Synthesis of 3,3′-di(2-pyridyl)-1,1′-bi-2-naphthol derivatives

Article abstract of DOI:10.1081/SCC-200064925

A new kind of (S)-3,3′-dipyridyl BINOLs (3a-d) with C ₂-symmetry were synthesized in 79-84% yields by Suzuki coupling of the diboronic acid dipinacol ester (S)-1 containing a (S)-binaphthyl group with bromopyridine derivatives (2a-d) followed b

Full text of DOI:10.1081/SCC-200064925

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Synthesis of
3,3′‐Di(2‐Pyridyl)‐1,1′‐Bi‐2‐Naphth
Derivatives
Ri‐zhe Jin a , Zheng Bian a , Chuan‐qing Kang a
Hai‐quan Guo a & Lian‐xun Gao a
,
a State Key Laboratory of Polymer Physics and
Chemistry , Changchun Institute of Applied
Chemistry, Chinese Academy of Science and
Graduate School of Chinese Academy of Sciences ,
Changchun, China
Published online: 16 Aug 2006.
To cite this article: Ri‐zhe Jin , Zheng Bian , Chuan‐qing Kang , Hai‐quan Guo &
Lian‐xun Gao (2005) Synthesis of 3,3′‐Di(2‐Pyridyl)‐1,1′‐Bi‐2‐Naphthol Derivatives,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:14, 1897-1902, DOI: 10.1081/SCC-200064925
To link to this article: http://dx.doi.org/10.1081/SCC-200064925
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Synthetic Communicationsw, 35: 1897–1902, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200064925
Synthesis of 3,30-Di(2-Pyridyl)-1,10-Bi-2-
Naphthol Derivatives
Ri-zhe Jin, Zheng Bian, Chuan-qing Kang, Hai-quan Guo, and
Lian-xun Gao
State Key Laboratory of Polymer Physics and Chemistry, Changchun
Institute of Applied Chemistry, Chinese Academy of Science and
Graduate School of Chinese Academy of Sciences, Changchun, China
Abstract: A new kind of (S)-3,30-dipyridyl BINOLs (3a–d) with C2-symmetry were
synthesized in 79–84% yields by Suzuki coupling of the diboronic acid dipinacol
ester (S)-1 containing a (S)-binaphthyl group with bromopyridine derivatives (2a–d)
followed by hydrolysis.
Keywords: Chiral ligand, dipyridyl BINOLs, Suzuki coupling
INTRODUCTION
As important C2-symmetrical ligands, 1,10-bi-2-naphthol (BINOL) and its
derivatives have been widely used in asymmetric catalysis.[1] Recently, the
synthesis of 3,30-phenyl BINOLs and their applications as catalysts in asym-
metric synthesis, such as phenylactylene addition to aromatic aldehydes,
Mannich type reactions, and Diels–Alder reactions, has been reported.[2]
However, little attention was paid to BINOLs with heteroaryl substituents at
the 3,30-positions. Simonsen et al. attempted to synthesize 3,30-bis(heteroaryl)
BINOLs, but failed.[2a] Furthermore, the introduction of heteroaryls to the
BINOLs could provide good catalytic effects in some reactions, such as
1,3-dipolar cycloaddition of nitrones.[3] Considering that chiral pyridines
Received in Japan January 22, 2005
Address correspondence to Lian-xun Gao, State Key Laboratory of Polymer
Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese
Academy of Science and Graduate School of Chinese Academy of Sciences,
Changchun, 130022, China. Tel.: 86(431)5269759; Fax: 86-431-5697831; E-mail:
lxgao@ciac.jl.cn
1897

1898
R.-z. Jin et al.
have shown great potential as ligands in asymmetric reactions,[4] we
researched the synthesis and catalytic application of chiral BINOLs containing
pyridine groups.
Herein, we reported the synthesis of several new chiral ligands, 3,30-di(2-
pyridyl)-1,10-bi-2-naphthols (3a–d) in good yields containing two pyridine
groups line at 3,30-positions of BINOL (Scheme 1).
The 2-aryl-6-bromopyridines (2b–d) were prepared via Suzuki coupling
of 2,6-dibromopyridine with corresponding aryl boronic acid pinacol esters
4a–c in 47–66% yields.[5c] Applying Suzuki coupling again, the bromopyri-
dines (2a–d) were reacted with (S)-1, followed by hydrolysis with conc. HCl
in catalytic amounts to give (S)-3a–d in 80%, 83%, 79%, and 84% yields,
respectively (Scheme 1).[5] The structures were confirmed by EA, MS, IR,
and NMR. As anticipated, the signals of the phenolic protons appeared at
1
around 14 ppm in the H NMR. This shows that these phenolic protons with
the nitrogen atoms form intromolecular hydrogen bonds.
In summary, a series of (S)-3,30-dipyridyl BINOLs [(S)-3a–d] with
C2-symmetry were conveniently synthesized by Suzuki coupling of (S)-1
with bromopyridine derivatives (2a–d) followed by hydrolysis in 79–84%
yields. Further research to the application of these compounds in asymmetric
reactions and self-assembly is in progress.
EXPERIMENTAL
General Procedures
All chemicals were purchased from commercial suppliers and used without
further purification. Toluene was distilled before use for degassing. Other
Scheme 1. Synthesis of 3,30-dipyridyl BINOLs.

3,30-Di(2-Pyridyl)-1,10-Bi-2-Naphthol
1899
solvents were used without dryness. NMR spectra were recorded on
1
Bruker-AV 600, 400, and 300 MHz spectrometers. The H chemical shifts
were obtained with DMSO-d6 or CDCl3 as solvents and TMS as internal
standard. Optical rotations were measured on a Perkin Elmer 341C
polarimeter. ESI-MS measurements were measured with an LCQ instrument.
Melting points were measured with a hot-stage microscope XT-4. Elemental
analyses were carried out with a GmbH VarioEL V2.8 instrument. FT-IR
spectra were recorded on a Bio-Rad FTS135 infrared spectrometer.
All products were purified by column chromatography on silica gel
(230–400 mesh).
Preparation of (S)-3,30-bis(Pinacolborane)-2,20-
di(methoxymethoxy)-1,10-Binaphthyl (S)-1
In a 500-mL, flame-dried, three-necked, round-bottomed flask equipped with
an N2-inlet were placed dry Et2O (300 mL) and TMEDA (12 mL, 80 mmol).
To this solution was added 2.5 M n-BuLi in hexane (32 mL, 80 mmol). The
solution was stirred for 30min at room temperature, solid (S)-2,20-di(methoxy-
methoxy)-1,10-binaphthyl (10 g, 26 mmol) was added in one portion, the
reaction mixture was cooled to 2788C, and 2-isopropyl-4,4,5,5-tetramethyl-
1,3,2,-dioxabrolane (32 mL, 160 mmol) was added via syringe over a period
of 20 min. The solution was allowed to warm to room temperature and was
stirred overnight. The reaction mixture was cooled to 08C, saturated NH4Cl
aqueous (150 mL) was added, and the reaction mixture was stirred for 1 h.
The organic phase was separated and washed with saturated aqueous NH4Cl
(100 mL) and saturated aqueous NaCl (100 mL), respectively, and dried
over Na2SO4. NaSO4 was removed by filtration and the solvent was
removed. The resulting solid was purified by column chromatography
[CH2Cl2/petroleum ether (v/v), 1/3] to give 11 g of product (S)-1 as
yellow solid. Yield 67%, mp ¼ 188–1908C, [a]2D5 ¼ 221.3 (c 1.0,
1
CH2Cl2). H NMR (CDCl3, 300 MHz): d ¼ 8.45 (d, 2H, J ¼ 1.5 Hz), 7.89
(d, 2H, J ¼ 8.1 Hz), 7.35 (td, 2H, J ¼ 6.6, 1.5 Hz), 7.26 (m, 2H), 7.18
(d, 2H, J ¼ 8.1 Hz), 4.90–4.87 (m, 4H), 2.28 (s, 6H), 1.38 (s, 24H). IR
(KBr disk) n ¼ 3070, 2957, 2925, 2856, 1564, 1449, 1137, 987 cm21
.
Elemental analysis calculated for C36H44B2O8: C, 69.03; H, 7.08; found: C,
68.81; H, 6.77. ESI-MS: 627.3 m/z (100, M þ 1).
Preparation of 2-Aryl-6-bromopyridines 2b–d
To a degassed solution of 2,6-dibromopyridine (0.947 g, 4.0 mmol) in 60 mL
of toluene was added Pd(PPh3)4 (0.230 g, 0.2 mmol). After stirring for 10 min
at room temperature, a solution of aqueous 1 M Na2CO3 (24 mL, 24 mmol)
and the corresponding aryl boronic acid pinacol esters 4a–c (4 mmol) were

1900
R.-z. Jin et al.
added. The reaction mixture was refluxed for 24 h. The solvent was evaporated
and the residue was purified by column chromatography [CH2Cl2/petroleum
ether (v/v), 1/40] to give products 2b–d as white solids.
2-Bromo-6-phenylpyridine 2b
Yield: 66%, mp ¼ 57–598C. 1H NMR (DMSO-d6, 400 MHz): d ¼ 8.05–8.04
(m, 2H), 8.02 (d, 1H, J ¼ 8.0 Hz), 7.80 (t, 1H, J ¼ 8.0 Hz), 7.60 (d, 1H,
J ¼ 8.0 Hz), 7.53–7.46 (m, 3H). IR (KBr disk) n ¼ 3040, 1548, 1431,
1125, 760 cm21. Elemental analysis calculated for C11H8BrN: C, 56.44;
H, 3.44; N, 5.98; found: C, 56.21; H, 3.09; N, 4.44. ESI-MS: 233.2 m/z
(100, M þ 1).
2-Bromo-6-(1-naphthyl)pyridine 2c
Yield: 57%, mp ¼ 50–528C. 1H NMR (DMSO-d6, 400 MHz): d ¼ 8.06–8.00
(m, 3H), 7.93 (t, 1H, J ¼ 8.0 Hz), 7.73 (d, 1H, J ¼ 8.0 Hz), 7.72 (d, 1H,
J ¼ 8.0 Hz), 7.63–7.62 (m, 2H), 7.58–7.53 (m, 2H). IR (KBr disk)
n ¼ 3082, 1548, 1390, 1117, 773 cm21. Elemental analysis calculated for
C15H10BrN: C, 63.40; H, 3.55; N, 4.93; found: C, 63.20; H, 3.66; N, 4.54.
ESI-MS: 284.1 m/z (100, M þ 1).
2-(9-Anthyl)-6-bromopyridine 2d
1
Yield: 47%, mp ¼ 170–1728C. H NMR (DMSO-d6, 400 MHz): d ¼ 8.55
(s, 1H) 8.05 (d, 2H, J ¼ 8.4 Hz), 7.79 (t, 1H, J ¼ 8.0 Hz), 7.67 (dd, 1H,
J ¼ 8.0, 0.8 Hz), 7.57 (dd, 2H, J ¼ 8.0, 0.8 Hz), 7.50–7.44 (m, 3H),
7.42–7.38 (m, 2H). IR (KBr disk) n ¼ 3046, 1544, 1118, 728 cm21
.
Elemental analysis calculated for C19H12BrN: C, 68.28; H, 3.62; N, 4.19;
found: C, 68.00; H, 3.47; N, 3.93. ESI-MS: 334.5 m/z (100, M þ 1).
Preparation of (S)-3,30-Di(2-pyridyl)-2,20-dihydroxy-1,10-
dinaphthyls 3a–d
To a degassed solution of compound 2a (0.2 mL, 2.0 mmol) in 20 mL of
toluene was added Pd(PPh3)4 (0.057 g, 0.05 mmol). After stirring for 10 min
at room temperature, a solution of aqueous 1 M Na2CO3 (12 mL, 12 mmol)
and the boronic acid pinacol ester (S)-1 (0.662 g, 1 mmol) were added, and
then the reaction mixture was refluxed for 24 h. After the solvent was
evaporated in vacuum, CH2Cl2 (25 mL) was added to the residue followed
by conc. HCl (1.5 mL), and the mixture was stirred at room temperature.

3,30-Di(2-Pyridyl)-1,10-Bi-2-Naphthol
1901
After 24 h, the mixture was poured into water and neutralized with aqueous
Na2CO3, extracted twice with CH2Cl2 (25 mL). The combined organic
phase was washed with brine, dried (Na2SO4), and purified by column chro-
matography [AcOEt/CH2Cl2/petroleum ether (v/v), 1/2/30] to give product
(S) (S)-3,30-di(2-pyridyl)-2,20-dihydroxy-1,10-dinaphthyl (S)-3a 0.352 g as
yellow solid. Yield: 80%, mp ¼ 304–3068C, [a]2D5 ¼ þ 48.4 (c 1.0,
1
CH2Cl2). H NMR (DMSO-d6, 400 MHz): d ¼ 14.20 (s, 2H), 8.86 (s, 2H),
8.60–8.57 (m, 4H), 8.15 (td, 2H, J ¼ 8.0, 2.0 Hz), 8.03 (d, 2H, J ¼ 8.0,
1.2 Hz), 8.53–8.50 (m, 2H), 7.31 (td, 2H, J ¼ 8.0, 1.2 Hz), 7.25 (td, 2H,
J ¼ 8.0, 1.2 Hz), 7.03 (d, 2H, J ¼ 8.0 Hz). 13C NMR (CDCl3, 75.41 MHz):
d ¼ 158.4, 155.0, 146.2, 138.4, 129.2, 128.1, 127.9, 127.5, 125.1, 123.5,
122.4, 121.7, 120.7, 118.8. IR (KBr disk) n ¼ 3050, 1592, 1477, 1322,
789 cm21. Elemental analysis calculated for C30H20N2O2: C, 81.80; H,
4.58; N, 6.36; found: C, 81.66; H, 4.19; N, 6.07. ESI-MS: 441.1 m/z (100,
M þ 1).
(S)-3,30-di[2-(6-phenylpyridyl)]-2,20-dihydroxy-1,10-dinaphthyl (S)-3b
was prepared as yellow solid by the same method previously mentioned.
1
Yield: 83%, mp ¼ 202–2048C, [a]2D5 ¼ þ107.2 (c 1.0, CH2Cl2). H NMR
(DMSO-d6, 600 MHz): d ¼ 14.64 (s, 2H), 8.99 (s, 2H), 8.60 (d, 2H,
J ¼ 8.4 Hz), 8.26 (d, 2H, J ¼ 8.4 Hz), 8.07 (d, 2H, J ¼ 8.4 Hz), 8.05
(d, 2H, J ¼ 7.8 Hz), 7.90 (d, 4H, J ¼ 7.2 Hz), 7.48 (d, 4H, J ¼ 7.2 Hz),
7.43 (t, 2H, J ¼ 7.8 Hz), 7.33 (d, 2H, J ¼ 7.2 Hz), 7.26 (t, 2H, J ¼ 7.2 Hz),
7.04 (d, 2H, J ¼ 8.4 Hz). 13C NMR (DMSO-d6, 75.41 MHz): d ¼ 157.9,
155.0, 147.0, 139.8, 135.5, 129.8, 128.2, 124.9, 123.7, 121.8, 121.7, 118.6.
IR (KBr disk) n ¼ 3054, 1564, 1461, 762 cm21. Elemental analysis
calculated for C42H28N2O2: C, 85.11; H, 4.76; N, 4.73; found: C, 84.79;
H, 4.51; N, 4.57. ESI-MS: 593.9 m/z (100, M þ 1).
(S)-3,30-di[2-(6-(1-naphthyl)pyridyl)]-2,20-dihydroxy-1,10-dinaphthyl (S)-3c
was prepared as yellow solid by the same method previously mentioned.
1
Yield: 79%, mp ¼ 208–2108C, [a]2D5 ¼ þ72.2 (c 1.0, CH2Cl2). H NMR
(DMSO-d6, 400 MHz): d ¼ 14.17 (s, 2H), 8.94 (s, 2H), 8.64 (d, 2H,
J ¼ 8.0 Hz), 8.30 (t, 2H, J ¼ 8.0 Hz), 8.02–7.98 (m, 6H), 7.88 (d, 2H,
J ¼ 8.4 Hz), 7.75 (d, 2H, J ¼ 8.4 Hz), 7.62 (dd, 2H, J ¼ 7.2, 1.2 Hz), 7.58
(t, 2H, J ¼ 8.0 Hz), 7.50 (td, 2H, J ¼ 8.0, 1.2 Hz), 7.44 (td, 2H, J ¼ 8.4,
1.2 Hz), 7.28 (td, 2H, J ¼ 8.4, 1.2 Hz), 7.22 (td, 2H, J ¼ 8.4, 1.2 Hz), 6.97
(d, 2H, J ¼ 8.4 Hz). 13C NMR (DMSO-d6, 75.41 MHz): d ¼ 157.9, 155.7,
155.0, 140.4, 137.3, 135.4, 134.2, 130.9, 130.1, 129.8, 129.4, 128.5, 128.2,
128.1, 127.8, 127.1, 126.4, 125.3, 124.8, 123.8, 121.7, 120.4, 118.5. IR
(KBr disk) n ¼ 3051, 1565, 1464, 799, 775 cm21. Elemental analysis calcu-
lated for C50H32N2O2: C, 86.68; H, 4.66; N, 4.04; found: C, 86.52; H, 4.51;
N, 3.77. ESI-MS: 693.9 m/z (100, M þ 1).
(S)-3,30-di[2-(6-(9-anthyl)pyridyl)]-2,20-dihydroxy-1,10-dinaphthyl (S)-3d
was prepared as yellow solid by the same method previously mentioned.
1
Yield: 84%, mp ¼ 242–2448C, [a]2D5 ¼ þ18.2 (c 1.0, CH2Cl2). H NMR
(DMSO-d6, 600 MHz): d ¼ 13.86 (s, 2H), 8.92 (s, 2H), 8.73 (s, 2H), 8.70

1902
R.-z. Jin et al.
(d, 2H, J ¼ 8.4 Hz), 8.36 (t, 2H, J ¼ 7.8 Hz), 8.15 (d, 2H, J ¼ 8.4 Hz),
8.13 (d, 2H, J ¼ 8.4 Hz), 7.97 (d, 2H, J ¼ 8.4 Hz), 7.69 (d, 2H,
J ¼ 7.8 Hz), 7.51 (d, 2H, J ¼ 7.8 Hz), 7.49–7.47 (m, 4H), 7.42 (d, 2H,
J ¼ 8.4 Hz), 7.38 (d, 2H, J ¼ 8.4 Hz), 7.29 (t, 2H, J ¼ 7.2 Hz), 7.22
(d, 2H, J ¼ 7.8 Hz), 7.15 (t, 2H, J ¼ 7.8 Hz), 6.85 (d, 2H, J ¼ 8.4 Hz).
13C NMR (DMSO-d6, 75.41 MHz): d ¼ 158.4, 154.8, 154.5, 140.4, 135.4,
133.7, 131.5, 130.0, 129.4, 128.8, 128.5, 128.3, 128.1, 127.5, 127.4,
126.3, 125.8, 124.7, 123.7, 121.7, 120.8, 118.4. IR (KBr disk) n ¼ 3051,
1565, 1201, 733 cm21. Elemental analysis calculated for C58H36N2O2: C,
86.68; H, 4.66; N, 4.04; found: C, 86.39; H, 4.31; N, 3.92. ESI-MS:
793.9 m/z (100, M þ 1).
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