Synthesis of new bis-BINOLs linked by a 2,2e′-bipyridine bridge

Article abstract of DOI:10.1055/s-2004-837306

A series of new C₂-symmetric chiral ligands 8, 9, 11 and 12, consisting of two binaphthyl units linked by a 2,2′-bipyridine bridge, has been synthesized via Suzuki cross-coupling reactions.

Full text of DOI:10.1055/s-2004-837306

458
PAPER
Synthesis of New Bis-BINOLs Linked by a 2,2¢-Bipyridine Bridge
S
ynthesis of Bis(B
i
IN
O
L)
a
-
2,2
¢
-Bipyr
o
idines -Li Bai, Xu-Dong Liu, Mang Wang, Chuan-Qing Kang, Lian-Xun Gao*
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences,
Graduate School of Chinese Academy of Sciences, Chang Chun, 130022, P. R. China
Fax +86(431)5697831; E-mail: lxgao@ciac.jl.cn
Received 13 September 2004; revised 19 October 2004
which 2,5-dibromopyridine (1) reacted almost exclusive-
Abstract: A series of new C2-symmetric chiral ligands 8, 9, 11 and
ly at the 2-position leading to the desired product 2 in 75%
12, consisting of two binaphthyl units linked by a 2,2¢-bipyridine
yield in the presence of Pd(0)(PPh3)4 at 130 °C. 6,6¢-Di-
bromo-2,2¢-bipyridine (4) was synthesized from 2,6-di-
bromopyridine (3) (Scheme 2); 3 was converted into 6-
bromopyridyl-2-lithium by treatment with one equivalent
of n-BuLi at –60 °C in Et2O under Ar atmosphere, fol-
lowed by oxidative coupling with POCl3 (0.25 equiv) or
SOCl2 (0.33 equiv) in 45% yield.8
bridge, has been synthesized via Suzuki cross-coupling reactions.
Key words: cross-coupling reactions, BINOL, bipyridine, ligands,
chiral
As a kind of important C2-symmetrical ligands 1,1¢-bi-2-
naphthol (BINOL) and their derivatives have been exten-
sively used to provide a chiral environment in asymmetric
synthesis.1 BINOL itself, however, does not always give
satisfactory results in asymmetric catalysis. Recently, bis-
BINOLs in which two BINOL units are connected by an
appropriate structural unit have presented new possibili-
ties for multifunctional asymmetric catalysis.2 Shibasaki
and co-workers have reported that linked BINOL ligands,
carbon-linked bis-BINOLs,2a oxygen-linked bis-
BINOLs2d and sulfur-linked bis-BINOLs2i have been suc-
cessfully applied to catalyze many stereoselective reac-
tions.
n-Bu6Sn2
Br
Br
Br
Br
Pd(PPh3)4
75%
N
N
N
2
1
Scheme 1 Synthesis of 5,5¢-dibromo-2,2¢-bipyridine.
1 equiv n-BuLi
0.25 equiv POCl3
N
N
Br
N
Br
45%
Br
Br
4
3
Therefore, the synthesis of new C2-symmetric chiral
ligands consisting of two binaphthyl units linked by an ap-
propriate bridge is potentially useful for investigating cat-
alytic asymmetric reaction. Transition metal complexes
with sp2-nitrogen(s) as the ligating atom(s) constitute an
important class of chiral catalysts.1a,3 in which substituted
2,2¢-bipyridyl can be viewed as potentially promising
group since they can be rendered chiral by appending ad-
ditional substituents.4 By combining two chiral BINOL
units with 2,2¢-bipyridine unit, it is expected to obtain a
sort of useful compounds with new catalytic activities and
special physical properties. Herein, we report the synthe-
ses of new bis-binaphthyl units containing 2,2¢-bipy-
ridines 8, 9, 11 and 12 by assembling 5,5¢/6,6¢-dibromo-
2,2¢-bipyridines and 6/3-boronic acid-binaphthyl units via
Suzuki-cross coupling reaction.5
Scheme 2 Synthesis of 6,6¢-dibromo-2,2¢-bipyridine.
The syntheses of bis(binaphthyl)-2,2¢-bipyridines started
from enantiopure 1,1¢-binaphthyl (R)-5a–c.9 Scheme 3
outlines the synthesis of enantiopure bis(binaphthyl)-2,2¢-
bipyridines (R,R)-8a–c and (R,R)-9a–c. First, (R)-6-bro-
mo-1,1¢-binaphthyls (R)-6a–c can be obtained from lithi-
um-halogen exchange of 6,6¢-dibromo-1,1¢-binaphthyl
with one equivalent of n-BuLi followed by quenching
with water.10 Alternatively, a straightforward and efficient
method involves the bromination of 1,1¢-binaphthyl with
1.1 equivalents of bromine at 0 °C. In order to retard bis-
bromination at 6,6¢-position, bromine was diluted in
CH2Cl2 and added slowly. A mixture of 6,6¢-dibromo-
(30%) and 6-mono-bromo-1,1¢-binaphthyl (70%) was ob-
tained as a sticky yellow solid and directly used for the
following procedure without further separation. The lithi-
um-halogen exchange with n-BuLi followed by reduction
with B(OMe)3 and hydrolysis with 2 M HCl, afforded 6-
boronic acid-1,1¢-binaphthyls (R)-7a–c in 46–51% yield.
Suzuki coupling of 7a–c with 2/4 in the presence of aq 1
M K2CO3 and Pd(PPh3)4 (5 mol%) in DMF at 80 °C for 72
hours yielded (R,R)-8a–c and (R,R)-9a–c in 38–66%
yield. Starting from (R)-5b,c, a mixture of 3-boronic acid-
1,1¢-binaphthyls (R)-10a,b and the 3,3¢-diboronic acid-
1,1¢-binaphthyl11 was obtained by treatment with n-BuLi
(1.5 equiv) and TMEDA (1.5 equiv) in anhdrous Et2O at
According to the known procedure, 5,5¢-dibromo-2,2¢-bi-
pyridine (2) was previously prepared from 2,2¢-bipyridine
by bromination.6 But the tedious and harsh reaction con-
ditions and many by-products usually gave the low reac-
tion yield. Then an efficient method was found that used
about 50 mol% hexa-n-butyldistannane and a catalytic
amount of Pd(0) to give superior results7 (Scheme 1), in
SYNTHESIS 2005, No. 3, pp 0458–0464
x
x
.
x
x
.2
0
0
5
Advanced online publication: 23.12.2004
DOI: 10.1055/s-2004-837306; Art ID: F12704SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Bis(BINOL)-2,2′-Bipyridines
459
room temperature for three hours, generating the dilithiat- by 2,2¢-bipyridines (R,R)-12c, (R,R)-8d and (R,R)-9d
ed (minor) and monolithiated (major) compounds, which were obtained through a deprotection reaction of MOM
reacted with B(OMe)3 at –78 °C. During acidic workup protected ligands (R,R)-12b, (R,R)-8c and (R,R)-9c with
the borate was hydrolyzed to give the corresponding (R)- concd HCl in MeOH–THF in high yields (Scheme 5). At-
10a,b in pure form in 51–55% yield after purification by tempts to remove the ethyl groups of (R,R)-11 using BBr3
chromatography. In the same way, (R,R)-11 and (R,R)- resulted in a complex mixture of unidentified products.
12a,b were obtained from the Suzuki coupling reactions All the intermediates and products (R,R)-8a–d, (R,R)-9a–
1
of 10a,b with 2 and 4, respectively, in the yield of 49– d, (R,R)-11, (R,R)-12a–c have been characterized by H
64%.(Scheme 4) In fact, the synthesis of 11 and 12a,b NMR, 13C NMR and ESI–MS.
proved to need longer reaction time due to the hindrance
In conclusion, we have described an asymmetric synthesis
of protecting groups of 10a,b. However, even if the reac-
of novel bis-binaphthyls substituted bipyridine ligands 8,
tion time was prolonged to 5 days, we failed to synthesize
9, 11, 12 by using Suzuki cross-coupling reaction. The
coupling reaction between 7/10 and 2/4 gave products in
reasonable yields. Through final deprotection of the
5,5¢-di[2,2¢-bis(methoxymethoxy)-1,1¢-binaphthyl-3-]-
2,2¢-bipyridine by treating 2 with 10b; most likely due to
steric factors.
MOM
protected
products,
the
corresponding
The coupling reaction of 7/10 with 2/4 gave bis(binaphth- bis(BINOL)-2,2¢-bipyridine ligands 8d, 9d, 12c were ob-
yl) substituted bipyridine ligands in reasonable yields. tained. To the best of our knowledge, bis-BINOLs directly
The results are presented in Table 1. Bis-BINOLs linked linked by 2,2¢-bipyridine at 5,5¢- and 6,6¢-position of 2,2¢-
(HO)2B
Br
a
b
OR
OR
OR
OR
OR
OR
70%
46-51%
5a R=C6H13
5b R=C2H5
5c R=MOM
7a R=C6H13
7b R=C2H5
7c R= MOM
6a R=C6H13
6b R=C2H5
6c R= MOM
c
38-66%
N
N
N
N
RO
RO
OR
OR
RO
RO
OR
OR
8a R=C6H13
8b R=C2H5
8c R=MOM
9a R=C6H13
9b R=C2H5
9c R=MOM
Scheme 3 Synthesis of bis(binaphthyl) substituted bipyridines 8 and 9. Reagents and conditions: (a) 1.1 equiv bromine, CH2Cl2, 0 °C.
(b) n-BuLi, B(OMe)3, THF. (c) Pd(PPh3)4, 1 M K2CO3, 2 or 4, DMF, 80 °C.
B(OH)2
OR
OR
a
OR
OR
51-55%
10a R=C2H5
10b R=MOM
5b R=C2H5
5c R=MOM
b
49-64%
N
N
N
N
OR
RO
RO
OR
OR
RO
RO
OR
12a R=C2H5
12b R=MOM
11 R=C2H5
Scheme 4 Synthesis of bis(binaphthyl) substituted bipyridines 11 and 12. Reagents and conditions: (a) TMEDA, n-BuLi, B(OMe)3, Et2O.
(b) Pd(PPh3)4, 1 M K2CO3, 2 or 4, DMF, 80 °C.
Synthesis 2005, No. 3, 458–464 © Thieme Stuttgart · New York

460
X.-L. Bai et al.
PAPER
N
N
N
N
HO
HO
OH
OH
8d
THF/MeOH
HO
HO
OH
OH
12b, 8c, 9c
HCl
9d
88–93%
N
N
OH
OH
HO
HO
12c
Scheme 5 Deprotection of 12b, 8c, 9c.
Table 1 Synthesis of Bis-binaphthyls Substituted Bipyridines 8, 9, 11, 12.
Entry
bpy
Boronic acid
Coupling product Yield (%)
Deprotection
product
Yield (%)
1
2
3
4
5
6
7
8
9
2
2
2
2
4
4
4
4
4
(R)-7a
(R)-7b
(R)-7c
(R)-10a
(R)-7a
(R)-7b
(R)-7c
(R)-10a
(R)-10b
(R,R)-8a
(R,R)-8b
(R,R)-8c
(R,R)-11
(R,R)-9a
(R,R)-9b
(R,R)-9c
(R,R)-12a
(R,R)-12b
48
60
42
55
38
58
66
49
64
–
–
–
–
(R,R)-8d
87.5
–
–
–
–
–
–
(R,R)-9d
–
93
–
(R,R)-12c
89
mesh). Reactions were carried out in anhydrous solvents under an
Ar atmosphere, unless otherwise stated. THF and Et2O were dis-
tilled from sodium benzophenone ketyl. Toluene was distilled from
sodium. DMF and CH2Cl2 were dried over CaH2. 2,5-Dibromopyri-
dine, hexa-n-butyldistannane, tetrakis(triphenylphosphine)palladi-
um, n-BuLi solutions were purchased from Acros. 2,6-
Dibromopyridine was purchased from Aldrich.
bipyridine have never been reported before. These ligands
can be used for investigating asymmetric reactions, which
utilize BINOL or bipyridine ligands. The further investi-
gations on the utilizations and properties of these ligands
are in progress.
IR spectra were recorded on a Bio-Rad FTS135 infrared spectro-
meter. NMR spectra were recorded on Bruker-300, 400, 600 MHz
spectrometers. Chemical shifts are reported downfield from TMS
(d = 0) for 1H NMR spectra. For 13C NMR spectra, chemical shifts
are reported on the scale relative to deuterated solvent as internal
standard. Optical rotations were measured on a 341LC polarimeter.
ESI–MS measurements were conducted with a LCQ instrument.
Melting points were measured with a hot-stage microscope XT-4.
Elemental analyses were carried out with a VarioEL instrument.
TLC was performed on aluminum TLC-layers Silica gel GF254.
Detection was done by UV light (254 nm and 365 nm). Products
were purified by column chromatography on silica gel (100–200
5,5¢-Dibromo-2,2¢-bipyridine (2)
To a flask evacuated and put under Ar, 2,5-dibromopyridine (5 g,
21.1 mmol) was charged into anhyd toluene (175 mL) from a sy-
ringe, followed by n-Bu6Sn2 (5.9 mL, 50 mol%). Ar was bubbled
through the stirred solution for 1 h before Pd(PPh3)4 (0.585 g, 0.506
mmol) was added from a tip tube. The reaction mixture was heated
to 120 °C for 3 d until all starting material was consumed. The mix-
ture was extracted with CHCl3 and dried over Na2SO4. After evap-
oration of solvents, the crude product was flash chromotographed
(CH2Cl2 as eluent) to yield 2 as a white solid (2.48 g, 75%). Recrys-
tallization from CHCl3 gave colorless plates.
Synthesis 2005, No. 3, 458–464 © Thieme Stuttgart · New York

PAPER
Synthesis of Bis(BINOL)-2,2′-Bipyridines
ESI–MS: m/z (%) = 386.17 (100) [M+].
461
1H NMR (400 MHz, CDCl3): d = 8.709 (d, 4J = 2.0 Hz, 2 H), 8.297
(d, 3J = 8.4 Hz, 2 H), 7.950 (dd, 4J = 2.0, 3J = 8.4 Hz, 2 H).
2,2¢-Bis(methoxymethoxy)-1,1¢-binaphthyl-6-boronic Acid [(R)-
13C NMR (400 MHz, CDCl3): d = 153.67, 150.28, 139.60, 122.23,
7c]
121.45.
Yield: 51%; mp 190–192 °C; [a]D 60 (c = 0.1, THF).
IR (KBr): 3412, 1374, 1016 cm–1.
ESI–MS: m/z (%) = 315.1 (100) [M+].
6,6¢-Dibromo-2,2¢-bipyridine (4)
1H NMR (400 MHz, CDCl3): d = 8.82 [s, B(OH)2, 2 H], 8.14 (d,
3J = 8.8 Hz, 1 H), 8.02 (dd, 3J = 8.4 Hz, 4J = 1.2 Hz, 1 H), 7.98 (d,
3J = 9.2 Hz, 1 H), 7.90 (d, 3J = 8.0 Hz, 1 H), 7.65 (d, 3J = 8.8 Hz, 1
H), 7.60 (d, 3J = 8.8 Hz, 1 H), 7.37 (td, 3J = 8.0 Hz, 4J = 1.2 Hz, 1
H), 7.21 (m, 4 H), 5.15 (m, 4 H), 3.18 (m, 6 H).
To a solution of 2,6-dibromopyridine (5 g, 21.1 mmol) in Et2O (30
mL) with stirring at –60 °C under Ar atmosphere, a solution of n-
BuLi in hexane (13.2 mL, 21.1 mmol) was added. After the reaction
mixture had been stirred for 2 h at –40 °C, a solution of phosphorous
oxychoride (0.49 mL, 5.3 mmol) in Et2O (20 mL) was slowly added
at –40 °C. The reaction mixture was stirred for 2 h, warmed to r.t.
and then mixed with water (30 mL). The Et2O layer was washed
with water and dried over Na2SO4. After removal of solvent, the
crude product was separated by column chromatography on silica
gel (hexane–EtOAc, 8:1). The total yield of 4 was 1.48 g (45%).
ESI–MS: m/z (%) = 418.16 (100) [M+].
2,2¢-Diethoxy-1,1¢-binaphthyl-3-boronic Acid [(R)-10a]
In a 500 mL flame-dried three-necked round-bottomed flask
equipped with a N2-inlet were placed ananhyd Et2O (300 mL) and
TMEDA (3.3 mL, 21.9 mmol). To this solution was added 1.6 M n-
BuLi in hexane (13.5 mL, 21.9 mmol). The solution was stirred for
30 min at r.t. (R)-2,2¢-Diethoxy-1,1¢-binaphthyl (5 g, 14.6 mmol)
was added in one portion, and the reaction was stirred for 3 h. The
resulting light brown suspension was cooled to –78 °C, and
B(OMe)3 (14 mL, 122 mmol) was added via syringe over a period
of 10 min. The solution was allowed to warm to r.t. and was left stir-
ring overnight. The reaction mixture was cooled to 0 °C, 1 M HCl
(150 mL) was added, and the reaction mixture was stirred for 2 h.
The phases were separated, and organic phase was washed with 1
M HCl (2 × 100 mL), sat. aq NaCl (100 mL) and dried over
Na2SO4. The solvent was removed under reduced pressure, and re-
sulting white solid was purified by chromatography on silica gel.
The total yield was 51% (2.85 g); mp 160–162 °C; [a]D 97 (c = 0.1,
THF).
1H NMR (400 MHz, CDCl3): d = 8.388 (d, 3J = 7.6 Hz, 2 H), 7.691
(t, 3J = 7.6, 8.1 Hz, 2 H), 7.517 (d, 3J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 155.59, 141.58, 139.29, 128.58,
120.14.
ESI–MS: m/z (%) = 315.1 (100) [M+].
2,2¢-Bis(hexyloxy)-1,1¢-binaphthyl-6-boronic Acid [(R)-7a]
To a CH2Cl2 (100 mL) solution of (R)-2,2¢-bis(hexyloxy)-1,1¢-bi-
naphthyl (10 g, 22.1 mmol) at –78 °C was dropwise added Br2 (1.25
mL in 20 mL CH2Cl2) during 30 min. After stirring at –78 °C for 2
h, the solution was warmed to r.t. and stirred for another 3 h. Then
the resulting solution was washed with aq NaHSO3, water and brine
successively, dried with Mg2SO4. After evaporation of solvents, a
mixture of 6,6¢-dibromo- and 6-monobromo-1,1¢-binaphthyl was
obtained as a sticky yellow solid. To the mixture in THF (200 mL)
at –78 °C was slowly added n-BuLi (27.6 mL, 1.6 M in hexane, 44.2
mmol), and after stirring at –78 °C for 2 h, the resulting greenish
yellow solution was cannulated into a solution of B(OMe)3 (10 mL,
88.3 mmol) in THF (20 mL). The mixture was warmed to r.t. and
stirred overnight. Excess 2 M HCl was then added at 0 °C. The mix-
ture was extracted with EtOAc and dried over Mg2SO4. The crude
product was purified by chromatography on silica gel (CH2Cl2–
MeOH) to collect the second batch and give pure (R)-7a as a white
solid (5.1 g, 46%); [a]D 51 (c = 0.1, CH2Cl2).
IR (KBr): 3359, 1342, 747 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.536 [s, B(OH)2, 2 H], 7.995 (d,
3J = 8.8 Hz, 1 H), 7.955 (d, 3J = 8.0 Hz, 1 H), 7.878 (d, 3J = 8.0 Hz,
1 H), 7.445 (d, 3J = 9.2 Hz, 1 H), 7.406 (td, 3J = 8.0 Hz, 4J = 1.2 Hz,
1 H), 7.356 (td, 3J = 8.0 Hz, 4J = 1.2 Hz, 1 H), 7.283 (m, 3 H), 7.168
(d, 3J = 8.0 Hz, 2 H), 4.111 (m, 2 H), 3.621 (m, 2 H), 1.089 (t, 3J =
6.8, 7.2 Hz, 3 H), 0.895 (t, 3J = 7.2, 6.8 Hz, 3 H).
ESI–MS: m/z (%) = 386.17 (100) [M+].
2,2¢-Bis(methoxymethoxy)-1,1¢-binaphthyl-3-boronic Acid [(R)-
10b]
IR (KBr): 3434, 1320, 728 cm–1.
Yield: 55%; mp 204 °C; [a]D 149 (c = 0.1, THF).
IR (KBr): 3452, 1332, 750 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.490 [s, B(OH)2, 2 H], 7.938 [d,
3J = 8.8 Hz, 1 H], 7.908 (d, 3J = 7.74 Hz, 1 H), 7.831 (d, 3J = 8.04
Hz, 1 H), 7.548 (d, 3J = 9.09 Hz, 1 H), 7.371 (m, 2 H), 7.244 (m, 3
H), 7.124 (m, 2 H), 5.067 (m, 2 H), 4.574 (d, 4J = 5.4 Hz, 1 H), 4.411
(d, 4J = 5.1 Hz, 1 H), 3.108 (m, 6 H).
1H NMR (400 MHz, CDCl3): d = 8.812 [s, B(OH)2, 2 H], 8.095 (d,
3J = 9.2 Hz, 1 H), 7.980 (d, 3J = 8.4 Hz, 1 H), 7.930 (d, 3J = 9.2 Hz,
1 H), 7.871 (d, 3J = 8.0 Hz, 1 H), 7.445 (d, 3J = 9.2 Hz, 1 H), 7.410
(d, J = 8.8 Hz, 1 H), 7.303 (m, 1 H), 7.246 (m, 2 H), 7.163 (m, 2 H),
3.952 (m, 4 H), 1.388 (m, 4 H), 0.942 (m, 12 H), 0.677 (m, 6 H).
13C NMR (150 MHz, CDCl3): d = 155.97, 154.57, 137.89, 136.76,
134.21, 130.91, 130.42, 129.29, 129.07, 128.60, 127.78, 126.04,
125.45, 125.00, 124.81, 123.37, 120.54, 120.44, 115.82, 115.34.
ESI–MS: m/z (%) = 418.16 (100) [M+].
ESI–MS: m/z (%) = 498.29 (100) [M+].
Suzuki Cross-Coupling Reaction; General Procedure
2,2¢-Diethoxy-1,1¢-binaphthyl-6-boronic Acid [(R)-7b]
Yield: 50%; [a]D 35 (c = 0.1, CH2Cl2).
IR (KBr): 3359, 1342, 746 cm–1.
A mixture of 2 (100 mg, 0.318 mmol), 7a (317 mg, 0.636 mmol)
and Pd(PPh3)4 (36.8 mg, 0.0318 mmol) in degassed DMF (10 mL)
was stirred at r.t. for 60 min, then degassed aq 1 M K2CO3 (8 mL)
was added. The reaction mixture was heated under Ar at 80 °C for
3 d (TLC monitored). EtOAc (20 mL) was added, and the solution
was stirred for 10 min. The organic phase was separated and the
aqueous phase was extracted with EtOAc (2 × 20 mL). The com-
bined organic phase was dried over MgSO4. The crude product was
purified by chromatography on silica gel (hexane–EtOAc, 10:1) to
yield 8a as a yellow solid.
1H NMR (400 MHz, CDCl3): d = 8.80 [s, B(OH)2, 2 H], 8.11 (d,
3J = 8.8 Hz, 1 H), 7.99 (d, 3J = 8.4 Hz, 1 H), 7.96 (d, 3J = 9.2 Hz, 1
3
3
H), 7.87 (d, J = 8.0 Hz, 1 H), 7.47 (d, J = 9.2 Hz, 2 H), 7.33 (t,
3J = 7.2 Hz, 1 H), 7.21 (m, 4 H), 4.13 (m, 4 H), 1.10 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 155.97, 154.57, 138.10, 136.96,
134.31, 131.91, 130.42, 129.29, 129.07, 128.80, 128.00, 126.04,
125.65, 125.20, 125.01, 123.67, 120.64, 120.54, 116.02, 115.64,
65.45, 65.18, 15.24, 15.17.
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X.-L. Bai et al.
PAPER
5,5¢-Bis[2,2¢-bis(hexyloxy)-1,1¢-binaphthalen-6-yl]-2,2¢-bipyri-
dine [(R,R)-8a]
Mp 66–68 °C; [a]D 44 (c = 0.1, CH2Cl2).
IR (KBr): 2927, 1244, 803 cm–1.
13C NMR (150 MHz, CDCl3): d = 156.40, 155.94, 155.17, 154.57,
137.14, 134.58, 134.37, 134.21, 129.93, 129.24, 129.06, 127.76,
126.30, 126.00, 125.45, 124.86, 123.36, 120.54, 120.11, 119.12,
115.95, 115.80, 69.73, 65.57, 31.29, 29.37, 29.30, 25.32, 25.26,
22.43, 22.41, 13.88.
1H NMR (400 MHz, CDCl3): d = 9.039 (d, 4J = 2.0 Hz, 2 H), 8.559
(d, 3J = 8.4 Hz, 2 H), 8.153 (dd, 3J = 8.4 Hz, 4J = 2.0 Hz, 4 H), 8.038
(d, 3J = 9.2 Hz, 2 H), 7.958 (d, 3J = 9.2 Hz, 2 H), 7.874 (d, 3J = 8.0
Hz, 2 H), 7.532 (dd, 3J = 9.2 Hz, 4J = 2.0 Hz, 2 H), 7.480 (d, 3J = 9.2
Hz, 4 H), 7.336 (m, 4 H), 7.226 (m, 4 H), 4.010 (m, 8 H), 1.411 (m,
8 H), 1.010 (m, 24 H), 0.769 (m, 12 H).
13C NMR (100 MHz, CDCl3): d = 155.12, 154.52, 147.59, 136.46,
135.08, 134.13, 133.87, 132.22, 129.47, 129.33, 129.22, 129.17,
127.81, 126.56, 126.10, 125.98, 125.30, 124.95, 123.38, 120.95,
120.61, 120.22, 116.30, 115.66, 69.66, 69.58, 31.27, 29.33, 29.27,
25.31, 25.24, 22.43, 22.39, 13.86.
ESI–MS: m/z (%) = 1061.4 (100) [M+].
Anal. Calcd for C74H80N2O4: C, 83.73; H, 7.60; N, 2.64. Found: C,
83.70; H, 7.71; N, 2.68.
6,6¢-Bis(2,2¢-diethoxy-1,1¢-binaphthalen-6-yl)-2,2¢-bipyridine
[(R,R)-9b]
Mp 69–71 °C; [a]D 11 (c = 0.1, CH2Cl2).
IR (KBr): 2976, 1234, 801 cm–1.
1H NMR (400 MHz, DMSO): d = 8.825 (d, 4J = 1.2 Hz, 2 H), 8.567
(d, 3J = 7.6 Hz, 2 H), 8.239 (d, 3J = 9.2 Hz, 2 H), 8.146 (m, 4 H),
8.077 (m, 4 H), 7.961 (d, 3J = 8.4 Hz, 2 H), 7.657 (d, 3J = 9.2 Hz, 4
H), 7.351 (t, 3J = 7.2, 7.2 Hz, 2 H), 7.238 (t, 3J = 7.2, 7.2 Hz, 2 H),
7.073 (d, 3J = 8.8 Hz, 2 H), 6.991 (d, 3J = 8.8 Hz, 2 H), 4.124 (m, 8
H), 1.047 (m, 12 H).
ESI–MS: m/z (%) = 1061.4 (100) [M+].
Anal. Calcd for C74H80N2O4: C, 83.73; H, 7.60; N, 2.64. Found: C,
83.72; H, 7.72; N, 2.66.
5,5¢-Bis[2,2¢-diethoxy-1,1¢-binaphthalen-6-yl]-2,2¢-bipyridine
13C NMR (100 MHz, DMSO): d = 155.46, 155.08, 154.61, 153.89,
138.14, 134.55, 133.85, 133.40, 130.57, 130.16, 129.23, 128.67,
128.08, 127.93, 126.25, 126.10, 125.24, 124.59, 123.24, 120.34,
119.18, 119.06, 118.98, 115.75, 115.43, 64.14, 64.07, 14.72, 14.68.
[(R,R)-8b]
[a]D 33 (c = 0.1, CH2Cl2).
IR (KBr): 2976, 1237, 800 cm–1.
ESI–MS: m/z (%) = 837.38 (100) [M+].
1H NMR (400 MHz, DMSO): d = 9.129 (s, 2 H), 8.534 (d, 3J = 8.0
Hz, 2 H), 8.437 (s, 2 H), 8.348 (d, 3J = 8.0 Hz, 2 H), 8.174 (d, 3J =
9.2 Hz, 2 H), 8.065 (d, 3J = 8.8 Hz, 2 H), 7.957 (d, 3J = 8.0 Hz, 2 H),
Anal. Calcd for C58H48N2O4: C, 83.23; H, 5.78; N, 3.35. Found: C,
83.26; H, 5.74; N, 3.34.
3
3
7.711 (d, J = 8.0 Hz, 2 H), 7.662 (d, J = 9.2 Hz, 2 H), 7.608 (d,
3J = 9.2 Hz, 2 H), 7.351 (t, 3J = 6.8, 7.6 Hz, 2 H), 7.259 (t, 3J = 7.6,
7.2 Hz, 2 H), 7.051 (d, 3J = 8.8 Hz, 2 H), 6.972 (d, 3J = 8.4 Hz, 2 H),
4.110 (m, 8 H), 1.050 (m, 12 H).
6,6¢-Bis[2,2¢-bis(methoxymethoxy)-1,1¢-binaphthalen-6-yl]-2,2¢-
bipyridine [(R,R)-9c]
[a]D 17 (c = 0.1, THF).
13C NMR (100 MHz, CDCl3): d = 154.23, 153.66, 153.48, 146.67,
134.96, 134.05, 133.20, 132.88, 131.14, 129.07, 128.66, 128.53,
127.16, 125.31, 125.24, 124.08, 122.65, 119.91, 119.65, 119.40,
116.19, 115.61, 64.17, 14.04, 13.97.
IR (KBr): 1565, 1014, 804 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.665 (d, 4J = 1.6 Hz, 2 H), 8.602
(dd, 3J = 7.4 Hz, 4J = 1.2 Hz, 2 H), 8.118 (d, 3J = 9.0 Hz, 2 H), 8.086
(dd, 3J = 8.9 Hz, 4J = 1.8 Hz, 2 H), 7.986 (d, 3J = 9.0 Hz, 2 H), 7.927
(m, 6 H), 7.643 (d, 3J = 9.0 Hz, 4 H), 7.378 (td, 3J = 8.0 Hz, 4J = 1.8
Hz, 2 H), 7.304 (d, 3J = 8.9 Hz, 2 H), 7.225 (m, 4 H), 5.132 (m, 4
H), 5.024 (m, 4 H), 3.177 (s, 6 H), 3.173 (s, 6 H).
ESI–MS: m/z (%) = 837.38 (100) [M+].
Anal. Calcd for C58H48N2O4: C, 83.23; H, 5.78; N, 3.35. Found: C,
83.25; H, 5.74; N, 3.32.
ESI–MS: m/z (%) = 900.34 (100) [M+].
5,5¢-Bis[2,2¢-bis(methoxymethoxy)-1,1¢-binaphthalen-6-yl]-2,2¢-
bipyridine [(R,R)-8c]
[a]D = 21 (c = 0.1, THF).
IR (KBr): 1481, 1016, 804 cm–1.
1H NMR (600 MHz, DMSO): d = 9.024 (d, 4J = 1.8 Hz, 2 H), 8.525
(d, 3J = 8.4 Hz, 2 H), 8.173 (d, 4J = 0.6 Hz, 2 H), 8.122 (dd, 3J = 7.8
Hz, 4J = 1.8 Hz, 2 H), 8.061 (d, 3J = 9.6 Hz, 2 H), 7.985 (d, 3J = 9.6
Hz, 2 H), 7.900 (d, 3J = 7.8 Hz, 2 H), 7.656 (d, 3J = 9.0 Hz, 2 H),
7.611 (d, 3J = 9.0 Hz, 2 H), 7.554 (dd, 3J = 9.0 Hz, 4J = 1.2 Hz, 2 H),
7.363 (t, 3J = 8.4 Hz, 2 H), 7.301 (d, 3J = 8.4 Hz, 2 H), 7.253 (t, 2
H), 7.197 (d, 3J = 8.4 Hz, 2 H), 5.131 (m, 4 H), 5.033 (m, 4 H), 3.191
(s, 6 H), 3.172 (s, 6 H).
5,5¢-Bis[2,2¢-diethoxy-1,1¢-binaphthalen-3-yl]-2,2¢-bipyridine
[(R,R)-11]
[a]D 94 (c = 0.1, CH2Cl2).
IR (KBr): 2977, 1232, 747 cm–1.
1H NMR (600 MHz, CDCl3): d = 9.101 (d, 4J = 1.8 Hz, 2 H), 8.565
4
(d, 3J = 8.4 Hz, 2 H), 8.310 (dd, 3J = 8.4 Hz, J = 2.4 Hz, 2 H), 8.030
3
3
(s, 2 H), 7.991 (d, J = 9.0 Hz, 2 H), 7.957 (d, J = 7.8 Hz, 2 H),
3
3
7.884 (d, J = 7.8 Hz, 2 H), 7.470 (d, J = 9.0 Hz, 2 H), 7.424 (t,
3J = 8.4 Hz, 2 H), 7.342 (t, 3J = 8.4 Hz, 2 H), 7.265 (m, 6 H), 7.207
(d, 3J = 8.4 Hz, 2 H), 4.162 (m, 4 H), 3.390 (m, 2 H), 3.291 (m, 2
H), 1.171 (t, 3J = 6.0 Hz, 6 H), 0.582 (t, 3J = 6.0 Hz, 6 H).
ESI–MS: m/z (%) = 900.34 (100) [M+].
13C NMR (150 MHz, CDCl3): d = 154.62, 154.38, 153.38, 149.58,
137.93, 134.94, 134.13, 134.04, 131.86, 130.71, 129.84, 129.54,
129.06, 128.07, 127.88, 126.55, 126.45, 126.40, 125.85, 125.38,
125.02, 123.54, 120.32, 120.13, 115.24, 69.04, 65.04, 15.22, 15.07.
6,6¢-Bis[2,2¢-bis(hexyloxy)-1,1¢-binaphthalen-6-yl]-2,2¢-bipyri-
dine [(R,R)-9a]
[a]D 41 (c = 0.1, CH2Cl2).
IR (KBr): 2927, 1242, 800 cm–1.
ESI–MS: m/z (%) = 837.38 (100) [M+].
Anal. Calcd for C58H48N2O4: C, 83.23; H, 5.78; N, 3.35. Found: C,
83.24; H, 5.76; N, 3.34
1H NMR (600 MHz, CDCl3): d = 8.645 (s, 2 H), 8.603 (d, 3J = 7.2
Hz, 2 H), 8.087 (d, 3J = 9.0 Hz, 2 H), 8.040 (d, 3J = 9.0 Hz, 2 H),
7.950 (d, 3J = 9.0 Hz, 2 H), 7.914 (t, 3J = 7.8, 7.8 Hz, 2 H), 7.869 (t,
3J = 6.6, 7.2 Hz, 4 H), 7.460 (d, 3J = 9.0 Hz, 4 H), 7.322 (m, 4 H),
7.226 (m, 4 H), 4.014 (m, 8 H, OCH2), 1.423 (m, 8 H, CH2), 1.052
[m, 24 H, (CH2)3] 0.754 (m, 12 H, CH3).
6,6¢-Bis[2,2¢-diethoxy-1,1¢-binaphthalen-3-yl]-2,2¢-bipyridine
[(R,R)-12a]
[a]D 87 (c = 0.1, CH2Cl2).
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Synthesis of Bis(BINOL)-2,2′-Bipyridines
463
IR (KBr): 2976, 1237, 750 cm–1.
1H NMR (600 MHz, DMSO): d = 9.377 (s, 2 H), 9.247 (s, 2 H),
8.750 (s, 2 H), 8.547 (d, 3J = 7.8 Hz, 2 H), 8.098 (m, 8 H), 7.897 (t,
3J = 9.0, 8.4 Hz, 4 H), 7.403 (d, 3J = 9.0 Hz, 2 H), 7.363 (d, 3J = 8.4
Hz, 2 H), 7.267 (t, 3J = 7.2 Hz, 2 H), 7.215 (t, 3J = 7.8, 6.6 Hz, 2 H),
7.101 (d, 3J = 9.0 Hz, 2 H), 7.014 (d, 3J = 8.4 Hz, 2 H).
13C NMR (150 MHz, DMSO): d = 154.90, 153.71, 153.01, 147.26,
137.37, 134.84, 134.06, 133.84, 129.30, 128.74, 128.34, 128.11,
127.86, 125.97, 125.90, 125.45, 124.55, 124.29, 122.28, 120.50,
120.41, 119.22, 118.51, 115.47, 115.10.
1H NMR (600 MHz, CDCl3): d = 8.748 (s, 2 H), 8.574 (s, 2 H),
8.167 (s, 2 H), 7.995 (d, 3J = 9.0 Hz, 6 H), 7.888 (d, 3J = 8.4 Hz, 2
H), 7.458 (d, 3J = 9.0 Hz, 2 H), 7.434 (t, 3J = 7.8, 7.2 Hz, 2 H), 7.348
(m, 2 H), 7.285 (m, 6 H), 7.200 (d, 3J = 8.4 Hz, 2 H), 4.122 (m, 4
H), 3.534 (m, 2 H), 3.412 (m, 2 H), 1.110 (t, 3J = 6.0 Hz, 6 H), 0.634
(t, 3J = 6.0 Hz, 6 H).
13C NMR (150 MHz, CDCl3): d = 156.04, 154.45, 153.59, 136.89,
134.32, 134.25, 134.13, 134.04, 131.09, 130.87, 129.42, 129.11,
128.65, 127.84, 126.45, 126.42, 126.38, 125.75, 125.52, 125.26,
124.79, 123.52, 120.48, 119.71, 115.32, 69.53, 65.09, 15.29 15.10.
ESI–MS: m/z (%) = 725.3 (100) [M+].
Anal. Calcd for C50H32N2O4: C, 82.86; H, 4.45; N, 3.86 Found: C,
83.81; H, 4.39; N, 3.79.
ESI–MS: m/z (%) = 837.38 (100) [M+].
Anal. Calcd for C58H48N2O4: C, 83.23; H, 5.78; N, 3.35. Found: C,
83.27; H, 5.71; N, 3.38.
Bis(BINOL)-2,2¢-bipyridine [(R,R)-12c]
Mp 288–290 °C; [a]D 309 (c = 0.1, THF).
6,6¢-Bis[2,2¢-bis(methoxymethoxy)-1,1¢-binaphthalen-3-yl]-2,2¢-
bipyridine [(R,R)-12b]
[a]D 153 (c = 0.1, CH2Cl2).
IR (KBr): 1565, 1012 cm–1.
1H NMR (600 MHz, CDCl3): d = 8.513 (s, 2 H), 8.247 (d, 3J = 7.8
Hz, 2 H), 8.108 (d, 3J = 7.8 Hz, 2 H), 8.016 (d, 3J = 7.2 Hz, 2 H),
7.984 (t, 3J = 8.4, 7.8 Hz, 2 H), 7.914 (d, 3J = 7.8 Hz, 4 H), 7.630 (d,
3J = 9.0 Hz, 2 H), 7.376 (t, 3J = 7.2, 6.6 Hz, 2 H), 7.327 (t, 3J = 8.4,
7.8 Hz, 4 H), 7.288 (m, 4 H), 7.116 (d, 3J = 8.4 Hz, 2 H), 5.166 (d,
3J = 6.6 Hz, 4 H), 5.018 (d, 3J = 7.2 Hz, 4 H), 3.192 (s, 6 H), 3.167
(s, 6 H).
IR (KBr): 3514, 3439, 1565, 810 cm–1.
1H NMR (400 MHz, DMSO): d = 13.820 (s, 2 H), 9.260 (s, 2 H),
8.932 (s, 2 H), 8.685 (d, 3J = 8.4 Hz, 2 H), 8.316 (t, 3J = 8.4, 8.0 Hz,
2 H), 8.066 (d, 3J = 8.0 Hz, 2 H), 8.020 (d, 3J = 8.0 Hz, 2 H), 7.925
(t, 3J = 9.2 Hz, 4 H), 7.377 (d, 3J = 8.8 Hz, 2 H), 7.324 (t, 3J = 7.2,
6.6 Hz, 2 H), 7.254 (m, 4 H), 7.198 (t, 3J = 8.4, 6.8 Hz, 2 H), 7.038
(d, 3J = 8.4 Hz, 2 H), 6.963 (d, 3J = 8.4 Hz, 2 H).
13C NMR (100 MHz, DMSO): d = 157.29, 153.99, 153.06, 151.28,
140.40, 134.88, 134.02, 128.96, 128.75, 128.20, 128.12, 127.87,
127.40, 125.97, 125.99, 124.30, 124.09, 123.00, 122.31, 122.10,
121.09, 119.54, 118.65, 117.66, 115.30.
ESI–MS: m/z (%) = 900.34 (100) [M+].
ESI–MS: m/z (%) = 725.2 (100) [M+].
Anal. Calcd for C50H32N2O4: C, 82.86; H, 4.45; N, 3.86 Found: C,
82.73; H, 5.50; N, 3.83.
Bis(BINOL)-2,2¢-bipyridine [(R,R)-8d]: Deprotection of the
MOM Groups; Typical Procedure
To a solution of (R,R)-8c (100 mg, 0.111 mmol) in THF (10 mL)
and MeOH (10 mL) was added concd HCl (2 mL) and the mixture
was stirred at r.t. for 24 h. The mixture was poured into water,
washed with aq NaHCO3 and extracted twice with CHCl3. The com-
bined organic layers were washed with brine, dried (Na2SO4), and
concentrated in vacuo.
References
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Wiley: New York, 1994. (b) Noyori, R. Angew. Chem. Int.
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(2) (a) Vogl, E. M.; Matsunaga, S.; Kanai, M.; Iida, T.;
Shibasaki, M. Tetrahedron Lett. 1998, 39, 7917.
Bis(BINOL)-2,2¢-bipyridine (R,R)-8d
(b) Ishitani, H.; Kitazawa, T.; Kobayashi, S. Tetrahedron
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(j) Kumagai, N.; Matsunaga, S.; Kinoshita, T.; Harada, S.;
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4712.
Mp 206–208 °C; [a]D = 65.4 (c = 0.1, THF).
IR (KBr): 3390, 1483, 817 cm–1.
1H NMR (600 MHz, DMSO): d = 9.413 (s, 2 H), 9.289 (s, 2 H),
9.113 (dd, 3J = 10.2 Hz, 4J = 1.8 Hz, 2 H), 8.522 (d, 3J = 8.4 Hz, 2
H), 8.361(dd, 3J = 6.0 Hz, 4J = 1.8 Hz, 2 H), 8.328 (td, 3J = 8.4 Hz,
4J = 1.8 Hz, 2 H), 8.004 (d, 3J = 9.0 Hz, 2 H), 7.891 (t, 3J = 9.0, 8.4
Hz, 4 H), 7.680 (td, 3J = 8.4, 2.4 Hz, 2 H), 7.398 (d, 3J = 9.0 Hz, 2
H), 7.351 (d, 3J = 8.4 Hz, 2 H), 7.265 (t, 3J = 8.4, 6.6 Hz, 2 H), 7.215
(t, 3J = 7.2, 6.6 Hz, 2 H), 7.072 (d, 3J = 9.0 Hz, 2 H), 6.991 (d, 3J =
8.4 Hz, 2 H).
13C NMR (150 MHz, DMSO): d = 154.90, 153.71, 153.01, 147.26,
137.37, 134.84, 134.06, 133.84, 129.30, 128.74, 128.34, 128.11,
127.86, 125.97, 125.90, 125.45, 124.55, 124.29, 122.28, 120.50,
120.41, 119.22, 118.51, 115.47, 115.10.
ESI–MS: m/z (%) = 725.3 (100) [M+].
Anal. Calcd for C50H32N2O4: C, 82.86; H, 4.45; N, 3.86. Found: C,
82.82; H, 4.48; N, 3.81.
Bis(BINOL)-2,2¢-bipyridine [(R,R)-9d]
Mp 214–216 °C; [a]D 94 (c = 0.1, THF).
IR (KBr): 3506, 1566, 815 cm–1.
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Synthesis 2005, No. 3, 458–464 © Thieme Stuttgart · New York