
sterically bulky (hetero)arylboronic acids, which have methoxy or
11b
12b
91
92
a
Isolated yield.
b
c
CsF was used instead of Cs2CO3.
Not determined.

22
T. Yamamoto et al. / Tetrahedron 71 (2015) 19e26
Table 5
The scope and limitation of aryl- and heteroarylboronic acids in the Pd-catalyzed arylation of 2-naphthaldehyde 2b and formaldehyde 2n
Entry
1
Boronic acid 3
Product 4
Yield (%)a
93
2
3
95
94
4
5
6
94
96
93
7
89
8
9
92
81
10
86
11b
85
73
12c

T. Yamamoto et al. / Tetrahedron 71 (2015) 19e26
23
Table 5 (continued )
Entry
Boronic acid 3
Product 4
Yield (%)a
13
71
80
14d
15d
16d
79
84
a
Isolated yield.
1 mol % of [PdCl(
CsF was used instead of Cs2CO3.
K3PO4 was used instead of Cs2CO3.
b
h
3-allyl)]2 and 2 mol % of 1a were used.
c
d
methyl groups in ortho-position were also converted to corre-
sponding alcohols in satisfactory yields (entries 2, 3, 9 and 16).
Heteroarylboronic acids such as thiophenyl- and pyridylboronic
acids gave excellent yields (entries 7, 15 and 16).
taken with a JEOL MStaion JMS-700. Melting points were recorded
on a METTLER TOLEDO MP-70. Commercially available organic and
inorganic compounds were used without purification. [CpPd(h3
-
allyl)],15 1-(2-bromophenyl)-3-(2,6-diisopropylphenyl)imidazoli-
nium chloride 1a,6r 1-(2,6-diisopropylphenyl)-3-phenylimida
zolinium chloride 1b6r and 1-(2,6-diisopropylphenyl)-3-(2-(phe-
nylthio)- phenyl)imidazolinium chloride 1f6m were prepared
according to the literature procedures.
3. Conclusion
In conclusion, we found the combination of Pd(0) precursor and
1-(2-bromophenyl)-3-(2,6-diisopropylphenyl)imidazolinium chlo-
ride has remarkable catalytic activity for the addition of arylboronic
acids to aldehydes including aqueous formaldehyde. The results of
the survey of palladium sources and NHC ligands have showed that
the catalytic active species is NHC coordinated palladacycle, which
was generated from Pd(0) precursor with 1-(2-bromophenyl)-3-
(2,6-diisopropylphenyl)-imidazolidin-2-ylidene 1a0 via oxidative
addition or was generated from Pd(II) species with 1-(2,6-
diisopropylphenyl)-3-phenyl-imidazolidin-2-ylidene, which pre-
pared from 1b, via CeH bond cleavage insertion. The obtained
cyclometallated NHC Pd (II) complex exhibited much higher cata-
lytic activity than C,S-hetero-bidentated NHC Pd(II) complex in the
hydroxymethylation of arylboronic acids. Further examinations of
asymmetric catalytic reaction using chiral NHC palladium com-
plexes are underway in our laboratory.
General procedure for the synthesis of 1-(2-bromophenyl)-3-
mesitylimidazolinium chloride 1c: In a 50 mL round-bottom flask
were placed 2-(mesitylamino)-2-oxoacetic acid (0.62 g, 3.0 mmol),
oxalyl chloride (0.42 g, 3.3 mmol) and anhydrous CH2Cl2 (30 mL)
under argon atmosphere. After DMF (0.1 mL) was added dropwise,
the reaction mixture was stirred for 6 h at room temperature. Then
the solvent was removed and the residue was dissolved in 20 mL of
anhydrous CH2Cl2. 2-Bromoaniline (0.43 g, 2.5 mmol) and trie-
thylamine (0.56 mL, ca. 4 mmol) were added to the solution at 0 ꢀC
and the reaction mixture was stirred at room temperature for 16 h.
After the addition of water (20 mL), the aqueous layer was
extracted with ethyl acetate (3ꢁ50 mL). The organic layer was
washed with 2 M HCl aqueous solution (50 mL), saturated NaHCO3
aqueous solution (50 mL) and brine (50 mL), dried with Na2SO4 and
concentrated in vacuo. Purification by passing the obtained crude
residue through a silica gel column with a hexane/ethyl acetate (10/
0 to 7/3) eluent yielded 0.72 g of N1-(2-bromophenyl)-N2-mesity-
loxalamide (80% yield, 2.0 mmol) as a white solid. 1H NMR
4. Experimental section
4.1. General
(400 MHz, CDCl3, ppm):
d
9.99 (s, 1H), 8.76 (s, 1H), 8.46 (d, J¼8.2 Hz,
1H), 7.61 (dd, J¼1.5, 8.2 Hz, 1H), 7.39 (t, J¼7.8 Hz, 1H), 7.08 (dt, J¼1.5,
All reactions were carried out under an argon atmosphere. 1H,
13C, 19F and 11B NMR spectra were recorded on a Brucker AVANCE III
400 spectrometer (400.13 MHz) at ambient temperature. The
7.8 Hz, 1H), 6.94 (s, 2H), 2.30 (s, 3H), 2.23 (s, 6H); 13C NMR
(100 MHz, CDCl3, ppm)
129.1, 128.4, 126.3, 121.1, 114.1, 20.9, 18.3; Anal. Calcd for
17H17BrN2O2: C, 56.52; H, 4.74; N, 7.75. Found: C, 56.78; H, 4.70; N,
d 157.9, 157.7,137.7, 134.6,134.5,132.7, 129.5,
chemical shifts of 1H were reported in delta (
d
) units, parts per
million (ppm) downfield from tetramethylsilane (0.0 ppm).
Chemical shifts of 13C were reported in delta (
) units, ppm relative
C
7.65. Under an argon atmosphere, N1-(2-bromophenyl)-N2-mesi-
tyloxalamide (0.72 g, 2.0 mmol) was charged in a 100 mL round-
bottom flask. To this was added 1 M BH3eTHF solution (12 mL,
12 mmol) at room temperature. The reaction mixture was refluxed
for 16 h. After cooling to room temperature, methanol (5 mL) was
added slowly, until all bubbling ceased. 35% HCl aqueous solution
d
to the center of the triplet at 77.0 ppm for CDCl3. The chemical shifts
of 19F and 11B were referenced to the resonance frequency
(0.0 ppm), 19F 376.27 MHz and 11B 128.38 MHz, with a negative sign
indicating an upfield shift. High-resolution mass spectra were

24
T. Yamamoto et al. / Tetrahedron 71 (2015) 19e26
(2 mL) was added, and the solvent was removed. To this solid was
added triethyl orthoformate (10 mL, ca. 60 mmol) at room tem-
perature, and the mixture was stirred at 100 ꢀC for 3 h. The reaction
mixture was cooled to room temperature and the solvent was re-
moved completely. Recrystallization of obtained crude residue from
CH2Cl2/AcOEt yielded 0.43 g of the title compound 1c as a white
solid (55% yield, 1.1 mmol). Mp: 214e217 ꢀC; 1H NMR (400 MHz,
tube was placed in an oil bath preheated at 80 ꢀC. The reaction
mixture was stirred for 2e12 h and then cooled to room temper-
ature. Next, operation of (i) or (ii) was performed. (i) The obtained
crude was purified by passing it through a silica gel column with
a hexane/ethyl acetate eluent (Table 2 entry 1, Tables 3 and 5 entries
1e7). (ii) Diphenylmethane (168 mg, 1.0 mmol) as an internal
standard was added and then an aliquot of the organic layer of the
reaction mixture was subjected to the quantitative analysis by 1H
NMR (Tables 1 and 2).
CDCl3, ppm):
d
8.71 (s, 1H), 8.42 (dd, J¼1.3, 8.0 Hz, 1H), 7.66 (dd,
J¼1.3, 8.0 Hz, 1H), 7.49 (dt, J¼1.5, 7.8 Hz, 1H), 7.34 (dt, J¼1.5, 7.8 Hz,
1H), 6.96 (s, 2H), 4.93e4.88 (m, 2H), 4.58e4.53 (m, 2H), 2.47 (s,
6H),2.30 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm)
d
158.8, 140.6,
4.1.1. (4-(tert-Butyl)phenyl)(phenyl)methanol (4a).16 White solid;
mp 80e82 ꢀC; yield 213 mg (0.886 mmol, 89%); 1H NMR (400 MHz,
135.3, 134.1, 133.4, 131.6, 130.2, 130.0, 130.0, 129.7, 119.3, 52.9, 52.0,
20.9, 18.2; Anal. Calcd for C18H20BrClN2: C, 56.93; H, 5.31; N, 7.38.
Found: C, 56.71; H, 5.27; N, 7.56.; HRMS (FAB) m/z: [M]þ calcd for
CDCl3, ppm):
d
7.41e7.26 (m, 9H), 5.83 (d, J¼3.5 Hz, 1H), 2.16 (d,
J¼3.5 Hz, 1H), 1.30 (s, 9H); 13C NMR (100 MHz, CDCl3, ppm)
d 150.5,
C
18H20N2Br: 343.0810. Found: 343.0809.
143.9, 140.9, 128.4, 127.4, 126.5, 126.3, 125.4, 76.1, 34.5, 31.3.
General procedure for the synthesis of 1-(2,6-diisopropylphenyl)-
3-[1,10-biphenyl]-2-yl)-4,5-dihydroimidazoli-nium chloride 1d: In
a 100 mL round-bottom flask were placed N-([1,10-biphenyl]-2-yl)-
2-chloroacetamide (2.95 g, 12.0 mmol), potassium iodide (1.66 g,
10.0 mmol), potassium bromide (0.58 g, 4.9 mmol), potassium
carbonate (1.68 g, 12.2 mmol), 2,6-diisopropylaniline (5.52 g,
31.3 mmol) and anhydrous DMF (10 mL) under argon atmosphere.
The reaction mixture was stirred for 12 h at 80 ꢀC. After the reaction
mixture was cooled to room temperature, ethyl acetate (100 mL)
was added. The organic layer was washed with water (50 mL) and
brine (50 mL), dried with Na2SO4 and concentrated in vacuo. Pu-
rification by passing the obtained crude residue through a silica gel
column with a hexane/ethyl acetate (100/0 to 85/15) eluent yiel-
ded 3.02 g of N-([1,10-biphenyl]-2-yl)-2-((2,6-diisopropylphenyl)
amino)acetami-de (65% yield, 7.8 mmol) as a white solid. 1H NMR
4.1.2. Naphthalen-2-yl(phenyl)methanol (4b).6r White solid; mp
86e87 ꢀC; yield 226 mg (0.964 mmol, 96%); 1H NMR (400 MHz,
CDCl3, ppm):
d 7.87 (s, 1H), 7.84e7.76 (m, 3H), 7.49e7.39 (m, 5H),
7.35e7.24 (m, 3H), 5.97 (d, J¼3.2 Hz, 1H), 2.36 (d, J¼3.2 Hz, 1H); 13
C
NMR (100 MHz, CDCl3, ppm) d 143.6, 141.1, 133.2, 132.9, 128.5, 128.3,
128.1, 127.7, 127.6, 126.7, 126.2, 125.9, 125.0, 124.8, 76.4.
4.1.3. Naphthalen-1-yl(phenyl)methanol (4c).8d Colorless liquid;
yield 233 mg (0.994 mmol, 99%); 1H NMR (400 MHz, CDCl3, ppm):
d
8.04(dd, J¼2.4, 6.7 Hz, 1H), 7.90e7.78 (m, 2H), 7.64 (d, J¼7.1 Hz,
1H), 7.51e7.41 (m, 5H), 7.36e7.26 (m, 3H), 6.55 (d, J¼3.9 Hz, 1H),
2.33 (d, J¼3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
d 143.1,
138.8, 133.9, 130.7, 128.7, 128.50, 128.46, 127.6, 127.0, 126.1, 125.6,
125.3, 124.6, 124.0, 73.6.
(400 MHz, CDCl3, ppm):
d
9.30 (s, 1H), 8.76 (s, 1H), 8.51 (d, J¼8.2 Hz,
1H), 7.45e7.37 (m, 5H), 7.33e7.27 (m, 2H), 7.22 (ddd, J¼1.0, 7.5,
7.5 Hz, 1H), 7.06 (s, 3H), 3.58 (d, J¼8.6 Hz, 2H), 3.13 (t, J¼8.6 Hz, 1H),
2.94 (sept, J¼6.8 Hz, 2H),1.12 (d, J¼6.8 Hz,12H); 13C NMR (100 MHz,
4.1.4. (4-Methoxyphenyl)(phenyl)methanol (4d).6r White solid; mp
64e66 ꢀC; yield 211 mg (0.985 mmol, 99%); 1H NMR (400 MHz,
CDCl3, ppm):
d
7.37e7.23 (m, 7H), 6.85 (d, J¼8.7 Hz, 2H), 5.79 (d,
CDCl3, ppm)
d
168.8, 142.2, 141.4, 138.2, 134.6, 132.5, 130.2, 129.2,
J¼3.2 Hz, 1H), 3.77 (s, 3H), 2.21 (d, J¼3.2 Hz, 1H); 13C NMR
128.9, 128.5, 128.0, 124.8, 124.4, 123.7, 120.9, 55.7, 27.8, 24.0;
Under an argon atmosphere, N-([1,10-biphenyl]-2-yl)-2-((2,6-
diisopropylphenyl)amino)aceta-mide (2.32 g, 6.0 mmol) was
charged in a 100 mL round-bottom flask. To this was added 1 M
BH3eTHF solution (24 mL, 24 mmol) at room temperature. The
reaction mixture was refluxed for 16 h. After cooling to room
temperature, methanol (15 mL) was added slowly, until all bubbling
ceased. 35% HCl aqueous solution (6 mL) was added, and the sol-
vent was removed. To this solid was added triethyl orthoformate
(30 mL, ca. 180 mmol) at room temperature, and the mixture was
stirred at 120 ꢀC for 2 h. The reaction mixture was cooled to room
temperature and the solvent was removed completely. Re-
crystallization of obtained crude residue from CH2Cl2/AcOEt yiel-
ded 2.02 g of the title compound 1d as a white solid (80% yield,
4.8 mmol). Mp: 199e202 ꢀC; 1H NMR (400 MHz, CDCl3, ppm):
(100 MHz, CDCl3, ppm)
126.4, 113.9, 75.8, 55.3.
d 159.1, 144.0, 136.2, 128.4, 127.9, 127.4,
4.1.5. (2-Methoxyphenyl)(phenyl)methanol (4e).6r Colorless liquid;
yield 202 mg (0.943 mmol, 94%); 1H NMR (400 MHz, CDCl3, ppm):
d
7.38e7.21 (m, 7H), 6.94e6.85 (m, 2H), 6.03 (d, J¼5.4 Hz,1H), 3.76 (s,
3H), 3.07 (d, J¼5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
d 156.8,
143.4, 132.1, 128.7, 128.2, 127.9, 127.2, 126.6, 120.8, 110.8, 72.2, 55.4.
4.1.6. Phenyl(o-tolyl)methanol (4f).6r White solid; mp 89e90 ꢀC;
yield 189 mg (0.953 mmol, 95%); 1H NMR (400 MHz, CDCl3, ppm):
d
7.48 (d, J¼7.5 Hz, 1H), 7.35e7.11 (m, 8H), 5.94 (s, 1H), 2.27 (s, 1H),
2.22 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm)
d
142.9, 141.5, 135.4,
130.6, 128.5, 127.59, 127.56, 127.2, 126.3, 126.2, 73.4, 19.4.
d
8.43 (s, 1H), 8.19 (d, J¼7.7 Hz, 1H), 7.58e7.39 (m, 9H), 7.21 (d,
4.1.7. Methyl 4-(hydroxy(phenyl)methyl)benzoate (4g).6r White
solid; mp 65e67 ꢀC; yield 236 mg (0.974 mmol, 97%); 1H NMR
J¼7.8 Hz, 2H), 4.77e4.71 (m, 2H), 4.40e4.35 (m, 2H), 2.92 (sept,
J¼6.7 Hz, 2H), 1.27 (d, J¼6.7 Hz, 6H), 1.18 (d, J¼6.7 Hz, 6H); 13C NMR
(400 MHz, CDCl3, ppm):
d
7.98 (d, J¼8.3 Hz, 2H), 7.45 (d, J¼8.2 Hz,
(100 MHz, CDCl3, ppm)
d
157.7, 146.3, 137.51, 137.47, 132.8, 131.5,
2H), 7.34e7.25 (m, 5H), 5.85 (d, J¼3.1 Hz, 1H), 3.88 (s, 3H), 2.56 (d,
131.3, 130.2, 129.9, 129.6, 129.4, 128.8, 128.7, 127.4, 125.0, 54.5, 53.2,
28.6, 25.0, 24.6; HRMS (FAB) m/z: [M]þ calcd for C27H31N2:
383.2482. Found: 383.2487.
J¼3.1 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
d 166.9, 148.7, 143.2,
129.7, 129.1, 128.6, 127.9, 126.6, 126.3, 75.8, 52.0.
General procedure for the palladium catalyzed arylation of alde-
hyde 2aem using arylboronic acid 3aeh: Palladium source
(0.01 mmol), imidazolinium salt 1 (0.01 mmol), phenylboronic acid
(1.50 mmol) and an inorganic base (2.0 mmol) were charged in
a 10 mL test tube sealed with a rubber septum. The test tube was
evacuated and backfilled with argon. This sequence was repeated
five times. Then solvent (2 mL) and aldehyde (1.0 mmol) were
added via the rubber septum with syringe. In an argon flow, the
rubber septum was replaced with a Teflon liner screw cap. The test
4.1.8. 4-(Hydroxy(phenyl)methyl)benzonitrile (4h).6r White solid;
mp 68e69 ꢀC; yield 196 mg (0.937 mmol, 94%); 1H NMR (400 MHz,
CDCl3, ppm):
d
7.59(dd, J¼1.2, 8.1 Hz, 2H), 7.49 (d, J¼8.1 Hz, 2H),
7.38e7.27 (m, 5H), 5.84 (s, 1H), 2.52 (s, 1H); 13C NMR (100 MHz,
CDCl3, ppm)
111.1, 75.6.
d 148.9, 142.8, 132.3, 128.9, 128.3, 127.0, 126.7, 118.8,
4.1.9. (4-Chlorophenyl)(phenyl)methanol (4i).8d Colorless liquid;
yield 212 mg (0.969 mmol, 97%); 1H NMR (400 MHz, CDCl3, ppm):

T. Yamamoto et al. / Tetrahedron 71 (2015) 19e26
25
d
7.34e7.23(m,9H), 5.74(s,1H), 2.43(s,1H);13C NMR (100 MHz, CDCl3,
ppm) 143.5, 142.2, 133.3, 128.7, 128.6, 127.91, 127.87, 126.6, 75.6.
d 142.0, 140.7, 133.4, 133.2, 132.9, 128.6, 128.5, 128.02, 128.01, 127.7,
126.3, 126.1, 125.1, 124.5, 75.7.
d
4.1.10. Phenyl(thiophen-2-yl)methanol (4k).8d Colorless liquid;
4.1.19. Naphthalen-2-yl(thiophen-3-yl)methanol
(4bh).6m Yellow
yield 169 mg (0.888 mmol, 89%); 1H NMR (400 MHz, CDCl3, ppm):
glairy liquid; yield 215 mg (0.894 mmol, 89%); 1H NMR (400 MHz,
d
7.41e7.27 (m, 6H), 7.18 (ddd, J¼1.0, 1.2, 2.1 Hz, 1H), 7.00 (dd, J¼1.2,
CDCl3, ppm): d 7.77e7.70 (m, 4H), 7.43e7.34 (m, 3H), 7.17 (s, 1H),
5.0 Hz, 1H), 5.90 (d, J¼3.9 Hz, 1H), 2.23 (d, J¼3.9 Hz, 1H); 13C NMR
7.09 (s, 1H), 6.91 (d, J¼4.8 Hz, 1H), 5.86 (s, 1H), 2.87 (s, 1H); 13C NMR
(100 MHz, CDCl3, ppm)
126.2, 121.6, 72.8.
d
145.3, 143.3, 128.5, 127.7, 126.45, 126.36,
(100 MHz, CDCl3, ppm) d 145.2, 140.7, 133.3, 133.0, 128.4, 128.1,
127.7, 126.4, 126.25, 126.21, 126.0, 125.0, 124.6, 121.8, 72.9.
4.1.11. Phenyl(thiophen-3-yl)methanol (4l).17 Pale yellow solid; mp
88e90 ꢀC; yield 173 mg (0.909 mmol, 91%); 1H NMR (400 MHz,
4.2. General procedure for the palladium catalyzed hydrox-
ylmethylation of arylboronic acid 3b and ieq using aqueous
formaldehyde 2n
CDCl3, ppm):
d
7.41e7.27 (m, 6H), 7.19 (ddd, J¼1.1, 2.0, 2.0 Hz, 1H),
7.00 (dd, J¼1.2, 5.0 Hz, 1H), 5.90 (d, J¼3.9 Hz, 1H), 2.19 (d, J¼3.9 Hz,
1H); 13C NMR (100 MHz, CDCl3, ppm)
126.6, 126.3, 125.4, 124.9, 72.4.
d
148.1, 143.1, 128.5, 128.0,
[PdCl(h
3-allyl)]2 (0.00125e0.005 mmol), imidazolinium salt 1a
(0.0025e0.01 mmol), arylboronic acid (0.50 mmol) and an in-
organic base (2.0 mmol) were charged in a 10 mL test tube sealed
with a rubber septum. The test tube was evacuated and backfilled
with argon. This sequence was repeated five times. Then solvent
(0.5 mL) and 37 wt % formaldehyde in H2O (102 mg, formaldehyde
1.25 mmol) were added via the rubber septum with syringe. In an
argon flow, the rubber septum was replaced with a Teflon liner
screw cap. The test tube was placed in an oil bath preheated at
100 ꢀC. The reaction mixture was stirred for 2 h and was cooled to
room temperature. Then, operation of (i) or (ii) was performed. (i)
The obtained crude was purified by passing it through a silica gel
column with a hexane/ethyl acetate eluent (Table 4 entry 2 and
Table 5 entries 8e16). (ii) Diphenylmethane (84.1 mg, 0.50 mmol)
as an internal standard was added and then an aliquot of the or-
ganic layer of the reaction mixture was subjected to the quantita-
tive analysis by 1H NMR (Table 4).
4.1.12. Cyclohexyl(phenyl)methanol (4m).6m Colorless liquid; yield
175 mg (0.924 mmol, 92%); 1H NMR (400 MHz, CDCl3, ppm):
d
7.35e7.24 (m, 5H), 4.35 (dd, J¼3.3, 7.1 Hz, 1H), 1.99e1.56 (m, 6H),
1.39e0.87 (m, 6H); 13C NMR (100 MHz, CDCl3, ppm)
d 143.6, 128.2,
127.4, 126.6, 79.4, 45.0, 29.3, 28.8, 26.4, 26.1, 26.0.
4.1.13. Di(naphthalen-2-yl)methanol (4bb).18 White solid; mp
110e112 ꢀC; yield 264 mg (0.928 mmol, 93%); 1H NMR (400 MHz,
CDCl3, ppm):
d 7.93 (s, 2H), 7.84e7.77 (m, 6H), 7.50e7.44 (m, 6H),
6.15 (d, J¼3.2 Hz, 1H), 2.45 (d, J¼3.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3, ppm)
d 140.9, 133.3, 132.9, 128.4, 128.1, 127.7, 126.2, 126.0,
125.2, 124.9, 76.5.
4.1.14. Naphthalen-1-yl(naphthalen-2-yl)methanol (4bc).6e White
solid; mp 107e109 ꢀC; yield 269 mg (0.946 mmol, 95%); 1H NMR
(400 MHz, CDCl3, ppm):
d
8.11 (dd, J¼1.4, 8.0 Hz, 1H), 7.93e7.77 (m,
4.2.1. Naphthalen-2-ylmethanol
79e82 ꢀC; yield 66.0 mg (0.417 mmol, 83%); 1H NMR (400 MHz,
CDCl3, ppm): 7.85e7.80 (m, 4H), 7.51e7.45 (m, 3H), 4.85 (s, 2H),
1.82 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm)
138.3, 133.4, 132.9,
(4nb).20 White
solid;
mp
6H), 7.65 (d, J¼7.1 Hz, 1H), 7.51e7.40 (m, 6H), 6.70 (d, J¼4.0 Hz, 1H),
2.43 (d, J¼4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
d
140.6,
d
138.7, 134.0, 133.3, 132.9, 130.8, 128.8, 128.6, 128.3, 128.1, 127.6,
126.2, 126.1, 126.0, 125.7, 125.6, 125.3, 125.1, 124.9, 124.0, 73.7.
d
128.3, 127.9, 127.7, 126.2, 125.9, 125.4, 125.1, 65.5.
4.1.15. (2-Methoxyphenyl)(naphthalen-2-yl)methanol (4bd).6m Pale
yellow solid; mp 100e102 ꢀC; yield 248 mg (0.938 mmol, 94%); 1H
4.2.2. (4-(tert-Butyl)phenyl)methanol (4ni).20 Pale yellow liquid;
yield 75.7 mg (0.461 mmol, 92%); 1H NMR (400 MHz, CDCl3, ppm):
NMR (400 MHz, CDCl3, ppm):
d
7.87e7.78 (m, 4H), 7.50e7.44 (m,
d
7.40 (d, J¼8.5 Hz, 2H), 7.31 (d, J¼8.5 Hz, 2H), 4.66 (s, 2H), 1.61 (s,
3H), 7.30e7.23 (m, 2H), 6.96e6.90 (m, 2H), 6.23 (d, J¼5.4 Hz, 1H),
1H), 1.32 (s, 9H); 13C NMR (100 MHz, CDCl3, ppm)
126.9, 125.5, 65.2, 34.6, 31.4.
d 150.8, 137.9,
3.82 (s, 3H), 3.11 (d, J¼5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
d
156.8, 140.7, 133.2, 132.7, 131.8, 128.8, 128.03, 127.98, 127.8, 127.6,
125.9, 125.6, 125.0, 124.9, 120.8, 110.7, 72.1, 55.4.
4.2.3. o-Tolylmethanol (4nj).21 White solid; mp 36e38 ꢀC; yield
49.2 mg (0.403 mmol, 81%); 1H NMR (400 MHz, CDCl3, ppm):
4.1.16. Naphthalen-2-yl(p-tolyl)methanol (4be).6i White solid; mp
91e92 ꢀC; yield 226 mg (0.910 mmol, 91%); 1H NMR (400 MHz,
d 7.36e7.33 (m, 1H), 7.22e7.16 (m, 3H), 4.70 (s, 2H), 2.36 (s, 3H), 1.57
(s, 1H); 13C NMR (100 MHz, CDCl3, ppm)
127.6, 126.1, 63.6, 18.6.
d 138.7, 136.1, 130.4, 127.8,
CDCl3, ppm):
d 7.90 (s, 1H), 7.85e7.77 (m, 3H), 7.49e7.41 (m, 3H),
7.30 (d, J¼8.1 Hz, 2H), 7.15 (d, J¼7.9 Hz, 2H), 5.98 (d, J¼3.6 Hz, 1H),
2.33 (s, 3H), 2.26 (d, J¼3.6 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
4.2.4. (3,5-Dimethoxyphenyl)methanol (4nk).22 White solid; mp
49e51 ꢀC; yield 72.0 mg (0.428 mmol, 86%); 1H NMR (400 MHz,
d
141.3, 140.8, 137.4, 133.3, 132.8, 129.2, 128.2, 128.1, 127.6, 126.7,
126.1, 125.9, 124.9, 124.8, 76.2, 21.1.
CDCl3, ppm):
d
6.52 (d, J¼2.3 Hz, 2H), 6.39 (t, J¼2.3 Hz, 1H), 4.63 (d,
J¼6.1 Hz, 2H), 3.79 (s, 6H), 1.74 (t, J¼6.1 Hz, 1H); 13C NMR (100 MHz,
4.1.17. (4-Fluorophenyl)(naphthalen-2-yl)methanol
(4bf).6h Pale
CDCl3, ppm) d 161.0, 143.4, 104.6, 99.7, 65.4, 55.4.
yellow solid; mp 67e68 ꢀC; yield 243 mg (0.963 mmol, 96%); 1H NMR
(400 MHz, CDCl3, ppm):
d
7.85e7.78 (m, 4H), 7.50e7.44 (m, 2H),
4.2.5. (3,5-Bis(trifluoromethyl)phenyl)methanol (4nl).23 White solid;
mp 54e56 ꢀC; yield 104 mg (0.427 mmol, 85%); 1H NMR (400 MHz,
7.39e7.34 (m, 3H), 7.04e6.98 (m, 2H), 5.97 (d, J¼3.1 Hz, 1H), 2.36 (d,
J¼3.1 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
d
162.2 (d, J¼24.5 Hz,
CDCl3, ppm):
d
7.84 (s, 2H), 7.81 (s, 1H), 4.86 (d, J¼5.7 Hz, 2H), 1.95 (t,
1C), 140.9, 139.4 (d, J¼0.3 Hz, 1C), 133.2, 132.9, 128.4 (d, J¼0.1 Hz, 1C),
128.3,128.0,127.7,126.3,126.1,125.0,124.6,115.3(d, J¼2.1Hz,1C), 75.7.
J¼5.7 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm)
d 143.2, 131.8 (q,
J¼33.1 Hz), 126.6 (q, J¼3.6 Hz), 123.3 (q, J¼270.9 Hz), 121.4 (sept,
J¼3.8 Hz), 63.7; 19F NMR (376 MHz, CDCl3, ppm)
ꢂ62.9 (s, 6F).
d
4.1.18. (4-Chlorophenyl)(naphthalen-2-yl)methanol
yellow liquid; yield 250 mg (0.930 mmol, 93%); 1H NMR (400 MHz,
CDCl3, ppm): 7.80e7.75 (m, 4H), 7.49e7.44 (m, 2H), 7.35e7.22 (m,
5H), 5.89 (s, 1H), 2.51 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm)
(4bg).19 Pale
4.2.6. (3-Nitrophenyl)methanol (4nm).24 Colorless liquid; yield
55.6 mg (0.363 mmol, 73%); 1H NMR (400 MHz, CDCl3, ppm):
8.25
(s, 1H), 8.14 (d, J¼7.9 Hz, 1H), 7.71 (d, J¼7.9 Hz, 1H), 7.54 (dd, J¼7.9,
d
d

26
T. Yamamoto et al. / Tetrahedron 71 (2015) 19e26
7.9 Hz, 1H), 4.83 (d, J¼4.4 Hz, 2H), 2.00 (t, J¼4.4 Hz, 1H); 13C NMR
5. For selected recent papers, see: (a) Zhang, C.; Yun, J. Org. Lett. 2013, 15,
3416e3419; (b) Low, D. W.; Pattison, G.; Wieczysty, M. D.; Churchill, G. H.; Lam,
H. W. Org. Lett. 2012, 14, 2548e2551; (c) Liao, Y.-X.; Xing, C.-H.; Hu, Q.-S. Org.
Lett. 2012, 14, 1544e1547; (d) Xing, C.-H.; Liao, Y.-X.; He, P.; Hu, Q.-S. Chem.
(100 MHz, CDCl3, ppm) d 148.4,142.8,132.6,129.4,122.5,121.5, 64.0.
4.2.7. (4-(Hydroxymethyl)phenyl)(phenyl)methanone (4nn).25 White
solid; mp 63e64 ꢀC; yield 75.6 mg (0.356 mmol, 71%); 1H NMR
ꢀ
Commun. 2010, 3010e3012; (e) Jacq, J.; Bessieres, B.; Einhorn, C.; Einhorn, J. Org.
Biomol. Chem. 2010, 8, 4927e4933; (f) Xing, C.-H.; Liu, T.-P.; Zheng, J. R.; Ng, J.;
Esposito, M.; Hu, Q.-S. Tetrahedron Lett. 2009, 50, 4953e4957; (g) Ros, A.; Ag-
garwal, V. K. Angew. Chem., Int. Ed. 2009, 48, 6289e6292; (h) Trindade, A. F.;
Gois, P. M. P.; Veiros, L. F.; Andre, V.; Duarte, M. T.; Afonso, C. A. M.; Caddick, S.;
Cloke, F. G. N. J. Org. Chem. 2008, 73, 4076e4086.
(400 MHz, CDCl3, ppm): d 7.81e7.78 (m, 4H), 7.61e7.46 (m, 5H), 4.80
(s, 2H), 2.11 s, 1H); 13C NMR (100 MHz, CDCl3, ppm)
137.6, 136.7, 132.4, 130.4, 130.0, 128.3, 126.4, 64.6.
d 196.5, 145.6,
6. (a) Das, T.; Chakraborty, A.; Sarkar, A. Tetrahedron Lett. 2014, 55, 5174e5178; (b)
Kuriyama, M.; Hamaguchi, N.; Sakata, K.; Onomura, O. Eur. J. Org. Chem. 2013,
3378e3385; (c) Kuriyama, M. Chem. Pharm. Bull. 2012, 60, 419e428; (d) Ye, Z.;
Qian, P.; Lv, G.; Luo, F.; Cheng, J. J. Org. Chem. 2010, 75, 6043e6045; (e) Zhang,
R.; Xu, Q.; Zhang, X.; Zhang, T.; Shi, M. Tetrahedron: Asymmetry 2010, 21,
1928e1935; (f) Kuriyama, M.; Ishiyama, N.; Shimazawa, R.; Onomura, O. Tet-
rahedron 2010, 66, 6814e6819; (g) Yamamoto, T.; Okabe, T.; Iizuka, M.; Ito, Y.;
Oe, Y.; Ohta, T. Sci. Eng. Rev. Doshisha Univ. 2010, 50, 159e163; (h) Suzuma, Y.;
Hayashi, S.; Yamamoto, T.; Oe, Y.; Ohta, T.; Ito, Y. Tetrahedron: Asymmetry 2009,
20, 2751e2758; (i) Kuriyama, M.; Ishiyama, N.; Shimazawa, R.; Shirai, R.;
Onomura, O. J. Org. Chem. 2009, 74, 9210e9213; (j) Yamamoto, T.; Iizuka, M.;
Takenaka, H.; Ohta, T.; Ito, Y. J. Organomet. Chem. 2009, 694, 1325e1332; (k)
Francesco, I. N.; Wagner, A.; Colobert, F. Eur. J. Org. Chem. 2008, 5692e5695; (l)
Kuriyama, M.; Shimazawa, R.; Enomoto, T.; Shirai, R. J. Org. Chem. 2008, 73,
6939e6942; (m) Kuriyama, M.; Shimazawa, R.; Shirai, R. J. Org. Chem. 2008, 73,
1597e1600; (n) Yu, A.; Cheng, B.; Wu, Y.; Li, J.; Wei, K. Tetrahedron Lett. 2008,
49, 5405e5407; (o) Novodomska, A.; Dudicova, M.; Leroux, F. R.; Colobert, F.
Tetrahedron: Asymmetry 2007, 18, 1628e1634; (p) He, P.; Lu, Y.; Dong, C. G.; Hu,
Q. S. Org. Lett. 2007, 9, 343e346; (q) Suzuki, K.; Arao, T.; Ishii, S.; Maeda, Y.;
Kondo, K.; Aoyama, T. Tetrahedron Lett. 2006, 47, 5789e5792; (r) Yamamoto, T.;
Ohta, T.; Ito, Y. Org. Lett. 2005, 7, 4153e4155; (s) Yamamoto, T.; Zhumagazin, A.;
Furusawa, T.; Tanaka, R.; Yamakawa, T.; Oe, Y.; Ohta, T. Adv. Synth. Catal. 2014,
356, 3525e3529.
7. (a) Phan, N. T. S.; Nguyen, T. T.; Ta, A. H. J. Mol. Catal. A 2012, 365, 95e102; (b)
Berinia, C.; Navarro, O. Chem. Commun. 2012, 1538e1540; (c) Chen, W.; Bagh-
banzadeh, M.; Kappe, C. O. Tetrahedron Lett. 2011, 52, 1677e1679; (d) Xing, C.-
H.; Hu, Q.-S. Tetrahedron Lett. 2010, 51, 924e927; (e) Zhou, L.; Du, X.; He, R.; Ci,
Z.; Bao, M. Tetrahedron Lett. 2009, 50, 406e408; (f) Mori, S.; Nambo, M.; Chi, L.-
C.; Bouffard, J.; Itami, K. Org. Lett. 2008, 10, 4609e4612; (g) Sakurai, F.; Kondo,
K.; Aoyama, T. Tetrahedron Lett. 2009, 50, 6001e6003; (h) Arao, T.; Kondo, K.;
Aoyama, T. Tetrahedron Lett. 2007, 48, 4115e4117.
8. (a) Zheng, H.; Zhang, Q.; Chen, J.; Liu, M.; Cheng, S.; Ding, J.; Wu, H.; Su, W. J.
Org. Chem. 2013, 78, 6350e6355; (b) Yamamoto, Y.; Shirai, T.; Miyaura, N. Chem.
Commun. 2012, 2803e2805; (c) Yamamoto, Y.; Yohda, M.; Shirai, T.; Ito, H.;
Miyaura, N. Chem.dAsian J. 2012, 7, 2446e2449; (d) Yamamoto, Y.; Kurihara, K.;
Miyaura, N. Angew. Chem., Int. Ed. 2009, 48, 4414e4416.
4.2.8. (4-(1H-Naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)phe-nyl)
methanol (4no). Off white solid; mp 147e150 ꢀC; yield 110 mg
(0.400 mmol, 80%); IR (neat, cmꢂ1) 3543, 3438, 3381, 1593, 1523,
1492, 1406, 1369, 1327, 1234, 1084, 1038, 1007, 818, 764; 1H NMR
(400 MHz, CDCl3, ppm):
2H), 7.16e7.04 (m, 4H), 6.41 (ddd, J¼0.9, 7.3 Hz, 2H), 6.02 (s, 2H),
4.73 (s, 2H), 1.74 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm)
143.0,
d
7.64 (d, J¼8.0 Hz, 2H), 7.43 (d, J¼8.1 Hz
d
141.0, 136.4, 131.7, 127.6, 126.7, 119.9, 117.9, 106.0, 65.2, The boron-
bound carbon was not detected due to quadrupolar relaxation;
11B NMR (128 MHz, CDCl3, ppm) 29.0; HRMS (FAB) m/z: [M]þ calcd
d
for C17H15BN2O: 274.1277. Found: 274.1271.
ꢀ
ꢀ
4.2.9. (6-Methoxypyridin-3-yl)methanol (4np).26 Colorless liquid;
yield 54.5 mg (0.392 mmol, 78%); 1H NMR (400 MHz, CDCl3, ppm):
d
8.12 (s, 1H), 7.62 (dd, J¼2.4, 8.5 Hz, 1H), 6.75 (d, J¼8.5 Hz, 1H), 4.62
(s, 2H), 3.94 (s, 3H), 1.76 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm)
164.0, 145.8, 138.4, 128.9, 110.9, 62.6, 53.5.
d
4.2.10. (2-Methoxypyridin-3-yl)methanol (4nq).27 White solid; mp
36e38 ꢀC; yield 58.3 mg (0.419 mmol, 84%); 1H NMR (400 MHz,
CDCl3, ppm):
d
8.10 (dd, J¼1.8, 5.0 Hz, 1H), 7.59e7.57 (m, 1H), 6.88
(dd, J¼5.0, 7.2 Hz,1H), 4.62 (s, 2H), 3.94 (s, 3H),1.76 (s,1H); 13C NMR
(100 MHz, CDCl3, ppm)
d 161.6, 145.8, 136.5, 123.3, 116.9, 61.1, 53.4.
Acknowledgements
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8989e8992.
We thank Prof. Inoue and Ms. Ishikawa, Tokyo Institute of
Technology, for the HRMS measurements.
11. (a) Zheng, H.; Zhang, Q.; Chen, J.; Liu, M.; Cheng, S.; Ding, J.; Wu, H.; Su, W. J.
Org. Chem. 2009, 74, 943e945; (b) Tomita, D.; Kanai, M.; Shibasaki, M. Chem.
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Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.11.051.
12. Zou, T.; Pi, S.-S.; Li, J.-H. Org. Lett. 2009, 11, 453e456.
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