Practical preparation of chiral keto-imine type ONO Schiff base ligands

Article abstract of DOI:10.1016/j.tetasy.2013.03.017

A practical preparation of chiral keto-imine type ONO Schiff base ligands has been reported. Metal complexes of these Schiff bases work as efficient chiral catalysts in a variety of asymmetric reactions.

Full text of DOI:10.1016/j.tetasy.2013.03.017

Tetrahedron: Asymmetry 24 (2013) 543–547
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Practical preparation of chiral keto-imine type ONO Schiff base ligands
⇑
Vasudevan Dhayalan, Ryo Murakami, Masahiko Hayashi
Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 February 2013
Accepted 11 March 2013
A practical preparation of chiral keto-imine type ONO Schiff base ligands has been reported. Metal
complexes of these Schiff bases work as efficient chiral catalysts in a variety of asymmetric reactions.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
20 mol% Ti(O-i-Pr)4
O
NC OSiMe3
22 mol% chiral Schiff base
Me3SiCN
+
R
H
Since our first report using a chiral ONO-type Schiff base–tita-
nium alkoxide complex in the asymmetric silylcyanation of alde-
hydes (Scheme 1),1 there have been many reports using this type
of ONO tridentate chiral Schiff base in asymmetric reactions. Some
representative examples include asymmetric Mukaiyama aldol
reactions,2 asymmetric oxidations of sulfides,3,4 asymmetric oxida-
tions of disulfides,5 asymmetric hetero Diels–Alder reactions,6,7
asymmetric pinacol couplings,8 asymmetric allylations9 and asym-
metric hydrophosphonylations.10 The general formula of these
Schiff bases is shown in Figure 1. All the Schiff bases used in the
above reactions2–10 are of the aldo-imine type (R3 = H in Fig. 1).
We also reported on the enantioselective addition of diketenes to
aldehydes,11 asymmetric alkylations using dialkylzincs12 and asym-
metric Reformatsky reactions.13 In these reactions, the introduction
of bulky substituents, such as a t-butyl group or an adamantyl group
at the ortho-position of the phenolic hydroxyl group (see the R1
substituent in the general formula of Fig. 1) is essential for obtaining
highly enantioselective reactions. Furthermore, we have also
reported that the introduction of an R3 group, leads to the formation
of keto-imine type Schiff bases with an increase in both the
reactivity (chemical yield) and enantioselectivity when compared
to those of the corresponding aldo-imine type Schiff bases. Some
examples are shown in Schemes 2 and 3.
R
H
CH2Cl2
up to 96% ee
t-Bu
N
OH
OH
Schiff base 1
Scheme 1.
R2
R3
R1
R4
N
OH
OH
Figure 1.
Despite its utility, there have only been a few reports using
keto-imine type Shiff bases.14 This is probably because of the diffi-
culty of the introduction of the R3 group. Previous methods for the
synthesis of keto-imine type Schiff bases include an oxidation step
as shown in Scheme 4.
Reagents, conditions and yields of the oxidation step were as
follows (R2 = t-Bu, R3 = Ph): (1) CrO3 in CH2Cl2, 31__35% yield.11c
(2) Pd/C under CH2@CH2 in CH3CN, 84% yield.15 (3) Activated
carbon under O2 in xylene, 77% yield.16
2. Results and discussion
Herein we report a novel synthetic route for keto-imine Schiff
bases without using an oxidation step. We used 3,5-di-tert-butyl-
2-hydroxybenzoic acid as the starting material and treated this
compound with benzotriazole to afford o-hydroxyarylacylbenzo-
triazole 5 in 88% yield (Scheme 5), which proved to be a crucial
intermediate for the preparation of a variety of ketones using
Grignard reagents (Table 1).17
Comparing the present method (Scheme 5 and Table 2) the con-
ventional method (Scheme 4), it is clear that the present method is
⇑
Corresponding author. Tel.: +81 788035687.
E-mail address: mhayashi@kobe-u.ac.jp (M. Hayashi).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.03.017

544
V. Dhayalan et al. / Tetrahedron: Asymmetry 24 (2013) 543–547
O
1 mol%
t-Bu
t-Bu
OH
Schiff base
ref.12
+
Et2Zn
1H-benzo[d][1,2,3]triazole
Ph
H
hexane, 0 °C, 24 h
Ph
Et
SOCl2
N
HO
N
N
CH2Cl2, rt
t-Bu
t-Bu
O
OH
O
OH
Ph
t-Bu
t-Bu
5
N
OH
N
OH
Scheme 5.
OH
OH
intermediate has been reported. These chiral ligands exhibited a
high performance in catalytic asymmetric reactions.
3
4
81% ee
(44% yield)
96% ee
(94% yield)
4. Experimental
4.1. General
Scheme 2.
much more efficient. This is because in the previous method, in
order to prepare a variety of keto-imines, a Grignard reaction
followed by an oxidation step are necessary. However, in our pres-
ent method, the common active amide intermediate, o-hydrox-
yarylacylbenzotriazole 5, can be prepared on a large scale, and a
variety of keto-imines can be obtained by changing only the
Grignard reagents, while an oxidation step is not necessary. Thus,
the obtained ketones were condensed with b-amino alcohols to
give the desired keto-imine type Schiff bases (Table 2).
All reactions were carried out in oven-dried glassware with
magnetic stirring. Operations were performed under an atmo-
sphere of dry argon using Schlenk and vacuum techniques. All
starting materials were obtained from commercial sources and
used without further purification unless otherwise stated. Melting
points were measured by a Yanaco MP-500D and are not corrected.
1H and 13C NMR spectra (400 and 100.6 MHz, respectively) were
recorded on a JEOL JNM-LA 400 instrument using Me4Si as an inter-
nal standard (0 ppm). The following abbreviations are used in con-
nection with NMR; s = singlet, d = doublet, t = triplet, q = quartet
and m = multiplet. Mass spectra were measured using a Thermo
Quest LCQ DECA plus. IR spectra were measured with a Thermo
SCIENTIFIC NICOLET iS 5. Elemental analyses were carried out
3. Conclusion
In conclusion, a practical method for the synthesis of keto-imine
type Schiff bases using o-hydroxyarylacylbenzotriazole as a key
OH
O
Ti(O-i-Pr)4
Schiff base
ref.11c
CO2-i-Pr
Me3Si
CHO
+
O
Me3Si
O
Ph
t-Bu
t-Bu
N
OH
N
OH
OH
OH
1
2
81% ee
(44% yield)
91% ee
(69% yield)
Scheme 3.
R2
R2
H3O+
R3MgBr
THF
R3
H
t-Bu
t-Bu
OH
OH
O
OH
R2
R2
R4
NH2
OH
R3
t-Bu
R3
oxidation
R4
N
OH
t-Bu
Na2SO4
toluene
O
OH
OH
6
7
Scheme 4.

V. Dhayalan et al. / Tetrahedron: Asymmetry 24 (2013) 543–547
545
Table 1
added and filtered. After removing the solvent under vacuum from
the filtrate, it was recrystallized from methanol to give (1H-
benzo[d][1,2,3]triazol-1-yl)(3,5-di-tert-butyl-2-hydroxy-phenyl)
methanone 5 as a yellow solid.
Synthesis of diketones 6a–6h from o-hydroxyarylacylbenzotriazoles 5a
t-Bu
t-Bu
1) R3MgX, THF
2) H3O+
Yield: 88%; mp 86.2–87.7 °C (methanol). IR (neat):
m 2960, 1656,
1589 cmꢀ1 1H NMR (400 MHz, CDCl3): d 11.19 (s, 1H), 8.28–8.25
.
R3
N
N
(m, 2H), 8.17 (d, J = 8.0 Hz, 1H), 7.71–7.67 (m, 2H), 7.54 (t,
J = 7.2 Hz, 1H), 1.49 (s, 9H), 1.34 (s, 9H). 13C NMR (100.6 MHz,
CDCl3): d 170.5, 160.9, 145.5, 140.8, 137.7, 132.6, 132.3, 130.3,
127.9, 126.2, 120.2, 114.8, 112.7, 35.3, 34.5, 31.3, 29.4. MS (ESI)
m/z: 352 (M+H+). Anal. Calcd for C21H25N3O2: C, 71.77; H, 7.17;
N, 11.96. Found: C, 71.87; H, 7.32; N, 11.85.
t-Bu
t-Bu
N
O
OH
O
OH
Entry
R3
Temp (°C)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Me
i-Pr
Ph
4-MeC6H4
4-t-BuC6H4
3,5-(CF3)2C6H3
4-CF3C6H4
3,4,5-F3C6H2
25
23
23
23
25
23
24
24
15
18
17
18
20
16
14
17
6a; 60
6b; 76
6c; 79
6d; 80
6e; 94
6f; 98
6g; 59
6h; 51
4.3. General procedure for synthesis of diaryl ketones 6a–6h
A solution of bromo compound (2.50 mmol) in dry THF (5 mL)
was added (10 min) to
a mixture of magnesium turnings
(2.60 mmol) containing a catalytic amount of iodine (1 mg) in
dry THF (10 mL) under an Ar atmosphere. After the addition of
the bromo compound, the reaction mixture was stirred at room
temperature for 6 h to ensure the completion of the Grignard for-
mation. Next, this Grignard reagent was slowly added via an addi-
tional funnel to a solution of (1H-benzo[d][1,2,3]triazol-1-yl)(3,5-
di-tert-butyl-2-hydroxy-phenyl)methanone 5 (1.0 mmol) in dry
THF (3 mL) at room temperature. The reaction mixture was stirred
at room temperature for the indicated reaction time (Table 1) and
poured over ice-cold water (100 mL) containing ammonium chlo-
ride. It was then extracted with CHCl3 (30 mL ꢁ 3) and dried
(Na2SO4). Removal of the solvent followed by silica-gel column
chromatography (eluent, hexane/ethyl acetate = 5:1) and recrystal-
lization afforded the corresponding ketones 6a–6h.
a
Reaction conditions: Substrate 5 (1.0 mmol), R3MgX (2.5 mmol), THF, room
temperature.
b
Isolated yield after column chromatographic purification.
Table 2
Synthesis of keto-imine type (ONO) tridentate chiral Schiff base ligands 7a–7ha
t-Bu
R4
NH2
OH
t-Bu
R3
t-Bu
R3
t-Bu
R4
N
OH
Na2SO4
toluene
110 °C
O
OH
4.3.1. 1-(3,5-Di-tert-butyl-2-hydroxyphenyl)ethanone 6a
Yield: 60%; pale yellow solid; mp 50.5–51.4 °C (methanol) (lit.18
mp 43.0–44.5 °C). 1H NMR (400 MHz, CDCl3): d 12.99 (s, 1H), 7.57–
7.55 (m, 2H), 2.64 (s, 3H), 1.42 (s, 9H), 1.32 (s, 9H). 13C NMR
(100.6 MHz, CDCl3): d 205.2, 160.1, 140.1, 138.0, 131.4, 124.3,
118.7, 35.1, 34.2, 31.4, 29.3, 27.0.
OH
6a-6h
7a-7h
Entry
R3
R4
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
Me
Ph
Ph
i-Pr
i-Pr
t-Bu
t-Bu
t-Bu
i-Pr
t-Bu
i-Pr
i-Pr
48
46
52
48
51
47
48
49
48
7a; 66
7c; 72
7c0; 68
7d0; 60
7e0; 70
7f; 48
7f0; 50
7g; 80
7h; 43
4.3.2. 1-(3,5-Di-tert-butyl-2-hydroxyphenyl)-2-methylpropan-
1-one 6b
4-MeC6H4
4-t-BuC6H4
3,5-(CF3)2C6H3
3,5-(CF3)2C6H3
4-CF3C6H4
Yield: 76%; pale yellow solid; mp 34.8–35.6 °C (methanol) (lit.18
mp 33.5–34.5 °C). 1H NMR (400 MHz, CDCl3): d 13.26 (s, 1H), 7.65
(d, J = 2.4 Hz, 1H), 7.55 (d, J = 2.4 Hz, 1H), 3.71–3.61 (m, 1H), 1.43
(s, 9H), 1.32 (s, 9H), 1.26 (d, J = 6.8 Hz, 6H). 13C NMR (100.6 MHz,
CDCl3): d 211.4, 160.8, 139.8, 131.1, 123.5, 117.1, 35.2, 35.0, 34.2,
31.4, 29.3, 19.5.
3,4,5-F3C6H2
a
Reaction conditions: Salicylketone 6a–6h (1 mmol), (S)-(+)-valinol or (S)-(+)-
tert-leucinol (1.2 mmol), Na2SO4 (1.0 g), toluene, 110 °C.
b
Isolated yield after column chromatographic purification.
4.3.3. Di-tert-butyl-2-hydroxyphenyl)phenylmethanone 6c
Yield: 79%; pale yellow solid; mp 59.3–61.5 °C (ethanol) (lit.19
mp 60–62 °C). 1H NMR (400 MHz, CDCl3): d 12.71 (s, 1H), 7.67 (d,
J = 6.8 Hz, 2H), 7.59–7.55 (m, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.43–
7.42 (m, 1H), 1.47 (s, 9H), 1.24 (s, 9H). 13C NMR (100.6 MHz,
CDCl3): d 202.5, 160.7, 139.8, 138.6, 137.8, 131.6, 131.2, 129.2,
128.1, 127.8, 118.2, 35.2, 34.2, 31.3, 29.4.
using a Yanako CHN recorder MT-5. Preparative column chroma-
tography was carried out using Fuji Silysia BW-820MH silica gel
or YMC-GEL Silica (6 nm I-40-63 lm). Thin layer chromatography
(TLC) was carried out on Merck 25 TLC aluminium sheets silica
gel 60 F254. Optical rotations were measured on a HORIBA SEPA-
300 polarimeter for solution in a 1 dm cuvette.
4.3.4. (3,5-Di-tert-butyl-2-hydroxyphenyl)p-tolylmethanone 6d
4.2. (1H-Benzo[d][1,2,3]triazol-1-yl)(3,5-di-tert-butyl-2-hydroxy
Yield: 80%; yellow solid; mp 70.5–72.9 °C (ethanol). IR (neat):
m
phenyl)methanone 5
2955, 1614, 1239 cmꢀ1. 1H NMR (400 MHz, CDCl3): d 12.68 (s, 1H),
7.60–7.56 (m, 3H), 7.45 (d, J = 2.4 Hz, 1H), 7.29 (d, J = 7.6 Hz, 2H),
2.45 (s, 3H), 1.47 (s, 9H), 1.24 (s, 9H). 13C NMR (100.6 MHz, CDCl3):
d 202.2, 160.5, 142.3, 139.6, 137.8, 135.9, 130.9, 129.5, 128.8,
127.8, 118.3, 35.2, 34.2, 31.3, 29.4, 21.6. MS (ESI) m/z: 325
(M+H+). Anal. Calcd for C22H28O2: C, 81.44; H, 8.70. Found: C,
81.18; H, 8.78.
To a solution of benzotriazole (17.87 g, 150 mmol) in CH2Cl2
(60 mL), SOCl2 (3.7 mL, 50 mmol) was added dropwise with stir-
ring at room temperature. After 45 min, a solution of carboxylic
acid (12.52 g, 50 mmol) in CH2Cl2 (60 mL) was added. After 24 h,
the solid was filtered and washed with hexane. The solvent was re-
moved under vacuum from the filtrate. To the residue, hexane was

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V. Dhayalan et al. / Tetrahedron: Asymmetry 24 (2013) 543–547
4.3.5. 4-tert-Butylphenyl(3,5-di-tert-butyl-2-hydroxy-
4.4.2. (S,E)-2,4-Di-tert-butyl-6-(1-hydroxy-3-methylbutan-2-
phenyl)methanone 6e
ylimino)phenylmethylphenol 7c
Yield: 94%; yellow thick liquid. IR (neat):
m
2958, 1615,
Yield: 72%; yellow solid; mp: 65.8–68.5 °C. ½a D28
¼ ꢀ30:5 (c 1.0,
ꢂ
1241 cmꢀ1 1H NMR (400 MHz, CDCl3): d 12.66 (s, 1H), 7.55 (d,
.
CHCl3) (lit.11c mp: 67–69 °C, ½a 2D4
ꢂ
¼ ꢀ29:0 (c 1.0, CHCl3). 1H NMR
J = 8.4 Hz, 2H), 7.50 (d, J = 2.4 Hz, 1H), 7.43–7.41 (m, 3H), 1.39 (s,
9H), 1.29 (s, 9H), 1.17 (s, 9H). 13C NMR (100.6 MHz, CDCl3): d
202.1, 160.5, 155.4, 139.6, 137.7, 135.8, 130.9, 129.4, 127.8,
125.1, 118.3, 35.2, 35.0, 34.2, 31.3, 31.2, 29.4. MS (ESI) m/z: 367
(M+H+). Anal. Calcd for C25H34O2: C, 81.92; H, 9.35. Found: C,
81.63; H, 9.46.
(400 MHz, CDCl3): d 7.44–7.7.17 (m, 6H), 6.62 (t, J = 2.0 Hz, 1H),
3.79–3.70 (m, 2H), 3.30–3.26 (m, 1H), 1.93–1.85 (m, 1H), 1.48 (s,
9H), 1.09 (s, 9H), 0.93 (d, J = 6.8 Hz, 3H), 0.85 (d, J = 6.8 Hz, 3H).
13C NMR (100.6 MHz, CDCl3): d 175.9, 160.7, 160.6, 138.1, 137.1,
134.6, 128.5, 128.3, 128.0, 127.8, 127.1, 126.3, 118.7, 67.7, 64.9,
35.2, 33.9, 31.2, 30.4, 29.5, 19.6, 18.8.
4.3.6. 3,5-Bis(trifluoromethyl)phenyl-(3,5-di-tert-butyl-2-hydr-
oxyphenyl)methanone 6f
4.4.3. (S,E)-2,4-Di-tert-butyl-6-(1-hydroxy-3,3-dimethylbutan-
2-ylimino)phenyl-methylphenol 7c0
Yield: 98%; yellow thick liquid. IR (neat):
m
2960, 1628, 1275,
Yield: 68%; yellow solid; mp: 179.5–180.8 °C. ½a D28
¼ ꢀ34:1 (c
ꢂ
1132 cmꢀ1 1H NMR (400 MHz, CDCl3): d 12.36 (s, 1H), 8.16 (s,
.
1.0, CHCl3); (lit.12b mp: 180–181 °C, ½a 2D5
¼ ꢀ25:9 (c 1.0, CHCl3).
ꢂ
2H), 8.09 (s, 1H), 7.66 (d, J = 1.6 Hz, 1H), 7.25 (d, J = 2.4 Hz, 1H),
1.48 (s, 9H), 1.24 (s, 9H). 13C NMR (100.6 MHz, CDCl3): d 198.7,
161.2, 140.8, 140.2, 138.8, 132.5, 132.0 (q, JC–F = 34.8 Hz), 129.6
(m), 127.1, 126.9, 125.0 (m), 124.3, 121.6, 118.9, 117.4, 35.4,
34.3, 31.2, 29.4. MS (ESI) m/z: 447 (M+H+). Anal. Calcd for
1H NMR (400 MHz, CDCl3):
d 7.43–7.37 (m, 5H), 7.17 (d,
J = 4.8 Hz, 1H), 6.62 (d, J = 2.8 Hz, 1H), 3.85–3.77 (m, 2H), 3.29–
3.23 (m, 1H), 1.49 (s, 9H), 1.09 (s, 9H), 0.91 (s, 9H). 13C NMR
(100.6 MHz, CDCl3): d 176.0, 160.6, 138.0, 137.0, 134.5, 129.0,
128.5, 128.1, 127.8, 127.0, 126.5, 118.2, 70.8, 63.4, 35.2, 34.0,
33.8, 31.2, 29.5, 27.1.
C23H24F6O2: C, 61.88; H, 5.42. Found: C, 61.63; H, 5.70.
4.3.7. 3,5-Di-tert-butyl-2-hydroxyphenyl-(4-trifluoromethylphenyl)-
methanone 6g
4.4.4. (S,E)-2,4-Di-tert-butyl-6-(1-hydroxy-3,3-dimethylbutan-
2-ylimino)p-tolyl-methylphenol 7d0
Yield: 59%; yellow solid; mp 96.4–97.2 °C (ethanol). IR (neat):
m
Yield: 60%; yellow solid; mp: 200.4–202.0 °C. ½a D27
ꢂ
¼ ꢀ38:7 (c
2960, 1613, 1322, 1137 cmꢀ1 1H NMR (400 MHz, CDCl3): d 12.60
.
1.0, CHCl3). IR (neat):
m
3422, 2955, 1580 cmꢀ1
.
1H NMR
(s, 1H), 7.77 (s, 4H), 7.64 (d, J = 2.4 Hz, 1H), 7.34 (d, J = 2.4 Hz,
1H), 1.48 (s, 9H), 1.24 (s, 9H). 13C NMR (100.6 MHz, CDCl3): d
201.1, 160.9, 141.9, 141.8, 140.3, 138.3, 133.1 (q, JC–F = 33.1 Hz),
131.9, 129.3, 127.3, 125.2 (m), 125.0, 122.3, 117.8, 35.2, 34.2,
31.2, 29.4. MS (ESI) m/z: 379 (M+H+). Anal. Calcd for C22H25F3O2:
C, 69.82; H, 6.66. Found: C, 69.62; H, 6.80.
(400 MHz, CDCl3): d 7.38 (d, J = 2.8 Hz, 1H), 7.25–7.22 (m, 3H),
7.05 (d, J = 7.2 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 3.81–3.77 (m, 2H),
3.31–3.24 (m, 1H), 2.42 (s, 3H), 1.48 (s, 9H), 1.10 (s, 9H), 0.90 (s,
9H). 13C NMR (100.6 MHz, CDCl3): d 176.4, 160.7, 138.2, 137.9,
137.0, 131.5, 128.8, 128.4, 128.1, 127.0 126.6, 118.9, 70.6, 63.4,
35.2, 34.0, 33.8, 31.3, 29.5, 27.1, 21.4. MS (ESI) m/z: 424 (M+H+).
Anal. Calcd for C28H41NO2: C, 79.39; H, 9.76; N, 3.31. Found: C,
79.15; H, 9.50; N, 3.42.
4.3.8. 3,5-Di-tert-butyl-2-hydroxyphenyl-(3,4,5-trifluorophenyl)-
methanone 6h
Yield: 51%; yellow solid; mp 103.8–104.5 °C (ethanol). IR (neat):
4.4.5. (S,E)-2,4-Di-tert-butyl-6-(4-tert-butylphenyl)(1-hydroxy-
m
2960, 1613, 1359, 1048 cmꢀ1. 1H NMR (400 MHz, CDCl3): d 12.26
3,3-dimethylbutan-2-ylimino)methylphenol 7e0
(s, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.37–7.32 (m, 3H), 1.46 (s, 9H), 1.26
(s, 9H). 13C NMR (100.6 MHz, CDCl3): d 198.2, 160.8, 152.1
(q, JC–F = 3.3 Hz), 149.6 (q, JC–F = 3.3 Hz), 143.4 (t, JC–F = 14.9 Hz),
140.8 (t, JC–F = 15.7 Hz), 140.4, 138.5, 134.1 (q, JC–F = 6.6 Hz),
132.1, 126.8, 117.3, 114.0 (q, JC–F = 5.8 Hz), 35.3, 34.3, 31.2, 29.3.
MS (ESI) m/z: 365 (M+H+). Anal. Calcd for C21H23F3O2: C, 69.22;
H, 6.36. Found: C, 68.92; H, 6.51.
Yield: 70%; yellow thick liquid; ½a D27
¼ ꢀ33:7 (c 1.0, CHCl3). IR
ꢂ
(neat):
m .
3393, 2956, 1583 cmꢀ1 1H NMR (400 MHz, CDCl3): d
7.45 (t, J = 8.4 Hz, 2H), 7.36 (d, J = 2.4 Hz, 1H), 7.28 (d, J = 8.0 Hz,
1H), 7.10 (d, J = 7.2 Hz, 1H), 6.58 (d, J = 2.4 Hz, 1H), 3.86–3.78 (m,
2H), 3.35–3.28 (m, 1H), 1.48 (s, 9H), 1.37 (s, 9H), 1.08 (s, 9H),
0.92 (s, 9H); 13C NMR (100.6 MHz, CDCl3) d 176.5, 160.7, 151.5,
137.9, 137.0, 131.5, 128.6, 127.9, 127.0, 126.5, 124.9, 124.6,
119.0, 70.7, 63.4, 35.2, 34.7, 33.9, 33.8, 31.3, 31.2, 29.5, 27.1,
22.6, 14.1. MS (ESI) m/z: 466 (M+H+). Anal. Calcd for C31H47NO2:
C, 79.95; H, 10.17; N, 3.01. Found: C, 79.67; H, 10.49; N, 3.05.
4.4. General procedure for the synthesis of keto-imine type
chiral Schiff bases 7a–7h
A mixture of toluene (10 mL), (S)-valinol or (S)-tert-leucinol
(1.20 mmol), salicylketone 6a–6h (1.0 mmol) and anhydrous
Na2SO4 (1.0 g) was refluxed at 115 °C for the indicated reaction
time (Table 2). The mixture was filtered through a glass filter and
the filtrate was evaporated. The residue was subjected to column
chromatography on silica gel using hexane/ethyl acetate (5:1) as
an eluent to afford the corresponding ONO-tridentate chiral Schiff
base ligands 7a–7h.
4.4.6. (S,E)-2-3,5-Bis(trifluoromethyl)phenyl-(1-hydroxy-3-
methylbutan-2-ylimino)methyl-4,6-di-tert-butylphenol 7f
Yield: 48%; yellow solid; mp: 131.8–132.8 °C. ½a D27
ꢂ
¼ ꢀ7:3 (c
1.0, CHCl3). IR (neat):
m .
3585, 2960, 1583, 1277, 1129 cmꢀ1 1H
NMR (400 MHz, CDCl3): d 8.00 (s, 1H), 7.95 (s, 1H), 7.68 (s, 1H),
7.42 (d, J = 2.4 Hz, 1H), 6.39 (d, J = 2.4 Hz, 1H), 3.84–3.79 (m, 2H),
3.16–3.11 (m, 1H), 1.93–1.85 (m, 1H), 1.48 (s, 9H), 1.09 (s, 9H),
0.95 (d, J = 6.8 Hz, 3H), 0.85 (d, J = 6.8 Hz, 3H). 13C NMR
(100.6 MHz, CDCl3): d 172.1, 160.2, 139.0, 137.7, 136.9, 131.7 (q,
JC–F = 18.2 Hz), 129.8, 128.4, 127.7, 125.5, 124.4, 122.4 (m), 121.7,
117.9, 68.7, 65.0, 35.3, 34.0, 31.1, 30.7, 29.5, 19.7, 18.7. MS (ESI)
m/z: 532 (M+H+). Anal. Calcd for C28H35F6NO2: C, 63.26; H, 6.64;
N, 2.63. Found: C, 63.43; H, 6.74; N, 2.74.
4.4.1. (S,E)-2,4-Di-tert-butyl-6-1-(1-hydroxy-3-methylbutan-2-
ylimino)ethylphenol 7a
Yield: 66%; yellow solid; mp 32.1–33.5 °C. ½a D28
¼ ꢀ30:4 (c 1.0,
ꢂ
CHCl3) {lit.11c mp: 32–34 °C, ½a 2D4
ꢂ
¼ ꢀ31:6 (c 1.0, CHCl3)}. 1H
NMR (400 MHz, CDCl3):
d 7.44 (d, J = 2.8 Hz, 1H), 7.40 (d,
J = 2.0 Hz, 1H), 3.86–3.70 (m, 3H), 2.41 (s, 3H), 2.01–1.92 (m, 1H),
1.44 (s, 9H), 1.32 (s, 9H), 0.97–0.95 (m, 6H). 13C NMR
(100.6 MHz, CDCl3): d 172.9, 161.1, 137.9, 137.7, 127.1, 122.4,
118.1, 66.4, 64.9, 35.2, 34.2, 31.5, 30.6, 29.5, 19.6, 18.8, 15.1.
4.4.7. (S,E)-2-3,5-Bis(trifluoromethyl)phenyl-(1-hydroxy-3,3-
dimethylbutan-2-ylimino)methyl-4,6-di-tert-butylphenol 7f0
Yield: 50%; yellow solid; mp: 149.4–150.8 °C. ½a D28
¼ ꢀ8:1 (c
ꢂ
1.0, CHCl3) (lit.12b mp: 149–150 °C, ½a 2D9
ꢂ
¼ ꢀ7:6 (c 1.0, CHCl3). 1H

V. Dhayalan et al. / Tetrahedron: Asymmetry 24 (2013) 543–547
547
NMR (400 MHz, CDCl3): d 8.02 (s, 1H), 7.99 (s, 1H), 7.67 (s, 1H),
7.42 (d, J = 1.6 Hz, 1H), 6.38 (d, J = 2.4 Hz, 1H), 3.92–3.79 (m, 2H),
3.08–3.05 (m, 1H), 1.49 (s, 9H), 1.09 (s, 9H), 0.92 (s, 9H). 13C
NMR (100.6 MHz, CDCl3): d 171.9, 160.2, 138.9, 137.6, 136.8,
131.5 (q, JC–F = 25.6 Hz), 130.2, 128.6, 127.6, 125.5, 124.3, 122.3
(m), 121.6, 118.0, 71.8, 63.1, 35.3, 34.0, 33.9, 31.1, 29.5, 27.0.
Directed toward Straightforward Synthesis’, No. B23350043 from
the Ministry of Education, Culture, Sports, Science and Technology,
Japan. Special Coordination Funds for Promoting Science and Tech-
nology, Creation of Innovation Centers for Advanced Interdisciplin-
ary Research Areas (Innovative Bioproduction Kobe), MEXT, Japan
is also acknowledged.
4.4.8. (S,E)-2,4-Di-tert-butyl-6-(1-hydroxy-3-methylbutan-2-yl-
References
imino)(4-trifluoromethyl phenyl)methylphenol 7g
Yield: 80%; yellow solid; mp: 190.0–190.5 °C. ½a D27
ꢂ
¼ ꢀ15:6 (c
1. (a) Hayashi, M.; Miyamoto, Y.; Inoue, T.; Oguni, N. J. Chem. Soc., Chem. Commun.
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1.0, CHCl3). IR (neat):
m .
3465, 2960, 1584, 1322, 1121 cmꢀ1 1H
NMR (400 MHz, CDCl3):
d 7.74 (d, J = 8.4 Hz, 2H), 7.48 (d,
2. (a) Carreira, E. M.; Singer, R. A.; Lee, W. J. Am. Chem. Soc. 1994, 116, 8837; (b)
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J = 8.0 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H),
6.51 (d, J = 2.4 Hz, 1H), 3.80–3.75 (m, 2H), 3.20–3.15 (m, 1H),
1.92–1.82 (m, 1H), 1.48 (s, 9H), 1.09 (s, 9H), 0.93 (d, J = 6.8 Hz,
3H), 0.85 (d, J = 6.8 Hz, 3H). 13C NMR (100.6 MHz, CDCl3): d
174.3, 160.3, 138.7, 138.4, 137.4, 130.8 (q, JC–F = 32.2 Hz), 129.3,
128.4, 127.4, 125.9, 125.3 (m), 122.5, 118.3, 68.2, 65.0, 35.2, 34.0,
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for C27H36F3NO2: C, 69.95; H, 7.83; N, 3.02. Found: C, 69.77; H,
7.95; N, 3.08.
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4.4.9. (S,E)-2,4-Di-tert-butyl-6-(1-hydroxy-3-methylbutan-2-yli-
mino)(3,4,5-trifluorophenyl)methylphenol 7h
Yield: 43%; yellow solid; mp: 165.8–166.3 °C. ½a D26
ꢂ
¼ ꢀ13:8 (c
11. (a) Hayashi, M.; Inoue, T.; Oguni, N. J. Chem. Soc., Chem. Commun. 1994, 341; (b)
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1.0, CHCl3). IR (neat):
m .
3592, 2955, 1585, 1366, 1039 cmꢀ1 1H
NMR (400 MHz, CDCl3): d 7.41 (d, J = 2.4 Hz, 1H), 7.10 (s, 1H),
6.84 (s, 1H), 6.57 (d, J = 2.8 Hz, 1H), 3.78 (t, J = 5.2 Hz, 2H), 3.24–
3.20 (m, 1H), 1.90–1.84 (m, 1H), 1.47 (s, 9H), 1.14 (s, 9H), 0.93
(d, J = 6.8 Hz, 3H), 0.87 (d, J = 6.8 Hz, 3H). 13C NMR (100.6 MHz,
CDCl3): d 171.9, 160.1, 152.3, 149.8, 141.0 (t, JC–F = 14.9 Hz),
138.8, 138.5 (t, JC–F = 14.9 Hz), 137.5, 130.5 (q, JC–F = 6.6 Hz),
127.6, 125.5, 117.8, 113.8 (d, JC–F = 16.5 Hz), 112.5 (d,
JC–F = 19.9 Hz), 68.4, 64.9, 35.2, 34.0, 31.2, 30.6, 29.4, 19.6, 18.8.
MS (ESI) m/z: 450 (M+H+). Anal. Calcd for C26H34F3NO2: C, 69.46;
H, 7.62; N, 3.12. Found: C, 69.39; H, 7.72; N, 3.11.
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Acknowledgments
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This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas, MEXT, Japan ‘Molecular Activation