Synthesis of 3 or 3,3′-substituted BINOL ligands and their application in the asymmetric addition of diethylzinc to aromatic aldehydes

Article abstract of DOI:10.1016/j.tetasy.2005.09.018

Three new substituted BINOL ligands (R)-3-[4,6-bis(dimethylamino)-1,3,5- triazin-2-yl]-1,1′-bi-2-naphthol (R)-1, (R)-3,3′-bis[4,6- bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1′-bi-2-naphthol (R)-2 and 2,4-bis(2,2′-dihydroxy-1,1′-binaphthalen-3-yl)-6-(p-tolyl)-1,3, 5-triazine (R,R)-3 have been obtained by directed ortho-lithiation or Suzuki cross-coupling process. Ligand (R)-1 shows improved catalytic properties for the asymmetric diethylzinc addition to aromatic aldehydes.

Full text of DOI:10.1016/j.tetasy.2005.09.018

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3667–3671
0
Synthesis of 3 or 3,3 -substituted BINOL ligands and
their application in the asymmetric addition of diethylzinc
to aromatic aldehydes
Qun-Sheng Guo, Bing Liu, Yong-Na Lu, Fu-Yong Jiang, Hai-Bin Song and Jin-Shan Li*
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China
Received 28 July 2005;accepted 21 September 2005
Available online 10 November 2005
0
Abstract—Three new substituted BINOL ligands (R)-3-[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1 -bi-2-naphthol (R)-1, (R)-
0
0
0
0
3
,3 -bis[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1 -bi-2-naphthol (R)-2 and 2,4-bis(2,2 -dihydroxy-1,1 -binaphthalen-3-yl)-6-(p-
tolyl)-1,3,5-triazine (R,R)-3 have been obtained by directed ortho-lithiation or Suzuki cross-coupling process. Ligand (R)-1 shows
improved catalytic properties for the asymmetric diethylzinc addition to aromatic aldehydes.
ꢀ
2005 Elsevier Ltd. All rights reserved.
0
1
. Introduction
substituted-1,1 -bi-2-naphthols by directed ortho-metal-
3
lation and Suzuki cross-coupling methods.
0
Application of 1,1 -bi-2-naphthol (BINOL) and its
derivatives in asymmetric catalysis has been extensively
BINOL ligands substituted by the introduction of
heteroaromatic groups at the 3 or 3,3 -positions are less
reported. Jørgensen et al. reported the synthesis of 3,3 -
diaryl-BINOLs by reaction of 3,3 -diboronic acid of
bis(methoxy)-BINOL with aromatic bromides using a
Suzuki cross-coupling reaction. Heteroaromatic bro-
mides, such as 2-bromopyridine and 2-bromothiophene,
were also tried for the preparation of 3,3-bis(heteroaryl)-
BINOLs;however, only low yields were obtained. Ohta
et al. prepared 3,3 -bis(2-oxazolyl)-1,1 -bi-2-naphthol
1
0
studied. Substituents at the 3-position of BINOL are
0
normally introduced via a two-step protocol that
involves treatment of a suitably protected BINOL with
an organolithium reagent, followed by reaction with
an electrophile. Cram et al. synthesized two enantiome-
rically pure 3,3 -diaryl-substituted BINOLs by a Grig-
nard cross-coupling reaction of 3,3 -dibromo-BINOL-
0
0
0
2
4
dimethyl ether and arylmagnesium bromides. Snieckus
et al. reported an expedient synthetic route to 3 or 3,3 -
0
0
0
N
N
N
N
N
N
N
N
N
N
OH
OH
N
N
N
N
N
N
OH
OH
OHHO
OHHO
N
N
(
R)-1
(R)-2
(R,R)-3
Figure 1.
*
0
Corresponding author. E-mail: jinshan_li2001@yahoo.com.cn
957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.09.018

3668
Q.-S. Guo et al. / Tetrahedron: Asymmetry 16 (2005) 3667–3671
5
9
(
BINOL-Box). Gao et al. synthesized bis-binaphthyl
with dimethylamine, water and sodium hydroxide to
0
units containing 2,2 -bipyridines via Suzuki cross-
coupling reaction.
produce
(R)-3-[4,6-bis(dimethylamino)-1,3,5-triazin-
2-yl]-2,2 -bis(methoxymethoxy)-1,1 -binaphthalene (R)-
or (R)-3,3 -bis[4,6-bis(dimethylamino)-1,3,5-triazin-2-
yl]-2,2 -bis(methoxymethoxy)-1,1 -binaphthalene (R)-6.
6
0
0
0
5
0
0
Herein, we report the synthesis of three modified BINOL
ligands (R)-1, (R)-2 and (R,R)-3 via directed ortho-lithia-
tion or Suzuki cross-coupling processes starting from
After deprotection of compounds (R)-5 and (R)-6,
ligands (R)-1 and (R)-2 were obtained. The Suzuki
cross-coupling reaction was the general synthetic proce-
dure used to introduce aromatic or heteroaromatic
(
R)-BINOL and 2,4,6-trichloro-1,3,5-triazine (Fig. 1).
We also tested their effectiveness in the titanium
complex-catalyzed enantioselective addition of diethyl-
zinc to aldehydes.
0
groups at the 3 or 3,3 -positions of BINOL. Herein,
the direct coupling reaction was first used to prepare
2
. Results and discussion
(R)-5 and (R)-6.
The synthetic route to ligands (R)-1, (R)-2 and (R,R)-3 is
outlined in Scheme 1. The hydroxy groups of (R)-BINOL
were protected with methoxymethyl (MOM) groups to
The lithium salt of (R)-4 reacted with B(OMe) and the
3
mixture was hydrolyzed with 2 M HCl to afford (R)-
0
0
2,2 -bis(methoxymethoxy)-1,1 -binaphthyl-3-boronic
0
0
6
afford (R)-2,2 -bis(methoxymethoxy)-1,1 -binaphthalene
acid (R)-7. Suzuki coupling of (R)-7 with 2,4-dichloro-
6-p-tolyl-[1,3,5]-triazine in the presence of aq Na CO
7
10
(
R)-4. The lithium salt of (R)-4 reacted with cyanuric
2
3
8
chloride to afford (R)-3-(4,6-dichloro-1,3,5-triazin-
-yl)-2,2 -bis(methoxymethoxy)-1,1 -binaphthalene or
R)-3,3 -bis(4,6-dichloro-1,3,5-triazin-2-yl)-2,2 -bis(meth-
oxymethoxy)-1,1 -binaphthalene, which were treated
and Pd(PPh ) in THF at reflux for 36 h afforded 2,4-
3 4
0
0
0
0
2
(
bis[2,2 -bis(methoxymethoxy)-1,1 -binaphthalen-3-yl]-6-
(4-methylphenyl)-1,3,5-triazine (R,R)-8. Deprotection
0
0
11
0
of the MOM groups then afforded (R,R)-3.
N
N
N
N
N
a
OMOM
OMOM
e
(R)-1
52%
(R)-5
OMOM
OMOM
N
N
N
(
R)-4
N
N
N
b
OMOM
OMOM
e
(R)-2
c
5
1%
N
B(OH)2
N
N
(
R)-6
OMOM
OMOM
N
(R)-7
N
N
d
N
e
OX XO
OX XO
(
R,R)-3
60%
X=CH OCH
3
2
(
R,R)-8
Scheme 1. Reagents and conditions: (a) (i) 1.1 equiv n-BuLi, À78 ꢁC, (ii) 1.0 equiv cyanuric chloride, À78 ꢁC–rt, (iii) HNMe
, NaOH, H
, aq Na
2
, NaOH, H
O;(c) (i) 1.1 equiv n-BuLi, À78 ꢁC, (ii) B(OMe)
CO , THF/reflux;(e) CH Cl , CH OH, 6 M HCl,
2
O;(b) (i)
2
.0 equiv n-BuLi, À78 ꢁC, (ii) 2.0 equiv cyanuric chloride, À78 ꢁC–rt, (iii) HNMe
2
2
3
,
À78 ꢁC, (iii) 2 M HCl, 0 ꢁC;(d) 0.5 equiv 2,4-dichloro-6- p-tolyl-[1,3,5]-triazine, Pd(PPh
3
)
4
2
3
2
2
3
rt.

Q.-S. Guo et al. / Tetrahedron: Asymmetry 16 (2005) 3667–3671
3669
The colourless crystals of rac-1 were obtained from a
20% to 5% led to a large decrease in the enantioselectiv-
ity. The results are shown in Table 1.
CH Cl –petroleum ether solution. The crystal structure
2
2
1
2
of rac-1 was determined by X-ray diffraction (Fig. 2).
The dihedral angle of C(18)–C(19)–C(21)–N(3) is 9.5ꢁ,
and the dihedral angle between the two naphthalene sys-
tems is 98ꢁ.
The high enantioselectivity of ligand (R)-1 for the addi-
tion of diethylzinc to 1-naphthaldehyde prompted us to
examine its use for the reaction of various aromatic
aldehydes. These results are summarized in Table 2.
Table 2. Enantioselective addition of diethylzinc to aldehydes with
a
(
R)-1
O
i
OH
∗
Ti(O Pr) /(R)-1
4
+
Et Zn
2
R
H
toluene
R
b
c
Entry
R
Yield [a]
D
(c, solvent)
ee
(
%)
(%)
1
2
3
4
5
6
Ph
p-ClC
p-BrC
p-MeOC
o-MeOC
1-Naphthyl 99
99
99
77
65
94
+40.8 (3.75, CHCl
+18.8 (1.4, PhH)
+15.8 (1.49, PhH)
+31.9 (1.0, PhH)
3
)
85.6
74.5
90.3
83 (87)
87.3
6
H
4
6
H
4
6
H
H
4
4
6
+47.2 (1.15, Ph–CH
3
)
+55.4 (1.6, CHCl
3
)
90.1 (94.7)
Figure 2. The molecular structure of rac-1. Hydrogen atoms are
excluded for clarity.
a
i
(
R)-1/Ti(O Pr)
4
/Et
2
Zn/aldehyde = 0.2:1.4:3:1;solvent: toluene;reac-
tion temperature: 0 ꢁC;reaction time: 5 h.
Isolated yield.
Based on the reported value of [a]
phenyl-1-propanol; [a]
1-(4 -chlorophenyl)-1-propanol; [a] = +13.3 (c 1.0, PhH) in 76%
ee for (R)-1-(4 -bromophenyl)-1-propanol; [a]
b
c
D
= +45.6 (c 3.5, CHCl
3
) for (R)-1-
17
The effectiveness of the three new ligands in the titanium
complex-catalyzed enantioselective addition of diethyl-
zinc to 1-naphthaldehyde was tested.13 The active cata-
lyst was formed in situ by mixing the ligand with
D
= À28.2 (c 5.01, PhH) in 100% ee for (S)-
0
18
D
0
19
D
= À34.6 (c 5.0,
20
D
0
PhH) in 90% ee for (S)-1-(4 -methoxyphenyl)-1-propanol; [a]
=
1
4
À44.9 (c 1, toluene) in 83% ee for (S)-1-(20-methoxyphenyl)-1-pro-
titanium tetraisopropoxide in toluene. In this reaction,
21
0
D 3
panol; [a] = +45.5 (c 0.8, CHCl ) in 74% ee for (R)-1-(1 -naph-
15
i
the molar ratio of (R)-1 or (R)-2/Ti(O Pr) /Et Zn/1-
4
2
thyl)-1-propanol. Data in brackets were determined by GC analysis
naphthaldehyde was set up to be 0.2:1.4:3:1 and (R,R)-
16
i
using a chiral column (Chrompack Chirasil-DEX-CB column).
3
/Ti(O Pr) /Et Zn/1-naphthaldehyde was 0.1:1.4:3:1.
4 2
The three ligands exhibited very different catalytic prop-
erties from each other. Compound (R)-1 showed
improved catalytic properties in this reaction (94.7% ee).
The increasing steric effects of (R)-2 and (R,R)-3 proba-
bly led to their much lower enantioselectivity than (R)-1.
In addition, reducing the amount of (R)-1 catalyst from
3
. Conclusion
We have synthesized three new modified-BINOL ligands
R)-1, (R)-2 and (R,R)-3 from (R)-BINOL and 2,4,6-tri-
chloro-1,3,5-triazine. In particular, ligands (R)-1 and
R)-2 can be synthesized by a direct coupling reaction
(
(
Table 1. Catalytic asymmetric addition of diethylzinc (1 M in toluene)
to 1-naphthaldehyde
rather than Suzuki cross-coupling reaction. The tita-
nium complex of (R)-1 was found to be an effective cat-
alyst in the asymmetric addition of diethylzinc to a
variety of aromatic aldehydes.
HO
∗
CHO
Ti(OiPr)4/L*
toluene
+
Et Zn
2
a
b
c
Entry Ligand
Yield (%) [a]
D
(c, solvent)
ee (%)
4. Experimental
1
2
3
4
5
(R)-1
(R)-2
99
99
+55.4 (1.6, CHCl
+32.5 (2.0, CHCl
+16.1 (1.4, CHCl
+49.2 (0.72, CHCl
+38.9 (0.74, CHCl
3
3
3
)
)
)
90.1 (94.7)
52.9 (50.8)
26.3
77.5
61.3
4.1. General
d
(R,R)-3 82
e
(R)-1
(R)-1
85
87
3
)
)
1
13
The H and C NMR spectra were recorded on a Bru-
f
3
ker AC-300 instrument in CDCl solution with TMS as
3
a
i
L*/Ti(O Pr)
perature: 0 ꢁC;reaction time: 5 h.
Isolated yield.
Based on the reported value of [a]
for (R)-1-(1 -naphthyl)-1-propanol. Data in brackets were deter-
mined by GC analysis using a chiral column (Chrompack Chirasil-
DEX-CB column).
4
/Et
2
Zn/1-naphthaldehyde = 0.2:1.4:3:1;reaction tem-
internal standard. Optical rotations were measured on a
Perkin–Elmer 241 polarimeter. IR spectra were recorded
as KBr plates on a Bruker Equinox 55 spectrometer.
Elemental analysis was performed with a Yanaco
CHN Corder MT-3 elemental analyzer. All experiments,
which are sensitive to moisture or air, were carried out
under an argon atmosphere using standard Schlenk
techniques. Diethylzinc (1.0 M solution in toluene),
cyanuric chloride and Pd(PPh ) were purchased from
b
c
D
= +45.5 (c 0.8, CHCl
3
) in 74% ee
0
15
1
6
d
e
f
i
(
1
5
R,R)-3/Ti(O Pr)
4
/Et
0 mol % of catalyst was used.
mol % of catalyst was used.
2
Zn/1-naphthaldehyde = 0.1:1.4:3:1.
3
4

3670
Q.-S. Guo et al. / Tetrahedron: Asymmetry 16 (2005) 3667–3671
Aldrich. All anhydrous solvents were purified and dried
by standard techniques just before use.
J = 4.8 Hz, 2H), 4.97 (d, J = 4.5 Hz, 2H), 7.23–7.41
(m, 6H), 7.92 (d, J = 8.4 Hz, 2H); C NMR (75 MHz,
1
3
CDCl , d): 36.17, 56.04, 99.34, 124.92, 126.49, 126.83,
126.99, 128.41, 130.29, 131.76, 133.74, 134.80, 151.14,
3
4.2. Synthesis of (R)-3-[4,6-bis(dimethylamino)-1,3,5-
triazin-2-yl]-2,2 -bis(methoxymethoxy)-1,1 -binaphthal-
ene (R)-5
0
0
165.46, 171.78;IR (KBr): 2930, 1569, 1512, 1393, 818,
À1
752 cm . Anal. Calcd for C H N O : C, 64.76;H,
3
8
44 10
4
6
.29;N, 19.87. Found: C, 64.56;H, 6.42;N, 19.87.
To a solution of (R)-4 (3.74 g, 10 mmol) in anhydrous
THF (80 mL) was added n-BuLi (7.0 mL, 11 mmol,
0
0
4.4. Synthesis of 2,4-bis[2,2 -bis(methoxymethoxy)-1,1 -
binaphthalen-3-yl]-6-(p-tolyl)-1,3,5-triazine (R,R)-8
1
.57 M solution in hexane) at À78 ꢁC under argon and
the reaction mixture allowed to warm to room tempera-
ture and stirred for 2 h. The resulting solution was
slowly added to a solution of cyanuric chloride
Under argon, (R)-7 (1.73 g, 4.14 mmol) was combined
with 2,4-dichloro-6-p-tolyl-[1,3,5]-triazine (0.497 g,
2.07 mmol), Pd(PPh3)4 (0.09 g, 0.078 mmol), THF
(40 mL), H O (18 mL) and Na CO (1.75 g, 16.5 mmol).
The resulting mixture was heated at reflux for 36 h. The
organic layer was separated and the aqueous layer
extracted with AcOEt. The combined organic phases were
(
1.845 g, 10 mmol) in THF (30 mL) at À78 ꢁC. The mix-
ture was then warmed to room temperature and stirred
for another 9 h. A 33% aqueous solution of dimethyl-
amine (10 mL, 70 mmol) and NaOH (0.8 g, 20 mmol)
in water (20 mL) were added to the mixture and refluxed
for 6 h. After cooling to room temperature, the organic
layer was separated and the aqueous layer was extracted
with AcOEt. The combined organic phases were dried
2
2
3
dried over MgSO . After removal of the solvent, the res-
4
idue was submitted to column chromatography on silica
gel with petroleum ether/ethyl acetate (4/1) as eluent to
give (R,R)-8 (1.13 g, 60% yield) as a yellow powder.
over MgSO . After removal of the solvent, the residue
4
2
D
5
1
was submitted to column chromatographic separation
on silica gel with petroleum ether/ethyl acetate (5/1)
as eluent to give (R)-5 (2.81 g, 52% yield) as a pale yel-
½aŠ ¼ þ158:6 (c 0.57, CH Cl ); H NMR (300 MHz,
2
2
CDCl , d): 2.44 (s, 6H), 2.46 (s, 3H), 3.27 (s, 6H), 4.95
3
(d, J = 5.4 Hz, 2H), 4.99 (d, J = 4.8 Hz, 2H), 5.12 (d,
J = 7.8 Hz, 2H), 5.22 (d, J = 6.6 Hz, 2H), 7.27–7.41
(m, 12H), 7.47 (t, J = 6.6 Hz, 2H), 7.65 (d, J = 9.0 Hz,
2H), 7.90 (d, J = 7.2 Hz, 2H), 8.01 (d, J = 9.0 Hz, 2H),
8.06 (d, J = 8.4 Hz, 2H), 8.62 (d, J = 8.1 Hz, 2H), 8.84
2
D
5
1
low foam: ½aŠ ¼ þ88:2 (c 0.51, CH Cl ); H NMR
2
2
(
(
300 MHz, CDCl , d): 2.36 (s, 3H), 3.19 (s, 12H), 3.24
s, 3H), 4.84 (d, J = 5.4 Hz, 1H), 4.87 (d, J = 5.4 Hz,
3
1
H), 5.06 (d, J = 6.6 Hz, 1H), 7.21–7.39 (m, 6H), 7.59
1
3
(
d, J = 9.3 Hz, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.93 (d,
(s, 2H); C NMR (75 MHz, CDCl , d): 21.80, 56.07,
3
1
3
J = 9.3 Hz, 2H), 8.45 (s, 1H); C NMR (75 MHz,
94.79, 100.08, 116.32, 120.57, 124.15, 125.51, 125.83,
125.97, 126.75, 127.72, 127.80, 127.88, 129.14, 129.30,
129.59, 129.65, 129.88, 130.66, 132.00, 133.50, 133.55,
134.29, 135.33, 143.29, 151.22, 153.14, 171.59, 173.45;
IR (KBr): 3433, 3053, 1514, 1351, 817, 750 cm . Anal.
Calcd for C H N O : C, 76.05;H, 5.39;N, 4.59.
CDCl , d): 36.22, 55.80, 56.02, 94.73, 99.56, 116.34,
3
1
1
1
21.00, 123.99, 124.98, 125.76, 126.07, 126.46, 126.87,
27.00, 127.71, 128.71, 129.54, 129.60, 130.64, 131.82,
À1
33.79, 134.36, 134.51, 150.78, 153.10, 165.44, 171.82;
À1
IR (KBr): 2925, 1556, 1509, 1394, 808, 749 cm . Anal.
Calcd for C H N O : C, 69.00;H, 6.16;N, 12.98.
5
8
49
3
8
Found: C, 76.19;H, 5.60;N, 4.92. ESI-MS ( m/z):
3
1
33
5
4
+
Found: C, 69.06;H, 6.11;N, 12.90.
[M+H] 916.1.
0
4
1
.3. Synthesis of (R)-3,3 -bis[4,6-bis(dimethylamino)-
,3,5-triazin-2-yl]-2,2 -bis(methoxymethoxy)-1,1 -binaph-
4.5. (R)-3-[4,6-Bis(dimethylamino)-1,3,5-triazin-2-yl]-
1,1 -bi-2-naphthol (R)-1: deprotection of the MOM
groups; typical procedure
0
0
0
thalene (R)-6
To a solution of (R)-4 (1.87 g, 5 mmol) in anhydrous
THF (100 mL) was added n-BuLi (6.4 mL, 10 mmol,
To a solution of (R)-5 (2.81 g, 5.21 mmol) in CH Cl
2
2
(35 mL) and MeOH (35 mL) was added 6 M HCl
(15 mL) and the mixture was stirred at room tempera-
ture for 12 h. The mixture was poured into water
(80 mL), extracted with CH Cl , washed with water
1
.57 M solution in hexane) at 0 ꢁC under argon and
the reaction mixture was allowed to warm to room tem-
perature and stirred for 2 h. The resulting solution was
added slowly to a solution of cyanuric chloride
2
2
and then saturated NaHCO , dried over Na SO and
3
2
4
(
1.845 g, 10 mmol) in THF (40 mL) at À78 ꢁC. The mix-
concentrated in vacuo.
ture was then warmed to room temperature and stirred
for another 9 h. A 33% aqueous solution of dimethyl-
amine (10 mL, 70 mmol) and NaOH (0.8 g, 20 mmol)
in water (20 mL) were added to the mixture and then
refluxed for 6 h. After cooling to room temperature, the
organic layer was separated and the aqueous layer
extracted with AcOEt. The combined organic phases were
4.6. (R)-3-[4,6-Bis(dimethylamino)-1,3,5-triazin-2-yl]-
1,1 -bi-2-naphthol [(R)-1]
0
25
1
Mp > 300 ꢁC; ½aŠ ¼ þ61:1 (c 0.61, CH Cl ); H NMR
D
2
2
(300 MHz, CDCl , d): 3.21 (s, 12H), 5.27 (s, 1H), 7.08
3
(d, J = 8.1 Hz, 1H), 7.15–7.33 (m, 5H), 7.39 (d,
J = 9.0 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.91 (d,
J = 9.3 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 9.21 (s, 1H),
dried over MgSO . After removal of the solvent, the res-
4
idue was submitted to column chromatographic separa-
tion on silica gel with petroleum ether/ethyl acetate (4/1)
as eluent to give (R)-6 (1.8 g, 51% yield) as a pale yellow
1
3
14.32 (s, 1H); C NMR (75 MHz, CDCl , d): 36.35,
3
36.65, 113.35, 121.03, 123.20, 123.43, 124.53, 125.19,
126.38, 127.59, 128.21, 128.58, 129.34, 129.70, 129.80,
132.16, 133.86, 136.40, 151.61, 156.77, 163.49, 169.60;
2
D
5
1
foam: ½aŠ ¼ þ16:7 (c 0.52, CH Cl ); H NMR (300
2
2
MHz, CDCl , d): 2.50 (s, 6H), 3.19 (s, 24H), 4.85 (d,
3

Q.-S. Guo et al. / Tetrahedron: Asymmetry 16 (2005) 3667–3671
3671
IR (KBr): 3525, 3374, 2927, 1574, 1509, 1386, 810,
References
À1
7
46 cm . Anal. Calcd for C H N O : C, 71.82;H,
27 25 5 2
5
.58;N, 15.51. Found: C, 71.75;H, 5.40;N, 15.42.
1. (a) Pu, L. Chem. Rev. 1998, 98, 2405–2494;(b) Chen, Y.;
Yekta, S.;Yudin, A. K. Chem. Rev. 2003, 103, 3155–3211;
+
ESI-MS (m/z): [M+H] 452.3.
(
c) Ko cˇ ovsk u´ , P.;Vyskocˇil, S.;Smrcˇina, M. Chem. Rev.
0
2003, 103, 3213–3245;(d) Brunel, J. M. Chem. Rev. 2005,
105, 857–897.
. Lingenfelter, D. S.;Helgeson, R. C.;Cram, D. J. J. Org.
Chem. 1981, 46, 393–406.
3. Cox, P. J.;Wang, W.;Snieckus, V. Tetrahedron Lett. 1992,
33, 2253–2256.
4. Simonsen, K. B.;Gothelf, K. V.;Jørgensen, K. A. J. Org.
Chem. 1998, 63, 7536–7538.
4.7. (R)-3,3 -Bis[4,6-bis(dimethylamino)-1,3,5-triazin-2-
yl]-1,1 -bi-2-naphthol (R)-2
0
2
2
D
5
1
Mp > 300 ꢁC; ½aŠ ¼ þ79:15 (c 0.47, CH Cl ); H NMR
2
2
(
7
300 MHz, CDCl , d): 3.20 (s, 24H), 7.14–7.26 (m, 6H),
3
1
3
.94 (d, J = 9.0 Hz, 2H), 9.17 (s, 2H), 13.78 (s, 2H);
NMR (75 MHz, CDCl , d): 36.48, 117.50, 120.81,
22.73, 124.84, 127.41, 127.79, 129.53, 130.95, 136.50,
55.70, 163.57, 170.12;IR (KBr): 3448, 2926, 1583,
513, 1395, 826, 744 cm
C H N O : C, 66.22;H, 5.88;N, 22.71. Found: C,
6.21;H, 5.83;N, 22.19.
C
3
1
1
1
5. Kodama, H.;Ito, J.;Hori, K.;Ohta, T.;Furukawa, I.
Organomet. Chem. 2000, 603, 6–12.
J.
À1
6. Bai, X. L.;Liu, X. D.;Wang, M.;Kang, C. Q.;Gao, L. X.
Synthesis 2005, 458–464.
.
Anal. Calcd for
3
4
36 10
2
7
. Kitajima, H.;Aoki, Y.;Ito, K.;Katsuki, T.
995, 1113–1114.
Chem. Lett.
6
1
8
. The reactions of 2,4,6-trichloro-s-triazine with a lithiated
derivative of pyrrole, thiophene or furan have been
reported: (a) Chakrabarti, J. K.;Goulding, R. W.;Todd,
A. J. Chem. Soc., Perkin Trans. 1 1973, 2499–2503;(b)
Chakrabarti, J. K.;Tupper, D. E. J. Heterocycl. Chem.
1974, 11, 417–421;(c) Chakrabarti, J. K.;Tupper, D. E.
Tetrahedron 1975, 31, 1879–1882.
0
0
4
(
.8. 2,4-Bis(2,2 -dihydroxy-1,1 -binaphthalen-3-yl)-6-
p-tolyl)-1,3,5-triazine [(R,R)-3]
2
D
5
1
Mp > 300 ꢁC; ½aŠ ¼ þ202:2 (c 0.81, CH Cl ); H NMR
2
2
(
7
300 MHz, CDCl , d): 2.45 (s, 6H), 5.22 (s, 2H), 7.22–
3
.49 (m, 16H), 7.94 (d, J = 8.1 Hz, 2H), 8.01 (d,
J = 8.4 Hz, 2H), 8.17 (d, J = 8.1 Hz, 2H), 8.35 (d,
9
. Thurston, J. T.;Dudley, J. R.;Kaiser, D. W.;Hechen-
bleikner, I.;Schaefer, F. C.;Hansen, D. H. J. Am. Chem.
Soc. 1951, 73, 2981–2983.
1
3
J = 8.4 Hz, 2H), 9.53 (s, 2H), 13.17 (s, 2H); C NMR
75 MHz, CDCl , d): 21.89, 114.68, 115.13, 117.88,
19.06, 123.53, 124.46, 124.76, 126.76, 127.82, 128.39,
29.29, 129.35, 130.08, 130.21, 130.27, 130.30, 130.36,
33.66, 133.94, 137.70, 145.61, 151.57, 155.99, 169.29,
71.35;IR (KBr): 3537, 3494, 3438, 3060, 1522, 1353,
18, 745 cm . Anal. Calcd for C H N O : C, 81.17;
H, 4.50;N, 5.68. Found: C, 80.83;H, 4.72;N, 5.71.
ESI-MS (m/z): M 739.
(
3
1
0. The synthesis of 2,4-dichloro-6-(4-methylphenyl)-1,3,5-s-
triazine was reported: Chang, Y.;Kim, Y. N.;Noh, I.;
Kim, C. Macromol. Chem. Phys. 2000, 201, 1808–
1
1
1
1
8
1
812.
11. The reaction of 2-aryl-4,6-dichloro-1,3,5-triazine with
phenylboronic acid was reported: Janietz, D.;Bauer, M.
Synthesis 1993, 33–34.
À1
5
0
33
3
4
+
1
25 5 2
2. Crystal data for rac-1: C27H N O , M = 451.52, triclinic,
˚
˚
space group P-1, a = 10.753(3) A, b = 11.076(5) A,
˚
c = 11.185(4) A, a = 99.373(8)ꢁ, b = 110.368(9)ꢁ, c =
4.9. A typical procedure for the asymmetric addition of
diethylzinc to benzaldehyde
˚
3
À3
À1
1
05.908(8)ꢁ, V = 1150.7(7) A , Z = 2, D = 1.303 g cm
,
,
˚
MoKa (k = 0.71073 A), T = 293(2) K, l = 0.085 mm
crystal size (mm) 0.28 · 0.24 · 0.14. Area detector data
collected on a Bruker Smart 1000 diffractometer. A total
of 5921 reflections were collected (2.00 < h < 25.00).
Structure solution by direct method (SHELXS-97), refine-
ment by full-matrix least-squares using all reflections,
Titanium tetraisopropoxide (0.43 mL, 1.24 mmol) was
added to a solution of (R)-1 (0.08 g, 0.177 mmol) in
3
1
mL of toluene at room temperature and stirred for
5 min followed by the addition of diethylzinc
(
2.7 mL, 1.0 M solution in toluene) with continued stir-
R = 0.0602, wR = 0.1730, GOF = 1.035.
1 2
3. Chen, Y.;Yekta, S.;Martyn, L. J. P.; Zheng, J.; Yudin,
A. K. Org. Lett. 2000, 2, 3433–3436.
4. Mori, M.;Nankai, T. Tetrahedron Lett. 1997, 38, 6233–
1
1
1
1
ring for 15 min. The solution was cooled to 0 ꢁC and
benzaldehyde (0.09 mL, 0.88 mmol) was introduced
with a syringe. The reaction mixture was stirred at
6
236.
5. Williams, D. R.;Fromhold, M. G. Synlett 1997, 523–
24.
0
ꢁC for 5 h. The reaction was quenched with 20 mL
of saturated NH Cl solution. The mixture was extracted
with ethyl acetate. The combined organic layers were
dried over MgSO and concentrated to solvent free.
4
5
6. Zhang, F. Y.;Chan, A. S. C. Tetrahedron: Asymmetry
1997, 8, 3651–3655.
4
The residue was purified by column chromatography
on silica gel to afford 1-phenyl-1-propanol as a colour-
less liquid. The specific rotation was then measured.
17. Soai, K.;Watanabe, M. Tetrahedron: Asymmetry 1991, 2,
97–100.
18. Watanabe, M.;Araki, S.;Butsugan, Y.;Uemura, M.
J.
Org. Chem. 1991, 56, 2218–2224.
1
9. Chaloner, P. A.;Perena, S. A. R. J. Chem. Soc., Perkin
Trans. 1 1991, 2731–2735.
0. Ishizaki, M.;Fujita, K.;Shimamoto, M.;Hoshino, O.
Tetrahedron: Asymmetry 1994, 5, 411–424.
Acknowledgements
2
This work was supported by the National Natural Sci-
ence Foundation of China (Grant No. 20372037).
21. Smaardijk, A.;Wynberg, H. J. Org. Chem. 1987, 52, 135–
137.